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Background: Segmental duplications flanking the neurofibromatosis type 1 (NF1) gene locus on 17q11 mediate most gene deletions in NF1 patients. However, the large size of the gene and the complexity of the locus architecture pose difficulties in deletion analysis. We report the construction and application of the first NF1 locus specific microarray, covering 2.24 Mb of 17q11, using a non-redundant approach for array design. The average resolution of analysis for the array is ∼12 kb per measurement point with an increased average resolution of 6.4 kb for the NF1 gene. Methods: We performed a comprehensive array-CGH analysis of 161 NF1 derived samples and identified heterozygous deletions of various sizes in 39 cases. The typical deletion was identified in 26 cases, whereas 13 samples showed atypical deletion profiles. Results: The size of the atypical deletions, contained within the segment covered by the array, ranged from 6 kb to 1.6 Mb and their breakpoints could be accurately determined. Moreover, 10 atypical deletions were observed to share a common breakpoint either on the proximal or distal end of the deletion. The deletions identified by array-CGH were independently confirmed using multiplex ligation-dependent probe amplification. Bioinformatic analysis of the entire locus identified 33 segmental duplications. Conclusions: We show that at least one of these segmental duplications, which borders the proximal breakpoint located within the NF1 intron 1 in five atypical deletions, might represent a novel hot spot for deletions. Our array constitutes a novel and reliable tool offering significantly improved diagnostics for this common disorder. [ABSTRACT FROM AUTHOR]

Abstract Every year, influenza viruses infect approximately 5-20% of the population in the United States leading to over 200,000 hospitalizations and 36,000 deaths from flu-related complications. In this study, we characterized the immune and pathological progression of a seasonal strain of H1N1 influenza virus, A/Brisbane/59/2007 in a ferret model. The immune response of the animals showed a dose-dependent increase with increased virus challenge, as indicated by the presence of virus specific IgG, IgM, and neutralizing antibodies. Animals infected with higher doses of virus also experienced increasing severity of clinical symptoms and fever at 2 days post-infection (DPI). Interestingly, weight loss was more pronounced in animals infected with lower doses of virus compared to those infected with a higher dose; these results were consistent with viral titers of swabs collected from the nares, but not the throat. Analyzed specimens included nasal and throat swabs from 1, 3, 5, and 7 DPI as well as tissue samples from caudal lung and nasal turbinates. Viral titers of the swab samples in all groups were higher on 1 and 3 DPI and returned to baseline levels by 7 DPI. Analysis of nasal turbinates indicated presence of virus at 3 DPI in all infected groups, whereas virus was only detected in the lungs of animals in the two highest dose groups. Histological analysis of the lungs showed a range of pathology, such as chronic inflammation and bronchial epithelial hypertrophy. The results provided here offer important endpoints for preclinical testing of the efficacy of new antiviral compounds and experimental vaccines.

Abstract Background The ferret (Mustela putorius furo) represents an attractive animal model for the study of respiratory diseases, including influenza. Despite its importance for biomedical research, the number of reagents for molecular and immunological analysis is restricted. We present here a parallel sequencing effort to produce an extensive EST (expressed sequence tags) dataset derived from a normalized ferret cDNA library made from mRNA from ferret blood, liver, lung, spleen and brain. Results We produced more than 500000 sequence reads that were assembled into 16000 partial ferret genes. These genes were combined with the available ferret sequences in the GenBank to develop a ferret specific microarray platform. Using this array, we detected tissue specific expression patterns which were confirmed by quantitative real time PCR assays. We also present a set of 41 ferret genes with even transcription profiles across the tested tissues, indicating their usefulness as housekeeping genes. Conclusion The tools developed in this study allow for functional genomic analysis and make further development of reagents for the ferret model possible.

We propose a circuit quantum electrodynamics (QED) realization of a protocol to generate a Greenberger-Horne-Zeilinger (GHZ) state for N superconducting transmon qubits homogeneously coupled to a superconducting transmission line resonator in the dispersive limit. We derive an effective Hamiltonian with pairwise qubit exchange interactions of the XY type, g͂(XX + YY), that can be globally controlled. Starting from a separable initial state, these interactions allow us to generate a multi-qubit GHZ state within a time tGHZ ~ g͂-1. We discuss how to probe the nonlocal nature and the genuine N-partite entanglement of the generated state. Finally, we investigate the stability of the proposed scheme to inhomogeneities in the physical parameters. [ABSTRACT FROM AUTHOR]

Voice preferences are an integral part of interpersonal interactions and shape how people connect with each other. While a large number of studies have investigated the mechanisms behind (speaking) voice attractiveness, very little research was dedicated to other types of vocalizations. In this Registered Report, we proposed to investigate voice preferences with an integrative approach. To this end, we used a newly recorded and validated stimulus set of contrasting vocalizations by 22 highly trained female singers speaking and singing the same material (in Brazilian Portuguese) in contrasting styles (sung as a lullaby, as a pop song or as an opera aria; and spoken aloud as if directed to an adult audience and as if directed to an infant). We asked 62 participants to rate these vocalizations in terms of how much they liked them; and we compared the amount of shared taste (that is, how much participants agreed in their preferences) across styles. We found highly idiosyncratic preferences across all styles. Our predictions concerning shared taste were not confirmed: although shared taste was higher for lullaby than for pop singing, it was unexpectedly higher for operatic than pop singing, and higher for infant-directed than adult-directed speech. Conversely, our prediction of limited consistency in average preferences for some singers across styles was confirmed, contradicting sexual selection-based ideas of singing and speaking as 'backup' signals of individual fitness. Our findings draw attention to the role of individual differences in voice preferences and highlight the need for a broader approach to understanding the underlying mechanisms of voice preferences. Stage 1 recommendation and review history: https://rr.peercommunityin.org/articles/rec?id=357. Stage 2 recommendation and review history: https://rr.peercommunityin.org/articles/rec?id=802., Competing Interests: We declare we have no competing interests., (© 2024 The Author(s).)

Background: Primary care providers (PCPs) prescribe less often treatments for smoking cessation than for other major risk factors. We assessed the effect of training PCPs to offer smoking cessation treatments to current smokers as the default choice using an encounter decision aid (DA) on smoking cessation., Methods: Pragmatic, cluster-randomized controlled trial with PCPs in private practice in Switzerland and France. The intervention was a half-day course teaching PCPs the default choice approach using a DA. Control PCPs received a 1-h refresher training on smoking cessation aids. PCPs recruited daily smokers seen for routine care. The primary outcome was self-reported, 7-day, point prevalence smoking abstinence at 6 months. Secondary outcomes were quit attempts and use of smoking cessation aids at 3 weeks, 3 months, and 6 months, and a patient-reported measure of shared decision-making (CollaboRATE scale 1-10, higher scores = more involvement)., Results: Forty-two PCPs completed the training (76% Swiss) and recruited 287 current smokers (105 intervention group, 182 control group), with 51% women, mean age 48 (SD, 2.6), 77% who smoked <20 cigarettes/day, and 221 who responded at 6 months follow-up (77%). The intervention did not affect self-reported smoking abstinence rate at 6 months (9.5% intervention and 10.4% control groups, respectively; OR 0.88 (95%CI 0.37-2.10). It did however increase the number of quit attempts at 3 weeks (OR 2.09, 95%CI 1.04-4.20) and the use of smoking cessation aids at the 3-week and 3-month follow-ups (OR 2.57, 95%CI 1.21-5.45 and OR 2.00, 95%CI 1.11-3.60, respectively). The mean CollaboRATE score was 8.05/10 in the intervention group and 7.28/10 in the control group (p=0.02), reflecting more patient involvement in decision-making., Conclusion: Training PCPs to use a decision aid did not improve smoking abstinence rate, despite short-term increases in quit attempts and use of smoking cessation aids. It improved patient involvement in decision-making., Trial Registration: ClinicalTrials.gov identifier: NCT04868474., (© 2024. The Author(s).)

Both music and language are found in all known human societies, yet no studies have compared similarities and differences between song, speech, and instrumental music on a global scale. In this Registered Report, we analyzed two global datasets: (i) 300 annotated audio recordings representing matched sets of traditional songs, recited lyrics, conversational speech, and instrumental melodies from our 75 coauthors speaking 55 languages; and (ii) 418 previously published adult-directed song and speech recordings from 209 individuals speaking 16 languages. Of our six preregistered predictions, five were strongly supported: Relative to speech, songs use (i) higher pitch, (ii) slower temporal rate, and (iii) more stable pitches, while both songs and speech used similar (iv) pitch interval size and (v) timbral brightness. Exploratory analyses suggest that features vary along a "musi-linguistic" continuum when including instrumental melodies and recited lyrics. Our study provides strong empirical evidence of cross-cultural regularities in music and speech.

One of the central tasks in many-body physics is the determination of phase diagrams. However, mapping out a phase diagram generally requires a great deal of human intuition and understanding. To automate this process, one can frame it as a classification task. Typically, classification problems are tackled using discriminative classifiers that explicitly model the probability of the labels for a given sample. Here we show that phase-classification problems are naturally suitable to be solved using generative classifiers based on probabilistic models of the measurement statistics underlying the physical system. Such a generative approach benefits from modeling concepts native to the realm of statistical and quantum physics, as well as recent advances in machine learning. This leads to a powerful framework for the autonomous determination of phase diagrams with little to no human supervision that we showcase in applications to classical equilibrium systems and quantum ground states.

Why do we prefer some singers to others? We investigated how much singing voice preferences can be traced back to objective features of the stimuli. To do so, we asked participants to rate short excerpts of singing performances in terms of how much they liked them as well as in terms of 10 perceptual attributes (e.g.: pitch accuracy, tempo, breathiness). We modeled liking ratings based on these perceptual ratings, as well as based on acoustic features and low-level features derived from Music Information Retrieval (MIR). Mean liking ratings for each stimulus were highly correlated between Experiments 1 (online, US-based participants) and 2 (in the lab, German participants), suggesting a role for attributes of the stimuli in grounding average preferences. We show that acoustic and MIR features barely explain any variance in liking ratings; in contrast, perceptual features of the voices achieved around 43% of prediction. Inter-rater agreement in liking and perceptual ratings was low, indicating substantial (and unsurprising) individual differences in participants' preferences and perception of the stimuli. Our results indicate that singing voice preferences are not grounded in acoustic attributes of the voices per se, but in how these features are perceptually interpreted by listeners., (© 2024. The Author(s).)

We theoretically describe macroscopic quantum synchronization effects occurring in a network of all-to-all coupled quantum limit-cycle oscillators. The coupling causes a transition to synchronization as indicated by the presence of global phase coherence. We demonstrate that the microscopic quantum properties of the oscillators qualitatively shape the synchronization behavior in a macroscopically large network. Specifically, they result in a blockade of collective synchronization that is not expected for classical oscillators. Additionally, the macroscopic ensemble shows emergent behavior not present at the level of two coupled quantum oscillators.

Classical singers train intensively for many years to achieve a high level of vocal control and specific sound characteristics. However, the actual span of singers' activities often includes venues other than opera halls and requires performing in styles outside their strict training (e.g., singing pop songs at weddings). We examine classical singers' ability to adjust their vocal productions to other styles, in relation with their formal training. Twenty-two highly trained female classical singers (aged from 22 to 45 years old; vocal training ranging from 4.5 to 27 years) performed six different melody excerpts a cappella in contrasting ways: as an opera aria, as a pop song and as a lullaby. All melodies were sung both with lyrics and with a /lu/ sound. All productions were acoustically analyzed in terms of seven common acoustic descriptors of voice/singing performances and perceptually evaluated by a total of 50 lay listeners (aged from 21 to 73 years old) who were asked to identify the intended singing style in a forced-choice lab experiment. Acoustic analyses of the 792 performances suggest distinct acoustic profiles, implying that singers were able to produce contrasting sounding performances. Furthermore, the high overall style recognition rate (78.5% Correct Responses, hence CR) confirmed singers' proficiency in performing in operatic style (86% CR) and their versatility when it comes to lullaby (80% CR) and pop performances (69% CR), albeit with occasional confusion between the latter two. Interestingly, different levels of competence among singers appeared, with versatility (as estimated based on correct recognition in pop/lullaby styles) ranging from 62 to 83% depending on the singer. Importantly, this variability was not linked to formal training per se . Our results indicate that classical singers are versatile, and prompt the need for further investigations to clarify the role of singers' broader professional and personal experiences in the development of this valuable ability., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Bruder and Larrouy-Maestri.)

Aims of the Study: Canton Vaud, Switzerland, implemented an organised colorectal cancer  screening programme with colonoscopy and faecal occult blood tests in 2015, 4 to 6 years ahead of neighbouring cantons. Before its implementation, nearly half of Swiss citizens were already up to date with screening, primarily from opportunistic colonoscopies. We hypothesised that earlier implementation of an organised programme would be associated with greater increases in colorectal cancer testing rates., Methods: We analysed Swiss health insurance claim data from CSS, a Swiss health insurer covering 16% of the Swiss population and 10% of canton Vaud. We stratified 50-69-year-olds into groups from Vaud, its four neighbouring cantons (Fribourg, Geneva, Neuchâtel and Valais), and the rest of Switzerland. We analysed overall, faecal occult blood test and colonoscopy testing rates for each year between 2010 and 2018., Results: The overall testing rate increased from 7.6% in 2010 to 11.6% in 2018 (+4.0%) in Vaud, from 6.1% to 9.3% (+3.2%) in neighbouring cantons and from 7.4% to 8.6% (+1.2%) in the rest of Switzerland. The faecal occult blood test rate increased between 2016 and 2018 from 2.9% to 4.1% (+1.2%) in Vaud and from 1.7% to 2.6% (+0.9%) in neighbouring cantons, but it decreased from 3.1% to 1.5% (-1.6%) in the rest of Switzerland. The colonoscopy rate increased in all cantons, from 4.7% to 7.5% in Vaud (+2.8%), from 4.4% to 6.7% in neighbouring cantons (+2.3%) and from 4.3% to 7.1% in the rest of Switzerland (+2.8%). By 2018, 40% of faecal occult blood tests and 26% of colonoscopies in Vaud occurred in the organised programme. Those who completed an faecal occult blood test within the Vaud programme were younger, had fewer comorbidities and were more likely to have a high-deductible health plan than those tested outside the programme., Conclusions: Colorectal cancer testing rates increased between 2010 and 2018, with greater absolute increases in Vaud than in neighbouring cantons or the rest of Switzerland. Faecal occult blood test use increased in both Vaud and neighbouring cantons, possibly reflecting changes in testing patterns by general practitioners. By 2018, 40% of colonoscopies and 26% of faecal occult blood tests occurred within the screening programme.