bluuebunny/crossref_metadata_2025 huggingface dataset:
Perceptual adaptation to regional vowel variation
Authors: Dossey Ellen
Published: November 2019

Listeners cope with between-talker phonetic variation by adapting their phonemic category boundaries based on evidence from individuals’ speech. The current project examined perceptual adaptation to dialect-based variation in the vowels /ɛ/ and /ʌ/, which have lower second formant (F2) frequencies in the Northern dialect of American English relative to the Midland dialect. In a forced-choice lexical identification task, participants identified auditory word tokens which contained vowels along an /ɛ/-/ʌ/ continuum. Words were presented in carrier sentences spoken by either a Northern or Midland talker, and phonemic category boundaries were estimated based on perception of the vowel continuum. Phonemic category boundaries occurred at lower F2s when stimulus words were presented in Northern sentences rather than Midland sentences, indicating perceptual adaptation consistent with the acoustic difference between the dialects. However, this effect was influenced by the phonetic content of the carrier sentence. Adaptation was only consistently found for carrier sentences that included natural tokens of /ɛ/ or /ʌ/, even though all carrier sentences included dialect-specific phonetic features. This suggests that participants were not sensitive to patterns of co-variation among vowels within the two dialects. Rather, they adapted their /ɛ/-/ʌ/ boundary for individual talkers only when provided with direct evidence for that boundary.
Does noise sensitivity mediate physiological measures of listening effort?
Authors: Francis Alexander L. , Love Jordan , Boutin Mireille
Published: November 2019

Listening to speech in background noise is cognitively demanding and has been shown to engage frontal cortical regions associated with selective attention and cognitive control. However, especially for noise-sensitive individuals, the presence of interfering or distracting noise may also provoke anxiety or frustration, and these same frontal cortical regions also participate in brain networks associated with anxiety and distress. Thus, it is not clear whether previous results showing enhanced frontal activity when listening to speech in noise reflect cognitive effort, noise annoyance, or both. In order to investigate the possibility of dissociating these two aspects of listening to speech in adverse conditions, we will examine the degree to which measures of individual differences in personality traits, noise sensitivity, and cognitive capacities (attention, working memory) predict behavioral and physiological measures associated with listening effort and affective response. Specifically, we will record cardiovascular and electroencephalographic responses to listening to speech in three levels of two types of industrial background noise. The noise types differ only in terms of the relative degree of acoustic properties associated with noise annoyance (tonality, sharpness) instantiated mainly through differences at frequencies not overlapping with those of the speech target.
Speaking clearly improves speech segmentation in optimal listening conditions
Authors: Guo Zhe-chen , Smiljanic Rajka
Published: November 2019

Speaking clearly improves intelligibility particularly in noisy environments—a benefit that may be partly attributed to enhanced ease of speech segmentation. However, speech segmentation is facilitated by coarticulation (Fernandes et al., 2007), which may be reduced in hyper-articulated clear speech (Scarborough and Zellou, 2013). This study investigated the effect of clear speech on speech segmentation in quiet and in noise for native and non-native listeners with an artificial language (AL) learning experiment. Six trisyllabic AL words (e.g., /kutupi/) were produced by a native English speaker both clearly and conversationally. Six speech streams were created, each containing 20 pitch-flattened tokens of each AL word concatenated in random order without intervening pauses. In the learning phase, participants heard either conversational or clear AL speech streams in quiet or masked with speech-shaped noise. Next, in a two-alternative forced-choice test, participants identified the AL words spoken in quiet and in the style they were exposed to. Preliminary results showed that clear speech improved segmentation relative to conversational speech for native English listeners in quiet only. The results suggest that the use of exaggerated information about segment identity aids speech segmentation in optimal listening conditions but is disrupted under perceptual load.
Background music contributes to error in the operating room
Authors: Bruder Alexandra L. , Burdick Kendall , Beebe Russ , Rothwell Clayton , Schlesinger Joseph
Published: November 2019

Music and alarms have both been shown to improve performance in surgeons in the operating room (OR), but may interfere with anesthesiologist communication and performance. This experiment investigated the effects of music and alarms on speech intelligibility in a cognitively demanding multitask setting using simulated clinical, speech intelligibility, and visual vigilance tasks. Anesthesiology residents’ (n = 25) speech intelligibility performance was measured using the Coordinate Response Measure (CRM) in a 2 × 2 within-subjects design that varied background (simulated OR noise or OR noise with music, both normalized to 60 dB SPL) and alarm type (conventional or a novel auditory icon conforming to IEC 60601-1-8). Linear mixed-effects models showed music had a significant reduction in accuracy (p < 0.001), increased RT (p < 0.001), more instances of no response (p < 0.001). With music, average RT was increased by ∼0.2 s (95% CI: 0.07, 0.39), the odds of a correct response were reduced by ∼39% (95% CI: 25, 50), and the odds of no response were increased by 340% (95% CI: 246, 467). There was no evidence that alarm type impacted CRM performance. A device that modulates music volume during critical phases could reduce communication interference.
A multivariate analysis of vessel source levels from the enhancing Cetacean habitat observation (ECHO) ship noise database
Authors: MacGillivray Alexander O. , Hannay David E. , Frouin-Mouy Heloise
Published: November 2019

The Vancouver Fraser Port Authority’s Enhancing Cetacean Habitat Observation (ECHO) program acquired a large database of several thousand systematic commercial ship noise measurements between September 2015 and April 2017. These measurements were used to develop a multi-variate linear regression model of vessel source levels against several parameters that describe vessels and their measurement conditions. Covariates in the multi-variate model included ship category, ship length, dead-weight-tonnage, static draught, effective wind speed magnitude and direction, ship speed, and surface angle. The regression analysis examined the statistical significance of each covariate’s regression coefficient and produced a set of fit coefficients, one for each covariate for each frequency band. The multi-variate model was used to normalize the measurements for each category, and the remaining data variance reflected vessel-specific differences in noise emissions that could not be attributed to measurement circumstances. The multivariate analysis produced a powerful ship noise model that can predict decidecade band monopole source level (MSL) and radiated noise level (RNL), which is useful for understanding noise emissions variations with ship characteristics and under different operating conditions. [This research was funded by Transport Canada.]
Stormquakes: Tracing the path of ocean storms through the solid earth
Authors: de Groot-Hedlin Catherine , Fan Wenyuan , McGuire Jeffrey , Sloan Coats , Fiedler Julia
Published: November 2019

We have discovered a new geophysical phenomenon involving the coupling of the atmosphere-ocean and solid Earth using a novel array method. An analysis of ten years of seismic data recorded in the continental United States, mainly at the USArray, shows that large storms such as hurricanes and Nor’easters can excite transient seismic surface waves in the 20–50 s band with amplitudes equivalent to those excited by M3.5 earthquakes. These sources, which we label stormquakes, can produce transcontinental coherent Rayleigh wave packets observable in the time domain and are thus fundamentally different from previously reported atmosphere-ocean solid Earth couplings that produce incoherent seismic noise. We present unique observations and methods to pinpoint the source locations and timing, which clearly shows that these seismic waves are from interactions of seafloor bathymetry and ocean waves that are energized by large storms. Stormquakes migrate along continental shelfbreak, tracking the leading edge of large storms. We have documented features and identified a possible physical mechanism explaining the stormquake excitation. Stormquakes have potential use in oceanography and meteorology as a remote monitoring tool with high spatial and temporal resolution with which to investigate ocean wave dynamics during large storms.
Mesocopic wave physics in a dense fish school
Authors: Tallon Benoit , Roux Philippe , Matte Guillaume , Skipetrov Sergey
Published: November 2019

Multiple scattering phenomena of acoustic waves are studied in a dense school of fish. A 3-D multibeam sonar is used to probe the backscattered intensity from a dense school fish contained in an open sea cage. The signature of wave interferences in this mesoscopic and quasi-natural media is shown by measuring coherent backscattering (CBE) effects. In particular, the static and time-resolved measurements of the CBE profile provide estimations of transport parameters such as the transport mean free path l* and the energy velocity of diffusive waves ve. It turns out that fish can scatter sound very strongly, allowing one to achieve a transport mean free path comparable with the wavelength of ultrasound. In this case, traditional fisheries acoustics methods are compromised by multiple scattering effects. Thus, this new approach could help to overcome issues encountered in aquaculture to evaluate the total biomass of dense schools of fish.
Governing Integration in Sport Systems: A Case Study of Swimming Canada
Authors: Misener Laura , Bodin Kerri , Kay Marika
Published: November 2019

This case follows Katie, a sport manager, as she researches Swimming Canada, an early adopter of integration (governing both able-bodied and para-swimming within one organization). The case demonstrates the organizational challenges and opportunities of integrating parasport and the able-bodied counterpart into one national sport governing body. While philosophically integration seems to be a good direction, the case of Swimming Canada demonstrates some of the key issues that need to be considered around access and inclusion, human capital resources for sport delivery, governance mechanisms, and the structure of sport that is influenced by many different social constructs. This case is particularly useful for addressing how sport policy and politics impact organizational change, inclusion, equity, and sport governance. The case is appropriate for use at the undergraduate and graduate levels.
Recycling resected tonsils for lymphoma research
Authors: Jeyasekharan Anand D.
Published: November 2019

Tonsillectomy samples can be used to generate in vitro models of high-grade B cell lymphoma.
Chemical Targeting and Manipulation of Type III Secretion in the Phytopathogen Xanthomonas campestris for Control of Disease
Authors: Zhou Le , Wang Cheng , Wang Guo-Hua , Wei Zai-Wa , Fu Qiu-Xia , Hang Xiao-Hong , Yang Mei , Jiang Bo-Le , Tang Ji-Liang
Published: November 2019

The bacterium
Xanthomonas campestris
pv. campestris is known to cause black rot disease in many socioeconomically important vegetable crops worldwide. The management and control of black rot disease have been tackled with chemical and host resistance methods with variable success. This has motivated the development of alternative methods for preventing this disease. Here, we identify a set of novel small molecules capable of inhibiting
X. campestris
pv. campestris virulence, which may represent leading compounds for the further development of antivirulence agents that could be used in the control of black rot disease.
Clinically stable disease is associated with a lower risk of both income loss and disability pension for patients with multiple sclerosis
Authors: Chalmer Thor Ameri , Buron Mathias , Illes Zsolt , Papp Viktoria , Theodorsdottir Asta , Schäfer Jakob , Hansen Victoria , Asgari Nasrin , Skejø Pernille Bro , Jensen Henrik Boye , Sørensen Per Soelberg , Magyari Melinda
Published: November 2019

Objective

To assess the risk of losing income from salaries and risk disability pension for multiple sclerosis patients with a clinically stable disease course 3 years after the start of disease-modifying therapy (DMT).

Methods

Data from the Danish Multiple Sclerosis Registry were linked to other Danish nationwide population-based databases. We included patients who started treatment with a DMT between 2001 and 2014. Patients were categorised into a clinically stable group (No Evidence of Disease Activity (NEDA-2)) and a clinically active group (relapse activity or 6-month confirmed Expanded Disability Status Scale worsening). Outcomes were: (1) loss of regular income from salaries and (2) a transfer payment labelled as disability pension. We used a Cox proportional hazards model to estimate confounder-adjusted HRs, and absolute risks were plotted using cumulative incidence curves accounting for competing risks.

Results

We included 2406 patients for the income analyses and 3123 patients for the disability pension analysis. Median follow-up from index date was ~5 years in both analyses. The NEDA-2 group had a 26% reduced rate of losing income (HR 0.74; 95% CI 0.60 to 0.92). HRs were calculated for 5-year intervals in the disability pension analysis: year 0–5: a 57% reduced rate of disability pension for the NEDA-2 group (HR 0.43; 95% CI 0.33 to 0.55) and year 5–10: a 36% reduced rate (HR 0.64; 95% CI 0.40 to 1.01).

Conclusion

Clinically stable disease course (NEDA-2) is associated with a reduced risk of losing income from salaries and a reduced risk of disability pension.
Permutation groups and orbits on the power set
Authors: Yang Yong
Published: November 2019

Let [Formula: see text] be a permutation group of degree [Formula: see text] and let [Formula: see text] denote the number of set-orbits of [Formula: see text]. We determine [Formula: see text] over all groups [Formula: see text] that satisfy certain restrictions on composition factors.
Comparison of local cohomlogy modules of a ring and its amalgamated algebra along a given ideal
Authors: Naal Batoul , Khashyarmanesh Kazem
Published: November 2019

Let [Formula: see text] be a commutative Noetherian ring and let [Formula: see text] and [Formula: see text] be ideals of [Formula: see text]. The main purpose of this paper is to compare of the finiteness properties of [Formula: see text] and [Formula: see text], where [Formula: see text] is the [Formula: see text]th local cohomology module functor with respect to [Formula: see text] and [Formula: see text] is the amalgamated of [Formula: see text] along [Formula: see text].
Designing for Awareness in Interactions with Shared Systems
Authors: Niemantsverdriet Karin , Essen Harm Van , Pakanen Minna , Eggen Berry
Published: November 2019

Most systems that we use in everyday life are shared—because multiple people can interact or because an interaction by one person can affect other people. However, everyday Internet of Things systems are often designed for individual use. Prior research on collaboration technologies (Computer Supported Collaborative Work) has shown that to coordinate system sharing people require awareness of the social context, which interfaces can support by making salient information visible. Although literature exists on how to design for awareness, this can be fragmented and difficult to relate to other application domains. To introduce a broader audience of interaction designers to awareness, we aim to make the available design knowledge more generalizable and operational. With this aim, we construct the Designing for Awareness in Shared Systems framework that gives a structured and comprehensive overview of design considerations for awareness. The framework can stimulate reflection and inform decision-making when designing interactions with shared systems.
Passages
Authors: Groce Alex
Published: November 2019

Gerald M. Weinberg's An Introduction to General Systems Thinking is this month's Passages selection. Weinberg's Psychology of Computer Programming was last month's Passages selection. I believe that many more software engineers have read last month's selection than this month's. Some of the virtues of Psychology are shared by this book: Weinberg's engaging writing style, cultural and literary fluency, clever questions for further research, intellectually exciting suggested readings, and overall combination of a bigpicture theoretical framework that is suggestive and powerful with a practical, anecdotal approach that makes it possible to get down to brass tacks. However, the two books are also very different: unsurprisingly, the Psychology is clearly a very relevant book for software engineers, about the human dimension of programming computers. An Introduction to General Systems Thinking uses computer programming, as an example of a way to go about doing general systems thinking, but it is not really a "computer" book, specifically, at all. It is what it says it is.
SST'19 - Software and Systems Traceability
Authors: Steghöfer Jan-Philipp , Niu Nan , Guo Jin L.C. , Mahmoud Anas
Published: November 2019

Traceability is the ability to relate di erent artifacts during the development and operation of a system to each other. It enables program comprehension, change impact analysis, and facilitates the cooperation of engineers from di erent disciplines. The 10th International Workshop on Software and Systems Traceability (former International Workshop on Traceability in Emerging Forms of Software Engineering, TEFSE), explored the role and impact of traceability in modern software and systems development. The event brought together researchers and practitioners to examine the challenges of recovering, maintaining, and utilizing traceability for the myriad forms of software and systems engineering artifacts. SST'19 was a highly interactive working event focused on discussing the main problems related to software traceability in particular in the context of opportunities and challenges posed by the recent progress in Arti cial Intelligence techniques and proposing possible solutions for such problems.
Workshop Summary
Authors: Tonelli Roberto , Ortu Marco , Ducasse Stephane , Marchesi Michele
Published: November 2019

The second Workshop on Emerging Trends in Software Engineering for Blockchain (WETSEB 2019) intends to pursue the experience of WETSEB 2018 which inherited from the past eight editions of WETSoM (Workshop on Emerging Trends on Software Metrics) the challenges of gathering together researchers interested in emerging topics and trends in software engineering.

WETSEB 2018 marked a transition in the workshop interest from the software metrics to the newly emerging fields of research in a software technology whose powerful wide-spreading is disruptively invading academy, industry, finance and media: the Blockchain software technology.

Motivations for this workshop are augmented since last edition given the clear outstanding interest in software communities, in the academy, in the industry, in the finance and in the media on the new emerging software technology of the Blockchain witnessed by the larger and larger amount of publications, of start-ups and companies which last year exploited this new technology. We first outline the aims of the workshop, followed by a discussion of its keynote speech and technical program.
Design Science for PhD Research in the Software Engineering Domain
Authors: Pastor Oscar
Published: November 2019

The keynote introduced the principles of Design Science with the perspective developed by Prof. Roel Wieringa in his book "Design Science", clearly distinguishing between questions of knowledge and engineering problems, and introducing the research cycles that correspond to each case. A rigorous framework for the structuring and development of Doctoral Thesis work will be presented from a methodological point of view and with concrete examples, which participants will be able to apply to their Doctoral Thesis work. The final objective is that doctoral students know how to apply the principles of Design Science to the development and management of their scientific work and can use an effective research methodology, well supported by clear concepts and efficient in their application.
Zero-Interaction Security-Towards Sound Experimental Validation
Authors: Fomichev Mikhail , Maass Max , Hollick Matthias
Published: November 2019

Reproducibility and realistic datasets are crucial for advancing research. Unfortunately, they are often neglected as valid scientific contributions in many young disciplines, with computer science being no exception. In this article, we show the challenges encountered when reproducing the work of others, collecting realistic data in the wild, and ensuring that our own work is reproducible in turn. The presented findings are based on our study investigating the limits of zero-interaction security (ZIS)- a novel concept, leveraging sensor data collected by Internet of Things (IoT) devices to pair or authenticate devices. In particular, we share our experiences in reproducing five state-of-the-art ZIS schemes, collecting a comprehensive dataset of sensor data from the real world, evaluating these schemes on the collected data, and releasing the data, code, and documentation to facilitate reproducibility of our results.
Integration of BIM and Energy Consumption Modelling for Manufacturing Prefabricated Components: A Case Study in China
Authors: Xu Zhao , Wang Shaozhe , Wang Endong
Published: November 2019

Prefabrication is undergoing significant growth in the building and construction sector in China. Meanwhile, the integrated measurement and reduction solution for energy consumption is quickly becoming an important target of scientific efforts and research, especially in prefabricated buildings. Embedded energy consumption requirements can potentially be reduced during the manufacturing process of prefabricated components: the opportunity for its reduction can be significant. This paper aims to propose a BIM and LCA integrated approach that enables the energy consumption of prefabricated components in the manufacturing stage to be extracted and calculated in order to obtain a clear, precise understanding of the energy consumption management in prefabrication. To enhance the energy consumption description of prefabricated components, this paper clarifies the contents of energy consumption inventory and related calculation formula in raw material extraction and production, material transportation, and factorized production of prefabricated components, respectively. Specifically, considering that current Industry Foundation Classes (IFC) standard does not accommodate entities with energy consumption information or relationships, it applies the IFC extension method to connect the energy consumption inventory with the BIM model. The proposed approach is applied and verified in a case study from China. This study reveals that energy consumption control should be investigated in the element level considering the differences of various prefabricated components’ requirements in the manufacturing stage.
Dual Pharmacological Inhibition of Angiopoietin-2 and VEGF-A in Murine Experimental Sepsis
Authors: Hauschildt Janine , Schrimpf Claudia , Thamm Kristina , Retzlaff Jennifer , Idowu Temitayo O. , von Kaisenberg Constantin , Haller Hermann , David Sascha
Published: November 2019

Background: Sepsis is a pathological host response to infection leading to vascular barrier breakdown due to elevated levels of angiopoietin-2 (Angpt-2) and vascular endothelial growth factor-A (VEGF-A). Here, we tested a novel heterodimeric bispecific monoclonal IgG1-cross antibody of Angpt-2 and VEGF – termed “A2V.” Methods: Cecal ligation and puncture was used to induce murine polymicrobial sepsis. Organs and blood were harvested for fluorescence immunohistochemistry and RT-PCR, and survival was recorded. In vitro endothelial cells were stimulated with plasma from septic shock patients costimulated with A2V or IgG antibody followed by immunocytochemistry and real-time transendothelial electrical resistance. Results: Septic mice treated with A2V had a reduced induction of the endothelial adhesion molecule ICAM-1, leading to a trend towards less transmigration of inflammatory cells (A2V: 42.2 ± 1.0 vs. IgG 48.5 ± 1.7 Gr-1+ cells/HPF, p = 0.08) and reduced tissue levels of inflammatory cytokines (e.g., IL-6 mRNA: A2V 9.4 ± 3.2 vs. IgG 83.9 ± 36.7-fold over control, p = 0.03). Endothelial permeability was improved in vivo and in vitro in stimulated endothelial cells with septic plasma. Survival was improved by 38% (p = 0.02). Conclusion: Dual inhibition of Angpt-2 and VEGF-A improves murine sepsis morbidity and mortality, making it a potential therapeutic against vascular barrier breakdown.
2019 American Heart Association Focused Update on Systems of Care: Dispatcher-Assisted Cardiopulmonary Resuscitation and Cardiac Arrest Centers: An Update to the American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care
Authors: Panchal Ashish R. , Berg Katherine M. , Cabañas José G. , Kurz Michael C. , Link Mark S. , Del Rios Marina , Hirsch Karen G. , Chan Paul S. , Hazinski Mary Fran , Morley Peter T. , Donnino Michael W. , Kudenchuk Peter J.
Published: November 2019

Survival after out-of-hospital cardiac arrest requires an integrated system of care (chain of survival) between the community elements responding to an event and the healthcare professionals who continue to care for and transport the patient for appropriate interventions. As a result of the dynamic nature of the prehospital setting, coordination and communication can be challenging, and identification of methods to optimize care is essential. This 2019 focused update to the American Heart Association systems of care guidelines summarizes the most recent published evidence for and recommendations on the use of dispatcher-assisted cardiopulmonary resuscitation and cardiac arrest centers. This article includes the revised recommendations that emergency dispatch centers should offer and instruct bystanders in cardiopulmonary resuscitation during out-of-hospital cardiac arrest and that a regionalized approach to post–cardiac arrest care may be reasonable when comprehensive postarrest care is not available at local facilities.
Digital India’s Smart Transform-Nation: Enabling or Discouraging a ‘Chatur Citizenry’?
Authors: Ruiz Andrade Michelle
Published: November 2019

Instead of exploring ‘smart cities’ as future utopias, this paper concentrates on historically constructed, yet actively contested socio-spatial inequalities. Drawing upon Chandigarh’s master-planning experience, it explores epistemic, material, and civic dimensions of Chandigarh’s Smart City Proposal to ask whether vernacular reinterpretations of ‘smart citizenry’ help the subaltern reclaim their ‘right to the city’. Thus, following a critical genealogy that shifts attention from ‘smart cities’ towards ‘citizen centeredness’, this research focuses on the construction and contestation of ‘smart citizenship’. Overall, technocratic and city-branding discourses, which legitimate restricting funds to a ‘smart enclave’ at the cost of evictions and banning ‘encroachers’, are confronted by housing rights activists. This motivates scholars to theorize a subversive identity, in which ‘smartness’ gains new meaning. However, epistemic contestations are not enough to create recognition for the needs and rights of the working poor, who work for but cannot reside in Chandigarh. Further alliances and political will are required.
Oreocharis maximowiczii var. mollis (Gesneriaceae), a new variety from Fujian, China

Authors: YI RAN , LI XIAO JING , LI JIA MEI
Published: November 2019

Oreocharis maximowiczii var. mollis, a new variety of Oreocharis (Gesneriaceae) from Taining county, Fujian, China, is described. The new variety is similar to Oreocharis maximowiczii var. maximowiczii, but differs in having peduncle and pedicel densely brown woolly and glandular pubescent, and corolla and pistil densely glandular pubescent.
Effects of Climate Modes on Interannual Variability of Upwelling in the Tropical Indian Ocean
Authors: Zhang Xiaolin , Han Weiqing
Published: November 2019

This paper investigates interannual variability of the tropical Indian Ocean (IO) upwelling through analyzing satellite and in situ observations from 1993 to 2016 using the conventional Static Linear Regression Model (SLM) and Bayesian Dynamical Linear Model (DLM), and performing experiments using a linear ocean model. The analysis also extends back to 1979, using ocean–atmosphere reanalysis datasets. Strong interannual variability is observed over the mean upwelling zone of the Seychelles–Chagos thermocline ridge (SCTR) and in the seasonal upwelling area of the eastern tropical IO (EIO), with enhanced EIO upwelling accompanying weakened SCTR upwelling. Surface winds associated with El Niño–Southern Oscillation (ENSO) and the IO dipole (IOD) are the major drivers of upwelling variability. ENSO is more important than the IOD over the SCTR region, but they play comparable roles in the EIO. Upwelling anomalies generally intensify when positive IODs co-occur with El Niño events. For the 1979–2016 period, eastern Pacific (EP) El Niños overall have stronger impacts than central Pacific (CP) and the 2015/16 hybrid El Niño events, because EP El Niños are associated with stronger convection and surface wind anomalies over the IO; however, this relationship might change for a different interdecadal period. Rossby wave propagation has a strong impact on upwelling in the western basin, which causes errors in the SLM and DLM because neither can properly capture wave propagation. Remote forcing by equatorial winds is crucial for the EIO upwelling. While the first two baroclinic modes capture over 80%–90% of the upwelling variability, intermediate modes (3–8) are needed to fully represent IO upwelling.
Why Halley Did Not Discover Proper Motion and Why Cassini Did
Authors: Verbunt Frank , van der Sluys Marc
Published: November 2019

In 1717, Halley compared contemporaneous measurements of the latitudes of four stars with earlier measurements by ancient Greek astronomers and by Brahe, and from the differences concluded that these four stars showed proper motion. An analysis with modern methods shows that the data used by Halley do not contain significant evidence for proper motion. What Halley found are the measurement errors of Ptolemaios and Brahe. Halley further argued that the occultation of Aldebaran by the Moon on 11 March 509 in Athens confirmed the change in latitude of Aldebaran. In fact, however, the relevant observation was almost certainly made in Alexandria where Aldebaran was not occulted. By carefully considering measurement errors, Jacques Cassini showed that Halley’s results from comparison with earlier astronomers were spurious, a conclusion partially confirmed by various later authors. Cassini’s careful study of the measurements of the latitude of Arcturus provides the first significant evidence for proper motion.
Nobody Knew How Complicated: Constraining The President's Power To (Re)Shape Health Reform
Authors: Sanford Sallie Thieme
Published: November 2019

Beginning on inauguration day, President Trump has attempted an executive repeal of the Affordable Care Act. In doing so, he has tested the limits of presidential power. He has challenged the force of institutional and non-institutional constraints. And, ironically, he has helped boost public support for the ACA's central features. The first two sections of this article respectively consider the use of the President's tools to advance and to subvert health reform. The final two sections consider the forces constraining the administration's attempted executive repeal. I argue that the most important institutional constraint, thus far, is found in multifaceted actions by states – and not only blue states. I also highlight the force of public voices. Personal stories, public opinion, and 2018 election results – bolstered by presidential messaging – reflect growing support for government-grounded options and statutory coverage protections. Indeed, in a polarized time, “refine and revise” seems poised to supplant “repeal and replace” as the conservative focus countering liberal pressure for a common option grounded in Medicare.
Giving Voice to Medicaid: Waivers, Public Comments and Kentucky's “Secret Sauce”
Authors: Stewart Cara , Watson Sidney D.
Published: November 2019

In the 21st century the opportunity for the public to comment to an administrative agency typically means an invitation to go to a website, type words into a box, and hit send. Many advocacy groups provide templates for people to submit a statement in support or opposition to specific proposals. However, standardized comments do not capture the voice of Medicaid. They do not share people's personal experiences and insights. This article describes how consumer advocates in Kentucky devised a strategy, their Secret Sauce, to help consumers participate in the public comment process that is now required for Section 1115 Medicaid demonstration waiver applications. It shows how advocates can help real people's voices be heard in the public comment process, not through templates but through a process that assists people to tell their own stories in their own words. This is Medicaid's voice, the stories of real people who rely on Medicaid. Medicaid's voice can help policy makers understand the real-life impact of policy choices they make. It can also provide relevant evidence for courts reviewing the Secretary's grant of a Section 1115 waiver. Medicaid's voice can also help build political momentum, bringing those who rely on Medicaid to the polls and into the political conversation about the future of Medicaid.
Semiquantitative Power Doppler Ultrasound Score to Predict Acute Kidney Injury in Patients With Sepsis or Cardiac Failure: A Prospective Observational Study
Authors: Zhi Hai Jun , Zhao Jing , Nie Shen , Ma Yun Jie , Cui Xiao Ya , Zhang Meng , Li Yong
Published: November 2019

Background:

Diagnosing acute kidney injury (AKI) stage 3 in critically ill patients may help physicians in making treatment decisions. This diagnosis relies chiefly on urinary output and serum creatinine, which may be of limited value. This study aimed to explore the diagnostic performance of renal resistive index (RRI) and semiquantitative power Doppler ultrasound (PDU) scores in predicting AKI stage 3 in patients with sepsis or cardiac failure.

Methods:

This study is a prospective observational study that included 83 patients (40 with sepsis and 43 with cardiac failure). Renal resistive index and semiquantitative PDU scores were measured within 6 hours following admission to the intensive care unit. Acute kidney injury was defined according to the criteria set by Kidney Disease Improving Global Outcomes.

Results:

The predictive values of RRI (area under the curve [AUC] = 0.772, 95% confidence interval [CI] = 0.658-0.886) and PDU score (AUC = 0.780, 95% CI = 0.667-0.892) were similar in all patients. Power Doppler ultrasound score (AUC = 0.910, 95% CI = 0.815-1.000) could effectively predict AKI stage 3 in the cardiac failure subgroup, and the optimal cutoff for this parameter was ≤ 1 (sensitivity = 87.5%, specificity = 92.6%, Youden index = 0.801, accuracy in our population = 90.7%). However, PDU scores (AUC = 0.620, 95% CI = 0.425-0.814) could not predict AKI stage 3 in the sepsis subgroup. The predictive values of RRI for AKI stage 3 in the cardiac failure (AUC = 0.820, 95% CI = 0.666-0.974) and sepsis (AUC = 0.724, 95% CI = 0.538-0.910) subgroups were similar.

Conclusions:

Power Doppler ultrasound scores could effectively predict AKI stage 3 in patients with cardiac failure but not in patients with sepsis. Renal resistive index is a poor predictor of AKI stage 3 in patients with sepsis or cardiac failure.
Intrinsic and Extrinsic Factors Driving Hematopoietic Stem Cell Aging and Bone Marrow Failure
Authors: Trowbridge Jennifer J.
Published: November 2019

Decline in function of the hematopoietic system and hematopoietic stem cells (HSCs) during aging increases the risk of hematological malignancies including the acquired bone marrow failure condition myelodysplastic syndrome (MDS). As median lifespan is increasing at a global level, the incidence of MDS and associated conditions is also anticipated to increase significantly. Given the poor survival rate and significant morbidities associated with MDS, there is an unmet critical need to develop prophylactic strategies for the prevention of MDS. Current barriers to achieving this goal include a lack of understanding of how to ameliorate functional hematopoietic decline during aging and whether successfully doing so will prevent or delay development of MDS. Understanding both the overlapping and distinct mechanistic alterations in HSCs causing benign physiological aging, aging-associated clonal hematopoiesis (CH) and MDS is needed. A number of HSC-intrinsic and extrinsic mechanisms have been implicated across physiological aging, CH, and MDS including cell cycle regulation, DNA damage, gene expression, chromatin modifications, altered composition and architecture of the bone marrow (BM) microenvironment, and altered chemokine and cytokine levels. Our group has recently determined that both HSC-intrinsic and extrinsic alterations accumulate by middle age and are jointly responsible for HSC aging including phenotypic expansion, impaired regenerative capacity, transcriptional and functional myeloid lineage bias, loss of polarization, and increased DNA damage. We find that diminished local production of insulin-like growth factor 1 (IGF1) by mesenchymal stromal cells (MSCs) in the BM microenvironment causes HSC aging and transient stimulation with IGF1 ligand is sufficient to restore aged HSC regenerative capacity, transcriptional and functional myeloid lineage bias, and polarization. In parallel to these studies, our group has recently generated a new mouse model of CH and its progression to MDS (Loberg et al. 2019). This model incorporates an inducible, canonical missense mutation in the DNA methyltransferase Dnmt3a (R878H) that drives not only long-term (LT)-HSC expansion but also progression to MDS with aging and/or replicative stress. Integrating the above concepts and models, we are now examining whether strategies to rescue benign physiological aging by transient stimulation with IGF1 are sufficient to prevent or delay HSC expansion observed in CH and/or progression of CH to MDS. Ultimately, the goal of this work and future studies will be to restore functional hematopoiesis during aging to prevent acquired bone marrow failure and its complications.

Loberg MA, Bell RK, Goodwin LO, et al. Sequentially inducible mouse models reveal that Npm1 mutation causes malignant transformation of Dnmt3a-mutant clonal hematopoiesis. Leukemia. 2019;33:1635-1649.

Disclosures

Trowbridge: Fate Therapeutics: Patents & Royalties: licensed patent.
The Power of ONE: Immunology in the Age of Single Cell Genomics
Authors: Amit Ido
Published: November 2019

The immune system is a complex, dynamic and plastic network composed of various interacting cell types that are constantly sensing and responding to environmental cues. From very early on, the immunology field has invested great efforts and ingenuity to characterize the various immune cell types and elucidate their functions. However, accumulating evidence indicates that current technologies and classification schemes are limited in their ability to account for the functional heterogeneity of immune processes. Single cell genomics hold the potential to revolutionize the way we characterize complex immune cell assemblies and study their spatial organization, dynamics, clonal distribution, pathways, and crosstalk. This emerging field can greatly affect basic and translational research of the immune system. I will discuss how recent single cell genomic studies are changing our perspective of various immune related pathologies from cancer to neurodegeneration. Finally, I will consider recent and forthcoming technological and analytical advances in single cell genomics and their potential impact on the future of immunology research and immunotherapy.

Disclosures

No relevant conflicts of interest to declare.
Aptamers as Rapid Onset and Rapidly Reversible Antithrombotic Agents
Authors: Sullenger Bruce A.
Published: November 2019

Clinical evaluation of our factor IXa RNA aptamer in two thousand patients undergoing percutaneous coronary intervention has demonstrated that aptamers can rapidly and potently inhibit their target proteins in patients and that antidote molecules can rapidly and precisely control such activity in the minute time frame. These observations suggest that aptamers represent useful molecules to tightly control biochemical processes in humans in real time. To begin to explore this potential further, we have started to evaluate the utility of antidote-mediated control of aptamers for a variety of other therapeutic and diagnostic applications. We will describe our recent progress developing a rapidly controllable factor Xa anticoagulant aptamer to effectively yet reversibly control blood coagulation during cardiopulmonary bypass surgery and a rapidly reversible VWF aptamer for improving the treatment of thrombotic stroke. We have observed that aptamers, which target exosites on coagulation factors, can complement active site inhibitors to yield potent anticoagulant regiments (Gunaratne et al., 2018) that can support circulation of blood through extracorporeal oxygenator circuits. Moreover we have observed that an aptamer targeting the A1 domain of VWF can serve as a rapid onset and rapidly reversible antithrombotic agent. This aptamer prevents platelet recruitment and can induce recanalization of occluded arteries while a matched antidote oligonucleotide can rapidly reverse such anti-platelet activity and thereby limit bleeding following vascular injury (Nimjee et al., 2019). Collectively these clinical and preclinical studies lead us to believe that rapidly controllable aptamers represent valuable therapeutic agents that will provide physicians the ability to monitor and precisely control blood coagulation, as well as other biological pathways, in real time in response to individual patients' needs.

GunaratneR, KumarS, FrederiksenJW, et al. Multimodal, antidote-controllable anticoagulation for cardiopulmonary bypass using aptamer-drug pairs. Nature Biotechnology 2018;36:606-613.

NimjeeSM, Dornbos, IIID, Pitoc GA, et al. Preclinical Development of a VWF Aptamer to Limit Thrombosis and Engender Arterial Recanalization of Occluded Vessels. Molecular Therapy. 2019;27:1228-1241.

Disclosures

Sullenger: Basking Biosciences: Consultancy, Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Other: Founder, Patents & Royalties.
Immune-Tumor Interactions in Resistance to Cancer Immunotherapy
Authors: Wucherpfennig Kai W.
Published: November 2019

MICA and MICB (MICA/B) are expressed by many human cancers due to cellular stress and tag cells for elimination by cytotoxic lymphocytes through NKG2D receptor activation. However, tumors evade this immune recognition pathway through proteolytic shedding of MICA/B proteins. We rationally designed antibodies targeting the MICA α3 domain, the site of proteolytic shedding, and found that these antibodies prevented loss of cell surface MICA/B by human cancer cells. These antibodies inhibited tumor growth in multiple fully immunocompetent mouse models and also reduced human melanoma metastases in a humanized mouse model. Anti-tumor immunity was mediated mainly by NK cells through activation of NKG2D and CD16 Fc receptors. This novel approach prevents the loss of important immunostimulatory ligands by human cancers and reactivates antitumor immunity.

Disclosures

Wucherpfennig: BMS: Research Funding; Novartis: Research Funding; TCR2: Consultancy; Tscan: Consultancy.
Blood Cell Fate Decisions: Insights from Single-cell RNA-seq
Authors: Socolovsky Merav
Published: November 2019

The manner by which multipotent hematopoietic progenitors commit to the erythroid lineage, and the subsequent processes that govern early erythroid progenitor development, are not well understood. Part of the challenge for investigating these was the lack of a rigorous strategy for isolating directly from tissue the early erythroid progenitors, which are functionally defined as the cell 'units' that give rise to erythroid colonies (CFU-e) or bursts (BFU-e) in culture. Indeed, the early erythroid trajectory, that starts with multi-potential progenitors and gives rise to BFU-e, CFU-e and to erythroblasts undergoing terminal differentiation, was not fully elucidated. We addressed these gaps using single cell transcriptomics, combined with functional assays that validated computational predictions 1. These showed that early hematopoietic progenitors form a continuous, hierarchical branching structure, in which the erythroid and basophil/mast cell fates are unexpectedly coupled. We delineated a novel flow-cytometric strategy that prospectively isolates CFU-e and BFU-e progenitors with high purity, and in combination with computational predictions, identified novel growth factor receptors that regulate early erythropoiesis. We further discovered that early erythroid development entails profound remodeling of both G1 and S phases of the cycle, resulting in cell cycle specializations that orchestrate the developmental process, including a gradual shortening of G1 during the CFU-e phase, followed by a sharp increase in the speed of S phase during the S-phase dependent activation of the erythroid terminal differentiation program 1-3(Figure 2).

1. Tusi BK, Wolock SL, Weinreb C, et al. Population snapshots predict early haematopoietic and erythroid hierarchies. Nature. 2018;555(7694):54-60.

2. Hwang Y, Futran M, Hidalgo D, et al. Global increase in replication fork speed during a p57KIP2-regulated erythroid cell fate switch. Science Advances. 2017;3:e1700298.

3. Pop R, Shearstone JR, Shen Q, et al. A key commitment step in erythropoiesis is synchronized with the cell cycle clock through mutual inhibition between PU.1 and S-phase progression. PLoS Biol. 2010;8(9).

Disclosures

No relevant conflicts of interest to declare.