Transcatheter Aortic Valve Replacement in Patients with Small Aortic Annuli: A Propensity-Matched Analysis of Sex-Based Outcomes.

BACKGROUND: Patients with small aortic annuli (SAA) are predominantly women. We sought to compare sex-based and propensity-matched outcomes of index transcatheter aortic valve replacement (TAVR) in patients with SAA. METHODS: In this retrospective institutional analysis (2012 - 2023), primary stratification was by gender. SAA was defined as aortic valve annulus diameter <23mm. 30-day and 1-year outcomes were compared between the groups. RESULTS: A total of 3911 patients underwent TAVR. Of those, 661 patients had a small aortic annulus of whom 23.8% were men & 76.2% were women. Propensity matching (1:1) identified 152 pairs. The mean age was 81 years. History of prior surgical or percutaneous coronary intervention was more prevalent in men (72.4% vs 48%, p<0.001). Men had a higher incidence of postoperative pacemaker implantation (8.6% vs 3.3%, p=0.05) while only women had iliofemoral dissections (4.6% vs 0%, p=0.007). The rates of moderate (23.0% vs 25.7%) and severe (2.6% vs 0.7%) prosthesis-patient mismatch was not statistically significantly different between the groups (p=0.364). 30-day mortality was 0% while 1-year mortality was 4.3% with no difference between groups. Increase in preoperative creatinine was associated with higher risk of death (HR 1.206, 95% CI 1.025-1.418, p=0.02), while sex was not. Kaplan-Meier survival estimates (Logrank, p=0.768) and cumulative incidence of stroke readmission (p=0.842) were similar in both groups. CONCLUSION: Outcomes of TAVR in SAA do not differ by sex with safety and efficacy evident in both men and women.

Persistence of a Delocalized Radical in Larger Clusters of Hydrated Copper(II) Hydroxide, CuOH+(H2O)3-7.

The structures, vibrational spectra, and electronic properties of copper hydroxide hydrates CuOH+(H2O)3-7 were investigated with quantum chemistry computations. As a follow-up to a previous analysis of CuOH+(H2O)0-2, this investigation examined the progression as the square-planar metal coordination environment was filled and as solvation shells expanded. Four-, five-, and six-coordinate structures were found to be low-energy isomers. The delocalized radical character, which was discovered in the small clusters, was found to persist upon continued hydration, although the hydrogen-bonded water network in the larger clusters was found to play a more significant role in accommodating this spin. Partial charges indicated that the electronic structure includes more Cu2+···OH- character than was observed in smaller clusters, but this structure remains decidedly mixed with Cu+···OH· configurations and yields roughly half-oxidation of the water network in the absence of any electrochemical potential. Computed vibrational spectra for n = 3 showed congruence with spectra from recent predissociation spectroscopy experiments, provided that the role of the D2 tag was taken into account. Spectra for n = 4-7 were predicted to exhibit features that are reflective of both the mixed electronic character and proton-/hydrogen-shuttling motifs within the hydrogen-bonded water network.

Structural, Thermodynamic, and Spectroscopic Evolution in the Hydration of Copper(II) Ions, Cu2+(H2O)2-8.

Gas-phase clusters of the hydrated Cu(II) cation with 2-8 water molecules were investigated using ab initio quantum chemistry. Isomer structures, energies, and vibrational spectra were computed across this size range, yielding a qualitative picture of this ion as an intact Cu2+ hydrate that also partially oxidizes the surrounding water network at equilibrium. At sufficient cluster sizes, these ion hydrates also become thermodynamically preferred over competitive Cu(II) hydroxide hydrates. Competitive coordination environments were found to exist at some cluster sizes, due to both hydrogen-bonding and d-orbital chemical effects, and the dominant coordination number was found in some cases to be temperature-dependent. Clear spectral signatures of the ion's coordination environment were computed to exist at each cluster size, which should make experimental verification of these computational predictions straightforward. Through comparison to recent studies of hydrated CuOH+, the effective charge on the metal center was shown to converge to approximately +1.5 in both cases, despite qualitatively different behavior of their radical spin densities. Therefore, nominally Cu(II) ions exhibit considerable electronic, chemical, and structural flexibility. The electronic origins of this flexibility─including key roles played by the water network itself─are investigated in this work and should provide a conceptual foundation for future studies of copper-based, water-oxidation catalysts.

Guided Ion Beam Studies of the Dy + O → DyO+ + e- Chemi-ionization Reaction Thermochemistry and Dysprosium Oxide, Carbide, Sulfide, Dioxide, and Sulfoxide Cation Bond Energies.

Guided ion beam tandem mass spectrometry (GIBMS) was used to measure the kinetic energy dependent product ion cross sections for reactions of the lanthanide metal dysprosium cation (Dy+) with O2, SO2, and CO and reactions of DyO+ with CO, O2, and Xe. DyO+ is formed through an exothermic process when Dy+ reacts with O2, whereas all other processes observed are found to be endothermic. The kinetic energy dependences of these cross sections were analyzed to yield 0 K bond dissociation energies (BDEs) for DyO+, DyC+, DyS+, DyO2+, and DySO+. The 0 K BDE for DyO+ is determined to be 5.60 ± 0.02 eV from the weighted average of six independent thresholds, which are dominated by the slightly endothermic reaction of Dy+ with SO2. Combined with the well-established Dy ionization energy (IE), this value indicates that the chemi-ionization reaction, Dy + O → DyO+ + e-, is endothermic by 0.33 ± 0.02 eV. Theoretical BDEs for Dy+-O, Dy+-C, Dy+-S, ODy+-O, and Dy+-SO were calculated at several levels of theory and basis sets for comparison with experiment with reasonable agreement achieved.

It happened again: Convergent evolution of acylglucose specialized metabolism in black nightshade and wild tomato.

Plants synthesize myriad phylogenetically restricted specialized (aka "secondary") metabolites with diverse structures. Metabolism of acylated sugar esters in epidermal glandular secreting trichomes across the Solanaceae (nightshade) family is ideal for investigating the mechanisms of evolutionary metabolic diversification. We developed methods to structurally analyze acylhexose mixtures by 2D NMR, which led to the insight that the Old World species black nightshade (Solanum nigrum) accumulates acylglucoses and acylinositols in the same tissue. Detailed in vitro biochemistry, cross-validated by in vivo virus-induced gene silencing, revealed two unique features of the four-step acylglucose biosynthetic pathway: A trichome-expressed, neofunctionalized invertase-like enzyme, SnASFF1, converts BAHD-produced acylsucroses to acylglucoses, which, in turn, are substrates for the acylglucose acyltransferase, SnAGAT1. This biosynthetic pathway evolved independently from that recently described in the wild tomato Solanum pennellii, reinforcing that acylsugar biosynthesis is evolutionarily dynamic with independent examples of primary metabolic enzyme cooption and additional variation in BAHD acyltransferases.

Electronic Structure and Vibrational Signatures of the Delocalized Radical in Hydrated Clusters of Copper("II") Hydroxide CuOH+(H2O)0-2.

The copper hydroxide ion, CuOH+, serves as the catalytic core in several recently developed water-splitting catalysts, and an understanding of its chemistry is critical to determining viable catalytic mechanisms. In spite of its importance, the electronic structure of this open-shell ion has remained ambiguous in the literature. In particular, computed values for both the thermodynamics of hydration and the vibrational signatures of the mono- and dihydrates have shown prohibitively large errors compared to values from recent experimental measurements. In this work, the source of this discrepancy is demonstrated to be the propensity of this ion to exist between traditional Cu(I) and Cu(II) oxidation-state limits. The spin density of the radical is accordingly shown to delocalize between the metal center and surrounding ligands, and increasing the hydration serves to exacerbate this behavior. Equation-of-motion coupled-cluster methods demonstrated the requisite accuracy to resolve the thermodynamic discrepancies. Such methods were also needed for spectral simulations, although the latter also required a direct simulation of the role of the deuterium "tag" molecules that are used in modern predissociation spectroscopy experiments. This nominally benign tag molecule underwent direct complexation with the open-valence metal ion, thereby forming a species akin to known metal-H2 complexes and strongly impacting the resulting spectrum. Thermal populations of this configuration and other more traditional noncovalently bound isomers led to a considerable broadening of the spectral lineshapes. Therefore, at least for the CuOH+(H2O)0-2 hydrates, these benchmark ions should be considered to be delocalized radical systems with some degree of multireference character at equilibrium. They also serve as a cautionary tale for the spectroscopy community, wherein the role of the D2 tag is far from benign.

Stepwise Activation of Water by Open-Shell Interactions, Cl(H2O)n=4-8,17.

Chemical activation of water by a single chlorine atom was examined computationally for clusters of chlorine radicals and water in a size regime just prior to internal hydration of water/ions, Cl·(H2O)n=4-8,17. This investigation follows a recent analysis of this radical-molecule interaction [Christensen et al. J. Phys. Chem. A 2019, 123, 8657] for n = 1-4, which demonstrated that n = 4 marked a transition in which an oxidized-water structural motif became viable, albeit high in energy. Thousands of unique isomers were computed in the present analysis, which resulted in three structural classes of isomers, including intact hydrated chlorine, hydrogen-transferred (HCl)(OH·)(H2O)n-1, and charge-transferred (Cl-)(H3O+)(OH·)(H2O)n-2 configurations. The electronic structures of these classes were investigated, along with harmonic vibrational signatures that probed the degree of water-network perturbations and generated experimentally verifiable computational predictions. The main outcome of this analysis is that the charge-transferred isomers were stabilized considerably upon increased hydration-leading to an energetic crossover with the hydrogen-transferred forms-but the degree of hydration was surprisingly still not sufficient to achieve crossover between the intact chlorine-water complexes and these charge-separated configurations. Internal hydration of the ions appears to be necessary in order to achieve this separation, which will likely occur at larger cluster sizes.

Probing the Partial Activation of Water by Open-Shell Interactions, Cl(H2O)1-4.

The partial chemical activation of water by reactive radicals was examined computationally for small clusters of chlorine and water, Cl•(H2O)n=1-4. Using an automated isomer-search procedure, dozens of unique, stable structures were computed. Among the resulting structural classes were intact, hydrated-chlorine isomers, as well as hydrogen-abstracted (HCl)(OH)(H2O)n-1 configurations. The latter showed increased stability as the degree of hydration increased, until n = 4, where a new class of structures was discovered with a chloride ion bound to an oxidized water network. The electronic structure of these three structural classes was investigated, and spectral signatures of this hydration-based evolution were connected to these electronic properties. An ancillary outcome of this detailed computational analysis, including coupled-cluster benchmarks, was the calibration of cost-effective quantum chemistry methods for future studies of these radical-water complexes.

Auditory development in early amplified children: factors influencing auditory-based communication outcomes in children with hearing loss.

OBJECTIVE: The purpose of this study was to determine the influence of selected predictive factors, primarily age at fitting of amplification and degree of hearing loss, on auditory-based outcomes in young children with bilateral sensorineural hearing loss. DESIGN: Forty-four infants and toddlers, first identified with mild to profound bilateral hearing loss, who were being fitted with amplification were enrolled in the study and followed longitudinally. Subjects were otherwise typically developing with no evidence of cognitive, motor, or visual impairment. A variety of subject factors were measured or documented and used as predictor variables, including age at fitting of amplification, degree of hearing loss in the better hearing ear, cochlear implant status, intensity of oral education, parent-child interaction, and the number of languages spoken in the home. These factors were used in a linear multiple regression analysis to assess their contribution to auditory-based communication outcomes. Five outcome measures, evaluated at regular intervals in children starting at age 3, included measures of speech perception (Pediatric Speech Intelligibility and Online Imitative Test of Speech Pattern Contrast Perception), speech production (Arizona-3), and spoken language (Reynell Expressive and Receptive Language). RESULTS: The age at fitting of amplification ranged from 1 to 72 mo, and the degree of hearing loss ranged from mild to profound. Age at fitting of amplification showed the largest influence and was a significant factor in all outcome models. The degree of hearing loss was an important factor in the modeling of speech production and spoken language outcomes. Cochlear implant use was the other factor that contributed significantly to speech perception, speech production, and language outcomes. Other factors contributed sparsely to the models. CONCLUSIONS: Prospective longitudinal studies of children are important to establish relationships between subject factors and outcomes. This study clearly demonstrated the importance of early amplification on communication outcomes. This demonstration required a participant pool that included children who have been fit at very early ages and who represent all degrees of hearing loss. Limitations of longitudinal studies include selection biases. Families who enroll tend to have high levels of education and rate highly on cooperation and compliance measures. Although valuable information can be extracted from prospective studies, not all factors can be evaluated because of enrollment constraints.

Newborn hearing screening speeds diagnosis and access to intervention by 20-25 months.

BACKGROUND: Newborn Hearing Screening (NHS) programs aim to reduce the age of identification and intervention of infants with hearing loss. It is generally accepted that NHS programs achieve that outcome, but few studies have compared children who were screened to those not screened in the same study and during the same time period. This study takes advantage of the emerging screening programs in California to compare children based on screening status on age at intervention milestones. PURPOSE: The purpose of this studywas to compare the outcomes of cohorts of children with hearing loss, some screened for hearing loss at birth and others not screened. Specifically, the measures compared are the benchmarks suggested by the Joint Committee on Infant hearing for determining the quality of screening programs. STUDY SAMPLE: Records from 64 children with bilateral permanent hearing loss who were enrolled in a study of communication outcomes served as data for this study. Of these children, 47 were screened with 39 failing and 8 passing, and 17 were not screened. INTERVENTION: This study was observational and involved no planned intervention. DATA COLLECTION AND ANALYSIS: Outcome benchmarks included age at diagnosis of hearing loss, age at fitting of amplification, and age at enrollment in early intervention. Delays between diagnosis and fitting or enrollment were also calculated. Hearing screening status of the children included screened with fail outcome, screened with pass outcome, and not screened. Analysis included simple descriptive statistics, and t-tests were used to compare outcomes by groups: screened/not screened, screened pass/screened failed, and passed/not screened. RESULTS: Children with hearing loss who had been screened as newborns were diagnosed with hearing loss 24.62 months earlier, fitted with hearing aids 23.51 months earlier, and enrolled in early intervention 19.98 months earlier than those infants who were not screened. Screening status did not influence delays in fitting of amplification or enrollment in intervention following diagnosis. Eight of the infants with hearing loss (12.5%) passed the NHS, and the ages at benchmarks of those children were slightly but not significantly earlier than infants who had not been screened. CONCLUSIONS: The age at achievement of benchmarks such as diagnosis, fitting of amplification, and enrollment in early intervention in children who were screened for hearing loss is on target with stated goals provided by the Academy of Pediatrics and the Joint Committee on Infant Hearing. In addition, children who are not screened for hearing loss continue to show dramatic delays in achievement of benchmarks by as much as 24 months. Evaluating achievement of benchmarks during the start-up period of NHS programs allowed a direct evaluation of ability of these screening programs to meet stated goals. This demonstrates, unequivocally, that the NHS process itself is responsible for improvements in age at diagnosis, hearing aid fitting, and enrollment in intervention.

Health risk assessment of chlorobenzenes in the air of residential houses using probabilistic techniques.

A human health risk assessment was performed to evaluate the risks due to chlorobenzenes in the air of residential houses. Chlorobenzenes found in the air in the toilets, rooms, and outdoors of three houses in Brisbane, Australia, were sampled by trapping on Tenax TA and analyzed using an automated thermal desorption (ATD)-gas chromatography/mass spectrometry (GC/MS) method. Concentrations of 1,4-dichlorobenzene (1,4-DCB) in the rooms, toilets, and outdoors were used as the exposure concentrations (E), while those in the toilets (microg/m3) were used as the high-exposure concentrations (HE). The exposure concentrations were transformed into exposure doses (EXD(E) and EXD(HE)). Dose-response data from the literature for a range of adverse effects in animals were obtained and exposure doses were expressed as human equivalent dose (HED). The HED values were higher than the EXD(E) and EXD(HE) values for all adverse effects, and a hazard quotient was calculated that indicated a low level of risk with the high-exposure environment. The lifetime average daily doses (LADDs) for a wide range of adverse effects observed in human case studies were estimated and compared to the doses in the high-exposure (HE) situation. Using the Monte Carlo simulation technique the probabilities of risk quotients higher than unity ranged from 0.02 to 0.26. This evaluation indicated that 1,4-DCB posed low risks to general residents; however, for individuals with susceptible characteristics and exposure to elevated 1,4-DCB, the probability of adverse responses was moderate to high.