Visual biases in evaluation of speakers' and singers' voice type by cis and trans listeners.

Introduction: A singer's or speaker's Fach (voice type) should be appraised based on acoustic cues characterizing their voice. Instead, in practice, it is often influenced by the individual's physical appearance. This is especially distressful for transgender people who may be excluded from formal singing because of perceived mismatch between their voice and appearance. To eventually break down these visual biases, we need a better understanding of the conditions under which they occur. Specifically, we hypothesized that trans listeners (not actors) would be better able to resist such biases, relative to cis listeners, precisely because they would be more aware of appearance-voice dissociations. Methods: In an online study, 85 cisgender and 81 transgender participants were presented with 18 different actors singing or speaking short sentences. These actors covered six voice categories from high/bright (traditionally feminine) to low/dark (traditionally masculine) voices: namely soprano, mezzo-soprano (referred to henceforth as mezzo), contralto (referred to henceforth as alto), tenor, baritone, and bass. Every participant provided voice type ratings for (1) Audio-only (A) stimuli to get an unbiased estimate of a given actor's voice type, (2) Video-only (V) stimuli to get an estimate of the strength of the bias itself, and (3) combined Audio-Visual (AV) stimuli to see how much visual cues would affect the evaluation of the audio. Results: Results demonstrated that visual biases are not subtle and hold across the entire scale, shifting voice appraisal by about a third of the distance between adjacent voice types (for example, a third of the bass-to-baritone distance). This shift was 30% smaller for trans than for cis listeners, confirming our main hypothesis. This pattern was largely similar whether actors sung or spoke, though singing overall led to more feminine/high/bright ratings. Conclusion: This study is one of the first demonstrations that transgender listeners are in fact better judges of a singer's or speaker's voice type because they are better able to separate the actors' voice from their appearance, a finding that opens exciting avenues to fight more generally against implicit (or sometimes explicit) biases in voice appraisal.

TiO2hierarchical nano blooming-flower decorated by Pt for formaldehyde detection.

To achieve an ultra-low concentration formaldehyde detection at low temperature, a platinum (Pt) assisted TiO2hierarchical nano blooming-flower sphere material is synthesized through hydrothermal method. SEM and transmission electron microscope characterizations show that the diameter of the nano sphere was around 2µm with dissilient rods of 60 nm in diameter and 1µm in length on the surface. The response (Ra/Rg) achieved form this nanomaterial to HCHO is 1.08 (100 ppb) and 5.82 (5 ppm) at 130 °C without an involvement of any light source or solution. The relationship curve between the responses and concentrations shows regular exponential trend. The verification of sensor stability done by a 3 month reliability test shows no response-degradation. The optimal response and stability is attributed to the massive dissilient rods on the surface of TiO2spheres and the assistance of Pt as a catalyzer disperses to intensify the formation of depletion area on the surface of TiO2. This study provide an attractive and cost effective solution for the detection of HCHO in air at a relatively low temperature.

Preclinical Evaluation of [18F]FACH in Healthy Mice and Piglets: An 18F-Labeled Ligand for Imaging of Monocarboxylate Transporters with PET.

The expression of monocarboxylate transporters (MCTs) is linked to pathophysiological changes in diseases, including cancer, such that MCTs could potentially serve as diagnostic markers or therapeutic targets. We recently developed [18F]FACH as a radiotracer for non-invasive molecular imaging of MCTs by positron emission tomography (PET). The aim of this study was to evaluate further the specificity, metabolic stability, and pharmacokinetics of [18F]FACH in healthy mice and piglets. We measured the [18F]FACH plasma protein binding fractions in mice and piglets and the specific binding in cryosections of murine kidney and lung. The biodistribution of [18F]FACH was evaluated by tissue sampling ex vivo and by dynamic PET/MRI in vivo, with and without pre-treatment by the MCT inhibitor α-CCA-Na or the reference compound, FACH-Na. Additionally, we performed compartmental modelling of the PET signal in kidney cortex and liver. Saturation binding studies in kidney cortex cryosections indicated a KD of 118 ± 12 nM and Bmax of 6.0 pmol/mg wet weight. The specificity of [18F]FACH uptake in the kidney cortex was confirmed in vivo by reductions in AUC0-60min after pre-treatment with α-CCA-Na in mice (-47%) and in piglets (-66%). [18F]FACH was metabolically stable in mouse, but polar radio-metabolites were present in plasma and tissues of piglets. The [18F]FACH binding potential (BPND) in the kidney cortex was approximately 1.3 in mice. The MCT1 specificity of [18F]FACH uptake was confirmed by displacement studies in 4T1 cells. [18F]FACH has suitable properties for the detection of the MCTs in kidney, and thus has potential as a molecular imaging tool for MCT-related pathologies, which should next be assessed in relevant disease models.

Development of Novel Analogs of the Monocarboxylate Transporter Ligand FACH and Biological Validation of One Potential Radiotracer for Positron Emission Tomography (PET) Imaging.

Monocarboxylate transporters 1-4 (MCT1-4) are involved in several metabolism-related diseases, especially cancer, providing the chance to be considered as relevant targets for diagnosis and therapy. [18F]FACH was recently developed and showed very promising preclinical results as a potential positron emission tomography (PET) radiotracer for imaging of MCTs. Given that [18F]FACH did not show high blood-brain barrier permeability, the current work is aimed to investigate whether more lipophilic analogs of FACH could improve brain uptake for imaging of gliomas, while retaining binding to MCTs. The 2-fluoropyridinyl-substituted analogs 1 and 2 were synthesized and their MCT1 inhibition was estimated by [14C]lactate uptake assay on rat brain endothelial-4 (RBE4) cells. While compounds 1 and 2 showed lower MCT1 inhibitory potencies than FACH (IC50 = 11 nM) by factors of 11 and 25, respectively, 1 (IC50 = 118 nM) could still be a suitable PET candidate. Therefore, 1 was selected for radiosynthesis of [18F]1 and subsequent biological evaluation for imaging of the MCT expression in mouse brain. Regarding lipophilicity, the experimental log D7.4 result for [18F]1 agrees pretty well with its predicted value. In vivo and in vitro studies revealed high uptake of the new radiotracer in kidney and other peripheral MCT-expressing organs together with significant reduction by using specific MCT1 inhibitor α-cyano-4-hydroxycinnamic acid. Despite a higher lipophilicity of [18F]1 compared to [18F]FACH, the in vivo brain uptake of [18F]1 was in a similar range, which is reflected by calculated BBB permeabilities as well through similar transport rates by MCTs on RBE4 cells. Further investigation is needed to clarify the MCT-mediated transport mechanism of these radiotracers in brain.

Preclinical Incorporation Dosimetry of [18F]FACH-A Novel 18F-Labeled MCT1/MCT4 Lactate Transporter Inhibitor for Imaging Cancer Metabolism with PET.

Overexpression of monocarboxylate transporters (MCTs) has been shown for a variety of human cancers (e.g., colon, brain, breast, and kidney) and inhibition resulted in intracellular lactate accumulation, acidosis, and cell death. Thus, MCTs are promising targets to investigate tumor cancer metabolism with positron emission tomography (PET). Here, the organ doses (ODs) and the effective dose (ED) of the first 18F-labeled MCT1/MCT4 inhibitor were estimated in juvenile pigs. Whole-body dosimetry was performed in three piglets (age: ~6 weeks, weight: ~13-15 kg). The animals were anesthetized and subjected to sequential hybrid Positron Emission Tomography and Computed Tomography (PET/CT) up to 5 h after an intravenous (iv) injection of 156 ± 54 MBq [18F]FACH. All relevant organs were defined by volumes of interest. Exponential curves were fitted to the time-activity data. Time and mass scales were adapted to the human order of magnitude and the ODs calculated using the ICRP 89 adult male phantom with OLINDA 2.1. The ED was calculated using tissue weighting factors as published in Publication 103 of the International Commission of Radiation Protection (ICRP103). The highest organ dose was received by the urinary bladder (62.6 ± 28.9 µSv/MBq), followed by the gall bladder (50.4 ± 37.5 µSv/MBq) and the pancreas (30.5 ± 27.3 µSv/MBq). The highest contribution to the ED was by the urinary bladder (2.5 ± 1.1 µSv/MBq), followed by the red marrow (1.7 ± 0.3 µSv/MBq) and the stomach (1.3 ± 0.4 µSv/MBq). According to this preclinical analysis, the ED to humans is 12.4 µSv/MBq when applying the ICRP103 tissue weighting factors. Taking into account that preclinical dosimetry underestimates the dose to humans by up to 40%, the conversion factor applied for estimation of the ED to humans would rise to 20.6 µSv/MBq. In this case, the ED to humans upon an iv application of ~300 MBq [18F]FACH would be about 6.2 mSv. This risk assessment encourages the translation of [18F]FACH into clinical study phases and the further investigation of its potential as a clinical tool for cancer imaging with PET.

Development and radiosynthesis of the first 18 F-labeled inhibitor of monocarboxylate transporters (MCTs).

Monocarboxylate transporters 1 and 4 (MCT1 and MCT4) are involved in tumor development and progression. Their expression levels are related to clinical disease prognosis. Accordingly, both MCTs are promising drug targets for treatment of a variety of human cancers. The noninvasive imaging of these MCTs in cancers is regarded to be advantageous for assessing MCT-mediated effects on chemotherapy and radiosensitization using specific MCT inhibitors. Herein, we describe a method for the radiosynthesis of [18 F]FACH ((E)-2-cyano-3-{4-[(3-[18 F]fluoropropyl)(propyl)amino]-2-methoxyphenyl}acrylic acid), as a novel radiolabeled MCT1/4 inhibitor for imaging with PET. A fluorinated analog of α-cyano-4-hydroxycinnamic acid (FACH) was synthesized, and the inhibition of MCT1 and MCT4 was measured via an L-[14 C]lactate uptake assay. Radiolabeling was performed by a two-step protocol comprising the radiosynthesis of the intermediate (E)/(Z)-[18 F]tert-Bu-FACH (tert-butyl (E)/(Z)-2-cyano-3-{4-[(3-[18 F]fluoropropyl)(propyl)amino]-2-methoxyphenyl}acrylate) followed by deprotection of the tert-butyl group. The radiofluorination was successfully implemented using either K[18 F]F-K2.2.2 -carbonate or [18 F]TBAF. The final deprotected product [18 F]FACH was only obtained when [18 F]tert-Bu-FACH was formed by the latter procedure. After optimization of the deprotection reaction, [18 F]FACH was obtained in high radiochemical yields (39.6 ± 8.3%, end of bombardment (EOB) and radiochemical purity (greater than 98%).

Causality as individual essence: its bearing on synchronicity.

Causality, time, and number are subjectively lived realities and need to be noticed as such. Fundamental to the wide range of living experience, they are also basic to scientific knowing. In this article I examine causality in relation to an article on synchronicity by Harald Atmanspacher and Wolfgang Fach. My examination is neither scientific nor metaphysical, but rather phenomenological, as it is a clarification of form as individual essence of a thing. This non-material form of an individual thing in the widest sense of the word 'thing' was rejected and so lost during modern seventeenth-century science but, renewed now, can help describe synchronicity. A commentary by William Willeford follows.