Trends in inpatient antiparkinson drug use in the USA, 2001-2012

Purpose: Although therapeutic options and clinical guidelines for Parkinson's disease (PD) have changed significantly in the past 15 years, prescribing trends in the USA remain unknown. The purpose of this population-based cohort study was to examine patterns of inpatient antiparkinson drug use between January 2001 and December 2012 in relation to clinical guideline publication, drug introduction/withdrawal, and emerging safety concerns. Methods: A total of 16,785 inpatients receiving pharmacological treatment for PD were identified in the Cerner Health Facts database. Our primary outcome was standardized (age, sex, race, and census region) annual prevalence of antiparkinson drug use. We also examined antiparkinson medication trends and polypharmacy by age and sex. Results: The most frequently prescribed antiparkinson drugs between 2001 and 2012 were levodopa (85 %) and dopamine agonists (28 %). Dopamine agonist use began declining in 2007, from 34 to 27 % in 2012. The decline followed publication of the American Academy of Neurology's practice parameter refuting levodopa toxicity, pergolide withdrawal, and pramipexole label revisions. Despite safety concerns for cognitive impairment and falls, individuals = 80 years of age demonstrated stable rates of dopamine agonist use from 2001 to 2012. Polypharmacy was most common in younger patients. Conclusions: Dopamine agonist use declined from 2007 to 2012, suggesting that increased awareness of safety issues and practice guidelines influenced prescribing. These events appear to have minimally influenced treatment provided to older PD patients. Antiparkinson prescribing trends indicate that safety and best practice information may be communicated effectively.Fil: Crispo, James. University of Ottawa; Canadá. University of Pennsylvania; Estados UnidosFil: Fortin, Yannick. University of Ottawa; CanadáFil: Thibault, Dylan P.. University of Pennsylvania; Estados UnidosFil: Emons, Matthew. Cerner Corporation; Estados UnidosFil: Bjerre, Lise M.. University of Ottawa; Canadá. Bruyère Research Institute; CanadáFil: Kohen, Dafna E.. University of Ottawa; CanadáFil: Pérez Lloret, Santiago. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Mattison, Donald. Risk Sciences International; Canadá. University of Ottawa; CanadáFil: Willis, Allison W.. University of Pennsylvania; Estados UnidosFil: Krewski, Daniel. University of Ottawa; Canad

Atomic Resonance and Scattering

Contains research objectives, summary of research and reports on four research projects.Joint Services Electronics Programs (U. S. Army, U. S. Navy, and U. S. Air Force) under Contract DAAB07-71-C-0300National Science Foundation (Grant GP-28679)National Bureau of Standards (Grant NBS2-9011)U. S. Air Force - Office of Scientific Research (Contract F44620-72-C-0057

The Transcription Factor AmrZ Utilizes Multiple DNA Binding Modes to Recognize Activator and Repressor Sequences of Pseudomonas aeruginosa Virulence Genes

AmrZ, a member of the Ribbon-Helix-Helix family of DNA binding proteins, functions as both a transcriptional activator and repressor of multiple genes encoding Pseudomonas aeruginosa virulence factors. The expression of these virulence factors leads to chronic and sustained infections associated with worsening prognosis. In this study, we present the X-ray crystal structure of AmrZ in complex with DNA containing the repressor site, amrZ1. Binding of AmrZ to this site leads to auto-repression. AmrZ binds this DNA sequence as a dimer-of-dimers, and makes specific base contacts to two half sites, separated by a five base pair linker region. Analysis of the linker region shows a narrowing of the minor groove, causing significant distortions. AmrZ binding assays utilizing sequences containing variations in this linker region reveals that secondary structure of the DNA, conferred by the sequence of this region, is an important determinant in binding affinity. The results from these experiments allow for the creation of a model where both intrinsic structure of the DNA and specific nucleotide recognition are absolutely necessary for binding of the protein. We also examined AmrZ binding to the algD promoter, which results in activation of the alginate exopolysaccharide biosynthetic operon, and found the protein utilizes different interactions with this site. Finally, we tested the in vivo effects of this differential binding by switching the AmrZ binding site at algD, where it acts as an activator, for a repressor binding sequence and show that differences in binding alone do not affect transcriptional regulation

Universal DNA methylation age across mammalian tissues

DATA AVAILABILITY STATEMENT : The individual-level data from the Mammalian Methylation Consortium can be accessed from several online locations. All data from the Mammalian Methylation Consortium are posted on Gene Expression Omnibus (complete dataset, GSE223748). Subsets of the datasets can also be downloaded from accession numbers GSE174758, GSE184211, GSE184213, GSE184215, GSE184216, GSE184218, GSE184220, GSE184221, GSE184224, GSE190660, GSE190661, GSE190662, GSE190663, GSE190664, GSE174544, GSE190665, GSE174767, GSE184222, GSE184223, GSE174777, GSE174778, GSE173330, GSE164127, GSE147002, GSE147003, GSE147004, GSE223943 and GSE223944. Additional details can be found in Supplementary Note 2. The mammalian data can also be downloaded from the Clock Foundation webpage: https://clockfoundation.org/MammalianMethylationConsortium. The mammalian methylation array is available through the non-profit Epigenetic Clock Development Foundation (https://clockfoundation.org/). The manifest file of the mammalian array and genome annotations of CpG sites can be found on Zenodo (10.5281/zenodo.7574747). All other data supporting the findings of this study are available from the corresponding author upon reasonable request. The chip manifest files, genome annotations of CpG sites and the software code for universal pan-mammalian clocks can be found on GitHub95 at https://github.com/shorvath/MammalianMethylationConsortium/tree/v2.0.0. The individual R code for the universal pan-mammalian clocks, EWAS analysis and functional enrichment studies can be also found in the Supplementary Code.SUPPLEMENTARY MATERIAL 1 : Supplementary Tables 1–3 and Notes 1–6.SUPPLEMENTARY MATERIAL 2 : Reporting SummarySUPPLEMENTARY MATERIAL 3 : Supplementary Data 1–14.SUPPLEMENTARY MATERIAL 4 : Supplementary Code.Aging, often considered a result of random cellular damage, can be accurately estimated using DNA methylation profiles, the foundation of pan-tissue epigenetic clocks. Here, we demonstrate the development of universal pan-mammalian clocks, using 11,754 methylation arrays from our Mammalian Methylation Consortium, which encompass 59 tissue types across 185 mammalian species. These predictive models estimate mammalian tissue age with high accuracy (r > 0.96). Age deviations correlate with human mortality risk, mouse somatotropic axis mutations and caloric restriction. We identified specific cytosines with methylation levels that change with age across numerous species. These sites, highly enriched in polycomb repressive complex 2-binding locations, are near genes implicated in mammalian development, cancer, obesity and longevity. Our findings offer new evidence suggesting that aging is evolutionarily conserved and intertwined with developmental processes across all mammals.https://www.nature.com/nataginghj2024Zoology and EntomologySDG-15:Life on lan

Pulse Detonation Engine Characterization and Control Using Tunable Diode-Laser Sensors

One of the phenomena limiting the performance of pulse detonation engines (PDEs) is detonation failure due to pulse-to-pulse interference. To better understand and control such interferences, two novel laser diagnostic techniques, based on absorption spectroscopy, have been developed and then used to demonstrate effective realtime control. The rst technique utilizes a tunable diode-laser (TDL) sensor to measure H2O temperature and concentration in the tube tail end at the Naval Postgraduate School’s (NPS) PDE facility and in the tube head end at Stanford University’s (SU) PDE facility. This sensor, capable of measuring temperatures from 300 to 1300 K at 3.33 kHz, reveals the temporal history of temperature for multipulse engines. In its application to the NPS facility, the sensor shows a distinct change in temperature pro le when the engine pulse rate is changed from 5 Hz, where successful detonations are achieved, to 7 Hz, where interference produces undesirable ame holding and subsequent de agrations on some pulses.We observed that the geometry evaluated possessed excess recirculation at the higher pulse rates resulting in ame holding at or near the point of injection. In its application to the SU PDE, this sensor reveals a temperature pro le characteristic of detonation failure that could be used in future control schemes. The second diagnostic technique developed is used to monitor fuel and is employed in an active, real-time control scheme. For this sensor, we monitor the C2H4 (ethylene) concentration at the tail end of the NPS PDE initiator tube, which is operating at 20 Hz. When fuel is detected at the tail end, the sensor sends a signal to re the ignitor. Compared to xed-timing ignitor actuation, this control promotes more consistent detonation initiation and reduces mis re events. These two new laser diagnostic techniques provide useful tools for studying pulse-to-pulse interference and lay the groundwork for future,more advanced TDL-based PDE control strategies.This work was supported by the U.S. Of ce of Naval Research (ONR), with Gabriel Roy as Technical Monitor, under the ONR Multidisciplinary University Research Initiative (MURI) on pulse detonation engines. D. Mattison was supported by the National Science Foundation Graduate Research Fellowship Program. The authors thank D. Netzer at the Rocket Propulsion and Combustion Laboratory at the Naval Postgraduate School for helpful discussions and for hosting visits to demonstrate these diagnostics and control schemes

Associations between anticholinergic burden and adverse health outcomes in Parkinson disease

Background Elderly adults should avoid medications with anticholinergic effects since they may increase the risk of adverse events, including falls, delirium, and cognitive impairment. However, data on anticholinergic burden are limited in subpopulations, such as individuals with Parkinson disease (PD). The objective of this study was to determine whether anticholinergic burden was associated with adverse outcomes in a PD inpatient population. Methods Using the Cerner Health Facts1database, we retrospectively examined anticholinergic medication use, diagnoses, and hospital revisits within a cohort of 16,302 PD inpatients admitted to a Cerner hospital between 2000 and 2011. Anticholinergic burden was computed using the Anticholinergic Risk Scale (ARS). Primary outcomes were associations between ARS score and diagnosis of fracture and delirium. Secondary outcomes included associations between ARS score and 30-day hospital revisits. Results Many individuals (57.8%) were prescribed non-PD medications with moderate to very strong anticholinergic potential. Individuals with the greatest ARS score (4) were morelikely to be diagnosed with fractures (adjusted odds ratio (AOR): 1.56, 95% CI: 1.29-1.88) and delirium (AOR: 1.61, 95% CI: 1.08-2.40) relative to those with no anticholinergic burden. Similarly, inpatients with the greatest ARS score were more likely to visit the emergency department (adjusted hazard ratio (AHR): 1.32, 95% CI: 1.10-1.58) and be readmitted (AHR: 1.16, 95% CI: 1.01-1.33) within 30-days of discharge. Conclusions We found a positive association between increased anticholinergic burden and adverse outcomes among individuals with PD. Additional pharmacovigilance studies are needed to better understand risks associated with anticholinergic medication use in PD.Fil: Crispo, James A. G.. University of Ottawa; Canadá. University of Pennsylvania; Estados UnidosFil: Willis, Allison W.. University of Pennsylvania; Estados UnidosFil: Thibault, Dylan P.. University of Pennsylvania; Estados Unidos. University of Ottawa; CanadáFil: Fortin, Yannick. University of Ottawa; CanadáFil: Hays, Harlen D.. Cerner Corporation; Estados UnidosFil: McNair, Douglas S.. Cerner Corporation; Estados UnidosFil: Bjerre, Lise M.. University of Ottawa; CanadáFil: Kohen, Dafna E.. University of Ottawa; CanadáFil: Pérez Lloret, Santiago. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Cardiológicas; ArgentinaFil: Mattison, Donald R.. University of Ottawa; Canadá. Risk Sciences International; CanadáFil: Krewski, Daniel. University of Ottawa; Canadá. Risk Sciences International; Canad

Integrating socio-economics and ecology: A taxonomy of quantitative methods and a review of their use in agro-ecology

1. Answering many of the critical questions in conservation, development and environmental management requires integrating the social and natural sciences. However, understanding the array of available quantitative methods and their associated terminology presents a major barrier to successful collaboration. 2. We provide an overview of quantitative socio-economic methods that distils their complexity into a simple taxonomy. We outline how each has been used in conjunction with ecological models to address questions relating to the management of socio-ecological systems. 3. We review the application of social and ecological quantitative concepts to agro-ecology and classify the approaches used to integrate the two disciplines. Our review included all published integrated models from 2003 to 2008 in 27 journals that publish agricultural modelling research. Although our focus is on agro-ecology, many of the results are broadly applicable to other fields involving an interaction between human activities and ecology. 4. We found 36 papers that integrated social and ecological concepts in a quantitative model. Four different approaches to integration were used, depending on the scale at which human welfare was quantified. Most models viewed humans as pure profit maximizers, both when calculating welfare and predicting behaviour. 5. Synthesis and applications. We reached two main conclusions based on our taxonomy and review. The first is that quantitative methods that extend predictions of behaviour and measurements of welfare beyond a simple market value basis are underutilized by integrated models. The second is that the accuracy of prediction for integrated models remains largely unquantified. Addressing both problems requires researchers to reach a common understanding of modelling goals and data requirements during the early stages of a project