bluuebunny/crossref_metadata_2025 huggingface dataset:
Neural correlates of extremely large individual differences in interaural cross-correlation detection
Authors: Lertpoompunya Angkana , Ozmeral Erol J. , Higgins Nathan , Eddins Ann C. , Eddins David A.
Published: December 2020

Interaural cross-correlation is a primary feature that can predict the detection of dichotic signals in background noise. Perfectly correlated noise presented to the two ears is perceived as compact and centrally lateralized. As noise is binaurally de-correlated, the perceptual image widens and becomes more diffuse. Previous investigators have reported large variability across individuals' cross correlation just-noticeable differences (IACC-JNDs). Anecdotally, many listeners with normal pure tone thresholds present as extreme outliers in binaural tasks. It is unknown whether or not this variability across individuals is reflected in the neural activity recorded during passive listening to these stimuli. IACC-JNDs were measured in a behavioral task and compared to correlation-change evoked potentials using electroencephalography (EEG). Results indicate significantly smaller cortical responses (N1 and P2 amplitudes) to interaural change differences for individuals with large- compared to small-JND thresholds. Source localization of this effect was observed in multiple subdivisions of the auditory cortex, include Heschl's gyrus, planum temporale, and the temporal sulcus. These results provide objective electrophysiological evidence of a binaural processing deficit corresponding to extremely large JND thresholds. Interestingly, these listeners are indeed binaurally disadvantaged despite otherwise normal audiometric profiles and lack of spatial hearing complaints. [Work supported by NIH P01AG009524.]
Real-time implementation of an auditory nerve model using a system-on-chip field-programmable gate array
Authors: Blunt Matthew , Austin Hezekiah , Vannoy Trevor , Davis Tyler , Snider Ross
Published: December 2020

System-on-Chip (SoC) Field Programmable Gate Arrays (FPGAs) are ideal for real-time signal processing due to their low, deterministic latency and high performance. We target our Audio Blade platform that contains an Intel Arria 10 SoC FPGA with floating-point capability and 1.5 TFLOPS performance. In order to target the Arria 10, the auditory nerve model [1, 2] needed to be ported to a hardware description language. We accomplished this by first porting the MATLAB/C model to Simulink, and then used MathWorks HDL Coder to generate VHDL code. Our hardware-accelerated model will allow researchers to edit model parameters in real-time from Linux software running on the embedded ARM CPUs and view the resulting nerve responses in real-time. The goal is to create a real-time platform running multiple auditory nerve models, allowing researchers to inject hearing impairments and then develop hearing aid strategies to compensate for these hearing deficits. We will discuss performance measures of the FPGA-based auditory nerve models, including latency measures and how many auditory nerve models can run simultaneously in the Arria 10 FPGA fabric. 1. Bruce et al., Hearing Res. 360, 40–54 (2018). 2. Zilany et al., JASA 126, 2390–2412 (2009).
Preschool boys with hearing loss are exposed to greater vocal amplitude from parents
Authors: VanDam Mark , Morton Sean , Brown Karen E.
Published: December 2020

Children's ability to perceive auditory signals impacts speech and language development, cognition, academic performance, and social relationships. Vocal signals in the family environment produced by mothers, fathers, and children have different characteristics and likely contribute differently to development. Childhood hearing loss has been associated with developmental progress in children in some (but not all) domains. In particular, the level of auditory input to children from specific talkers is not well documented. The aim of this study is to examine the amplitude of speech from mothers and fathers in the presence of preschool boys and girls with and without hearing loss. We processed 688 daylong audio recordings using automatic speech processing routines to identify the amplitude of the vocal utterances of mothers (n = 1 368 108 utterances) and fathers (n = 591 335 utterances) when in the presence of their toddlers with and without hearing loss. Results suggest both mothers and fathers use increased vocal amplitude with children with hearing loss but that effect is driven by increased amplitude to boys with hearing loss. This sex effect may shed light on the different roles that family members play in the socio-cultural development of speech and language use.
Classification of accurate and misarticulated rhotic syllables for simplified ultrasound biofeedback therapy
Authors: Li Sarah R. , Dugan Sarah , Annand Colin , Eary Kathryn , Swearengen Michael , Terrell Gregory A. , Stack Sarah , Boyce Suzanne , Riley Michael A. , Mast T. Douglas
Published: December 2020

Ultrasound biofeedback therapy (UBT) provides real-time imaging of tongue movements and has demonstrated positive speech remediation outcomes; however, some individuals have limited or no response. UBT outcomes could be further improved by a simplified biofeedback display to enhance motor learning. Such simplification requires automatic processing of ultrasound images to determine biofeedback parameters and targets. We investigate potential biofeedback parameters using TonguePART, a method that automatically tracks the tongue surface on midsagittal ultrasound images to quantify displacement trajectories of the tongue root, dorsum, and blade. Our focus is rhotic syllables (/i/, /u/, /o/, /e/, /ε/, and /a/ with initial or final /r/) from children with residual speech sound disorders and children with typically developing speech. We train support vector machines on measured tongue part displacement trajectories to distinguish between accurate and misarticulated productions as determined from auditory perceptual ratings. Preliminary data indicate that a linear combination of the tongue dorsum and blade displacements, between the vowel and consonant, can distinguish between accurate and misarticulated productions of rhotic syllables. These results suggest a real-time biofeedback parameter based on projections of real-time dorsum and blade displacements, along with potential target values, different for each vowel, for this parameter in simplified UBT for speech remediation.
An acoustic analysis of St. Lawrence Island Yupik vowels
Authors: Hunt Benjamin , Kwon Harim , Schreiner Sylvia
Published: December 2020

St. Lawrence Island Yupik (ISO 639-3 ess; henceforth Yupik) is an endangered language spoken by 800–900 speakers in Alaska and Russia (Schwartz et al., 2020). Minimal research has been conducted on Yupik phonology, with its vowel inventory being impressionistically described as consisting of seven vowel phonemes: /i/, /i:/, /a/, /a:/, /u/, /u:/, and // (e.g., Krauss, 1975). We present the first known acoustic examination of Yupik vowels, using data from four native speakers. Materials included words beginning with the seven previously reported vowel phonemes followed by an obstruent varying in its place of articulation (labial, coronal, velar, uvular). Statistical analyses on duration and formant frequencies were combined with visualizations of the vowel space using normalized F1-F2. The findings largely aligned with previous descriptions of the seven vowel phonemes, with the phonemic length distinction primarily realized in duration. We furthermore found that the mid-vowels were mostly reduced (shorter in duration and often devoiced) in word-initial position; /i/, /i:/, and /e/ were backed and lowered when followed by a uvular obstruent; and non-front vowels were fronted in the coronal environment. The current findings suggest potential undocumented vowel allophonies in Yupik, including co-articulatory assimilation as well as vowel reduction.
Postaspiration in Sevillian Spanish: Beyond voiceless stops
Authors: Gilbert Madeline
Published: December 2020

Sevillian Spanish /s + ptk/ clusters are often produced with gemination of the consonant following /s/ and postaspiration (/pasta/:[pahta]-->[pat:ha]) (Ruch and Peters, 2016). Spanish voiceless stops are unaspirated, but some argue that postaspirated stops are phonologizing in Seville (O'Neill, 2010; Gylfadottir, 2015). Acoustically, postaspiration is long VOT. Articulatorily, it is described as a laryngeal gesture moving across the stop, continuing past the release (Torreira, 2007). Previous work focuses only on /s + ptk/. This acoustic study examines /sC/-clusters with voiceless stops, voiced stops, and sonorants, extending our understanding of the mechanisms behind postaspiration. Seven Sevillians read paragraphs containing /sC/ and /C/ words (/kaspa/-/kapa/). All clusters show gemination. Compared to /ptk/, /s + ptk/ clusters have long postaspiration, resist intervocalic voicing, and result in higher pitch on the following vowel (a cue to contrastive aspiration in many languages, Dmitrieva et al., 2015). /s + bdg/ clusters have stronger constriction, higher COG, and less voicing than intervocalic (spirantized) /bdg/. /s + mnl/ clusters differ from /mnl/ only in gemination. Gestural overlap thus occurs in voiced and voiceless clusters, and appears to result from higher-level realignment as opposed to unintentional mistiming (Parrell, 2012). Postaspirated voiceless stops are unlikely to phonologize because the process occurs with both /s + bdg/ and /s + ptk/, giving different results.
Random matrix theory and underwater sound propagation
Authors: Tomsovic Steven , Hegewisch Katherine
Published: December 2020

Random matrix theory originated as the statistical theory of strongly interacting quantum systems, and has since been applied in an extremely broad range of applications. For example, it has been developed to accurately and efficiently model long range acoustic propagation in the ocean, including the construction of propagating acoustic time fronts. This problem can be viewed as dynamical symmetry breaking, i.e., the breaking of integrability, which has been explored in a variety of quantum mechanical contexts. The theory is expressed in terms of unitary propagation matrices that represent the scattering between acoustic modes due to sound speed fluctuations induced by the ocean's internal waves. The scattering exhibits a power-law decay as a function of the differences in mode numbers thereby generating a power-law, banded, random unitary matrix ensemble. In addition to its efficiency, the theory helps identify which information about the ocean environment can be deduced from the timefronts and how to connect features of the data to that environmental information. It also makes direct connections to methods used in other disordered wave guide contexts where the use of random matrix theory has a multi-decade history.
The Animal Audiogram Database: A new resource for presenting and evaluating audiogram data on the web
Authors: Jäckel Denise , Ortiz Troncoso Alvaro , Bölling Christian
Published: December 2020

Knowledge of hearing abilities, as represented in audiograms, is vital for understanding animal acoustic physiology, behaviour, and ecology. Additionally, such knowledge plays an important role for measuring, predicting, or counteracting effects of anthropogenic noise on the environment. Currently, audiogram data is usually only available embedded in individual scientific publications and in various unstandardized formats, which makes access to and analysis of audiograms across sources cumbersome. We established a newly database that presents audiograms along with data on the audio-physiological experiments and original publications in a structured and easily accessible way. The interface enables combination of audiogram data for comparative analysis of different species, experimental conditions or publications. Focusing currently on marine vertebrates its content is the result of an extensive survey of the scientific literature and manual curation of the contained audio-physiological data. The database is designed to accommodate audiogram data on any biological group and purposed to be extended and serve as a reference source for audiogram data. It is publicly accessible at https://animalaudiograms.museumfuernaturkunde.berlin. [The database was developed as part of the project “Hearing in Penguins” funded by the German Environment Agency (UBA) with means from the Federal Ministry for the Environment, Nature Conservation and Nuclear Safety (BMU, FKZ3717182440).]
Acoustic propagation in a seagrass meadow over diurnal and seasonal time scales
Authors: Lee Kevin M. , Ballard Megan S. , Venegas Gabriel R. , McNeese Andrew R. , Zeh Matthew C. , Wilson Preston S. , Rahman Abdullah F.
Published: December 2020

Acoustic propagation in seagrass meadows is highly sensitive to oxygen production through photosynthesis. In addition to gas volumes encapsulated within the seagrass, free bubbles are released into the water column as oxygen diffuses through the plant tissue, affecting acoustic dispersion, absorption, and scattering. Because the oxygen production cycle is largely driven by sunlight, these effects exhibit a diurnal dependence. Previous work explored using acoustics to monitor seagrass photosynthetic activity, but this study presents new results that span both diurnal and seasonal time scales. Acoustic propagation experiments were conducted in a seagrass meadow in a shallow bay on the Texas Gulf Coast. A piezoelectric sound source transmitted frequency-modulated chirps (0.1–100 kHz) over several diurnal cycles, and the received acoustic signals were match-filtered to obtain band-limited impulse responses. Water temperature, salinity, depth, dissolved oxygen, and solar irradiance were concurrently measured with oceanographic probes. Measurements were taken both in winter and summer to examine the seasonal dependence of seagrass photosynthesis and its effect on the acoustic propagation environment. Dependence of the received acoustic signal on various environmental parameters will be discussed with the goal of using acoustics to study seagrass photosynthesis and productivity. [Work supported by ARL:UT IR&D and ONR.]
Finite element modeling of the low-frequency sound speed of seagrass leaves
Authors: Torres Nicholas A. , Ballard Megan S. , Lee Kevin M. , Venegas Gabriel R. , Wilson Preston S.
Published: December 2020

Previous investigations related to acoustic propagation through seagrass have shown that sound waves are sensitive to the gas contained within seagrass tissue as well as free bubbles produced by photosynthesis. The acoustical effects include reduced low-frequency sound speed and increased sound attenuation. The effects are more pronounced when the density of vegetation is higher as well as during daylight hours when sunlight-driven photosynthesis occurs. However, the application of mathematical models to describe these phenomena have been limited to effective medium models for water containing spherical gas bubbles. These approaches neglect both the effects of elastic properties of seagrass tissue as well as the shape of the aspherical gas bodies constrained within the plant. In this work, a finite element model of an acoustic resonator containing seawater and seagrass blades was developed to explain previously published measurements. Themodel utilizes independently measured values of the elastic propertiesof seagrass tissue and microscopic cross-section imagery of the gas volumes contained within the seagrass tissue. These results represent a step towards defining an appropriate effective medium model for acoustic propagation through seagrass tissue. [Work supported by ARL:UT IR&D and ONR.]
Effects of aberration on super-resolution ultrasound imaging using microbubbles
Authors: Peralta Laura P. , Brown Jemma , Lee Tiarna , Christensen-Jeffries Kirsten M.
Published: December 2020

Visualizating vasculature beyond the diffraction limit can be achieved using ultrasound super-resolution (USR). Typically, ultrasound (US) scanners model the target medium as homogeneous, assuming a constant speed-of-sound for time-of-flight based calculations. However, variations in US propagation velocity caused by varying tissue layers affect beamforming operations. This aberration is likely to have considerable effect on USR accuracy when imaging at depth. Here we investigate the effect of aberration on USR localization accuracy. Wave propagation through different tissue media was modelled from a linear transducer using k-Wave, and the resulting pulse-echo data from a point scatterer located at 45mm depth was beamformed. Media included a control homogeneous propagation medium, and aberrating media typical of liver imaging. Aberration effects were estimated using RMS arrival-time fluctuations (ATF) and energy-level fluctuations (ELF) at the scatterer location. Signals were extracted and localized with existing localization techniques. Results indicated USR localisation accuracy decreased with increasing aberration. Axial localisation errors reached 836.6 mm for an ATF 30.9 ns. Furthermore, errors increased with decreasing frequency from 4 to 3 MHz. The scale of these errors relative to micro-vascular structures of interest suggests that aberration will have considerable impact on USR performance and requires attention to ensure its success.
Real-time, patient-adaptive ultrasonic intensity adjustment: Hepatic imaging observations
Authors: Huber Matthew , Flint Katelyn , Long James , Long Will , Bottenus Nick , Trahey Gregg
Published: December 2020

Increasing B-mode ultrasound transmit intensity improves signal to noise ratio (SNR) by increasing backscattered echo magnitude relative to thermal noise. To ensure ultrasound remains safe, acoustic output limits exist, and regulatory bodies advise observing the ALARA (As Low As Reasonably Achievable) principle. Despite this, studies show sonographers rarely adjust intensity, resulting in unnecessary acoustic exposure or sub-optimal image quality. We have developed a framework for automated transmit intensity adjustment which we demonstrate on a Verasonics Vantage ultrasound system and C5-2v transducer. The coherence of signals received by neighboring ultrasound array elements, the lag-one coherence (LOC), quantifies clutter and temporally varying noise and serves as the automation feedback parameter. In the automated sequence, receive data are quickly acquired over a region of interest (ROI) for nine intensities ranging from mechanical indices (MI) of 0.08 to 1.4. LOC asymptotically increases with acoustic intensity as the effect of thermal noise decreases until intensity increases minimally improve SNR; the intensity at 98% of the maximum LOC is used for B-mode scanning. In preliminary hepatic imaging studies, a ROI of 7 lateral lines extending 30Î» axially achieves temporally stable intensity updates. The optimization time for this ROI is 0.7 seconds, enabling real-time intensity adaptation.
Larry Royster's influence on my life and on noise and hearing conservation, as told by one of his students
Authors: Berger Elliott H.
Published: December 2020

I first met Larry Royster as a master's degree student in search of a thesis project and research funding, having heard that he was looking for a student to work on a potential grant concerning occupational hearing loss. The day I entered his office at NC State was one of the most impactful of my life, dramatically influencing the trajectory of my university work and professional career. Working with Larry gave me the opportunity to manage and conduct a research project in the textile industry, gain insights into the hearings at the Department of Labor that were to shape the Hearing Conservation Amendment, and to see first-hand how Larry influenced and guided the North Carolina DOL approach to noise and hearing conservation. He was there when I had my first postâ€‘graduate school job offer from E-A-R Division of Cabot Corporation, later Aearo Technologies and 3M, and then became an important friend and collaborator for much of my subsequent research. He chaired ANSI and NHCA working groups and received the ASA Silver Medal and other important society awards. Larry was a friend, mentor, and dedicated scientist whose impact on noise and hearing conservation will be the topic of my talk.
Population-based age-adjustment tables for use in hearing conservation programs
Authors: Flamme Gregory , Deiters Kristy K.
Published: December 2020

Starting in the 1970s, Larry Royster and his colleagues conducted a series of large-scale studies demonstrating that people with non-Hispanic Black race/ethnicity had better hearing sensitivity than their non-Hispanic White counterparts. One major outcome of this work was the adoption of specific age-related hearing sensitivity expectations by race in the original version of ANSI S3.44. Royster's accomplishments informed our work over the last decade, the goal of which was to develop age-adjustment tables for replacing those used in current U.S. regulations. The old age adjustment tables, which are frequently mislabeled age “corrections”, were developed by NIOSH based on cross-sectional observations available in the 1970s and included relatively few people. We developed nationally representative cross-sectional age trends based on 9,937 audiograms and validated them for men using 76,185 exam records from 9,340 noise-exposed workers. Results indicated that the 1970s-era age adjustments overestimate current trends, which is consistent with multiple studies showing an overall decline in the prevalence of hearing loss within the United States. The results also indicate a substantial reduction in age-related changes among people with non-Hispanic Black race/ethnicity. Our work confirmed and extended Royster's observations in a large regional sample to the U.S. population as a whole.
Larry H. Royster memorial session
Authors: Neitzel Richard L.
Published: December 2020

Larry Royster conducted pioneering research on the effectiveness of occupational hearing conservation programs, with a particular focus on the performance of hearing protection devices (HPDs) and audiometric database evaluation. Dr. Royster also conducted important early research into non-occupational noise exposures such as sporting events, recreational activities, and air travel. This presentation will briefly review key findings from Dr. Royster's work on these topics from the 1970s–1990s, and will then summarize the findings of a number of recent related studies. These will include: an evaluation of hearing conservation program effectiveness and hearing protector performance among aluminum manufacturing workers; an assessment of the contributions of occupational and non-occupational noise to hearing loss risk in a large sample of individuals in New York City; and a review of patterns and trends in occupational noise exposures in the US from 1979–2013. Collectively, these studies indicate that the risk of hearing loss from noise remains substantial among US workers, as well as in the general public that participates in noisy leisure-time activities, and highlight the importance of continuing the research that Dr. Royster started in order to protect the hearing health of Americans.
Time-domain simulation of acoustic wave scattering and internal propagation from gas bubbles of various shapes
Authors: Hou Jiacheng , Zheng Zhongquan C. , Allen John S.
Published: December 2020

Acoustic scattering and resonances of incident waves from a gas bubble are simulated using a time-domain simulation based on numerical solutions of the conservation laws. The time histories of scattering pressure and velocity, both outside and inside the bubble, are obtained simultaneously from an immersed-boundary method facilitating the investigation of both exterior and interior fields for complex geometries. The acoustic resonances of the bubble are investigated for various bubble sizes, shapes and inner gas parameters and compared to the partial wave scattering solutions for spherical bubbles. Agreement is shown with the analytical solutions in the linear acoustic limit. The resonance frequency increases with the bubble's inner background pressure and independent of the incident wave amplitude or frequency. In addition to scattering outside of the bubble, acoustic propagation inside the bubble is investigated with respect to the monopole resonance. A significant advantage is that this time-domain simulation combined with the immersed-boundary method can be readily adapted for various shapes of bubbles including oblate or prolate. The scattering and resonance behaviors are simulated and compared with the analytical results involving a shape factor and extended for previously less investigated shapes of significance to underwater and physical acoustics applications including “pancake shaped” bubbles.
Metamaterial lens for real-time ultrasound beam steering using single-channel scalar control
Authors: Kwon Hyung-Suk , Epureanu Bogdan I. , Popa Bogdan-Ioan
Published: December 2020

Ultrasound sensors currently used by autonomous vehicles have short ranges and low resolutions, which limit their uses to proximity sensing. Metamaterial lenses promise to extend the range significantly due to the lenses' excellent beamforming ability, but designs reported so far either have fixed acoustic properties and thus are not able to easily ensonify in desired directions or employ arrays of transducers that are non-scalable and have high power consumption. In this presentation, we introduce a new type of ultrasound sensor composed of a single transducer and a reconfigurable metamaterial lens operating in air. The metamaterial lens requires less than 0.5 mm movements of a carefully designed surface to form and steer acoustic beams in real-time. The metamaterial tunes all the unit cells simultaneously with only one moving element. Remarkably, steering angles of ±20 deg are achieved despite the small actuation. The ability to control the ultrasound produced by a single transducer with small actuation is demonstrated experimentally.
Pandemic lockdown stirs up ecological research
Authors: Stokstad Erik
Published: December 2020

Biologists launch studies of how wildlife around the world responded to the "anthropause."
Complete Genome Sequence of a Shiga Toxin-Producing Escherichia coli O26:H11 Strain (Sequence Type 21) and Two Draft Genome Sequences of Listeria monocytogenes Strains (Clonal Complex 1 [CC1] and CC59) Isolated from Fresh Produce in Germany
Authors: Fiedler Gregor , Kabisch Jan , Brinks Erik , Sprotte Sabrina , Boehnlein Christina , Franz Charles M. A. P.
Published: December 2020

The complete genome sequence of a Shiga toxin-producing
Escherichia coli
(STEC) O26:H11 strain, MBT-5 (sequence type 21 [ST21],
stx1a
,
stx2a
,
eae
,
ehxA
), and two draft genome sequences of
Listeria monocytogenes
strains MBT-6 and MBT-7 belonging to the virulent sequence types 1 (ST1, clonal complex 1 [CC1]) and 59 (ST59, CC59), respectively, were determined. The strains were isolated in 2015 from ready-to-eat mixed greens in Germany.
Genome Sequence of the Unusual Purple Photosynthetic Bacterium Phaeovibrio sulfidiphilus, Only Distantly Related to
Rhodospirillaceae
, Reveals Unique Genes for Respiratory Nitrate Reduction and Glycerol Metabolism
Authors: Dubey S. , Meyer T. E. , Kyndt J. A.
Published: December 2020

Phaeovibrio sulfidiphilus
was reported to be a divergent member of the purple photosynthetic bacteria with limited ability to metabolize organic compounds. Whole-genome-based analysis shows it is indeed only distantly related to freshwater species of
Rhodospirillaceae
. Unexpectedly, the genome contains unique gene clusters for potential respiratory nitrate reduction and anaerobic glycerol metabolism.
SITC cancer immunotherapy resource document: a compass in the land of biomarker discovery
Authors: Hu-Lieskovan Siwen , Bhaumik Srabani , Dhodapkar Kavita , Grivel Jean-Charles J B , Gupta Sumati , Hanks Brent A , Janetzki Sylvia , Kleen Thomas O , Koguchi Yoshinobu , Lund Amanda W , Maccalli Cristina , Mahnke Yolanda D , Novosiadly Ruslan D , Selvan Senthamil R , Sims Tasha , Zhao Yingdong , Maecker Holden T
Published: December 2020

Since the publication of the Society for Immunotherapy of Cancer’s (SITC) original cancer immunotherapy biomarkers resource document, there have been remarkable breakthroughs in cancer immunotherapy, in particular the development and approval of immune checkpoint inhibitors, engineered cellular therapies, and tumor vaccines to unleash antitumor immune activity. The most notable feature of these breakthroughs is the achievement of durable clinical responses in some patients, enabling long-term survival. These durable responses have been noted in tumor types that were not previously considered immunotherapy-sensitive, suggesting that all patients with cancer may have the potential to benefit from immunotherapy. However, a persistent challenge in the field is the fact that only a minority of patients respond to immunotherapy, especially those therapies that rely on endogenous immune activation such as checkpoint inhibitors and vaccination due to the complex and heterogeneous immune escape mechanisms which can develop in each patient. Therefore, the development of robust biomarkers for each immunotherapy strategy, enabling rational patient selection and the design of precise combination therapies, is key for the continued success and improvement of immunotherapy. In this document, we summarize and update established biomarkers, guidelines, and regulatory considerations for clinical immune biomarker development, discuss well-known and novel technologies for biomarker discovery and validation, and provide tools and resources that can be used by the biomarker research community to facilitate the continued development of immuno-oncology and aid in the goal of durable responses in all patients.
Bud break in sugar maple submitted to changing conditions simulating a northward migration
Authors: Ren Ping , Liang Eryuan , Raymond Patricia , Rossi Sergio
Published: December 2020

Assisted migration, the human-mediated movement of species and populations, is one adaptive strategy to climate change. Plant phenology affects the survival and distribution of species under local conditions, and its potential modifications need to be explored in the context of assisted migration. We conducted identical experiments in January and April (experiment I and II) and monitored the timing of bud break in sugar maple (Acer saccharum Marshall) under cooling and longer photoperiod to simulate a northward migration. The bud break in experiment II started 55 days earlier than experiment I. In experiment I, a longer photoperiod was more effective than warming in advancing bud break. Compared with experiment II, cooling and long photoperiod had stronger effect in experiment I. Our results demonstrated the significant effect of chilling and confirmed that photoperiod outweighs temperature in initiating bud break when the chilling requirement is unfulfilled. These findings suggest that the future mild winters in the southern range of sugar maple may reduce chilling accumulation and result in the delayed bud break. Sugar maples migrating northward could benefit from longer day lengths, which could partly counteract the delayed effects of colder springs in northern regions, thus ensuring a sufficient growth period.
A COMPLEX SIS SPREADING MODEL IN AD HOC NETWORKS WITH REDUCED COMMUNICATION EFFORTS
Authors: VARGA IMRE
Published: December 2020

In this work, spreading of information is investigated in a vehicular ad hoc network (VANET) by agent-based simulation. The proposed model is complex, containing two major states and some minor substates and additionally both reversible and irreversible state changes. According to our results, the spreading is really fast and widespread, the system can be in an up-to-date phase without external control. We show a very simple way to keep the system in this up-to-date status reducing dramatically the communication costs. Nevertheless, the topology of both the instantaneous and the aggregate communication network is also analyzed in this self-organized system and scale-free networks are found.
Designing bugs as drugs: exploiting the gut microbiome
Authors: Lamousé-Smith Esi , Kelly Denise , De Cremoux Isabelle
Published: December 2020

The extensive investigation of the human microbiome and the accumulating evidence regarding its critical relationship to human health and disease has advanced recognition of its potential as the next frontier of drug development. The rapid development of technologies, directed at understanding the compositional and functional dynamics of the human microbiome, and the ability to mine for novel therapeutic targets and biomarkers are leading innovative efforts to develop microbe-derived drugs that can prevent and treat autoimmune, metabolic, and infectious diseases. Increasingly, academics, biotechs, investors, and large pharmaceutical companies are partnering to collectively advance various therapeutic modalities ranging from live bacteria to small molecules. We review the leading platforms in current development focusing on live microbial consortia, engineered microbes, and microbial-derived metabolites. We will also touch on how the field is addressing and challenging the traditional definitions of pharmacokinetics and pharmacodynamics, dosing, toxicity, and safety to advance the development of these novel and cutting-edge therapeutics into the clinic.
News FLASH-RT: To Treat GBM and Spare Cognition, Fraction Size and Total Dose Matter
Authors: Huang Christina C. , Mendonca Marc S.
Published: December 2020

Data indicate that ultrahigh dose rate (>106 Gy/second) FLASH radiotherapy (FLASH-RT) delivery of radiation reduces normal tissue damage without compromising tumor response. Orthotopic glioblastoma mouse studies now demonstrate that radiation fraction size, total dose, and number of fractions are critical parameters for FLASH-RT cognitive sparing without compromising tumor response.

See related article by Montay-Gruel et al., p. 775
Overhydration Measured by Bioimpedance Spectroscopy and Urinary Serine Protease Activity Are Risk Factors for Progression of Chronic Kidney Disease
Authors: Schork Anja , Bohnert Bernhard N. , Heyne Nils , Birkenfeld Andreas L. , Artunc Ferruh
Published: December 2020

Background: Overhydration (OH) is common in chronic kidney disease (CKD) and might be related to the excretion of urinary serine proteases. Progression of CKD is associated with proteinuria; however, the interrelations of urinary serine proteases, OH, and progression of CKD remain unclear. Methods: In n = 179 patients with stable nondialysis-dependent CKD of all stages, OH was measured using bioimpedance spectroscopy (Body Composition Monitor; Fresenius), and urinary serine protease activity was determined using the peptide substrate S-2302. After a median follow-up of 5.9 (IQR: 3.9–6.5) years, progression to end-stage renal disease (ESRD) was analyzed retrospectively. Results: OH correlated with baseline MDRD-eGFR, urinary albumin creatinine ratio (ACR), and urinary aprotinin-sensitive serine protease activity. Progression to ESRD occurred in n = 33 patients (19%) and correlated with OH and urinary serine protease activity as well as MDRD-eGFR and ACR. Patients were divided into 2 groups determined by cutoff values from receiver operating characteristics for MDRD-eGFR (32 mL/min/1.73 m2), ACR (43 mg/g creatinine), urinary serine protease activity (0.9 RU/g creatinine), and OH (1 L/1.73 m2). Across these cutoff values, Kaplan-Meier curves for renal survival showed significant separations of the groups. In Cox regression adjusted for MDRD-eGFR, ACR, P-NT-pro-BNP, systolic blood pressure, and diabetes mellitus, patients with OH >1 L/1.73 m2 had a 3.32 (95% CI: 1.26–8.76)-fold higher risk for progression to ESRD. Conclusions: Our results corroborate that OH detected by bioimpedance spectroscopy in CKD patients is an independent risk factor for progression to ESRD in addition to GFR and albuminuria. Urinary serine protease activity is associated with OH and progression of CKD and provides a possible underlying mechanism.
Does the Diffuseness of the Nidus Affect the Outcome of Stereotactic Radiosurgery in Patients with Unruptured Cerebral Arteriovenous Malformations?
Authors: Yang Huai-Che , Peng Syu-Jyun , Lee Cheng-Chia , Wu Hsiu-Mei , Chen Yu-Wei , Lin Chung-Jung , Shiau Cheng-Ying , Guo Wan-Yuo , Pan David Hung-Chi , Liu Kang-Du , Chung Wen-Yuh , Lin Yung-Yang
Published: December 2020

Background: We proposed an algorithm to automate the components within the identification of components within the nidus of cerebral arteriovenous malformations (AVMs) which may be used to analyze the relationship between its diffuseness and treatment outcomes following stereotactic radiosurgery (SRS). Objectives: to determine the impact of the diffuseness of the AVM nidus on SRS outcomes. Methods: This study conducted regular follow-ups of 209 patients with unruptured AVMs who underwent SRS. The diffuseness of the AVM nidus was estimated by quantifying the proportions of vascular nidal component, brain parenchyma, and cerebrospinal fluid in T2-weighted MRIs. We used Cox regression analysis to characterize the association between nidal diffuseness and treatment outcomes in terms of obliteration rate and radiation-induced change (RICs) rate following SRS. Results: The median AVM volume was 20.7 cm3. The median duration of imaging follow-up was 51 months after SRS. The overall AVM obliteration rate was 68.4%. RICs were identified in 156 of the 209 patients (74.6%). The median proportions of the nidus of AVM and brain parenchyma components within the prescription isodose range were 30.2 and 52.2%, respectively. Cox regression multivariate analysis revealed that the only factor associated with AVM obliteration rate after SRS was AVM volume. However, a larger AVM volume (>20 mL) and a larger proportion of brain parenchyma (>50%) within the prescription isodose range were both correlated with a higher RIC rate following SRS. Conclusions: The diffuseness of the nidus indeed appears to affect the RIC rate following SRS in patients with unruptured AVMs.
Unusual Cerebral Aneurysm after Stereotactic Radiosurgery to Treat Trigeminal Neuralgia
Authors: Chung Ming Hsuan , Wang Peng-Wei , Wu Yi-Chieh , Yang Yun-Ju , Hong Kun-Ting , Hsu Tzu-Hsien , Chen Yi-An , Chung Tzu-Tsao , Tang Chi-Tun , Ju Da-Tong
Published: December 2020

Stereotactic radiosurgery is a treatment option for trigeminal neuralgia. This procedure is minimally invasive, but tumor development and facial numbness have been reported. Here, we report an unusual presentation after stereotactic radiosurgery to treat trigeminal neuralgia. A 60-year-old man demonstrated typical signs for type 1 trigeminal nerve neuralgia and was treated with medication for 5 years. Owing to an intolerance to that medication, he received stereotactic radiosurgery with 66 Gy. During a 9-year follow-up exam, dizziness with a spinning sensation was reported and a right superior cerebellar thrombosed aneurysm was diagnosed. He received transarterial embolization with coiling of aneurysm and subsequently reported no complications on follow-up exams. Although stereotactic radiosurgery is a promising treatment for trigeminal neuralgia, aneurysm development may be considered a possible complication. Long-term follow-up care of these patients should be considered. To understand the relationship between radiosurgery and the potential development of a cerebral aneurysm, further research is needed.
The Effect of Diagnostic Ureterorenoscopy on Intravesical Recurrence in Patients Undergoing Nephroureterectomy for Primary Upper Tract Urinary Carcinoma
Authors: İzol Volkan , Deger Mutlu , Ozden Ender , Bolat Deniz , Argun Burak , Baltaci Sumer , Celik Orcun , Akgul Hacı Murat , Tinay İlker , Bayazit Yildirim ,   Bladder Cancer Study Group of Association of Urooncology, Turkey
Published: December 2020

Objective: The objective of this study is to evaluate the effect of diagnostic ureterorenoscopy (URS) prior to radical nephroureterectomy (RNU) on intravesical recurrence (IVR), in patients with primary upper urinary tract urothelial carcinoma (UTUC). Materials and Methods: Retrospective analysis of 354 patients, who underwent RNU for UTUC from 10 urology centers between 2005 and 2019, was performed. The primary endpoint was the occurrence of IVR after RNU. Patients were divided into URS prior to RNU (Group 1) and no URS prior to RNU (Group 2). Rates of IVR after RNU were compared, and a Cox proportional hazards model was used to evaluate potential predictors of IVR. Results: After exclusion, a total of 194 patients were analyzed: Group 1 n = 95 (49.0%) and Group 2 n = 99 (51.0%). In Group 1, a tumor biopsy and histopathological confirmation during URS were performed in 58 (61.1%). The mean follow-up was 39.17 ± 39.3 (range 12–250) months. In 54 (27.8%) patients, IVR was recorded after RNU, and the median recurrence time within the bladder was 10.0 (3–144) months. IVR rate was 38.9% in Group 1 versus 17.2% in Group 2 (p = 0.001). In Group 1, IVR rate was 43.1% in those undergoing intraoperative biopsy versus 32.4% of patients without biopsy during diagnostic URS (p =0.29). Intravesical recurrence-free survival (IRFS) was longer in Group 2 compared to Group 1 (median IRFS was 111 vs. 60 months in Groups 2 and 1, respectively (p< 0.001)). Univariate analysis revealed that IRFS was significantly associated with URS prior to RNU (HR: 2.9, 95% CI 1.65–5.41; p < 0.001). In multivariate analysis, URS prior to RNU (HR: 3.5, 95% CI 1.74–7.16; p < 0.001) was found to be an independent prognostic factor for IRFS. Conclusion: Diagnostic URS was associated with the poor IRFS following RNU for primary UTUC. The decision for a diagnostic URS with or without tumor biopsy should be reserved for cases where this information might influence further treatment decisions.
Body Weight Changes in Hyperthyroidism: Timing and Possible Explanations during a One Year Repeated Measurement Study
Authors: Karmisholt Jesper , Carlé Allan , Andersen Stig
Published: December 2020

Background: Weight gain during treatment of hyperthyroidism is a frequent and for many patients unwanted outcome. With this repeated measurement study, we explored the timing of weight changes during the first year of antithyroid drug (ATD) treatment and assessed the correlation between body weight changes and changes in thyroid hormones, resting energy expenditure (REE), physical activity level, and energy efficiency. Methods: Patients with new onset hyperthyroidism were investigated every second month during the first year of ATD treatment. At each investigation, the following were measured: body weight, thyroid hormone concentrations, physical activity level, and daily number of steps, REE, and exercise performance. Results: Two men and eleven women, all sedentary, mean age 49(SD: 9.3) years were included. Significant changes after 1 year occurred for body weight (68.9–74.1 kg), thyroid hormones (free T3 [fT3] 17.5 to 4.42 pmol/L), REE (1,630–1,484 kcal/24 h), and energy efficiency at lower (50 W) workloads (16.0–17.6%). In individual patients, only REE and fT3 correlated to changes in body weight. Physical activity level did not change during treatment. Conclusion: In this study, treatment of hyperthyroidism was associated with marked increase in body weight in the patients. This increase correlated to a decrease in REE and only to a negligible extent to changes in energy efficiency and not at all to changes in physical activity level of daily living.
Vessel Wall Magnetic Resonance Imaging Biomarkers of Symptomatic Intracranial Atherosclerosis
Authors: Song Jae W. , Pavlou Athanasios , Xiao Jiayu , Kasner Scott E. , Fan Zhaoyang , Messé Steven R.
Published: December 2020

Background and Purpose:

Intracranial atherosclerotic disease is a common cause of stroke worldwide. Intracranial vessel wall magnetic resonance imaging may be able to identify imaging biomarkers of symptomatic plaque. We performed a meta-analysis to evaluate the strength of association of imaging features of symptomatic plaque leading to downstream ischemic events. Effects on the strength of association were also assessed accounting for possible sources of bias and variability related to study design and magnetic resonance parameters.

Methods:

PubMed, Scopus, Web of Science, EMBASE, and Cochrane databases were searched up to October 2019. Two independent reviewers extracted data on study design, vessel wall magnetic resonance imaging techniques, and imaging end points. Per-lesion odds ratios (OR) were calculated and pooled using a bivariate random-effects model. Subgroup analyses, sensitivity analysis, and evaluation of publication bias were also performed.

Results:

Twenty-one articles met inclusion criteria (1750 lesions; 1542 subjects). Plaque enhancement (OR, 7.42 [95% CI, 3.35–16.43]), positive remodeling (OR, 5.60 [95% CI, 2.23–14.03]), T1 hyperintensity (OR, 2.05 [95% CI, 1.27–3.32]), and surface irregularity (OR, 4.50 [95% CI, 1.39–8.57]) were significantly associated with downstream ischemic events. T2 signal intensity was not significant (
P
=0.59). Plaque enhancement was significantly associated with downstream ischemic events in all subgroup analyses and showed stronger associations when measured in retrospectively designed studies (
P
=0.02), by a radiologist as a rater (
P
<0.001), and on lower vessel wall magnetic resonance imaging spatial resolution sequences (
P
=0.02).

Conclusions:

Plaque enhancement, positive remodeling, T1 hyperintensity, and surface irregularity emerged as strong imaging biomarkers of symptomatic plaque in patients with ischemic events. Plaque enhancement remained significant accounting for sources of bias and variability in both study design and instrument. Future studies evaluating plaque enhancement as a predictive marker for stroke recurrence with larger sample sizes would be valuable.
Two routes to precarious success: Australia, New Zealand, COVID-19 and the politics of crisis governance
Authors: Bromfield Nicholas , McConnell Allan
Published: December 2020

Australia and New Zealand are routinely presented as sharing more in common than the federal and unitary systems separating them. As two modernising Antipodean settler societies, their governing trajectories have embraced waves of public administration/management reform. Shared pathways seem matched by their relative, although precarious and fragile, early successes in the crisis challenges of COVID-19. This article contextualises and examines one crucial point of separation: two very different crisis governance routes to such outcomes. Australia’s federal variant of multi-level governance, more used to addressing diverse regional challenges than shared national threats, has been characterised by an evolving balancing act of multi-jurisdictional agendas and bureaucratic–political conflicts. By contrast, New Zealand’s unitary system of governance, well-versed in the centralisation of power, has produced lower levels of intergovernmental conflict. Our analysis of these differing pathways also makes a contribution to our conceptual understanding of successful crisis governance.

Points for practitioners

Administrative arrangements based around federal or unitary systems are both quite capable of contributing to successful outcomes. Essential for both are inclusive crisis discussions that are consistent with the norms of the respective systems. Success can be fragile, especially in a pandemic. Appropriate inclusive discussions can facilitate responses to cascading crisis developments and act as a safeguard against complacency.