Controlling Electronic Coherences and the Curvature Induced by the Derivative Coupling at a Conical Intersection: A Quantum Ehrenfest (QuEh) Protocol for Reaction Path Following Application to "Channel 3" Benzene Photochemistry.

We report a protocol for the implementation of "reaction path following" from a transition state through a conical intersection, including both the path curvature induced by the derivative coupling and the corresponding induced electronic coherences. This protocol focuses on the "central" Gaussian wavepacket (initially unexcited) in the quantum Ehrenfest (QuEh) method. Like the reaction path following, the normal mode corresponding to the imaginary frequency at the transition state is given an initial momentum. The protocol is applied to the "channel 3" radiationless decay of benzene. We also demonstrate that one can enhance the effect of the derivative coupling and the electronic coherence with an IR pulse.

Incidence and management of Lyme disease: a Scottish general practice retrospective study.

BACKGROUND: The true burden of Lyme disease in primary care in Scotland is unknown. Epidemiological data is currently based on laboratory confirmed reports as there is no mandatory reporting of clinical cases AIM: To analyse data from general practice in NHS Highland (North) over a six year period to assess the incidence and management of Lyme disease in primary care. DESIGN & SETTING: This was a retrospective descriptive study. Study data was extracted from all 63 general practices within NHS Highland (North) from 2017 to 2022. METHOD: Lyme disease consultations were identified via Lyme-related clinical read codes, borrelia test requests, free text 'tags' and/or Lyme disease antibiotic scripts. RESULTS: Using read codes to identify patients with Lyme disease/ suspected Lyme disease gave an estimated average annual incidence of 124/100,000 population, which was 2.1-fold more than those based on laboratory confirmed reports only. Incidence figures increased to 5.2-fold more (362/100,000 population) when those patients with Lyme disease/ suspected Lyme disease (identified via readcodes, laboratory test requests and free text 'tags') who were given antibiotic treatment were taken into account. Local 'hotspots' of infection were identified. Analysis of the antibiotic data indicates that antibiotic prescribing in NHS Highland largely follows NICE guidelines. CONCLUSION: This data analysis pathway can, and should, be rolled out to assess the incidence and management of Lyme disease in primary care throughout the whole of Scotland to allow appropriate resources to be allocated.

Noise phenomena in distress cries of term and very preterm infants at term-equivalent age.

BACKGROUND AND AIM: To examine whether the noise components in distress cries of term infants differed from very preterm infants whose cries were collected at a comparable "corrected" gestational age. METHODS: Distress cries were collected from 20 term and 20 preterm infants. The cries were acoustically examined for the occurrence of aperiodic phonatory behavior within and across moments of crying. RESULTS: The findings indicated no significant differences between term and preterm infants at term age in the occurrence of noise. CONCLUSIONS: Distress cries of both term and term-equivalent preterm infants appear to contain high instances of phonatory noise. The high arousal associated with distress crying and associated increase in subglottal pressure appeared to influence both term and term-equivalent preterm infants similarly.

Coherent Mixing of Singlet and Triplet States in Acrolein and Ketene: A Computational Strategy for Simulating the Electron-Nuclear Dynamics of Intersystem Crossing.

We present a theoretical study of intersystem crossing (ISC) in acrolein and ketene with the Ehrenfest method that can describe a superposition of singlet and triplet states. Our simulations illustrate a new mechanistic effect of ISC, namely, that a superposition of singlets and triplets yields nonadiabatic dynamics characteristic of that superposition rather than the constituent state potential energy surfaces. This effect is particularly significant in ketene, where mixing of singlet and triplet states along the approach to a singlet/singlet conical intersection occurs, with the spin-orbit coupling (SOC) remaining small throughout. In both cases, the effects require many recrossings of the singlet/triplet state crossing seam, consistent with the textbook treatment of ISC.

How electronic superpositions drive nuclear motion following the creation of a localized hole in the glycine radical cation.

In this work, we have studied the nuclear and electron dynamics in the glycine cation starting from localized hole states using the quantum Ehrenfest method. The nuclear dynamics is controlled both by the initial gradient and by the instantaneous gradient that results from the oscillatory electron dynamics (charge migration). We have used the Fourier transform (FT) of the spin densities to identify the "normal modes" of the electron dynamics. We observe an isomorphic relationship between the electron dynamics normal modes and the nuclear dynamics, seen in the vibrational normal modes. The FT spectra obtained this way show bands that are characteristic of the energy differences between the adiabatic hole states. These bands contain individual peaks that are in one-to-one correspondence with atom pair (+·) ↔ (·+) resonances, which, in turn, stimulate nuclear motion involving the atom pair. With such understanding, we anticipate "designer" coherent superpositions that can drive nuclear motion in a particular direction.

Acoustic Cry Characteristics of Infants as a Marker of Neurological Dysfunction: A Systematic Review and Meta-Analysis.

BACKGROUND: Atypical cries have been identified in infants with neurological dysfunction. The aim of this study was to conduct a systematic review and meta-analysis to appraise existing evidence for associations between acoustic cry characteristics and neurological dysfunction in infants aged 18 months or less. METHODS: PubMed/MEDLINE, PsycINFO, CINAHL, and Embase were searched for original, peer-reviewed studies published in English reporting cry variables in infants aged 18 months or less with or at risk of neurological dysfunction. Studies without a nonneurologically impaired control sample were excluded. Pooled effect sizes were estimated using standardized mean difference (SMD) and odds ratio (OR). I2 indicated study heterogeneity, and the risk of bias was assessed using the Newcastle-Ottawa Scale. RESULTS: From March 2018 to February 2019, 28,294 studies were retrieved. Eight were meta-analyzed. Infants with or at risk of neurological dysfunction exhibited higher mean (SMD = 0.11 [95% confidence interval, 0.00 to 0.23]) and minimum (SMD = 0.93 [0.64 to 1.23]) fundamental frequency; higher odds of hyperphonation (OR = 13.17 [1.05 to 165.87]), biphonation (OR = 10.62 [1.53 to 73.59]), rise-fall-rise melodies (OR = 4.66 [1.16 to 18.66]), and flat melodies (OR = 4.47 [1.27 to 15.68]); and lower odds of fall-rise-fall melodies (OR = 0.21 [0.05 to 0.83]). CONCLUSIONS: Infants with underlying neuropathology have unique cries characterized by higher fundamental frequency, dysphonation, and atypical melodies, although study heterogeneity and imprecision of effect size estimates limited our interpretation. Assessment of acoustic cry characteristics offers the potential for noninvasive, rapid, point-of-care screening for neurologically high-risk infants.

Differential stuttering during conversation and oral reading in Kuwaiti-Arabic speakers: a note on diglossia.

The current study aimed to explore the frequency and types of stuttering in the oral reading and conversational samples of Arabic adults who stutter (AWS). Twelve Kuwaiti-Arabic AWS (mean age: 27.3 years) participated in the study. Each participant's stuttering was analyzed in two speaking contexts -oral reading of a standard Arabic passage and spontaneous conversational speech. The results showed that among a majority of the participants the amount of stuttering in conversation was significantly lower than that of reading. However, no significant differences were found in disfluency types within and between samples. The higher occurrence of stuttering in reading may be related to the diglossic nature of Arabic. The linguistic and rhythmic distinctions between Modern Standard Arabic (MSA) and Kuwaiti dialectal Arabic are explored to further explain the findings.

Properties of Relative Timing and Phonetic Complexity in Adults with Dysarthria Secondary to Amyotrophic Lateral Sclerosis.

INTRODUCTION: This study examined the relative timing in individuals with dysarthria secondary to amyotrophic lateral sclerosis (ALS). The aim was to examine whether the relative timing was influenced by severity of dysarthria and phonetic complexity of the speech being produced. METHODS: Twenty-one adults with dysarthria secondary to ALS, who presented with a range of dysarthria severity, participated in the study. A group of nonimpaired, age-matched adults served as controls. All participants produced a single phrase, across which four measures of relative timing were calculated, and the phonetic composition (complexity) of each measure was considered. Both participant groups completed the Sentence Intelligibility Test, which provided measures of speech intelligibility and speaking rate. RESULTS: Relative timing did not significantly differ between speaker groups across the four measures, regardless of phonetic complexity. Neither Sentence Intelligibility Test score nor speaking rate were significantly correlated with relative timing. DISCUSSION: Relative timing of phrase-level speech appears to remain intact regardless of the phonetic complexity of speech among individuals with dysarthria secondary to ALS. The potential of an internal phonological system organizing speech gestures is discussed to explain why the consistency in relative timing occurs.

Unlocking the Double Bond in Protonated Schiff Bases by Coherent Superposition of S1 and S2.

The primary event occurring during the E-to-Z photoisomerization reaction of retinal protonated Schiff base (rPSB) is single-to-double bond inversion. In this work we examine the nuclear dynamics that occurs when the initial excited state is a superposition of the S1 and S2 electronic excited states that might be created in a laser experiment. The nuclear dynamics is dominated by double bond inversion that is parallel to the derivative coupling vector of S1 and S2. Thus, the molecule behaves as if it were at a conical intersection even if the states are nondegenerate.

Melody complexity of infants' cry and non-cry vocalisations increases across the first six months.

In early infancy, melody provides the most salient prosodic element for language acquisition and there is huge evidence for infants' precocious aptitudes for musical and speech melody perception. Yet, a lack of knowledge remains with respect to melody patterns of infants' vocalisations. In a search for developmental regularities of cry and non-cry vocalisations and for building blocks of prosody (intonation) over the first 6 months of life, more than 67,500 melodies (fundamental frequency contours) of 277 healthy infants from monolingual German families were quantitatively analysed. Based on objective criteria, vocalisations with well-identifiable melodies were grouped into those exhibiting a simple (single-arc) or complex (multiple-arc) melody pattern. Longitudinal analysis using fractional polynomial multi-level mixed effects logistic regression models were applied to these patterns. A significant age (but not sex) dependent developmental pattern towards more complexity was demonstrated in both vocalisation types over the observation period. The theoretical concept of melody development (MD-Model) contends that melody complexification is an important building block on the path towards language. Recognition of this developmental process will considerably improve not only our understanding of early preparatory processes for language acquisition, but most importantly also allow for the creation of clinically robust risk markers for developmental language disorders.

Disfluency characteristics of Omani Arabic-English bilingual speakers.

This study examined the oral reading and conversational speech of eight bilinguals who stutter (BWS). The participants spoke Omani Arabic as the dominant and English as the less-dominant language. The samples were examined with particular reference to the production of overall disfluency, stuttering-like disfluencies (SLDs) and other-disfluencies (ODs) occurring at the syllable and word level. The results indicated no difference in the amount of overall disfluency or ODs between the two languages in either reading or conversation. A significantly higher amount of SLDs were found to occur in words during reading in Arabic compared to English, which was attributed to the linguistic complexity of formal Arabic. A higher amount of SLDs in syllables were found in English compared to Arabic during conversation, although no such difference was found at the word level. The results align with a small body of research suggesting equivalent amounts of stuttering between dominant and less-dominant languages during conversation. The finding of a higher amount of stuttering during reading in Arabic is suggestive of motor differences in the production of the two languages that differentially affect speech fluency.

How educational are 'educational' apps for young children? App store content analysis using the Four Pillars of Learning framework.

Experts have expressed concerns about the lack of evidence demonstrating that children's "educational" applications (apps) have educational value. This study aimed to operationalize Hirsh-Pasek, Zosh, et al.'s (2015) Four Pillars of Learning into a reliable coding scheme (Pillar 1: Active Learning, Pillar 2: Engagement in the Learning Process, Pillar 3: Meaningful Learning, Pillar 4: Social Interaction), describe the educational quality of commercially-available apps, and examine differences in educational quality between free and paid apps. We analyzed 100 children's educational apps with the highest downloads from Google Play and Apple app stores, as well as 24 apps most frequently played by preschool-age children in a longitudinal cohort study. We developed a coding scheme in which each app earned a value of 0-3 for each Pillar, defining lower-quality apps as those scoring ≤ 4, summed across the Four Pillars. Overall scores were low across all Pillars. Free apps had significantly lower Pillar 2 (Engagement in Learning Process) scores (t-test, p < .0001) and overall scores (t-test, p < .0047) when compared to paid apps, due to the presence of distracting enhancements. These results highlight the need for improved design of educational apps guided by developmental science.

Control of nuclear dynamics in the benzene cation by electronic wavepacket composition.

The study of coupled electron-nuclear dynamics driven by coherent superpositions of electronic states is now possible in attosecond science experiments. The objective is to understand the electronic control of chemical reactivity. In this work we report coherent 8-state non-adiabatic electron-nuclear dynamics simulations of the benzene radical cation. The computations were inspired by the extreme ultraviolet (XUV) experimental results in which all 8 electronic states were prepared with significant population. Our objective was to study the nuclear dynamics using various bespoke coherent electronic state superpositions as initial conditions in the Quantum-Ehrenfest method. The original XUV measurements were supported by Multi-configuration time-dependent Hartree (MCTDH) simulations, which suggested a model of successive passage through conical intersections. The present computations support a complementary model where non-adiabatic events are seen far from a conical intersection and are controlled by electron dynamics involving non-adjacent adiabatic states. It proves to be possible to identify two superpositions that can be linked with two possible fragmentation paths.

The quantum-Ehrenfest method with the inclusion of an IR pulse: Application to electron dynamics of the allene radical cation.

We describe the implementation of a laser control pulse in the quantum-Ehrenfest method, a molecular quantum dynamics method that solves the time-dependent Schrödinger equation for both electrons and nuclei. The oscillating electric field-dipole interaction is incorporated directly in the one-electron Hamiltonian of the electronic structure part of the algorithm. We then use the coupled electron-nuclear dynamics of the π-system in the allene radical cation (•CH2=C=CH2)+ as a simple model of a pump-control experiment. We start (pump) with a two-state superposition of two cationic states. The resulting electron dynamics corresponds to the rapid oscillation of the unpaired electron between the two terminal methylenes. This electron dynamics is, in turn, coupled to the torsional motion of the terminal methylenes. There is a conical intersection at 90° twist, where the electron dynamics collapses because the adiabatic states become degenerate. After passing the conical intersection, the electron dynamics revives. The IR pulse (control) in our simulations is timed to have its maximum at the conical intersection. Our simulations show that the effect of the (control) pulse is to change the electron dynamics at the conical intersection and, as a consequence, the concomitant nuclear dynamics, which is dominated by the change in the torsional angle.

Multifaceted highly targeted sequential multidrug treatment of early ambulatory high-risk SARS-CoV-2 infection (COVID-19).

The SARS-CoV-2 virus spreading across the world has led to surges of COVID-19 illness, hospitalizations, and death. The complex and multifaceted pathophysiology of life-threatening COVID-19 illness including viral mediated organ damage, cytokine storm, and thrombosis warrants early interventions to address all components of the devastating illness. In countries where therapeutic nihilism is prevalent, patients endure escalating symptoms and without early treatment can succumb to delayed in-hospital care and death. Prompt early initiation of sequenced multidrug therapy (SMDT) is a widely and currently available solution to stem the tide of hospitalizations and death. A multipronged therapeutic approach includes 1) adjuvant nutraceuticals, 2) combination intracellular anti-infective therapy, 3) inhaled/oral corticosteroids, 4) antiplatelet agents/anticoagulants, 5) supportive care including supplemental oxygen, monitoring, and telemedicine. Randomized trials of individual, novel oral therapies have not delivered tools for physicians to combat the pandemic in practice. No single therapeutic option thus far has been entirely effective and therefore a combination is required at this time. An urgent immediate pivot from single drug to SMDT regimens should be employed as a critical strategy to deal with the large numbers of acute COVID-19 patients with the aim of reducing the intensity and duration of symptoms and avoiding hospitalization and death.

Laryngeal Constriction Phenomena in Infant Vocalizations.

Purpose Instances of laryngeal constriction have been noted as a feature of infant vocal development. The purpose of this study was to directly evaluate the developmental occurrence of laryngeal constriction phenomena in infant crying, cooing, and babbling vocalizations. Method The cry and noncry vocalizations of 20 healthy term-born infants between the ages of 1 and 7 months were examined for instances of laryngeal constriction. Approximately 20,000 vocalization samples were acoustically evaluated, applying a combined visual (frequency spectra and melody curves) and auditory analysis; the occurrence of instances of different constriction phenomena was analyzed. Results Laryngeal constrictions were found during the production of cry and noncry vocalizations. The developmental pattern of constrictions for both vocalizations was charac-terized by an increase in constrictions followed by a decrease. During the age period of 3-5 months, when cry and noncry vocalizations were co-occurring, laryngeal constrictions were observed in 14%-22% of both types of vocalizations. An equal percentage of constrictions was found for both vocalizations at 5 months of age. Conclusions The findings confirm that the production of laryngeal constriction is a regularly occurring phenomenon in healthy, normally developing infants' spontaneous crying, cooing, and marginal babbling. The occurrence of constriction in both cry and noncry vocalizations suggests that an infant is exploiting physiological constraints of the sound-generating system for articulatory development during vocal exploration. These results lend support to the notion that the laryngeal articulator is the principal articulator that infants 1st start to control as they test and practice their phonetic production skills from birth through the 1st several months of life.

Estimates of functional cerebral hemispheric differences in monolingual and bilingual people who stutter: dichotic listening paradigm.

Recent studies indicate functional cerebral hemispheric processing differences between monolinguals and bilinguals who stutter, as well as monolinguals and bilinguals who do not stutter. Eighty native German speakers, half of whom were also proficient speakers of English as a second language (L2), were assessed on a dichotic listening paradigm using CV syllables as stimuli. The participants were organised into four different groups according to speech status and language ability: 20 monolinguals who stutter, 20 bilinguals who stutter, 20 monolinguals who do not stutter, and 20 bilinguals who do not stutter. A right ear advantage (REA) was observed across all groups with no significant group differences in regard to hemispheric asymmetry. Although MWS (18 dB) and BWS (16 dB) crossed over to an LEA at an earlier point compared to the MWNS (5 dB) and BWNS (2 dB), the difference between groups was minor and not significant. Thus, a significant difference in REA resistance, as proposed by other researchers, was not reflected in the current study neither for people who stutter nor for bilinguals. In addition, no meaningful relationship was found between dichotic listening and stuttering severity, as well as the four language modalities (listening, speaking, reading, writing). Thus, we contend that neither stuttering nor bilingualism has any non-trivial effect on functional cerebral hemispheric differences in language processing in dichotic listening.

Molecular Vertical Excitation Energies Studied with First-Order RASSCF (RAS[1,1]): Balancing Covalent and Ionic Excited States.

RASSCF calculations of vertical excitation energies were carried out on a benchmark set of 19 organic molecules studied by Thiel and co-workers [ J. Chem. Phys. 2008 , 128 , 134110 ]. The best results, in comparison with the MS-CASPT2 results of Thiel, were obtained using a RASSCF space that contains at most one hole and one particle in the RAS1 and RAS3 spaces, respectively, which we denote as RAS[1,1]. This subset of configurations recovers mainly the effect of polarization and semi-internal electronic correlation that is only included in CASSCF in an averaged way. Adding all-external correlation by allowing double excitations from RAS1 and RAS2 into RAS3 did not improve the results, and indeed, they were slightly worse. The accuracy of the first-order RASSCF computations is demonstrated to be a function of whether the state of interest can be classified as covalent or ionic in the space of configurations built from orbitals localized onto atomic sites. For covalent states, polarization and semi-internal correlation effects are negligible (RAS[1,1]), while for ionic states, these effects are large (because of inherent diffusiveness of these states compared to the covalent states) and, thus, an acceptable agreement with MS-CASPT2 can be obtained using first-order RASSCF with the extra basis set involving 3p orbitals in most cases. However, for those ionic states that are quasi-degenerate with a Rydberg state or for nonlocal nπ* states, there remains a significant error resulting from all external correlation effects.

Curve crossing in a manifold of coupled electronic states: direct quantum dynamics simulations of formamide.

Quantum dynamics simulations are an important tool to evaluate molecular behaviour including the, often key, quantum nature of the system. In this paper we present an algorithm that is able to simulate the time evolution of a molecule after photo-excitation into a manifold of states. The direct dynamics variational multi-configurational Gaussian (DD-vMCG) method circumvents the computational bottleneck problems of traditional grid-based methods by computing the potential energy functions on-the-fly, i.e. only where required. Unlike other commonly used direct dynamics methods, DD-vMCG is fully quantum mechanical. Here, the method is combined with a novel on-the-fly diabatisation scheme to simulate the short-time dynamics of the key molecule formamide and its acid analogue formimidic acid. This is a challenging test system due to the nature and large number of excited states, and eight coupled states are included in the calculations. It is shown that the method is able to provide unbiased information on the product channels open after excitation at different energies and demonstrates the potential to be a practical scheme, limited mainly by the quality of the quantum chemistry used to describe the excited states.