bluuebunny/crossref_metadata_2025 huggingface dataset:
A model-experiment validation of near-range phase center breakdown
Authors: Warner Jonah , Blanford Thomas E. , Brown Daniel C.
Published: July 2024

Spatial coherence of a scattered field has helped to improve sensor navigation techniques and field imagery. Under the phase center approximation (PCA), a bistatic sensor geometry is approximated as a monostatic phase center. In the far field, the approximation is valid, and signals with common phase centers are highly coherent. The approximation fails when a non-trivial spatiotemporal delay appears in the sensor’s near-field, and signals that share phase centers are less coherent. A model by Brown and Blanford shows this near-field degradation of PCA, using comparisons between the van Cittert-Zernike Theorem and a point-based scattering model. Experimental validation of the model was performed using an in-air sonar mounted on a linear actuator. The sonar collected returns from a shallow bed filled with plastic beads, which approximates rough interfaces typical of underwater environments. Multiple trials were conducted using a variety of transmitters, receiver placements, and ping intervals. These geometries were simulated using the point-based scattering model and the two sets of data were compared in order to validate the model. Results from this model-data comparison, along with future applications for sonar imaging and navigation, will be discussed.
Monodisperse microbubble-mediated drug delivery: Influence of microbubbles size on drug delivery outcome
Authors: Wang Yuchen , Li Hongchen , Meijlink Bram , Luo Jiali , Beurskens Robert , Johnson Benjamin , Kooiman Klazina
Published: July 2024

As the microbubble's resonance frequency is size-dependent, polydisperse microbubbles induce varying drug delivery outcomes at one ultrasound frequency. This study aimed to investigate drug delivery outcome of monodisperse MBs (mMBs) with radii ranging from 1.5–2.9 μm insonified at 2 MHz. Phospholipid-coated mMBs were generated using the Horizon microfluidic flow-focusing device. In vitro experiments were conducted on single microbubble-endothelial cells (n = 68) using confocal microscopy and 10 Mfps ultra-high-speed imaging. At 220 kPa PNP for 10 cycles, the 1.5 μm mMBs exhibited the highest PI uptake in 81.3% of cases, followed by 77.3% for 2.2 μm, 36.8% for 2.7 μm and 13.3% for 2.9 μm mMBs. Conversely, the 1.5 μm mMBs had the second lowest excursion amplitude (R;max-R;0) of 0.8 ± 0.3 μm as this was 1.2 ± 0.3 μm for 2.2 μm mMBs, 1.0 ± 0.3 μm for 2.7 μm mMBs, and 0.7 ± 0.2 μm for 2.9 μm mMBs. Additionally, for the 1.5, 2.2, and 2.7 μm mMBs, PI uptake and tunnel formation occurred more often (1.6, 1.8, and 1.3 times, respectively) than PI uptake and a resealing membrane pore. During insonification, mMB pinch-off occurred more frequently in tunnel formation (70.8%) than resealing pore formation (53.3%). This research revealed the impact of mMBs size on drug delivery outcome.
Is pickleball a good neighbor?
Authors: Way Evelyn
Published: July 2024

Upscale multi-family residences need the latest amenities to attract tenants. A recent project featured a party room, exercise facility, and pickleball court on the top floor of a low-rise, adaptive reuse of an office building to residential renovation. Pickleball courts located directly above residential units allowed for measurements of sound transmission during pickleball play and comparison to traditional airborne and impact isolation metrics.
Preliminary analysis of more than 60 pickleball noise consultant reports
Authors: Leahy Charles E.
Published: July 2024

Over 60 consulting reports authored by over 30 different US and Canadian consultants have been gathered from municipal agendas, court filings, and HOA members. The reports are analyzed with respect to tools, metrics, and criteria used to make findings and recommendations to city officials, HOA Boards, and lawsuit litigants. The reports range greatly in length and purpose, many with sound meter data, excerpts from municipal ordinances, and specifications for noise mitigation including setbacks, full enclosures, barriers, and equipment recommendations. Particular attention is given to the consultant’s choice of sound meter metrics and the attention or lack of attention to the impulsive nature of pickleball noise and applicability of ANSI Standard 12.9 Part 4. When a local ordinance is referenced, we examine whether the consultant limited the report to provisions specifying a decibel limit and excluded comment on the general nuisance and plainly audible standards that are often present. Anecdotes are drawn from the data to identify best practices and worst practices of the consultants and their reports. This paper may be useful to consultants in planning their future pickleball studies; useful in deciding whether to refer these projects to a more experienced pickleball noise boutique firm; and/or useful to attorneys in recognizing the challenges of using the consultant report in the litigation setting.
Strong diffraction of nonlinear surface acoustic waves in crystals
Authors: McCollom Brittany A. , Cormack John M. , Baldini Edoardo , Hamilton Mark F.
Published: July 2024

Nonlinear distortion and shock formation in planar surface acoustic waves in anisotropic crystals have been modeled without [Hamilton et al., JASA (1999)] and with [Cormack et al., JASA 2022] piezoelectricity. Weak diffraction has been included in the paraxial approximation for nonlinear surface wave beams in isotropic solids [Shull et al., JASA (1995)]. Here, a procedure for including strong diffraction, i.e., without the paraxial approximation, in the model for nonlinear surface waves in crystals is presented, which incorporates the angular spectrum approach described by Kharusi and Farnell (JASA 1970). Anisotropy is defined by expressing the phase speed of a plane wave, and therefore, the magnitude of the corresponding wavenumber, as a function of the direction of propagation. Next, an explicit expression relating the two wavenumber components in the planar surface along which the wave propagates must be obtained as a function of direction, requiring iterative solution of a transcendental relation. The beam is then propagated incrementally away from the source, advancing the angular spectrum in k-space and including nonlinear interactions in the spatial domain to characterize the combined effects of diffraction and nonlinearity. Preliminary results are presented for converging nonlinear surface waves in crystals. [Work supported by IR&D at ARL:UT.]
Sensing touch location on an elastic surface by monitoring structural vibrations
Authors: Thompson Benjamin R. , DiPassio Tre , Rutowski Jenna , Bocko Mark , Heilemann Michael C.
Published: July 2024

In recent years, touchscreens have become ubiquitous, and projected capacitance (p-cap) has arisen as the dominant touch-sensing technology. Though powerful, p-cap has some characteristics that make it less suited for certain applications. Active acoustic sensing (AAS) systems work by sensing the vibration response of an elastic surface to a system-generated excitation and associating specific response characteristics with touch locations on the surface. These systems have the potential to offer advantages over p-cap in terms of scalability, cost, and performance in harsh environments. AAS systems may also offer the ability to sense touch pressure as an additional input parameter. We developed an empirical model of surface vibrational response as a function of the location of an applied force and then used this model to inform the signal processing and machine learning approaches employed in a prototype AAS system. In this presentation, we provide results from our empirical model as well as details of the prototype system, including its construction and performance.
Coupling the force analysis technique and full-field vibration measurements for the identification of a time-space-varying sound pressure loading on a membrane
Authors: Mougey Anaïs , Melon Manuel , Foucart Félix , Robin Olivier
Published: July 2024

This work is grounded on the force analysis technique, an identification method that directly uses a structure's equation of motion to formulate an inverse problem, explicitly identifying the force causing the structure's motion. Prior research employing this technique has been predominantly conducted in the frequency domain and was limited to stationary, mechanical excitations using physical sensor arrays such as accelerometers. The objective of this research was mostly quantitative (amplitude, location), while the proposed approach is rather qualitative identification. Indeed and by combining the force analysis technique with full-field and non-contact vibration measurements conducted on a system, here a membrane, this communication describes a proof-of-concept for the identification of a time-space-varying sound pressure loading. A compact and tonal sound source is used to draw freehand shapes against the membrane surface, and the objective is to follow/reconstruct the trajectory followed by this source. Results are provided for different drawn shapes or letters, and the effect of mechanical or calculation parameters on the reconstructed information is studied. Finally, potential research directions are discussed and fed by preliminary measurements on a percussion instrument.
Leak detection in an operational underground water distribution network using active acoustics
Authors: Agrawal Pranav , Fong Stan , Friesen Dirk , Narasimhan Sriram
Published: July 2024

Leaks present in the water distribution networks (WDNs) lead to an enormous loss of a valuable resource, not only affecting the economic efficiency of water utilities but also posing significant potential safety hazards, and an increased burden on infrastructure maintenance. In the past, several studies have focused on passive acoustic-based leak detection by primarily sensing and analyzing the acoustic signals emitted from the leak source. In this study, we installed a low-frequency transducer in the water column of an operational WDN near Los Angeles, California, and excited the system using steady-state sinusoidal and sine burst signals. The acoustic pressure signals inside the pipe network were measured at multiple locations using state-of-the-art hydrophone-enabled devices retrofitted to fire hydrants. The experiments were conducted in the presence of a simulated leak in the network. The leak acts as an impedance discontinuity for the acoustic wave propagation, and therefore, the excited signals undergo partial reflection at the leak location. Based on signal processing techniques, we attempt to detect and localize the leaks in the WDN. The goal of using the active acoustics is to detect small leaks and increase the range of sensing.
Performance analysis of a dilated attention fast GAN for speech enhancement
Authors: Ashkani Vahid , Parsa Vijay
Published: July 2024

Recent advancements in speech enhancement have witnessed the emergence of generator-based methodologies. However, several of these approaches exhibit complexity in handling input variations, either excelling at low signal-to-noise ratios (SNRs) by utilizing intricate representations of noisy and clean speech or demonstrating superior performance only at higher SNRs. In this work, we investigated speech enhancement using a Dilated Attention Fast Generative Adversarial Network (DAF-GAN). The proposed DAF-GAN framework achieves stability in performance across different SNR conditions by efficiently processing large-scale signal lengths. The DFS-GAN features a dilated discriminator model operating via patches. The generator architecture incorporates multi-decoding and attention gates facilitated through skip-connections, strategically integrated within the Fast-U-Net model to optimize processing speed. An ideal ratio mask was used in the test phase to further refine the enhanced signal by emphasizing target speech while suppressing residual noise or artifacts. The DAF-GAN performance was assessed using objective metrics such as PESQ on a number of noisy speech databases. Results revealed that the DAF-GAN performed modestly in comparison with the state-of-the-art models. For example, analyses of the VoiceBank-DEMAND dataset yielded a PESQ score of 2.50 for the DAF-GAN.
You good?: Examining the role of intonation and eyebrow movements in sentence type distinction
Authors: Lowe Kendall , Lee Yoonjeong , Krivokapić Jelena , Abner Natasha
Published: July 2024

By analyzing the pitch accents, edge tones, and eyebrow movements of African American English (AAE) speakers, this study examines the coordination of prosody and co-speech gestures. Twelve self-identified AAE speakers engaged in scripted dialogues with an AAE-speaking confederate via Zoom. Half of the dialogues contained the polysemous AAE idiomatic phrase “you good” which has declarative and interrogative forms hypothesized to be distinguished by various eyebrow and intonation patterns. The other dialogues included non-idiomatic phrases semantically related to their “you good” equivalents. These dialogues were designed to explore whether the coordination patterns for the idioms occur with non-idiomatic utterances of the same sentence type. Acoustic data is prosodically annotated using the MAE-ToBI transcription system and visual eyebrow data is tracked using OpenFace 2.0, a facial landmark detection toolkit. The derived eyebrow movement trajectories are time-aligned with the pitch trajectories for the semi-automatic labeling of multimodal signals. The temporal relationship between eyebrow movement landmarks, pitch accents, and edge tones is examined to investigate how different meanings and sentence types are created through their coordination. Preliminary examination indicates intonationally similar contours for the idiomatic and non-idiomatic interrogative phrases, but shared and consistent intonational contours are not evident in the declarative data.
The impact of remote microphones and facial masks on speech production and conversational behaviors in hearing-impaired individuals
Authors: Ellag Menatalla K. , Qian Jinyu , Ishida Ieda , MacDonald Ewen
Published: July 2024

This study investigates the acoustics and conversation behavior of the speech produced during conversations among groups of hearing-impaired individuals. Four groups of four hearing-impaired individuals, all using hearing aids, engaged in discussions on provided topics in the presence of background noise. Conversations were held in four conditions based on two factors (using versus not using a remote microphone; wearing versus not wearing a face mask). Analysis of recorded conversations focused on speech production measures (e.g., fundamental frequency, articulation rate, formant frequencies, etc.) and conversational behaviors (e.g., inter-pausal unit length, floor-transfer offsets, turn duration, etc.). Although both influence the potential difficulty of holding a conversation, distinct effects of mask, remote microphone, and their interaction were observed for measures of speech production and conversational behaviors.
The effect of task on speech production and conversation behavior during conversation
Authors: Ellag Menatalla K. , Avison Kate , MacDonald Ewen
Published: July 2024

The purpose of this study was to investigate how native-English, healthy-hearing individuals adapt their speech production and conversation behavior in the presence of noise and how this can vary based on conversational goal. Pairs of participants engaged in both free-form conversations as well as conversations based on solving a task (a “spot the difference” task using the Diapix UK pictures). Although seated in separate rooms, talkers could communicate via headset microphones and headphones with gains set to simulate levels that would be present if they were seated in the same room. The effects of task and noise on measures of speech production (e.g., articulation rate, speech level, etc.) and conversational behaviors (e.g. floor transfer offsets, turn length, etc.) are investigated. These results provide insights into how to infer listening effort via acoustical measures of communication in a broader range of settings.
Performance analysis of passive acoustic ranging using a single hydrophone in shallow waters
Authors: Jang Jeong Bin , Byun Sung-Hoon
Published: July 2024

Passive source range estimation is one of the important research fields on the sonar system. Recent research has carried out range estimation using single hydrophone. This study presents the result of analyzing the impact of environmental conditions on range estimation performance when estimating the range of a moving source with a single hydrophone. Range estimation of a moving source using a single hydrophone estimates source velocity from the cross-correlated fields of the signal measured at time intervals. This method of estimating the source range from estimated source velocity is used. Therefore, it is important to accurately estimate the source velocity for ranging, and the accuracy of estimating the source velocity is affected by the propagating mode characteristics in waveguide. This study investigates the changes in velocity estimation performance of a moving source according to various underwater environment and mode formation characteristics through simulation analysis and discusses ways to reduce velocity estimation error. [Work supported by KRIT (Contract No. 22-305-B00-001).]
Generalization performance analysis of anomaly detection-based active sonar classifier using anomaly score landscape
Authors: Kim Geunhwan , Hwang YoungSang , Lee Keunhwa , Choo Youngmin
Published: July 2024

This study explores generalization performance of anomaly detection-based active sonar classifier using the deep neural network (NN). Despite its superior performance, NN remains challenging to interpret its decision due to black-box nature, which, consequently, makes it hard to trust the results. To address this, we employ the loss landscape method used to analyze the generalization performance of supervised learning-based NN. Owing to the inapplicability of the conventional loss landscapes to anomaly detection-based classifier, we propose a novel anomaly score landscape for the anomaly detection-based classifier. Experimental results using active sonar datasets reveal that anomaly detection-based classifier maintains consistent landscape structures between train and test datasets, compared to supervised learning counterparts. This study provides insights into the interpretability and generalization capabilities of supervised- and anomaly detection-based active sonar classifiers.
Acoustic diversity, bearing estimation, and localization of sound sources in shallow water and deep ocean off the U.S. Northeast coast using a coherent hydrophone array
Authors: Seri Sai Geetha , Radermacher Max , Mohebbi-Kalkhoran Hamed , Makris Purnima R.
Published: July 2024

An in-house developed 160-element large-aperture hydrophone array from Northeastern University was utilized for ocean monitoring in both the shallow waters of the Great South Channel (GSC) and the deep-water area off the continental slope south of Rhode Island in September 2021. Utilizing passive ocean acoustic waveguide remote sensing (POAWRS) technology, the system enabled real-time, broad-area surveillance of the oceanic environment. A novel multistage clustering was introduced for annotating the vast volume of underwater acoustic data, drawing inspiration from the human cognitive process of categorizing sounds. Initially, sounds are separated into broad groups, akin to a first human listening pass. Subsequent stages of clustering refine these categories, utilizing different sets of features to achieve a granularity of annotation that closely mirrors expert human annotation processes. It was found that the acoustic landscape of the GSC was primarily composed of diverse marine mammal sounds, such as fin whale 20 Hz pulses, humpback whale songs, minky whale buzz sequences, sperm whale and dolphin echolocation clicks, and unidentified whale calls. Conversely, the deep-water area off the continental slope featured predominantly fish sounds, chorus-like sounds, and dolphin vocalizations. Detailed analyses of the most prevalent vocalizations are presented, including their bearing-time trajectories and localizations.
Multi-sensor acoustic intensity analysis of the NG-19 Antares 230 launch
Authors: Cunningham Carson F. , Shepherd Micah , Gee Kent L.
Published: July 2024

In August 2023, the Antares 230 successfully launched for the NG-19 resupply mission to the International Space Station. Acoustical data were collected from various locations surrounding the launch pad from 60-200 m away from the vehicle. Each measurement location was configured such that acoustic intensity could be determined for a wide range of frequencies. Intensity calculations are made using the phase and amplitude gradient estimate (PAGE) method for information past the spatial Nyquist frequency of the station configuration. For the analyses presented here, the PAGE method utilized the generic MATLAB phase unwrapping function. This paper will show intensity vectors as a function of frequency and time to estimate the approximate location of the sound source. A least-squares optimization routine is used for the intersection point of each stations’ intensity vector.
Sono-catalytic syngas production by low-temperature biomass gasification
Authors: Wong Cherie , Kwan James
Published: July 2024

Syngas holds a crucial role in diverse industrial applications, including chemical synthesis and power generation. It has been traditionally generated through high-temperature processes, such as steam reforming or biomass gasification, demanding temperatures of up to 1200 °C, which results in substantial energy consumption. Consequently, there is a growing interest in exploring alternative, low-temperature biomass gasification processes. This paper introduces an innovative method for syngas production through sono-catalytic biomass conversion at significantly lower temperatures. The approach employs a sonochemical reactor that concentrates acoustic waves to activate inertial cavitation. Furfural, a biomass-derived platform chemical, was chosen as the primary chemical for the study, showcasing the potential of sonochemical syngas production. The reaction converted furfural into various gas products, particularly a mixture of hydrogen and carbon monoxide, with the chemical reaction hypothesized to be triggered by pyrolysis during bubble collapse hot spots. The incorporation of heterogeneous metal foams into the system further enhanced furfural conversion rates. This improvement was attributed to the preferential nucleation of cavitation bubbles on the porous metal foam surface, bringing the hot spots into proximity with furfural molecules. This application of sonochemistry in furfural pyrolysis at low temperatures holds promise for a more economical approach to biomass valorization.
Bistatic spatial coherence for micronavigation of a volumetric synthetic aperture sonar
Authors: Dalton Kyle S. , Blanford Thomas E. , Brown Daniel C.
Published: July 2024

Combining multiple passes of a volumetric synthetic aperture sonar (SAS) may open new possibilities for sonar imaging, if the passes can be precisely aligned. Previous work suggests that coherence-based micronavigation is a potential approach to achieve this alignment. However, existing coherence-based techniques require assumptions that break down in many volumetric imaging geometries. This breakdown leads to a loss of coherence that has not been widely studied, and consequently, has hindered the application of micronavigation to volumetric SAS systems. This work will explore the impact of sensing range and bistatic separation on spatial coherence in downward-looking, volumetric sonar applications where the far-field assumption no longer holds. As signals transmitted from downward-looking sonars may penetrate into the sediment floor, this analysis will consider both interface and volumetric scattering. First, using both simulated and experimental sonar data, we will quantify the loss in coherence that occurs in these near-field geometries. Then, methods to regain lost coherence will be examined in an effort to enable spatial coherence-based navigation for a volumetric SAS. Finally, the work’s relevancy for ongoing efforts in acoustic navigation and repeat-pass imaging will be discussed.
The use of Navy range bottom-mounted, bi-directional transducers for long-term, deep-ocean prey mapping
Authors: Muniz Alexander , Watwood Stephanie , Morrissey Ronald , Benoit-Bird Kelly
Published: July 2024

Beaked whales have been shown to be particularly sensitive to mid-frequency active sonar but continue to spend considerable time on Navy training ranges, where exposure to sonar is frequent. Understanding the underlying movements of their prey could help to explain the distribution and abundance patterns seen for beaked whales. Beaked whales are among the deepest diving marine mammals and have been shown to feed near the ocean bottom, at depths up to 3000 m. Typical surface-deployed prey mapping technology is not suitable for probing these deep foraging depths. This pilot study aims to us the bi-directional nodes on Navy hydrophone ranges that were developed for underwater communications as a rudimentary prey mapping system. A 1 ms 2 kHz signal was broadcast on an 8 kHz carrier signal and resulting returns were processed to estimate depths of the reflectors. Data are presented from three different time periods on the Southern California Anti-Submarine Warfare Range.
An overview of the calibration process for a digital hydrophone
Authors: Wood Nicolas
Published: July 2024

Digital hydrophones are instruments for measuring underwater sound that incorporate the entire data chain into a single unit. Calibration of analog and digital hydrophones is largely similar but differs in measurement signal type. Digital hydrophone calibration is not currently captured in the standards outlining hydrophone calibration (such as IEC 60565), so they currently cannot be calibrated to a recognized standard. The testing setup and calibration methods are the same as for an analog hydrophone but without needing external digitization or analog signal conditioning. Potential issues regarding digital hydrophone calibration: careful calculation of signal amplitudes is required at upper frequency band; the lack of analog output requires different units of measure or information on counts/volt conversion. The first point here is also a current issue for analog hydrophones where the digitization and the processing of data during the calibration are not prescribed. Ideally, both of these issues would be addressed in future standards updates, which would improve the operation of both analog and digital hydrophones. This paper will expand on the issues highlighted here involving digital hydrophone calibration and offer recommendations for best practice. It will also provide an outline of the current calibration procedure as used at Ocean Sonics.
The ONR three octave research array at Penn State
Authors: Smith Chad M. , Troiano Luigi , Markovic Milan , Bernardini Marco
Published: July 2024

A new, large diameter towed research array has been built to support the experimental efforts of the Office of Naval Research (ONR) Ocean Acoustics Program. Array development was a collaborative effort between the Centre for Maritime Research and Experimentation (CMRE) in La Spezia, Italy, and the Penn State Applied Research Laboratory (PSU). PSU chose the array specifications based on discussions within the underwater acoustics community, prior measurement experience, cost efficiency, and flexibility in scientific measurements, while CMRE designed and assembled the array. The design includes three, forward-nested acoustic apertures cut for 1, 2, and 4 kHz, and hence, has been dubbed the Three Octave Research Array (THORA) in deference to its predecessor, the Five Octave Research Array (FORA). However, this system has a modular design to allow addition of acoustic apertures if scientific interest and sponsor support warrant. The array currently consists of a 50 m acoustic module and a 25 m vibration isolation module to help isolate the acoustic module from cable strum. This ship towed system has nearly 1 km of tow cable and a maximum measurement depth of 500 m. The array’s design, its use in the ONR NESMA23 Pilot experiment, and data quality will be discussed.
Optimizing the timing of an end-of-outbreak declaration: Ebola virus disease in the Democratic Republic of the Congo
Authors: Hart William S. , Buckingham Jack M. , Keita Mory , Ahuka-Mundeke Steve , Maini Philip K. , Polonsky Jonathan A. , Thompson Robin N.
Published: July 2024

Following the apparent final case in an Ebola virus disease (EVD) outbreak, the decision to declare the outbreak over must balance societal benefits of relaxing interventions against the risk of resurgence. Estimates of the end-of-outbreak probability (the probability that no future cases will occur) provide quantitative evidence that can inform the timing of an end-of-outbreak declaration. An existing modeling approach for estimating the end-of-outbreak probability requires comprehensive contact tracing data describing who infected whom to be available, but such data are often unavailable or incomplete during outbreaks. Here, we develop a Markov chain Monte Carlo–based approach that extends the previous method and does not require contact tracing data. Considering data from two EVD outbreaks in the Democratic Republic of the Congo, we find that data describing who infected whom are not required to resolve uncertainty about when to declare an outbreak over.
An essential host dietary fatty acid promotes TcpH inhibition of TcpP proteolysis promoting virulence gene expression in
Vibrio cholerae
Authors: Demey Lucas M. , Sinha Ritam , DiRita Victor J.
Published: July 2024

Vibrio cholerae
is a Gram-negative gastrointestinal pathogen responsible for the diarrheal disease cholera. Expression of key virulence factors, cholera toxin and toxin-coregulated pilus, is regulated directly by ToxT and indirectly by two transmembrane transcription regulators (TTRs), ToxR and TcpP, that promote the expression of
toxT
. TcpP abundance and activity are controlled by TcpH, a single-pass transmembrane protein, which protects TcpP from a two-step proteolytic process known as regulated intramembrane proteolysis (RIP). The mechanism of TcpH-mediated protection of TcpP represents a major gap in our understanding of
V. cholerae
pathogenesis. The absence of
tcpH
leads to unimpeded degradation of TcpP
in vitro
and a colonization defect in a neonate mouse model of
V. cholerae
colonization. Here, we show that TcpH protects TcpP from RIP
via
direct interaction. We also demonstrate that α-linolenic acid, a dietary fatty acid, promotes TcpH-dependent inhibition of RIP
via
co-association of TcpP and TcpH molecules within detergent-resistant membranes (DRMs) in a mechanism requiring the TcpH transmembrane domain. Taken together, our data support a model where
V. cholerae
cells use exogenous α-linolenic acid to remodel the phospholipid bilayer
in vivo
, leading to co-association of TcpP and TcpH within DRMs where RIP of TcpP is inhibited by TcpH, thereby promoting
V. cholerae
pathogenicity.

IMPORTANCE

Vibrio cholerae
continues to pose a significant global burden on health and an alternative therapeutic approach is needed, due to evolving multidrug resistance strains. Transcription of
toxT
, stimulated by TcpP and ToxR, is essential for
V. cholerae
pathogenesis. Our results show that TcpP, one of the major regulators of
toxT
gene expression, is protected from proteolysis by TcpH,
via
direct interaction. Furthermore, we identified a gut metabolite, α-linolenic acid, that stimulates the co-association of TcpP and TcpH within detergent-resistant membranes (also known as lipid-ordered membrane domains), thereby supporting TcpH-dependent antagonism of TcpP proteolysis. Data presented here extend our knowledge of RIP, virulence gene regulation in
V. cholerae
, and, to the best of our knowledge, provides the first evidence that lipid-ordered membranes exist within
V. cholerae
. The model presented here also suggests that TTRs, common among bacteria and archaea, and co-component signal transduction systems present in
Enterobacteria
, could also be influenced similarly.
Going fishing: how to get what you want from a fungal genetic screen
Authors: O'Meara Teresa R.
Published: July 2024

Five years ago, as I was starting my lab, I wrote about two functional genomic screens in fungi that had inspired me (mSphere 4:e00299-19,
https://doi.org/10.1128/mSphere.00299-19
). Now, I want to discuss some of the principles and questions that I ask myself and my students as we embark on our own screens. A good screen, whether it is a genetic or chemical screen, can be the starting point for new discovery and an excellent basis for the beginning of a scientific research project. However, screens are often criticized for being “fishing expeditions.” To stretch this metaphor to the extreme, this is because people are worried that we do not know how to fish, that we will come home without any fish, bring home the wrong fish, or not know what to do with a fish if we caught it. How you set up the screen and analyze the results determines whether the screen will be useful. In this mini-review, and in the spirit of teaching a scientist to fish, I will discuss recent excellent fungal genetic and chemical screens that illustrate some of the key aspects of a successful screen.
Tracking the porphyry-epithermal mineralization transition using U-Pb carbonate dating
Authors: Mottram Catherine M. , Kellett Dawn A. , Barresi Tony , Chapman Glenn G. , Halle Jesse
Published: July 2024

Key metals important for the green energy transition concentrate during magmatic-hydrothermal processes. In porphyry deposits, epithermal mineralization can overprint earlier higher-temperature systems. It is not well understood whether mineralization occurs in a single evolving system or forms during pulsed, episodic overprinting events. The timing and duration of fluid flow therefore remain key data gaps in deposit models, but they are essential factors for understanding metal (re)mobilization and concentration processes. Carbonates are common gangue minerals that precipitate during fluid flow and can be dated using the U-Pb method, thereby directly dating hydrothermal processes. Here, 41 new U-Pb dates from a fault-controlled porphyry-epithermal system in Yukon, Canada, reveal a >50 m.y. record of carbonate precipitation between ca. 77 and 19 Ma. Results support a model of pulsed, episodic fluid flow, rather than a single evolving system, where epithermal carbonate precipitation at ca. 74–67 Ma was both coeval with and significantly postdated Cretaceous porphyry-related magmatism. Overprinting events at ca. 62–56 Ma, ca. 51–47 Ma, and younger than 40 Ma were not responsible for primary metal deposition but may have contributed to metal enrichment. Carbonate dates coincide with periods of brecciation and fault slip. Fault movement therefore enabled episodic overprinting by epithermal mineralization, mobilizing and (re)concentrating metals. This comprehensive reconstruction of a long-lived magmatic-hydrothermal system tracks the transition from porphyry to epithermal environments, demonstrating the power of carbonate U-Pb dating for critical minerals research.
Assessment of smoking care by stroke specialists in patients with recent TIA and minor stroke: an international prospective registry-based cohort study
Authors: Lavallee Philippa , Charles Hugo , Labreuche Julien , Albers Gregory W , Caplan Louis , Donnan Geoffrey A , Ferro José Manuel , Hennerici M G , Molina Carlos A , Rothwell Peter , Steg Gabriel , Touboul Pierre-Jean , Uchiyama Shinichiro , Vicaut Eric , Wong Lawrence K S , Amarenco Pierre
Published: July 2024

Objectives

The objectives are to assess smoking abstinence and its effects on vascular risk and to report tobacco-cessation counselling and pharmacotherapy use in patients who had a recent minor stroke or transient ischaemic attack (TIA).

Design and setting

The TIA registry.org project is a prospective, observational registry of patients with TIA and minor stroke that occurred in the previous 7 days with a 5-year follow-up, involving 61 sites with stroke specialists in 21 countries (Europe, Asia, Latin America and Middle East). Of those, 42 sites had 5-year follow-up data on more than 50% of their patients and were included in the present study.

Participants

From June 2009 through December 2011, 3847 patients were eligible for the study (80% of the initial cohort).

Outcomes

Tobacco counselling and smoking-cessation pharmacotherapy use in smoking patients were reported at discharge. Association between 3-month smoking status and risk of a major cardiovascular event (MACE) was analysed with multivariable Cox regression model.

Results

Among 3801 patients included, 835 (22%) were smokers. At discharge, only 35.2% have been advised to quit and 12.5% had smoking-cessation pharmacotherapy prescription. At 3 months, 383/835 (46.9%) baseline smokers were continuers. Living alone and alcohol abuse were associated with persistent smoking; high level of education, aphasia and dyslipidaemia with quitting. The adjusted HRs for MACE at 5 years were 1.13 (95% CI 0.90 to 1.43) in former smokers, 1.31 (95% CI 0.93 to 1.84) in quitters and 1.31 (95% CI 0.94 to 1.83) in continuers. Using time-varying analysis, current smoking at the time of MACE non-significantly increased the risk of MACE (HR 1.31 (95% CI 0.97 to 1.78); p=0.080).

Conclusion

In the TIAregistry.org, smoking-cessation intervention was used in a minority of patients. Surprisingly, in this population in which, at 5 years, other vascular risk factors were well controlled and antithrombotic treatment maintained, smoking cessation non-significantly decreased the risk of MACE.
Maintenance proton pump inhibitor use and risk of colorectal cancer: a Swedish retrospective cohort study
Authors: Liu Qing , Wang Xinchen , Engstrand Lars , Sadr-Azodi Omid , Fall Katja , Brusselaers Nele
Published: July 2024

Objectives

We aimed to evaluate the risk of colorectal adenocarcinoma (CRA) associated with long-term use of proton pump inhibitors (PPIs) in a large nationwide cohort.

Design

Retrospective cohort study.

Setting

This research was conducted at the national level, encompassing the entire population of Sweden.

Participants

This study utilised Swedish national registries to identify all adults who had ≥180 days of cumulative PPI use between July 2005 and December 2012, excluding participants who were followed up for less than 1 year. A total of 754 118 maintenance PPI users were included, with a maximum follow-up of 7.5 years.

Interventions

Maintenance PPI use (cumulative≥180 days), with a comparator of maintenance histamine-2 receptor antagonist (H2RA) use.

Primary and secondary outcome measures

The primary outcome measure was the risk of CRA, presented as standardised incidence ratios (SIRs) with 95% confidence intervals (CIs). Subgroup analyses were performed to explore the impact of indications, tumour locations, tumour stages and the duration of follow-up. A multivariable Poisson regression model was fitted to estimate the incidence rate ratios (IRRs) and 95% CIs of PPI versus H2RA use.

Results

Maintenance PPI users exhibited a slightly elevated risk of CRA compared to the general population (SIR 1.10, 95% CI=1.06 to 1.13) for both men and women. Individuals aged 18–39 (SIR 2.79, 95% CI=1.62 to 4.47) and 40–49 (SIR 2.02, 95% CI=1.65 to 2.45) had significantly higher risks than the general population. Right-sided CRA showed a higher risk compared to the general population (SIR 1.26, 95% CI=1.20 to 1.32). There was no significant difference in the risk of CRA between maintenance PPI users and maintenance H2RA users (IRR 1.05, 95% CI=0.87 to 1.27,p<0.05).

Conclusions

Maintenance PPI use may be associated with an increased risk of CRA, but a prolonged observation time is needed.
Associations of air pollution exposures in preconception and pregnancy with birth outcomes and infant neurocognitive development: analysis of the Complex Lipids in Mothers and Babies (CLIMB) prospective cohort in Chongqing, China
Authors: Chen Yingxin , Kuang Tao , Zhang Ting , Cai Samuel , Colombo John , Harper Alex , Han Ting-Li , Xia Yinyin , Gulliver John , Hansell Anna , Zhang Hua , Baker Philip
Published: July 2024

Objectives

To investigate the associations of traffic-related air pollution exposures in early pregnancy with birth outcomes and infant neurocognitive development.

Design

Cohort study.

Setting

Eligible women attended six visits in the maternity clinics of two centres, the First Affiliated Hospital of Chongqing Medical University and Chongqing Health Centre for Women and Children.

Participants

Women who were between 20 and 40 years of age and were at 11–14 weeks gestation with a singleton pregnancy were eligible for participation. Women were excluded if they had a history of premature delivery before 32 weeks of gestation, maternal milk allergy or aversion or severe lactose intolerance. 1273 pregnant women enrolled in 2015–2016 and 1174 live births were included in this analysis.

Exposures

Air pollution concentrations at their home addresses, including particulate matter with diameter ≤2.5 µm (PM2.5) and nitrogen dioxide (NO2), during pre-conception and each trimester period were estimated using land-use regression models.

Outcome measures

Birth outcomes (ie, birth weight, birth length, preterm birth, low birth weight, large for gestational age and small for gestational age (SGA) status) and neurodevelopment outcomes measured by the Chinese version of Bayley Scales of Infant Development.

Results

An association between SGA and per-IQR increases in NO2was found in the first trimester (OR: 1.57, 95% CI: 1.06 to 2.32) and during the whole pregnancy (OR: 1.33, 99% CI: 1.01 to 1.75). Both PM2.5and NO2exposure in the 90 days prior to conception were associated with lower Psychomotor Development Index scores (β: −6.15, 95% CI: −8.84 to –3.46; β: −2.83, 95% CI: −4.27 to –1.39, respectively). Increased NO2exposure was associated with an increased risk of psychomotor development delay during different trimesters of pregnancy.

Conclusions

Increased exposures to NO2during pregnancy were associated with increased risks of SGA and psychomotor development delay, while increased exposures to both PM2.5and NO2pre-conception were associated with adverse psychomotor development outcomes at 12 months of age.

Trial registration number

ChiCTR-IOR-16007700
Same-visit hepatitis C testing and treatment to accelerate cure among people who inject drugs (the QuickStart Study): a cluster randomised cross-over trial protocol
Authors: Doyle Joseph S , Heath Katherine , Elsum Imogen , Douglass Caitlin , Wade Amanda , Kasza Jessica , Allardice Kate , Von Bibra Sally , Chan Kico , Camesella Beatriz , Guzman Rodney , Bryant Mellissa , Thompson Alexander J , Stoové Mark A , Snelling Thomas L , Scott Nick , Spelman Timothy , Anderson David , Richmond Jacqui , Howell Jessica , Andric Nada , Dietze Paul M , Higgs Peter , Sacks‐Davis Rachel , Forbes Andrew B , Hellard Margaret E , Pedrana Alisa E
Published: July 2024

Introduction

Despite universal access to government-funded direct-acting antivirals (DAAs) in 2016, the rate of hepatitis C treatment uptake in Australia has declined substantially. Most hepatitis C is related to injecting drug use; reducing the hepatitis C burden among people who inject drugs (PWID) is, therefore, paramount to reach hepatitis C elimination targets. Increasing DAA uptake by PWID is important for interrupting transmission and reducing incidence, as well as reducing morbidity and mortality and improving quality of life of PWID and meeting Australia’s hepatitis C elimination targets.

Methods and analysis

A cluster randomised cross-over trial will be conducted with three intervention arms and a control arm. Arm A will receive rapid hepatitis C virus (HCV) antibody testing; arm B will receive rapid HCV antibody and rapid RNA testing; arm C will receive rapid HCV antibody testing and same-day treatment initiation for HCV antibody-positive participants; the control arm will receive standard of care. The primary outcomes will be (a) the proportion of participants with HCV commencing treatment and (b) the proportion of participants with HCV achieving cure. Analyses will be conducted on an intention-to-treat basis with mixed-effects logistic regression models.

Ethics and dissemination

The study has been approved by the Alfred Ethics Committee (number HREC/64731/Alfred-2020-217547). Each participant will provide written informed consent. Reportable adverse events will be reported to the reviewing ethics committee. The findings will be presented at scientific conferences and published in peer-reviewed journals.

Trial registration number

NCT05016609.

Trial progression

The study commenced recruitment on 9 March 2022 and is expected to complete recruitment in December 2024.
What do Australian primary care clinicians need to provide long-acting reversible contraception and early medical abortion? A content analysis of a virtual community of practice
Authors: Srinivasan Sonia , James Sharon Maree , Kwek Joly , Black Kirsten , Taft Angela J , Bateson Deborah , Norman Wendy V , Mazza Danielle
Published: July 2024

Background

Uptake of long-acting reversible contraception (LARC) is lower in Australia compared with other high-income countries, and access to early medical abortion (EMA) is variable with only 11% of general practitioners (GPs) providing EMA. The AusCAPPS (Australian Contraception and Abortion Primary Care Practitioner Support) Network is a virtual community of practice established to support GPs, nurses and pharmacists to provide LARC and EMA in primary care. Evaluating participant engagement with AusCAPPS presents an opportunity to understand clinician needs in relation to LARC and EMA care.

Methods

Data were collected from July 2021 until July 2023. Numbers of online resource views on AusCAPPS were analysed descriptively and text from participant posts underwent qualitative content analysis.

Results

In mid-2023 AusCAPPS had 1911 members: 1133 (59%) GPs, 439 (23%) pharmacists and 272 (14%) nurses. Concise point-of-care documents were the most frequently viewed resource type. Of the 655 posts, most were created by GPs (532, 81.2%), followed by nurses (88, 13.4%) then pharmacists (16, 2.4%). GPs most commonly posted about clinical issues (263, 49% of GP posts). Nurses posted most frequently about service implementation (24, 27% of nurse posts). Pharmacists posted most about health system and regulatory issues (7, 44% of pharmacist posts).

Conclusions

GPs, nurses and pharmacists each have professional needs for peer support and resources to initiate or continue LARC and EMA care, with GPs in particular seeking further clinical education and upskilling. Development of resources, training and implementation support may improve LARC and EMA provision in Australian primary care.
Combined central and peripheral demyelination in two siblings, immune mediated or genetic?
Authors: Moodley Kaminie , Moodley Anandan A , Efthymiou Stephanie , Houlden Henry , Bill Pierre L A , Patel Vinod B , Rinaldi Simon
Published: July 2024

We report unusual cases of combined central and peripheral demyelination in two siblings related to pregnancy, each presenting with progressive tetraparesis and cranial nerve palsies. The elder sister had a relapsing–remitting course with optic nerve dysfunction and died during a relapse from respiratory insufficiency. The younger sister presented with disorientation and acute-onset limb and facial weakness. She responded well to corticosteroid therapy. Their clinical presentation, response to immunomodulatory therapy, nerve conduction studies, cerebrospinal fluid and histology supported an acquired demyelinating cause. Whole-exome sequencing identified variants in two genes not previously linked to this clinical phenotype. Serological tests for antibody-mediated demyelination were negative. Despite the undefined pathogenesis, these cases provide a platform to explore the confluence of genetic, immune and environmental factors in the context of acquired demyelination. We discuss the differential diagnosis and a diagnostic approach to such cases from the perspectives of neuroimmunology and neurogenetics.