Psychosis superspectrum II: neurobiology, treatment, and implications.

Alternatives to traditional categorical diagnoses have been proposed to improve the validity and utility of psychiatric nosology. This paper continues the companion review of an alternative model, the psychosis superspectrum of the Hierarchical Taxonomy of Psychopathology (HiTOP). The superspectrum model aims to describe psychosis-related psychopathology according to data on distributions and associations among signs and symptoms. The superspectrum includes psychoticism and detachment spectra as well as narrow subdimensions within them. Auxiliary domains of cognitive deficit and functional impairment complete the psychopathology profile. The current paper reviews evidence on this model from neurobiology, treatment response, clinical utility, and measure development. Neurobiology research suggests that psychopathology included in the superspectrum shows similar patterns of neural alterations. Treatment response often mirrors the hierarchy of the superspectrum with some treatments being efficacious for psychoticism, others for detachment, and others for a specific subdimension. Compared to traditional diagnostic systems, the quantitative nosology shows an approximately 2-fold increase in reliability, explanatory power, and prognostic accuracy. Clinicians consistently report that the quantitative nosology has more utility than traditional diagnoses, but studies of patients with frank psychosis are currently lacking. Validated measures are available to implement the superspectrum model in practice. The dimensional conceptualization of psychosis-related psychopathology has implications for research, clinical practice, and public health programs. For example, it encourages use of the cohort study design (rather than case-control), transdiagnostic treatment strategies, and selective prevention based on subclinical symptoms. These approaches are already used in the field, and the superspectrum provides further impetus and guidance for their implementation. Existing knowledge on this model is substantial, but significant gaps remain. We identify outstanding questions and propose testable hypotheses to guide further research. Overall, we predict that the more informative, reliable, and valid characterization of psychopathology offered by the superspectrum model will facilitate progress in research and clinical care.

Generation and Implementation of Continuum Infrared Pulses for Broadband Detection in 2D IR Spectroscopy.

In recent years, new methods of generating continuum mid-infrared pulses through filamentation in gases have been developed for ultrafast time-resolved infrared vibrational spectroscopy. The generated infrared pulses can have thousands of wavenumbers of bandwidth, spanning the entire mid-IR region while retaining pulse length below 100 fs. This technology has had a significant impact on problems involving ultrafast structural dynamics in congested spectra with broad features, such as those found in aqueous solutions and molecules with strong intermolecular interactions. This study describes the recent advances in generating and characterizing these pulses and the practical aspects of implementing these sources for broadband detection in transient absorption and 2D IR spectroscopy.

Precision psychiatry and Research Domain Criteria: Implications for clinical trials and future practice.

Psychiatric disorders are associated with significant social and economic burdens, many of which are related to issues with current diagnosis and treatments. The coronavirus (COVID-19) pandemic is estimated to have increased the prevalence and burden of major depressive and anxiety disorders, indicating an urgent need to strengthen mental health systems globally. To date, current approaches adopted in drug discovery and development for psychiatric disorders have been relatively unsuccessful. Precision psychiatry aims to tailor healthcare more closely to the needs of individual patients and, when informed by neuroscience, can offer the opportunity to improve the accuracy of disease classification, treatment decisions, and prevention efforts. In this review, we highlight the growing global interest in precision psychiatry and the potential for the National Institute of Health-devised Research Domain Criteria (RDoC) to facilitate the implementation of transdiagnostic and improved treatment approaches. The need for current psychiatric nosology to evolve with recent scientific advancements and increase awareness in emerging investigators/clinicians of the value of this approach is essential. Finally, we examine current challenges and future opportunities of adopting the RDoC-associated translational and transdiagnostic approaches in clinical studies, acknowledging that the strength of RDoC is that they form a dynamic framework of guiding principles that is intended to evolve continuously with scientific developments into the future. A collaborative approach that recruits expertise from multiple disciplines, while also considering the patient perspective, is needed to pave the way for precision psychiatry that can improve the prognosis and quality of life of psychiatric patients.

Amplification of mid-IR continuum for broadband 2D IR spectroscopy.

We report the generation and characterization of microjoule level, broad bandwidth femtosecond pulses in the mid-infrared (MIR) using optical parametric amplification of continuum MIR seed pulses in GaSe. The signal (3 µm) and idler (6 µm) pulses have energies of 6 µJ and 3 µJ with bandwidths of ∼950 cm-1 and 650 cm-1 FWHM and pulse lengths of 34 fs and 80 fs. Broadband 2D IR spectra of O-H and N-H transitions are acquired with the signal beam demonstrating the capabilities of this source for cross peak and line shape measurements.

Structural Characterization of Protonated Water Clusters Confined in HZSM-5 Zeolites.

A molecular description of the structure and behavior of water confined in aluminosilicate zeolite pores is a crucial component for understanding zeolite acid chemistry under hydrous conditions. In this study, we use a combination of ultrafast two-dimensional infrared (2D IR) spectroscopy and ab initio molecular dynamics (AIMD) to study H2O confined in the pores of highly hydrated zeolite HZSM-5 (∼13 and ∼6 equivalents of H2O per Al atom). The 2D IR spectrum reveals correlations between the vibrations of both terminal and H-bonded O-H groups and the continuum absorption of the excess proton. These data are used to characterize the hydrogen-bonding network within the cluster by quantifying single-, double-, and non-hydrogen-bond donor water molecules. These results are found to be in good agreement with the statistics calculated from an AIMD simulation of an H+(H2O)8 cluster in HZSM-5. Furthermore, IR spectral assignments to local O-H environments are validated with DFT calculations on clusters drawn from AIMD simulations. The simulations reveal that the excess charge is detached from the zeolite and resides near the more highly coordinated water molecules in the cluster. When they are taken together, these results unambiguously assign the complex IR spectrum of highly hydrated HZSM-5, providing quantitative information on the molecular environments and hydrogen-bonding topology of protonated water clusters under extreme confinement.

Changing trends in Black-White racial differences in surgical menopause: a population-based study.

BACKGROUND: Bilateral oophorectomy before menopause, or surgical menopause, is associated with negative health outcomes, including an increased risk for stroke and other cardiovascular outcomes; however, surgical menopause also dramatically reduces ovarian cancer incidence and mortality rates. Because there are competing positive and negative sequelae associated with surgical menopause, clinical guidelines have not been definitive. Previous research indicates that White women have higher rates of surgical menopause than other racial groups. However, previous studies may have underestimated the rates of surgical menopause among Black women. Furthermore, clinical practice has changed dramatically in the past 15 years, and there are no population-based studies in which more recent data were used. Tracking actual racial differences among women with surgical menopause is important for ensuring equity in gynecologic care. OBJECTIVE: This population-based surveillance study evaluated racial differences in the rates of surgical menopause in all inpatient and outpatient settings in a large, racially diverse US state with historically high rates of hysterectomy. STUDY DESIGN: We evaluated all inpatient and outpatient surgeries in North Carolina from 2011 to 2014 for patients aged between 20 and 44 years. Surgical menopause was defined as a bilateral oophorectomy, with or without an accompanying hysterectomy, among North Carolina residents. International Classification of Diseases, Ninth Revision, and Current Procedural Terminology codes were used to identify inpatient and outpatient procedures, respectively, and diagnostic indications. We estimated age-, race-, and ethnicity-specific rates of surgical menopause using county-specific population estimates based on the 2010 United States census. We used Poisson regression with deviance-adjusted residuals to estimate the incidence rate ratios in the entire state population. We tested changes in surgery rates over time (reference year, 2011), differences by setting (reference, inpatient), and differences by race and ethnicity (reference, non-Hispanic White). We then described the surgery rates between non-Hispanic White and non-Hispanic Black patients. RESULTS: Between 2011 and 2014, 11,502 surgical menopause procedures for benign indications were performed in North Carolina among reproductive-aged residents. Most (95%) of these surgeries occurred concomitant with a hysterectomy. Over the 4-year study period, there was a 39% reduction in inpatient surgeries (incidence rate ratio, 0.61) and a 100% increase in outpatient surgeries (incidence rate ratio, 2.0). Restricting the analysis to surgeries among non-Hispanic White and Black patients, the increase in outpatient surgeries was significantly higher among non-Hispanic Black women (P<.01) for year-race interaction (reference, 2011 and non-Hispanic White). The overall rates of bilateral oophorectomy for non-Hispanic Black women rose more quickly than for non-Hispanic White women (P<.01). In 2011, the rate of surgical menopause was greater among White women than among Black women (17.7 vs 13.2 per 10,000 women). By 2014, the racial trends were reversed (rate, 24.8 per 10,000 for non-Hispanic White women and 28.4 per 10,000 for non-Hispanic Black women). CONCLUSION: Our findings suggest that the rates of surgical menopause increased in North Carolina in the early 2010s, especially among non-Hispanic Black women. By 2014, the rates of surgical menopause among non-Hispanic Black women had surpassed that of non-Hispanic White women. Given the long-term health consequences associated with surgical menopause, we propose potential drivers for the racially-patterned increases in the application of bilateral oophorectomy before the age of 45 years.

The Missouri Physician and Health Professional Wellness Program: A Comprehensive Resource for Physician Wellness.

Burnout is just one of many ways that physicians unintentionally become impaired. This article reviews the relevant literature and issues facing physician wellness and presents information about the Missouri Physician and Health Professional Wellness Program sponsored by the Missouri Association of Osteopathic Physicians (MAOPS) and Capital Region Medical Center in Jefferson City, Missouri. Considerations for when to reach out in addition to information on some of the program's preventative services are provided.

Les progrès dans la réalisation de la classification quantitative de la psychopathologie.

Shortcomings of approaches to classifying psychopathology based on expert consensus have given rise to contemporary efforts to classify psychopathology quantitatively. In this paper, we review progress in achieving a quantitative and empirical classification of psychopathology. A substantial empirical literature indicates that psychopathology is generally more dimensional than categorical. When the discreteness versus continuity of psychopathology is treated as a research question, as opposed to being decided as a matter of tradition, the evidence clearly supports the hypothesis of continuity. In addition, a related body of literature shows how psychopathology dimensions can be arranged in a hierarchy, ranging from very broad "spectrum level" dimensions, to specific and narrow clusters of symptoms. In this way, a quantitative approach solves the "problem of comorbidity" by explicitly modeling patterns of co-occurrence among signs and symptoms within a detailed and variegated hierarchy of dimensional concepts with direct clinical utility. Indeed, extensive evidence pertaining to the dimensional and hierarchical structure of psychopathology has led to the formation of the Hierarchical Taxonomy of Psychopathology (HiTOP) Consortium. This is a group of 70 investigators working together to study empirical classification of psychopathology. In this paper, we describe the aims and current foci of the HiTOP Consortium. These aims pertain to continued research on the empirical organization of psychopathology; the connection between personality and psychopathology; the utility of empirically based psychopathology constructs in both research and the clinic; and the development of novel and comprehensive models and corresponding assessment instruments for psychopathology constructs derived from an empirical approach.

Anti-inflammatory Combination Therapy for the Treatment of Schizophrenia.

BACKGROUND: Despite adequate antipsychotic treatment, most people with schizophrenia continue to exhibit persistent positive and negative symptoms and cognitive impairments. The current study was designed to examine the efficacy and safety of adjunctive anti-inflammatory combination therapy for these illness manifestations. METHODS: Thirty-nine people with either Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision, schizophrenia or schizoaffective disorder were entered into a 12-week double-blind, 2-arm, triple-dummy, placebo-controlled, randomized clinical trial: 19 were randomized to anti-inflammatory combination therapy and 20 were randomized to placebo. The Brief Psychiatric Rating Scale positive symptom item total score was used to assess positive symptom change, the Scale for the Assessment of Negative Symptoms total score was used to assess negative symptom change, the Calgary Depression Scale total score was used to assess depressive symptom change, and the MATRICS Consensus Cognitive Battery was used to assess neuropsychological test performance. RESULTS: There was a significant time effect for Brief Psychiatric Rating Scale positive symptom item score (t226 = -2.66, P = 0.008), but the treatment (t54=1.52, P = 0.13) and treatment × time (t223 = 0.47, P = 0.64) effects were not significant. There were no significant time (t144 = 0.53, P = 0.72), treatment (t58=0.48, P = 0.63), or treatment × time (t143 = -0.20, P = 0.84) effects for the Scale for the Assessment of Negative Symptoms total score; or for any of the other symptom measures. There were no significant group differences in the change in the MATRICS Consensus Cognitive Battery composite score over the course of the study (F1,26=2.20, P = 0.15). CONCLUSIONS: The study results suggest that there is no significant benefit of combined anti-inflammatory treatment for persistent positive symptoms or negative symptoms or cognitive impairments (clinicaltrials.gov trial number: NCT01514682).

Decoding the 2D IR spectrum of the aqueous proton with high-level VSCF/VCI calculations.

The aqueous proton is a common and long-studied species in chemistry, yet there is currently intense interest devoted to understanding its hydration structure and transport dynamics. Typically described in terms of two limiting structures observed in gas-phase clusters, the Zundel H5O2 + and Eigen H9O4 + ions, the aqueous structure is less clear due to the heterogeneity of hydrogen bonding environments and room-temperature structural fluctuations in water. The linear infrared (IR) spectrum, which reports on structural configurations, is challenging to interpret because it appears as a continuum of absorption, and the underlying vibrational modes are strongly anharmonically coupled to each other. Recent two-dimensional IR (2D IR) experiments presented strong evidence for asymmetric Zundel-like motifs in solution, but true structure-spectrum correlations are missing and complicated by the anharmonicity of the system. In this study, we employ high-level vibrational self-consistent field/virtual state configuration interaction calculations to demonstrate that the 2D IR spectrum reports on a broad distribution of geometric configurations of the aqueous proton. We find that the diagonal 2D IR spectrum around 1200 cm-1 is dominated by the proton stretch vibrations of Zundel-like and intermediate geometries, broadened by the heterogeneity of aqueous configurations. There is a wide distribution of multidimensional potential shapes for the proton stretching vibration with varying degrees of potential asymmetry and confinement. Finally, we find specific cross peak patterns due to aqueous Zundel-like species. These studies provide clarity on highly debated spectral assignments and stringent spectroscopic benchmarks for future simulations.

Factors influencing prostate cancer treatment decisions for African American and white men.

BACKGROUND: Prostate cancer racial disparities in mortality outcomes are the largest in all of oncology, and less aggressive treatment received by African American (AA) patients versus white patients is likely a contributing factor. However, the reasons underlying the differences in treatment are unclear. METHODS: This study examined a prospective, population-based cohort of 1170 men with newly diagnosed nonmetastatic prostate cancer enrolled from 2011 to 2013 before treatment throughout North Carolina. By phone survey, each participant was asked to rate the aggressiveness of his cancer, and his response was compared to the actual diagnosis based on a medical record review. Participants were also asked to rate the importance of 10 factors for their treatment decision-making process. RESULTS: Among AA and white patients with low-risk cancer (according to National Comprehensive Cancer Network guidelines), 78% to 80% perceived their cancers to be "not very aggressive." However, among high-risk patients, 54% of AA patients considered their cancers to be "not very aggressive," whereas 24% of white patients did (P < .001). Although both AA and white patients indicated that a cure was a very important decision-making factor, AAs were significantly more likely to consider cost, treatment time, and recovery time as very important. In a multivariable analysis, perceived cancer aggressiveness and cure as the most important factor were significantly associated with receiving any aggressive treatment and were associated with surgery (vs radiation). After adjustments for these factors and sociodemographic factors, race was not significantly associated with the treatment received. CONCLUSIONS: Racial differences in perceived cancer aggressiveness and factors important in treatment decision making provide novel insights into reasons for the known racial disparities in prostate cancer as well as potential targets for interventions to reduce these disparities.

Randomized controlled trial of a gluten-free diet in patients with schizophrenia positive for antigliadin antibodies (AGA IgG): a pilot feasibility study

Background: Approximately one-third of people with schizophrenia have elevated levels of anti-gliadin antibodies of the immunoglobulin G type (AGA IgG) ­ a higher rate than seen in healthy controls. We performed the first double-blind clinical trial of gluten-free versus gluten-containing diets in a subset of patients with schizophrenia who were positive for AGA IgG. Methods: In this pilot feasibility study, 16 participants with schizophrenia or schizoaffective disorder who had elevated AGA IgG (≥ 20 U) but were negative for celiac disease were admitted to an inpatient unit for a 5-week trial. All participants received standardized gluten-free meals and were randomized in a double-blind fashion to receive a shake containing 10 g of gluten flour or 10 g of rice flour each day. Participants were rated for psychiatric, cognitive and gastrointestinal symptoms at baseline and endpoint. Results: Of the 16 participants, 14 completed the 5-week trial (2 discontinued early for administrative reasons). Compared with participants on the gluten-containing diet, participants on the gluten-free diet showed improvement on the Clinical Global Impressions scale (Cohen d = ­0.75) and in negative symptoms (Cohen d = ­0.53). We noted no improvement in positive or global cognitive symptoms, but did observe an improvement in attention favouring the gluten-free diet (Cohen d = 0.60). Robust improvements in gastrointestinal adverse effects occurred in the gluten-free group relative to the glutencontaining group. Adverse effects were similar between groups. Limitations: This study was limited by its small sample size; larger studies are needed. Conclusion: This feasibility study suggests that removal of gluten from the diet is associated with improvement in psychiatric and gastrointestinal symptoms in people with schizophrenia or schizoaffective disorder.

Entropic barriers in the kinetics of aqueous proton transfer.

Aqueous proton transport is uniquely rapid among aqueous processes, mediated by fluctuating hydrogen bond reorganization in liquid water. In a process known as Grotthuss diffusion, the excess charge diffuses primarily by sequential proton transfers between water molecules rather than standard Brownian motion, which explains the anomalously high electrical conductivity of acidic solutions. Employing ultrafast IR spectroscopy, we use the orientational anisotropy decay of the bending vibrations of the hydrated proton complex to study the picosecond aqueous proton transfer kinetics as a function of temperature, concentration, and counterion. We find that the orientational anisotropy decay exhibits Arrhenius behavior, with an apparent activation energy of 2.4 kcal/mol in 1M and 2M HCl. Interestingly, acidic solutions at high concentration with longer proton transfer time scales display corresponding decreases in activation energy. We interpret this counterintuitive trend by considering the entropic and enthalpic contributions to the activation free energy for proton transfer. Halide counteranions at high concentrations impose entropic barriers to proton transfer in the form of constraints on the solution's collective H-bond fluctuations and obstruction of potential proton transfer pathways. The corresponding proton transfer barrier decreases due to weaker water-halide H-bonds in close proximity to the excess proton, but the entropic effects dominate and result in a net reduction in the proton transfer rate. We estimate the activation free energy for proton transfer as ∼1.0 kcal/mol at 280 K.

The Evolution of Cement Fixation in Total Knee Arthroplasty.

Aseptic loosening and infection are two of the leading causes of revision in total knee arthroplasty. While several patient-related factors can play a role in the development of these complications, there are certain modifiable surgeon factors that can help mitigate the risk. Intraoperatively, this can begin with the curing process of bone cement which is broken down into four different stages: mixing, waiting, working, and setting. Understanding each stage of the process is beneficial in obtaining successful long-term outcomes. Developing optimal bone-cement penetration is of utmost importance in establishing a strong interface. Proper penetration of cement is dependent on multiple factors including the cement's properties along with its application to the prosthesis and bone surfaces. Combinations of different cement application techniques have yielded results with varying bone-cement interface strength. While a proper cementation technique is critical to the long-term success of a total knee replacement, other factors, such as antibiotic-loaded bone cement (ALBC), can help prevent and treat complications (such as infection). Although ALBC was not approved in North America by the Food and Drug Administration (FDA) until 2003, it was first described in 1970 and has been routinely used in revision total knee arthroplasty with reliable antibiotic elution properties and an acceptable safety profile.

Anti gliadin antibodies (AGA IgG) related to peripheral inflammation in schizophrenia.

Altered immune function and inflammation are seen in schizophrenia, however, peripheral inflammatory markers are not consistently elevated in all people, suggesting inflammation may be present only in a subgroup. We measured TNF-α and IL-Iß in 100 people with schizophrenia or schizoaffective disorder and correlated these with antibodies to gliadin, a protein found in wheat, barley and rye that has been found to be elevated in some people with schizophrenia. We hypothesized that higher peripheral antigliadin antibodies (AGA IgG) would be associated with higher peripheral inflammation as measured by TNF-α and IL-1ß. Mean log transformed values of TNF-α, (p=.029) and IL-1ß (p=.016) were over twofold higher in people with schizophrenia who had high levels of AGA IgG (≥7 U) compared to those who did not have positivity to AGA IgG. We found a significant positive correlation between AGA IgG and the log transformed TNF-α (r=0.42, p<.0001) as well as IL-Iß (r=0.51, p<.0001). The relationship was independent of cigarette smoking, body mass index and antipsychotic medications. People with schizophrenia having higher levels of AGA IgG show higher levels of peripheral inflammation and may define a subgroup with distinct pathophysiology and potentially novel treatment targets.

Using Procedure Codes to Define Radiation Toxicity in Administrative Data: The Devil is in the Details.

BACKGROUND: Systematic coding systems are used to define clinically meaningful outcomes when leveraging administrative claims data for research. How and when these codes are applied within a research study can have implications for the study validity and their specificity can vary significantly depending on treatment received. SUBJECTS: Data are from the Surveillance, Epidemiology, and End Results-Medicare linked dataset. STUDY DESIGN: We use propensity score methods in a retrospective cohort of prostate cancer patients first examined in a recently published radiation oncology comparative effectiveness study. RESULTS: With the narrowly defined outcome definition, the toxicity event outcome rate ratio was 0.88 per 100 person-years (95% confidence interval, 0.71-1.08). With the broadly defined outcome, the rate ratio was comparable, with 0.89 per 100 person-years (95% confidence interval, 0.76-1.04), although individual event rates were doubled. Some evidence of surveillance bias was suggested by a higher rate of endoscopic procedures the first year of follow-up in patients who received proton therapy compared with those receiving intensity-modulated radiation treatment (11.15 vs. 8.90, respectively). CONCLUSIONS: This study demonstrates the risk of introducing bias through subjective application of procedure codes. Careful consideration is required when using procedure codes to define outcomes in administrative data.

A Randomized Clinical Trial of Oxytocin or Galantamine for the Treatment of Negative Symptoms and Cognitive Impairments in People With Schizophrenia.

PURPOSE/BACKGROUND: Negative symptoms and cognitive impairments tend to co-occur in people with schizophrenia. If their association with each other is due, in part, to shared pathophysiology, then this suggests that a single drug could potentially be effective for both domains. The current study was designed to examine this hypothesis. METHODS/PROCEDURES: Fifty-eight participants with either Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision schizophrenia or schizoaffective disorder entered into a 6-week double-blind, placebo-controlled, double-dummy, randomized clinical trial of intranasal oxytocin and galantamine. Seventeen participants were randomized to intranasal oxytocin, 20 were randomized to galantamine, and 21 were randomized to placebo. The Scale for the Assessment of Negative Symptoms total score was used to assess change in negative symptoms (the primary outcome measure for oxytocin). The MATRICS Consensus Cognitive Battery composite score was used to assess cognition (the primary outcome measure for galantamine). FINDINGS/RESULTS: There were no significant group differences for negative symptoms (oxytocin vs placebo: F2,47.4 = 0.19, P = 0.83; galantamine vs placebo: F2,52.5 = 0.41, P = 0.67). There were no significant group differences for cognitive impairments (galantamine vs placebo: t40 = 0.71, P = 0.48; oxytocin vs placebo: t40 = 0.50, P = 0.62). There were also no significant group differences for the functional capacity or ancillary symptom measures. IMPLICATIONS/CONCLUSIONS: The lack of an efficacy signal for either compound precluded our ability to test whether pharmacological treatment pathways for negative symptoms and cognitive impairments overlap or are independent.

Delocalization and stretch-bend mixing of the HOH bend in liquid water.

Liquid water's rich sub-picosecond vibrational dynamics arise from the interplay of different high- and low-frequency modes evolving in a strong yet fluctuating hydrogen bond network. Recent studies of the OH stretching excitations of H2O indicate that they are delocalized over several molecules, raising questions about whether the bending vibrations are similarly delocalized. In this paper, we take advantage of an improved 50 fs time-resolution and broadband infrared (IR) spectroscopy to interrogate the 2D IR lineshape and spectral dynamics of the HOH bending vibration of liquid H2O. Indications of strong bend-stretch coupling are observed in early time 2D IR spectra through a broad excited state absorption that extends from 1500 cm-1 to beyond 1900 cm-1, which corresponds to transitions from the bend to the bend overtone and OH stretching band between 3150 and 3550 cm-1. Pump-probe measurements reveal a fast 180 fs vibrational relaxation time, which results in a hot-ground state spectrum that is the same as observed for water IR excitation at any other frequency. The fastest dynamical time scale is 80 fs for the polarization anisotropy decay, providing evidence for the delocalized or excitonic character of the bend. Normal mode analysis conducted on water clusters extracted from molecular dynamics simulations corroborate significant stretch-bend mixing and indicate delocalization of δHOH on 2-7 water molecules.

IR spectral assignments for the hydrated excess proton in liquid water.

The local environmental sensitivity of infrared (IR) spectroscopy to a hydrogen-bonding structure makes it a powerful tool for investigating the structure and dynamics of excess protons in water. Although of significant interest, the line broadening that results from the ultrafast evolution of different solvated proton-water structures makes the assignment of liquid-phase IR spectra a challenging task. In this work, we apply a normal mode analysis using density functional theory of thousands of proton-water clusters taken from reactive molecular dynamics trajectories of the latest generation multistate empirical valence bond proton model (MS-EVB 3.2). These calculations are used to obtain a vibrational density of states and IR spectral density, which are decomposed on the basis of solvated proton structure and the frequency dependent mode character. Decompositions are presented on the basis of the proton sharing parameter δ, often used to distinguish Eigen and Zundel species, the stretch and bend character of the modes, the mode delocalization, and the vibrational mode symmetry. We find there is a wide distribution of vibrational frequencies spanning 1200-3000 cm-1 for every local proton configuration, with the region 2000-2600 cm-1 being mostly governed by the distorted Eigen-like configuration. We find a continuous red shift of the special-pair O⋯H+⋯O stretching frequency, and an increase in the flanking water bending intensity with decreasing δ. Also, we find that the flanking water stretch mode of the Zundel-like species is strongly mixed with the flanking water bend, and the special pair proton oscillation band is strongly coupled with the bend modes of the central H5O2+moiety.

For U.S. Black women, shift of hysterectomy to outpatient settings may have lagged behind White women: a claims-based analysis, 2011-2013.

BACKGROUND: Hysterectomy is among the most common surgeries performed on U.S. women. For benign conditions, minimally invasive hysterectomy is recommended, whenever permitted by clinical indication and previous surgery history. No study has examined whether the use of less invasive hysterectomy spread more slowly for Black women. METHODS: We used the hysterectomy that occurs in outpatient settings as a proxy for minimally invasive hysterectomy. Using claims-based surgery data and census denominators, we calculated age-standardized rates of all hysterectomies in North Carolina from 2011 to 2013. Study participants were 41,899 women (64.6% non-Hispanic White, 28.3% non-Hispanic Black) who underwent hysterectomy for non-malignant indications. We fit Poisson models to determine whether changes in outpatient hysterectomy rates differed by Black-White race. We employed a difference-in-difference approach to control for racial differences in the severity of clinical indication. Further, we restricted to one state to minimize confounding from geographic differences in where Black and White women live. RESULTS: From 2011 to 2013, the overall hysterectomy rate decreased from 42.3 per 10,000 women (n = 14,648) to 37.9 per 10,000 (n = 13,241) (p < 0.0001). Most hysterectomy (67.6%) occurred in outpatient settings. The inpatient rate decreased 35.2% (p < 0.0001), to 10.3 per 10,000, while the outpatient rate increased 4.6% (p < 0.01), to 27.5 per 10,000. From 2011 to 2013, Black women's outpatient rate increased 22% (p < 0.0001): from 25.8 per 10,000 to 31.5. In contrast, among White women, outpatient rates remained stable (p = 0.79): at 28.3 per 10,000 in 2013. CONCLUSIONS: Rapid increases in outpatient hysterectomy among Black women compared to stable rates among White women indicate a race-specific catch-up phenomenon in the spread of minimally invasive hysterectomy. These results are consistent with the hypothesis that minimally invasive hysterectomy may have been adopted more slowly for Black women than their White counterparts after its introduction in the early 2000s. The persistently high rates of hysterectomy among young Black women and potentially slower adoption of minimally invasive procedures among these women highlight a potential racial disparity in women's healthcare.