bluuebunny/crossref_metadata_2025 huggingface dataset:
Where does the gamma go?: Acoustics of the non-labialized voiced velar approximant in Tlingit
Authors: Cardoso Amanda , Brown Simone , Lahlou Omar , Paulin Ella , Crippen James A.
Published: July 2024

The acoustic properties of the voiced velar approximant [ɰ] are poorly characterized, partly from understudy of relevant languages and partly from uncertainty about the sound itself. We investigate this sound in Tlingit, a critically endangered indigenous language of northwestern North America, where [ɰ] contrasts with labialized [w] and palatal [j] in some dialects but not in others where it was lost through sound change (reductive primary split with merge). We use audio recordings of spoken narratives spanning much of the 20th century from speakers with and without [ɰ] to characterize this sound both dialectally and diachronically. We measure formants (f1–f3) to identify place information, amplitude for oral aperture, and harmonic-to-noise ratio for manner. Existing descriptions and phonological patterns predict that [ɰ] is an approximant and not a fricative so we compare against known approximants for differences in turbulence and spectral properties. We also compare against labialized sounds including contrastive [w] for absence of lowered f3 to exclude lip rounding in [ɰ]. We argue that it is the intersection of these acoustic cues that distinguishes [ɰ] from similar sounds, but that these cues are unstable so that dialectal sound change arises from misperception in perturbations of their production.
Acoustic propagation modeling using sound velocity profiles estimated from high resolution temperature data
Authors: Amaral Brian , Amaral Jennifer L. , Eliasen Antone B. , Shomberg Russell
Published: July 2024

An accurate sound velocity profile (SVP) is an important input for underwater acoustic propagation modeling. The SVP is largely driven by the temperature of the water column, especially at shallower depths. Measuring the SVP in high spatial and temporal resolution is challenging with traditional instrumentation, however techniques exist to produce high resolution temperature measurements that can be used to derive estimates of the SVP. Fiber optic distributed temperature sensing (DTS) offers an improvement of several orders of magnitude over traditional singular point measurement devices and has the ability to measure temperature over large range and depth scales in an efficient manner. A DTS system was towed for 172 nm off the coast of New England over several days. The measured temperature data was used to estimate the SVP across the range and depth and will be compared to traditional environmental data sets, such as HYCOM. A comparison of modeled acoustic propagation using different resolution SVPs will be presented.
Acoustic performance of screens designed to act as metamaterials
Authors: Berardi Umberto , Bevilacqua Antonella , Trematerra Amelia , Iannace Gino
Published: July 2024

Metamaterials are, nowadays, a mature field of research in acoustic and many applications with metamaterials have been developed in recent years. In metamaterials, the attenuation of sound is due to the interaction of the sound waves with their geometrically regular structures. The frequency at which the attenuation occurs is calculated with Braggs' law. This work presents sound attenuation measurements of structures made with metamaterials carried out in an anechoic chamber. The arrangements considered are both two- dimensional and three-dimensional: the 2D arrangement was obtained with a regular distribution of linear elements made with bars with diameters of 9, 15, and 20 mm; the 3D arrangement was obtained with a regular distribution of a lattice of spheres with a diameter of 23 mm. The results of the acoustic measurements are reported in terms of insertion loss in the range from 1000 to 10 000 Hz.
Robotic fabrication of clay acoustic resonators
Authors: Peters Brady , Hoban Nicholas , Nguyen John , Hassanin Nermine
Published: July 2024

Digital fabrication offers the potential for the creation of complex geometries and mass-customized products; however, most 3D printers do not scale sufficiently to create architectural scale components. Robotic fabrication methods may bridge the gap, offering the possibility of architectural-scale 3d-printing capabilities. It has been found that the combination of multiple Helmholtz resonators tuned to different frequencies can create broadband absorption. This research pairs CAD parametric design with robotic clay extrusion as a method of acoustic resonator mass customization. The history of architectural acoustics together with recent archeological discoveries unveils a long-established practice of using clay vases as acoustic devices. And while the efficacy of these vases in historical settings has been contested, the use of large arrays of carefully tuned acoustic vases remains largely unexplored in contemporary practice. This paper presents the acoustic vases' unique history, defines its geometry and performance, and projects the potentials of the acoustic vase in current practice through modelling, simulation, and fabrication. A full-scale prototype wall with 126 robotically 3d-printed clay resonator vases was designed and constructed. The 1:1 prototype was shown in the “Robotic Clay,” which was exhibited at the Canadian Clay and Glass Gallery in Waterloo, Canada.
Using ultrasound-targeted microbubble cavitation to open the blood–brain barrier for drug delivery in Alzheimer’s disease
Authors: Conway Grace E. , Chen Xucai , Rizzo Stacey J. , Silva Afonso C. , Villanueva Flordeliza S.
Published: July 2024

Drug delivery for Alzheimer’s disease (AD) is challenging due to restricted diffusion across the blood–brain barrier (BBB). Ultrasound-targeted microbubble cavitation (UTMC) can be used to transiently open the BBB. We hypothesized that opening the BBB with UTMC would increase the brain concentration of LY2886721 (LY), an orally administered drug developed for AD, in 5XFAD mice, a model of AD. We treated the right hemisphere using an RK-50 system (FUS Instruments Inc). Definity microbubbles were injected, and ultrasound (1.45 MHz, 2 Hz pulse repetition frequency, 10 ms pulse length, 0.6 MPa for 30 s) was applied to 11 locations across the right hemisphere. Thirty minutes after UTMC, mice were administered LY (30 mg/kg p.o.). In one cohort, 45 min after dosing with LY, there was an increase in the concentration of LY in the UTMC-treated hemisphere compared to the non-UTMC treated hemisphere (p < 0.05). In a second cohort, 2.5 h after dosing with LY, there was a decrease in soluble Aβ;40 (p < 0.05), insoluble Aβ;40 (p < 0.05), and insoluble Aβ;42 (p < 0.05) in the UTMC-treated hemisphere compared to the non-UTMC treated hemisphere. UTMC can be used to open the BBB to increase the concentration of LY and decrease Aβ in a preclinical model of AD.
Tri-axial ground-borne vibration measurements during rail pass-bys
Authors: Cai Harry Ao , Gara Nathan , Howe Brian
Published: July 2024

Ground-borne vibrations from rail pass-bys, transmitted from train wheels rolling on the rails, have the potential to cause various adverse effects at nearby receptors, such as annoyance and re-radiated noise. To assess the impact of rail pass-bys, surface-level vibration can be characterized in three components: one vertical and two horizontal directions. Prior experience, best-practice guidelines from the Federal Transit Administration Transit Noise and Vibration Impact Assessment Manual, and theory of propagation of Rayleigh surface waves indicate that the vertical component dominates the horizontal components, such that vibrations from rail pass-bys can be adequately characterized by the vertical component only. This purpose of this study is to assess the sufficiency of characterizing the impact of ground-borne vibrations caused by rail pass-bys based solely in the vertical direction. Tri-axial vibration measurements were conducted for freight and passenger trains in Ontario, Canada, using a multi-channel signal analyzer for simultaneous measurement of multiple-axis vibration levels. The measured levels were then examined across the three components.
Generalization of inter-articulator timing control: Evidence from tongue-jaw and lip-jaw kinematics using electromagnetic articulography
Authors: Masapollo Matthew , Rodriguez Ana , Kent Kara , Gendron Rosalie , Thomas Hannah , Maxfield Nathan , Nittrouer Susan
Published: July 2024

Recent research in speech production indicates that talkers reliably control the relative timing of articulator movement onsets across variation in production rate, syllable stress, and segmental makeup and that this precision of inter-articulator timing control instantiates phonetic structure. To date, these timing relations have been highly reliable for tongue-jaw kinematics. In the present study, we address the generality of these timing relations to lip-jaw kinematics. Eleven talkers recorded 240 /tV#Cat/ and 240 / bV#Cab/ utterances using electromagnetic articulography, with alternative V (/ɑ/-/ɛ/) and C (/t/−/d/ or /p/−/b/), across changes in production rate (fast-normal) and stress (first syllable stressed-unstressed). To quantify inter-articulator temporal coordination, the timing of either tongue-tip or lower-lip raising onset for the intervocalic C, relative to the jaw opening-closing cycle for V, was obtained. Results indicate that the same kinematic pattern occurred among both sets of articulators: any manipulation that shortened the jaw opening-closing cycle reduced the latency of either tongue-tip or lower-lip movement onset, relative to the onset of jaw opening. Furthermore, the movement onset latencies of the tongue-tip and lower-lip were both highly differentiated by utterance type, bolstering the view that inter-articulator timing relations instantiate phonetic structure in the resulting acoustic signal.
Simulation of sentence-level speech with an acoustically driven model of speech production
Authors: Story Brad H. , Bunton Kate
Published: July 2024

In a model of speech production developed by Story and Bunton [JASA, 146(4), 2522–2528 (2019)] speech segments are encoded by specifying relative acoustic events along a time axis that consist of directional changes of the vocal tract resonance frequencies called resonance deflection patterns (RDPs). These events are transformed via acoustic sensitivity functions, into time-varying modulations of the vocal tract shape. For example, RDPs specifying /b, p/, /d, t/, and /g, k/ would typically be coded as [−1 −1 −1], [−1 1 1], and [−1 1 −1], respectively. The RDP changes, indicate, from left to right, the targeted directional shift of the first, second, and third resonances of the vocal tract. In addition, events that produce nasalization, voiced versus voiceless sounds, and changes in fundamental frequency are also specified the time axis. The purpose of this study was to demonstrate the use of this model to generate word- and sentence-level speech for eventual speech intelligibility studies. The process for simulating several words and sentences will be demonstrated.
Developing an algorithm to characterize context-based speech patterns as cue production profiles
Authors: Chung Sofie C. , Choi Jeung-Yoon , Shattuck-Hufnagel Stefanie
Published: July 2024

The surface articulation of an underlying phoneme commonly fluctuates depending on the context. For instance, the associated acoustic cues for a /t/ phoneme produced at the beginning of an utterance may be distinct from the acoustic cues of a /t/ phoneme that is preceded and followed by a vowel. Thus, for an individual speaker or speaker group, we can investigate what specific phonemic contexts result in the associated acoustic cues to be produced. An algorithm has been developed which matches a target phoneme to its corresponding acoustic cues. For a given database, we can recover all of the contexts in which a phoneme was produced and tabulate the various acoustic cue production patterns that arose. Finally, we label these patterns by their speech production type (e.g., standard production, flapping, etc.) and produce an output in the form of a cue production profile. As a result, this profile would allow for the association of a set of acoustic cues in specific phonemic contexts for an individual speaker or speaker group, such as speakers from a specific dialect region. The algorithm can also be expanded to include prosodic cues to account for how stress and intonation can affect phoneme production.
Comparing speech to fine and gross motor skills in Parkinson’s patients
Authors: Diep Brian , Cho Sylvia , Shamei Arian , Gick Bryan
Published: July 2024

Parkinson’s Disease (PD) is a neurodegenerative motor disorder resulting from damage to dopaminergic neurons. The goal of this study is to evaluate the correspondence between speech and non-speech motor impairments. To explore this, we extract features from the mPower dataset [B. M. Bot et al., Sci Data 3, 160011 (2016)] containing mobile data from PD patients and healthy controls along with their performance on a vowel phonation, finger tapping, and walking task. We hypothesize that there is a shared motor system underlying each of these modalities and that disease progression will manifest in impairments to both speech and non-speech systems that rely on motor control. For acoustic features, we measure temporal consistency via F0-independent features (shimmer, jitter, and harmonics-to-noise ratio). For non-acoustic tasks, we adapt this set to measure spatial consistency and accuracy in finger tapping or walking. We perform clustering and multidimensional scaling (MDS) on our features to understand their correspondence across the modalities. Results will be reported with relevance to the relationship between PD and its effects on articulatory and general motor processes.
Using prosody to produce trust and doubt
Authors: Thomas Abbey L.
Published: July 2024

Work presented at a 2022 ASA meeting [Thomas, 2022] demonstrated that American English talkers use acoustic prosodic variables to distinguish attitudes of incredulity and trust from a “neutral tone of voice” when asking WH-questions. The present study largely replicates these findings in new data. These data comprise both WH-questions and Yes/No questions, read by a new set of talkers in six imagined scenarios. In the previous study, “doubt” was likely confounded with “authority” due to the imagined scenario used to elicit the stimuli. In the present study, the three attitudes (doubt, neutral, trust) were crossed with dominance (participant was +/− dominant relative to their imagined conversational partner). This study examines additional acoustic variables, including the variability of word duration within utterance and the F0 slope of the longest word in each utterance. Averaging across the + /− dominance conditions and the utterance type (yes/no or WH question), duration-based variables reliably distinguished doubting from neutral utterances (with doubting utterances showing greater duration and greater variability in word duration). In contrast, F0-based variables differentiated trusting from neutral utterances, with trusting utterances showing a higher F0 over the course of the entire utterance.
Duration imitation is not mediated by phonological contrast: Evidence from a checked-unchecked tonal contrast in Taiwanese Southern Min
Authors: Zhang Wei , Clayards Meghan , Lu Yu-An
Published: July 2024

Phonetic imitation is mediated by phonological contrast, as evident in features such as formant, VOT and F0. However, a recent study observed that duration imitation was not mediated by phonological contrast. In contrast to other studies, duration served as a non-primary cue to the phonological contrast in this recent study. This current study further investigates duration imitation in a case where duration serves as the primary cue. We utilized the tonal contrast of T3 versus T33 in Taiwanese Southern Min (TSM), to which duration was identified as the primary cue. We created a seven-step tonal continuum between T3 and T33 by manipulating the tone durations, and recruited seventeen native TSM speakers to imitate each step as closely as they could. The bi- or uni-modality of the distribution of the imitated durations for all seven steps was analyzed using Bayesian regression models. Results showed that the imitated durations were more consistent with an unimodal distribution, suggesting that, unlike other features, the imitation of duration is not mediated by tonal contrast, whether it acts as a primary cue or not. Thus, features exhibit different resistance to phonological mediation in phonetic imitation.
Ultrasonic measurement of milk heat coagulation time (HCT)
Authors: Harte Agustin , Katch Lauren , Harte Federico , Arguelles Andrea P.
Published: July 2024

The dairy industry relies on heat coagulation tests (HCTs) to determine high-quality milk heat stability for typical thermal processes. For the HCT, an oil bath heats 1–2 ml of milk to 140 °C. The test lasts 20–30 min and finishes with visual confirmation of milk coagulation. This time for coagulation is recorded as the HCT time. While standard in the industry, this test is time-consuming and prone to operator-dependent bias. Thus, an automated alternative for measuring HCT time is desirable. This work proposed the use of ultrasonic monitoring and employed 10 MHz contact and immersion ultrasonic transducers in combination with conventional pH and rheological sensors. Room-temperature skim milk was coagulated in standard containers with a Glucono-Delta-Lactone acid concentration of 3% while simultaneously being monitored by the ultrasound, rheological, and pH sensors, at testing rates of 1 s, ca. 6 s, and 2 min, respectively. The resulting ultrasonic wave speed measurements revealed an increasing trend throughout the coagulation process. Additionally, an inflection point within the increasing wave speed corresponded to rheological and pH parameters indicating coagulation. This work demonstrates the potential for ultrasonics to be used as sensors for coagulation within the dairy industry.
Acoustic signatures of helium abundance in hydrogen for planetary science
Authors: Chaudhary Rishabh , White Robert D. , Kosherbayeva Zarina , Banfield Don , Colaprete Anthony , Neeson Ian , Powell Andrew , Petculescu Andi
Published: July 2024

The aim of this work is to model and measure the acoustic signatures of varying mixtures of helium, ortho-hydrogen, and para-hydrogen. In particular, we hope to demonstrate a sensor for helium abundance and hydrogen ortho:para ratio for planetary science missions to Saturn or Uranus. Gas composition as a function of depth is important for understanding atmospheric dynamics and planetary formation of the gas giants but is not well known. In the presence of molecular relaxation, sound speed and absorption in polyatomic gas mixtures become dispersive due to frequency-dependent heat capacities. This may potentially allow the identification of gas composition through relaxational acoustic spectroscopy. We compare theoretical predictions to measurements done in a pressure vessel up to a maximum pressure of 20 bar of relevance to gas giant atmospheres. Experiments for different gas mixtures at various pressures and temperatures are conducted using wide-bandwidth ultrasound between 20 kHz and 10 MHz. A technique is proposed to determine the ratio of hydrogen to helium using speed of sound and attenuation spectra. This approach may be further utilized to determine the ortho:para ratio. Challenges include providing sufficient bandwidth and adjusting for temperature, diffraction, and reflections. [Work supported from NASA Center Innovation Fund.]
Evaluation of the performance of technologies for reducing ships' machinery noise using a small-scale ship-like structure in a Water Basin
Authors: Guy Marc-André , Kesour Kamal , Robin Olivier , St-Jacques Julien , Vulliez Mathis
Published: July 2024

Ocean ambient levels have increased in the last decades, especially in the low-frequency domain (under 500 Hz). This increase is partly due to underwater radiated noise (URN) from commercial ships. Excessive URN harms marine life and is, therefore, considered a pollution that needs to be reduced. At low speeds, machinery is the primary noise source on ships. Mitigation technologies exist to limit machinery’s contribution to URN. While implementing these technologies is costly, a lack of quantitative data regarding their exact performances usually results in limited concrete ship applications since the cost-to-benefit ratio is imprecise. This study aims to quantify better the performance of standard noise mitigation technologies using a small-scale ship-like structure in a water basin. The basin’s acoustic field is first characterized with and without the structure. The structure is then equipped with different mitigation technologies. A loudspeaker and a vibration shaker are fed with pink noise or measured signals on actual machinery. Hydrophones, microphones, accelerometers, and force sensors measure the response in the basin and on the structure. The performance of each tested technology is evaluated and ranked in terms of URN reduction. The relative contributions of airborne and structure-borne transmission paths on URN are also examined.
Mother-Coaches’ Experiences of Policy and Programs: “Whoever Wrote This Policy Doesn’t Understand What It Means to Be a Mom”
Authors: Porter Jesse , Trussell Dawn E. , Clutterbuck Ryan , Mooradian Jennifer
Published: July 2024

In this paper, we explore the lived experiences of mother-coaches who, while coaching, navigate policy and programs aimed at promoting gender equity. Specifically, this study took place within the context of an amateur national, 10-day multisport games event in Canada. Using critical feminist narrative inquiry, 14 mother-coaches (apprentice, assistant, or head coach), representing eight different provinces, and 10 different sports, participated in this study. Three themes were constructed that call attention to the Canadian sport system broadly, as well as the 10-day multisport games event specifically: (a) performative policies and gendered assumptions, (b) programs that are band-aids for a “shitty culture,” and (c) a pathway to nowhere for mother-coaches. The findings complicate the hegemonic work–family conflict narrative, suggesting that mother-coaches’ advancement, opportunities, and quality experiences are impacted by the current heteropatriarchal culture and structure of sport that these programs and policy are rooted in.
Downstream-of-gene (DoG) transcripts contribute to an imbalance in the cancer cell transcriptome
Authors: Abe Kouki , Maunze Brian , Lopez Pedro-Avila , Xu Jessica , Muhammad Nefertiti , Yang Guang-Yu , Katz David , Liu Yaping , Lauberth Shannon M.
Published: July 2024

Downstream-of-gene (DoG) transcripts are an emerging class of noncoding RNAs. However, it remains largely unknown how DoG RNA production is regulated and whether alterations in DoG RNA signatures exist in major cancers. Here, through transcriptomic analyses of matched tumors and nonneoplastic tissues and cancer cell lines, we reveal a comprehensive catalog of DoG RNA signatures. Through separate lines of evidence, we support the biological importance of DoG RNAs in carcinogenesis. First, we show tissue-specific and stage-specific differential expression of DoG RNAs in tumors versus paired normal tissues with their respective host genes involved in tumor-promoting versus tumor-suppressor pathways. Second, we identify that differential DoG RNA expression is associated with poor patient survival. Third, we identify that DoG RNA induction is a consequence of treating colon cancer cells with the topoisomerase I (TOP1) poison camptothecin and following TOP1 depletion. Our results underlie the significance of DoG RNAs and TOP1-dependent regulation of DoG RNAs in diversifying and modulating the cancer transcriptome.
Experimental evidence reveals the mobilization and mineralization processes of rare earth elements in carbonatites
Authors: Yuan Xueyin , Yang Zhiming , Mayanovic Robert A. , Hou Zengqian
Published: July 2024

Whereas the genesis of carbonatitic rare earth element (REE) deposits has long been a focus of study, the controls on mobilization and mineralization of REEs during magmatic-hydrothermal processes still remain open to debate. Here, we present our investigation of the dissolution and crystallization of REE (fluor)carbonate minerals in alkaline carbonate brine-melts up to 850°C and 11.6 kbar. Our results show that REEs are soluble in Na
2
CO
3
brine-melts, achieving concentrations exceeding 8 weight % at temperatures above 650°C. The addition of calcium and/or fluoride has minimal impact on REE mobilization, whereas introduction of silica suppresses REE solubilities by half, due to britholite formation above 550°C. Upon cooling, sodium and REEs combine to crystallize in burbankite or carbocernaite in sodium-enriched brine-melts, even at fluoride saturation. However, while the brine-melts contain substantial ferro- or aluminosilicate, REE mineralization in fluorcarbonates occurs after sufficient sodium precipitation in alkaline silicate minerals, hence revealing how silicate and sodium carbonate govern REE mineralization.
High-fidelity and high-speed wavefront shaping by leveraging complex media
Authors: Yu Li-Yu , You Sixian
Published: July 2024

High-precision light manipulation is crucial for delivering information through complex media. However, existing spatial light modulation devices face a fundamental speed-fidelity tradeoff. Digital micromirror devices have emerged as a promising candidate for high-speed wavefront shaping but at the cost of compromised fidelity due to the limited control degrees of freedom. Here, we leverage the sparse-to-random transformation through complex media to overcome the dimensionality limitation of spatial light modulation devices. We demonstrate that pattern compression by sparsity-constrained wavefront optimization allows sparse and robust wavefront representations in complex media, improving the projection fidelity without sacrificing frame rate, hardware complexity, or optimization time. Our method is generalizable to different pattern types and complex media, supporting consistent performance with up to 89% and 126% improvements in projection accuracy and speckle suppression, respectively. The proposed optimization framework could enable high-fidelity high-speed wavefront shaping through different scattering media and platforms without changes to the existing holographic setups, facilitating a wide range of physics and real-world applications.
Quantifying the regime of thermodynamic control for solid-state reactions during ternary metal oxide synthesis
Authors: Szymanski Nathan J. , Byeon Young-Woon , Sun Yingzhi , Zeng Yan , Bai Jianming , Kunz Martin , Kim Dong-Min , Helms Brett A. , Bartel Christopher J. , Kim Haegyeom , Ceder Gerbrand
Published: July 2024

The success of solid-state synthesis often hinges on the first intermediate phase that forms, which determines the remaining driving force to produce the desired target material. Recent work suggests that when reaction energies are large, thermodynamics primarily dictates the initial product formed, regardless of reactant stoichiometry. Here, we validate this principle and quantify its constraints by performing in situ characterization on 37 pairs of reactants. These experiments reveal a threshold for thermodynamic control in solid-state reactions, whereby initial product formation can be predicted when its driving force exceeds that of all other competing phases by ≥60 milli–electron volt per atom. In contrast, when multiple phases have a comparable driving force to form, the initial product is more often determined by kinetic factors. Analysis of the Materials Project data shows that 15% of possible reactions fall within the regime of thermodynamic control, highlighting the opportunity to predict synthesis pathways from first principles.
Prostate tissue ablation and drug delivery by an image-guided injectable ionic liquid in ex vivo and in vivo models
Authors: Demirlenk Yusuf M. , Albadawi Hassan , Zhang Zefu , Atar Dila , Cevik Enes , Keum Hyeongseop , Kim Jinjoo , Rehman Suliman , Gunduz Seyda , Graf Erin , Mayer Joseph L. , Dos Santos Pedro R. , Oklu Rahmi
Published: July 2024

Benign prostatic hyperplasia and prostate cancer are often associated with lower urinary tract symptoms, which can severely affect patient quality of life. To address this challenge, we developed and optimized an injectable compound, prostate ablation and drug delivery agent (PADA), for percutaneous prostate tissue ablation and concurrently delivered therapeutic agents. PADA is an ionic liquid composed of choline and geranic acid mixed with anticancer therapeutics and a contrast agent. The PADA formulation was optimized for mechanical properties compatible with hand injection, diffusion capability, cytotoxicity against prostate cells, and visibility of an x-ray contrast agent. PADA also exhibited antibacterial properties against highly resistant clinically isolated bacteria in vitro. Ultrasound-guided injection, dispersion of PADA in the tissue, and tissue ablation were tested ex vivo in healthy porcine, canine, and human prostates and in freshly resected human tumors. In vivo testing was conducted in a murine subcutaneous tumor model and in the canine prostate. In all models, PADA decreased the number of viable cells in the region of dispersion and supported the delivery of nivolumab throughout a portion of the tissue. In canine survival experiments, there were no adverse events and no impact on urination. The injection approach was easy to perform under ultrasound guidance and produced a localized effect with a favorable safety profile. These findings suggest that PADA is a promising therapeutic prostate ablation strategy to treat lower urinary tract symptoms.
Comparative pharmacodynamics and dose optimization of liposomal amphotericin B against
Candida
species in an
in vitro
pharmacokinetic/pharmacodynamic model
Authors: Beredaki Maria-Ioanna , Arendrup Maiken C. , Pournaras Spyros , Meletiadis Joseph
Published: July 2024

As comparative pharmacokinetic/pharmacodynamic (PK/PD) studies of liposomal amphotericin B (L-AMB) against
Candida
spp. are lacking, we explored L-AMB pharmacodynamics against different
Candida
species in an
in vitro
PK/PD dilution model. Eight
Candida glabrata
,
Candida parapsilosis
, and
Candida krusei
isolates (EUCAST/CLSI AMB MIC 0.125–1 mg/L) were studied in the
in vitro
PK/PD model simulating L-AMB
C
max
= 0.25–64 mg/L and
t
1/2
= 9 h. The model was validated with one susceptible and one resistant
Candida albicans
isolate. The
C
max
/MIC-log
10
CFU/mL reduction from the initial inoculum was analyzed with the
E
max
model, and Monte Carlo analysis was performed for the standard (3 mg/kg with
C
max
= 21.87 ± 12.47 mg/L) and higher (5 mg/kg with
C
max
= 83 ± 35.2 mg/L) L-AMB dose. A ≥1.5 log
10
CFU/mL reduction was found at L-AMB
C
max
= 8 mg/L against
C. albicans
,
C. parapsilosis
, and
C. krusei
isolates (MIC 0.25–0.5 mg/L) whereas L-AMB
C
max
≥ 32 mg/L was required for
C. glabrata
isolates. The
in vitro
PK/PD relationship followed a sigmoidal pattern (
R
2
≥ 0.85) with a mean
C
max
/MIC required for stasis of 2.1 for
C. albicans
(close to the
in vivo
stasis), 24/17 (EUCAST/CLSI) for
C. glabrata
, 8 for
C. parapsilosis
, and 10 for
C. krusei
. The probability of target attainment was ≥99% for
C. albicans
wild-type (WT) isolates with 3 mg/kg and for wild-type isolates of the other species with 5 mg/kg. L-AMB was four- to eightfold less active against the included non-
C
.
albicans
species than
C. albicans
. A standard 3-mg/kg dose is pharmacodynamically sufficient for
C. albicans
whereas our data suggest that 5 mg/kg may be recommendable for the included non-
C
.
albicans
species.
Mechanisms of action of microbicides commonly used in infection prevention and control
Authors: Gerba Charles P. , Boone Stephanie , Nims Raymond W. , Maillard Jean-Yves , Sattar Syed A. , Rubino Joseph R. , McKinney Julie , Ijaz M. Khalid
Published: July 2024

Understanding how commonly used chemical microbicides affect pathogenic microorganisms is important for formulation of microbicides. This review focuses on the mechanism(s) of action of chemical microbicides commonly used in infection prevention and control. Contrary to the typical site-specific mode of action of antibiotics, microbicides often act via multiple targets, causing rapid and irreversible damage to microbes. In the case of viruses, the envelope or protein capsid is usually the primary structural target, resulting in loss of envelope integrity or denaturation of proteins in the capsid, causing loss of the receptor-binding domain for host cell receptors, and/or breakdown of other viral proteins or nucleic acids. However, for certain virucidal microbicides, the nucleic acid may be a significant site of action. The region of primary damage to the protein or nucleic acid is site-specific and may vary with the virus type. Due to their greater complexity and metabolism, bacteria and fungi offer more targets. The rapid and irreversible damage to microbes may result from solubilization of lipid components and denaturation of enzymes involved in the transport of nutrients. Formulation of microbicidal actives that attack multiple sites on microbes, or control of the pH, addition of preservatives or potentiators, and so on, can increase the spectrum of action against pathogens and reduce both the concentrations and times needed to achieve microbicidal activity against the target pathogens.
Primary versus secondary psychosis in a patient with congenital liver disease
Authors: Nourbakhsh Sormeh , Ferrando Stephen J
Published: July 2024

In this article we report the case of a man with congenital liver disease who later developed psychotic illness and was diagnosed with schizophrenia. We illustrate how decompensation in liver function was associated with the exacerbation of psychotic symptoms. We discuss differential diagnostic challenges, and the possible overlapping neuropathology in these two conditions that may converge on glutamate/N-methyl-D-aspartate dysfunction. This patient’s case underscores the need for further research to elucidate the possible underlying mechanisms linking congenital liver disease and psychosis.
Chronotype and emotion processing: a pilot study testing timing of online cognitive bias modification training
Authors: Crisp Charlotte M , Mooney Emily , Howlader Mohini , Stoddard Joel , Penton-Voak Ian
Published: July 2024

Background

Circadian rhythms influence cognitive performance which peaks in the morning for early chronotypes and evening for late chronotypes. It is unknown whether cognitive interventions are susceptible to such synchrony effects and could be optimised at certain times-of-day.

Objective

A pilot study testing whether the effectiveness of cognitive bias modification (CBM) for facial emotion processing was improved when delivered at a time-of-day that was synchronised to chronotype.

Methods

173 healthy young adults (aged 18–25) with an early or late chronotype completed one online session of CBM training in either the morning (06:00 hours to 10:00 hours) or evening (18:00 hours to 22:00 hours).

Findings

Moderate evidence that participants learnt better (higher post-training balance point) when they completed CBM training in the synchronous (evening for late chronotypes, morning for early chronotypes) compared with asynchronous (morning for late chronotypes, evening for early chronotypes) condition, controlling for pre-training balance point, sleep quality and negative affect. There was also a group×condition interaction where late chronotypes learnt faster and more effectively in synchronous versus asynchronous conditions.

Conclusions

Preliminary evidence that synchrony effects apply to this psychological intervention. Tailoring the delivery timing of CBM training to chronotype may optimise its effectiveness. This may be particularly important for late chronotypes who were less able to adapt to non-optimal times-of-day, possibly because they experience more social jetlag.

Clinical implications

To consider delivery timing of CBM training when administering to early and late chronotypes. This may generalise to other psychological interventions and be relevant for online interventions where the timing can be flexible.
Principles and elements of patient-centredness in mental health services: a thematic analysis of a systematic review of reviews
Authors: Khosravi Mohsen , Azar Ghazaleh , Izadi Reyhane
Published: July 2024

Introduction

Mental health disorders, particularly depression and anxiety, are widespread globally and necessitate effective solutions. The patient-centred approach has been identified as a viable and effective method for addressing these challenges. This paper synthesised the principles of patient-centred mental health services and provides a comprehensive review of the existing literature.

Materials and methods

This is a qualitative content analysis study conducted in a systematic review framework in 2022. PubMed, Scopus, ProQuest and Cochrane databases were systematically searched, and by screening the titles, abstracts, and the texts of studies related to the purpose of the research, the data were extracted. Evaluation of the quality of the studies was done using the CASP checklist for qualitative studies. After selecting the final studies based on the entry and exit criteria, subsequently, a thematic analysis of findings was conducted on the data obtained from the systematic review.

Results

The database search produced 6649 references. After screening, 11 studies met the inclusion criteria. The quality scores indicated the studies were of high level of quality with acceptable risk of bias. The thematic analysis identified six major principles of patient-centredness in mental health services: education, involvement and cooperation, access, effectiveness and safety, health and well-being, and ethics.

Conclusions

Patient-centredness is a complex approach in mental health services. The principles and elements of patient-centredness foster positive patient outcomes, enhance healthcare quality and ensure compassionate and effective care. Upholding these principles is crucial for delivering patient-centred, ethical and effective mental health services. Furthermore, the study found that patient education can boost adherence and satisfaction, and decrease unnecessary hospitalisations. Patient involvement in decision-making is influenced by their age and the relationship with their psychologists. And, effective leadership and resource management can enhance clinical processes and patient-centredness in mental health services.
A narrative review of inherited arrhythmogenic syndromes in young population: role of genetic diagnosis in exercise recommendations
Authors: Sarquella-Brugada Georgia , Martínez-Barrios Estefanía , Cesar Sergi , Toro Rocío , Cruzalegui José , Greco Andrea , Díez-Escuté Nuria , Cerralbo Patricia , Chipa Fredy , Arbelo Elena , Diez-López Carles , Grazioli Gonzalo , Balderrábano Norma , Campuzano Oscar
Published: July 2024

Sudden cardiac death is a rare but socially devastating event, especially if occurs in young people. Usually, this unexpected lethal event occurs during or just after exercise. One of the leading causes of sudden cardiac death is inherited arrhythmogenic syndromes, a group of genetic entities characterised by incomplete penetrance and variable expressivity. Exercise can be the trigger for malignant arrhythmias and even syncope in population with a genetic predisposition, being sudden cardiac death as the first symptom. Due to genetic origin, family members must be clinically assessed and genetically analysed after diagnosis or suspected diagnosis of a cardiac channelopathy. Early identification and adoption of personalised preventive measures is crucial to reduce risk of arrhythmias and avoid new lethal episodes. Despite exercise being recommended by the global population due to its beneficial effects on health, particular recommendations for these patients should be adopted considering the sport practised, level of demand, age, gender, arrhythmogenic syndrome diagnosed but also genetic diagnosis. Our review focuses on the role of genetic background in sudden cardiac death during exercise in child and young population.
Dissecting the association between gut microbiota, body mass index and specific depressive symptoms: a mediation Mendelian randomisation study
Authors: Yu Tong , Chen Chengfeng , Yang Yuqing , Wang Mingqia , Yang Yantianyu , Feng Wanting , Yuan Shiqi , Ma Xiancang , Li Jie , Zhang Bin
Published: July 2024

Background

Observational studies highlight the association between gut microbiota (GM) composition and depression; however, evidence for the causal relationship between GM and specific depressive symptoms remains lacking.

Aims

We aimed to evaluate the causal relationship between GM and specific depressive symptoms as well as the mediating role of body mass index (BMI).

Methods

We performed a two-sample Mendelian randomisation (MR) analysis using genetic variants associated with GM and specific depressive symptoms from genome-wide association studies. The mediating role of BMI was subsequently explored using mediation analysis via two-step MR.

Results

MR evidence suggested theBifidobacteriumgenus (β=–0.03; 95% CI –0.05 to –0.02; p<0.001 and β=–0.03; 95% CI –0.05 to –0.02; p<0.001) and Actinobacteria phylum (β=–0.04; 95% CI –0.06 to –0.02; p<0.001 and β=–0.03; 95% CI –0.05 to –0.03; p=0.001) had protective effects on both anhedonia and depressed mood. The Actinobacteria phylum also had protective effects on appetite changes (β=–0.04; 95% CI –0.06 to –0.01; p=0.005), while the Family XI had an antiprotective effect (β=0.03; 95% CI 0.01 to 0.04; p<0.001). The Bifidobacteriaceae family (β=–0.01; 95% CI –0.02 to –0.01; p=0.001) and Actinobacteria phylum (β=–0.02; 95% CI –0.03 to –0.01; p=0.001) showed protective effects against suicidality. The two-step MR analysis revealed that BMI also acted as a mediating moderator between the Actinobacteria phylum and appetite changes (mediated proportion, 34.42%) and that BMI partially mediated the effect of theBifidobacteriumgenus (14.14% and 8.05%) and Actinobacteria phylum (13.10% and 8.31%) on both anhedonia and depressed mood.

Conclusions

These findings suggest a potential therapeutic effect of Actinobacteria andBifidobacteriumon both depression and obesity. Further studies are required to translate these findings into clinical practice.
Sudden cardiac arrest in patients with cancer in the general population: insights from the Paris-SDEC registry
Authors: Weizman Orianne , Eslami Assié , Bougouin Wulfran , Beganton Frankie , Lamhaut Lionel , Jost Daniel , Dumas Florence , Cariou Alain , Marijon Eloi , Jouven Xavier , Mirabel Mariana
Published: July 2024

Background

Data on the management of patients with cancer presenting with sudden cardiac arrest (SCA) are scarce. We aimed to assess the characteristics and outcomes of SCA according to cancer history.

Methods

Prospective, population-based registry including every out-of-hospital SCA in adults in Paris and its suburbs, between 2011 and 2019, with a specific focus on patients with cancer.

Results

Out of 4069 patients who had SCA admitted alive in hospital, 207 (5.1%) had current or past medical history of cancer. Patients with cancer were older (69.2 vs 59.3 years old, p<0.001), more often women (37.2% vs 28.0%, p=0.006) with more frequent underlying cardiovascular disease (41.1% vs 32.5%, p=0.01). SCA happened more often with a non-shockable rhythm (62.6% vs 43.1%, p<0.001) with no significant difference regarding witness presence and cardiopulmonary resuscitation (CPR) performed. Cardiac causes were less frequent among patients with cancer (mostly acute coronary syndromes, 25.5% vs 46.8%, p<0.001) and had more respiratory causes (pulmonary embolism and hypoxaemia in 34.2% vs 10.8%, p<0.001). Still, no difference regarding in-hospital survival was found after SCA in patients with cancer versus other patients (26.2% vs 29.8%, respectively, p=0.27). Public location, CPR by witness and shockable rhythm were independent predictors of in-hospital survival after SCA in the cancer group.

Conclusions

One in 20 SCA occurs in patients with a history of cancer, yet with fewer cardiac causes than in patients who are cancer-free. Still, in-hospital outcomes remain similar even in patients with known cancer. Cancer history should therefore not compromise the initiation of resuscitation in the context of SCA.
Black bodies in phenomenological bioethics: cultural othering, ‘Corporeal Uncanny’ and ethical quandaries of black nurses inTake My HandandSmall Great Things
Authors: Balasubramanian Adhitya , Balasubramanian Padmanabhan
Published: July 2024

The aims of the present article are twofold. First, it attempts to theorise the thematic and ontological intersection between phenomenological and black bioethics and proposes ‘Ontic-Black Bioethics’, a neologism to evince how the corporeal misconceptions (such as race construct, bodily othering and colourism) become the cultural impediment for black women healthcare professionals. The article draws specific insights from the philosophical anthropology of race, ranging from Richard Polt to Sarah Ahmed, to understand the epistemic structures of scientific racism. Second, it investigates how the racial attitudes of white healthcare professionals and supremacist patients towards black nurses can be potential triggers of cultural othering, corporeal burden and ethical quandaries by closely readingTake My Handby Dolen Perkins-Valdez (2022) andSmall Great Thingsby Jodi Picoult (2016). For this, the article relies on the theoretical frameworks of cultural phenomenology and somatic attention postulated by Thomas Csordas, Philipa Rothfield and other theoreticians of varying importance. While the corporeality of black nurses is replete with the images of biological misconception and racial-cultural constructs, the epistemic perspectives and literary representations underscoring their bodily and experiential agony have been scarcely examined through the lenses of bioethics. Thus, the article construes the corporeality of black nurses as the confluence of biological and cultural discourses under phenomenological bioethics.
Stochastic nonlinear model for nanoparticles and viruses escape from endosomes
Authors: Sholokhov Vladimir , Makoveeva Eugenya V. , Fedotov Sergei , Alexandrov Dmitri V.
Published: July 2024

A stochastic nonlinear model for Rab5 and Rab7 proteins describing the transformation of early endosomes into late endosomes was formulated. This model consists of two stochastic nonlinear differential equations for Rab5 and Rab7 protein levels on the endosome surface. The primary goal of this paper is to understand the impact of multiplicative noise on the nonlinear dynamics of Rab5 and Rab7. The main idea is to introduce the stochastic variable T, which defines the random time when the conversion from Rab5 to Rab7 occurs. It follows from the dynamics of pH level that T can also be considered as the escape time of pH-sensitive nanoparticles and viruses from endosomes. The probability density function for T was obtained numerically. It was shown that the average conversion time T is shifted to the right when compared to the deterministic one, potentially influencing the pH distribution function and, consequently, the average escape time of viruses and nanoparticles.