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Background: Direct-acting oral anticoagulants (DOACs) are recommended to reduce risk of stroke and systemic embolism in patients with non-valvular atrial fibrillation (NVAF). However, DOAC dosing inconsistent with FDA-approved product labels is common and associated with poor clinical outcomes., Objectives: Identify DOAC dosing inconsistent with FDA-approved product labels in ambulatory care patients with NVAF; identify variables associated with dosing lower and higher than label., Design: Retrospective analysis using electronic health records from nine US healthcare systems., Patients: Adults with NVAF receiving DOAC therapy in 2022., Main Measures: Rates of label-inconsistent dosing; multivariable regression analysis to identify demographic and clinical variables associated with dosing lower and higher than label., Key Results: Among 51,128 NVAF patients (56.1% male, 94.3% White, mean [SD] age 73.5 [10.5] years), 5008 (9.8%) were prescribed label-inconsistent doses of DOACs (6.8% lower and 3.0% higher than label). Age ≥ 75 years, renal impairment, and hypertension were significantly associated with inconsistent dosing both higher and lower than label. Female sex and higher weight were significantly associated with dosing lower than label, as were heart failure, vascular or liver disease, and bleeding history. Dosing higher than label was significantly associated with male sex, race (African American/Black), weight < 60 kg, and use of drugs with potential drug-drug interactions. When prescribed by primary care physicians, DOAC doses were 37% (95% CI, 27-49%) more likely to be lower than label and 30% (95% CI, 16-46%) more likely to be higher than label than when prescribed by cardiologists or electrophysiologists. Label-inconsistent dosing varied (6.7 to 15.8%) across participating systems., Conclusions: DOAC dosing inconsistent with label varied by demographics, clinical characteristics, prescriber specialty, and healthcare system, suggesting a need to monitor and assess dosing decisions in NVAF. Identification of variables associated with dosing inconsistencies may enable targeted interventions to ensure label-consistent dosing in vulnerable populations., (© 2024. The Author(s).)

Smell deficits and neurobiological changes in the olfactory bulb (OB) and olfactory epithelium (OE) have been observed in schizophrenia and related disorders. The OE is the most peripheral olfactory system located outside the cranium, and is connected with the brain via direct neuronal projections to the OB. Nevertheless, it is unknown whether and how a disturbance of the OE affects the OB in schizophrenia and related disorders. Addressing this gap would be the first step in studying the impact of OE pathology in the disease pathophysiology in the brain. In this cross-species study, we observed that chronic, local OE inflammation with a set of upregulated genes in an inducible olfactory inflammation (IOI) mouse model led to a volume reduction, layer structure changes, and alterations of neuron functionality in the OB. Furthermore, IOI model also displayed behavioral deficits relevant to negative symptoms (avolition) in parallel to smell deficits. In first episode psychosis (FEP) patients, we observed a significant alteration in immune/inflammation-related molecular signatures in olfactory neuronal cells (ONCs) enriched from biopsied OE and a significant reduction in the OB volume, compared with those of healthy controls (HC). The increased expression of immune/inflammation-related molecules in ONCs was significantly correlated to the OB volume reduction in FEP patients, but no correlation was found in HCs. Moreover, the increased expression of human orthologues of the IOI genes in ONCs was significantly correlated with the OB volume reduction in FEP, but not in HCs. Together, our study implies a potential mechanism of the OE-OB pathology in patients with psychotic disorders (schizophrenia and related disorders). We hope that this mechanism may have a cross-disease implication, including COVID-19-elicited mental conditions that include smell deficits., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Although opportunities for pharmacy technicians may be expanding, an increasing number of technicians have transitioned out of their roles. It is important to consider what could be done within education and training to promote the retention of pharmacy technicians., Objectives: The purpose of this study was to survey pharmacy technicians in the state of Ohio to identify key components of professional development., Methods: A survey was distributed through REDCap to 24,444 pharmacy technicians with active pharmacy technician licenses in the state of Ohio. Inclusion criteria required survey respondents to be at least 18 years old and currently working as a pharmacy technician., Results: A total of 1386 surveys were fully completed (approximately 6% response rate). Professional development opportunities provided by employers varied across most practice sites, but continuing education was the most reported opportunity. Attending conferences, taking specialized training courses, and tuition reimbursement were less common. The top 3 barriers to professional development participation included additional cost, time, and perceived value. Guidance and mentorship from peers, achieving national certification, and formal on-the-job training were the most helpful in job preparation and training. The main reasons to achieve certification included increased pay, development opportunity, or employer requirement. When considering preparation for new roles, 57% of pharmacy technicians felt prepared or very prepared for the job after 90 days. As technicians continued throughout their careers, the training transitioned from formal hands-on training to self-guided training., Conclusion: Pharmacy technicians have a desire to remain in their roles, but participation in professional development opportunities was lacking owing to availability of options and barriers. Pharmacy practice sites interested in retaining technicians should invest in offering and encouraging pharmacy technicians to participate in development opportunities. To continue to develop pharmacy technicians, ongoing education and training tied to increased compensation may improve retention and foster an improved learning environment., Competing Interests: Disclosure The authors declare no relevant conflicts of interest or financial relationships., (Copyright © 2023 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.)

Human generated environmental change profoundly affects organisms that reside across diverse ecosystems. Although nervous systems evolved to flexibly sense, respond, and adapt to environmental change, it is unclear whether the rapid rate of environmental change outpaces the adaptive capacity of complex nervous systems. Here, we explore neural systems mediating responses to, or impacted by, changing environments, such as those induced by global heating, sensory pollution, and changing habitation zones. We focus on rising temperature and accelerated changes in environments that impact sensory experience as examples of perturbations that directly or indirectly impact neural function, respectively. We also explore a mechanism involved in cross-species interactions that arises from changing habitation zones. We demonstrate that anthropogenic influences on neurons, circuits, and behaviors are widespread across taxa and require further scientific investigation to understand principles underlying neural resilience to accelerating environmental change. SIGNIFICANCE STATEMENT Neural systems evolved over hundreds of millions of years to allow organisms to sense and respond to their environments - to be receptive and responsive, yet flexible. Recent rapid, human-generated environmental changes are testing the limits of the adaptive capacity of neural systems. This presents an opportunity and an urgency to understand how neurobiological processes, including molecular, cellular, and circuit-level mechanisms, are vulnerable or resilient to changing environmental conditions. We showcase examples that range from molecular to circuit to behavioral levels of analysis across several model species, framing a broad neuroscientific approach to explore topics of neural adaptation, plasticity, and resilience. We believe this emerging scientific area is of great societal and scientific importance and will provide a unique opportunity to reexamine our understanding of neural adaptation and the mechanisms underlying neural resilience., (Copyright © 2023 the authors.)

Children with autism often have difficulty with Theory of Mind (ToM), the ability to infer mental states, and pragmatic skills, the contextual use of language. Neuroimaging research suggests ToM and pragmatic skills overlap, as the ability to understand another's mental state is a prerequisite to interpersonal communication. To our knowledge, no study in the last decade has examined this overlap further. To assess the emerging consensus across neuroimaging studies of ToM and pragmatic skills in autism, we used coordinate-based activation likelihood estimation (ALE) analysis of 35 functional magnetic resonance imaging (MRI) studies (13 pragmatic skills, 22 ToM), resulting in a meta-analysis of 1,295 participants (647 autistic, 648 non-autistic) aged 7 to 49 years. Group difference analysis revealed decreased left inferior frontal gyrus (LIFG) activation in autistic participants during pragmatic skills tasks. For ToM tasks, we found reduced anterior cingulate cortex (ACC), medial prefrontal cortex (MPFC), and temporoparietal junction (TPJ) activation in autistic participants. Collectively, both ToM and pragmatic tasks showed activation in IFG and superior temporal gyrus (STG) and a reduction in left hemispheric activation in autistic participants. Overall, the findings underscore the cognitive and neural processing similarities between ToM and pragmatic skills, and their underlying neurobiological differences in autism.

To date, comparisons between the balloon-expandable Edwards Sapien S3 (S3) versus the self-expanding Evolut R or PRO (Evolut) valves have been limited with respect to procedural outcomes. We aim to compare the safety, efficacy, and procedural efficiency of the S3 versus the Medtronic Evolut bioprostheses in patients who underwent transcatheter aortic valve implantation for severe aortic stenosis. Retrospective analysis was performed of all consecutive transcatheter aortic valve implantation procedures performed through the transfemoral approach with either S3 or Evolut at our hospital between September 2015 and January 2019. A total of 581 patients were included. There were no significant differences between S3 (n = 452) and Evolut (n = 129) concerning in-hospital or 30-day safety outcomes. S3 was associated with significantly shorter fluoroscopy times, lower fluoroscopy Air Kerma, and higher contrast use. S3 had lower postprocedure aortic valve area (1.71 ± 0.45 vs 1.84 ± 0.50 cm 2 , p = 0.004), larger peak gradient at 30 days (10.7 ± 3.8 vs 7.0 ± 3.2 mm Hg, p <0.001), and lower aortic regurgitation (AR) rates postprocedure (47% vs 33%, p = 0.024) and at 30 days (50% vs 33%, p = 0.008), driven by mild AR. Device type was an independent predictor of AR postprocedure and at 30 days. Patients with ≥mild AR were more likely to have had Evolut valves (odds ratio = 2.94, p <0.001), especially in larger valves (>26 mm). Severe prosthesis-patient mismatch was higher in S3 (14.8% vs 7.9%, p <0.001). In conclusion, S3 is associated with less radiation exposure, higher contrast use, and lower incidence of AR at 30 days. Alternately, S3 has a higher transaortic gradient at 30 days, and higher levels of severe prosthesis-patient mismatch., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The purpose of this article was to report on the nurse liaison role developed at a 400-bed community hospital in response to a previously published best practice project on the effect of family visitation in the PACU on family member anxiety. The evidence resulted in the development of the nurse liaison role, which changed nursing practice and involved each area of perioperative services as we embarked on family-centered care (FCC). The nurse liaison program has served as a model for other hospital departments as well as area hospitals. Guidelines for implementation of the program, which included FCC, are discussed as well as job guidelines, job descriptions, challenges, and outcomes., (Copyright © 2016 American Society of PeriAnesthesia Nurses. Published by Elsevier Inc. All rights reserved.)

Background: New approaches to ovarian cancer are needed to improve survival. Wilms' tumour 1 (WT1) is a tumour-associated antigen expressed in many ovarian cancers. P53 is also often altered. The clinical significance of the combined expression of these two transcription factors has not been studied., Methods: One hundred ninety-six ovarian tumours were classified histopathologically. Tumours were stained for WT1 and p53 immunohistochemically. Stains were analysed according to tumour type, grade and FIGO stage. Kaplan-Meier analyses on 96 invasive carcinomas determined whether categorical variables were related to survival., Results: WT1 and p53 were related to ovarian tumour type, grade, FIGO stage and patient survival. Uniform nuclear p53 expression was associated with invasion and WT1 expression was associated with advanced grade, FIGO stage and poor survival. When WT1 and p53 were both in the age-adjusted Cox model, WT1 was significant while p53 was not. When we combined tumours expressing WT1 and p53, then adjusted for age and tumour subtype, the hazard ratio compared to tumours without WT1 and with normal p53 was 2.70; when adjusted for age and FIGO stage, the hazard ratio was 2.40., Conclusions: WT1, an antigen target, is a biomarker for poor prognosis, particularly when combined with altered p53.

The neuropeptide PDF promotes the normal sequencing of circadian behavioral rhythms in Drosophila, but its signaling mechanisms are not well understood. We report daily rhythmicity in responsiveness to PDF in critical pacemakers called small LNvs. There is a daily change in potency, as great as 10-fold higher, around dawn. The rhythm persists in constant darkness and does not require endogenous ligand (PDF) signaling or rhythmic receptor gene transcription. Furthermore, rhythmic responsiveness reflects the properties of the pacemaker cell type, not the receptor. Dopamine responsiveness also cycles, in phase with that of PDF, in the same pacemakers, but does not cycle in large LNv. The activity of RalA GTPase in s-LNv regulates PDF responsiveness and behavioral locomotor rhythms. Additionally, cell-autonomous PDF signaling reversed the circadian behavioral effects of lowered RalA activity. Thus, RalA activity confers high PDF responsiveness, providing a daily gate around the dawn hours to promote functional PDF signaling., (Copyright © 2016 Elsevier Inc. All rights reserved.)

The dialysis patient is prone to elevations in the calcium phosphorus product and hyperparathyroidism, which contributes to valvular and vascular calcification. We present the case of a young lady on chronic dialysis that developed mitral calcification complicated by severe mitral stenosis, caseous calcification and retinal embolization. She subsequently required mitral valve replacement., (© 2013 International Society for Hemodialysis.)

We report measurements of the gain and phase-conjugation fidelity of a nondegenerate four-wave Brillouin mirror (FWBM) based on high-pressure methane. In the experiments we used a Nd:YAG laser that produced single-mode pulses of 13-nsec duration. Depending on the energy of the pump we measured signal reflectivities between 10 and 10(3), constant over six orders of magnitude of signal energy. We also determined the conjugation fidelity of the FWBM by measuring the Strehl ratio of the conjugated return as a function of the energy of the input signal. We show that the Strehl ratio reduces to 0.5 for an input energy of 1.5 x 10(-13) J/mode of the FWBM. This noise-equivalent signal energy constitutes the limiting sensitivity of the FWBM. Our experiments show that a gas-filled FWBM could be used as a phase conjugator and high-repetition-rate optical image intensifier.