Adverse Outcomes Associated with Psychotropic Medication Usage in Nursing Homes

The elderly population is growing in nursing homes (NHs), with an estimated 3 million seniors to be residing in NH facilities by year 2030. Many of these seniors are potentially at risk for falls or infections. NH residents with Alzheimer’s disease or other forms of dementia are also increasing, and they are vulnerable to the adverse effects of medications. Psychotropics are overused in NHs, with approximately half to two thirds of residents receiving one or more psychotropics. Many negative health outcomes, e.g. falls and infections, have been associated with their use. The usage of psychotropic medications among NH residents has been a concern and topic of scrutiny for nearly three decades. In 1986, the Institute of Medicine published a landmark report that identified the overuse of psychotropic medications in NHs. The following year, the federal government passed the Omnibus Budget Reconciliation Act that included reform legislation to address psychotropic drug overuse. Since then, additional policies and initiatives have endeavored to rectify the problem, and scientists have conducted research regarding psychotropics and negative health outcomes. However, newer research within the last decade and at a national level is lacking. Therefore, this dissertation explores the association of psychotropic medications with falls and infections among NH residents using a national dataset, and this document is organized into five chapters. The first chapter discusses the background, significance, and current challenges surrounding psychotropic medication use in NHs. The second chapter delineates the search of the literature and relevant findings. The third chapter describes the methodology upon which this analytics of this dissertation was conducted. The fourth chapter outlines the results from the analyses. Lastly, the fifth chapter provides a synthesis and discussion of the findings and recommendations for health policy, practice, and future research

Effects of the physical state of tropospheric ammonium-sulfate-nitrate particles on global aerosol direct radiative forcing

The effect of aqueous versus crystalline sulfate-nitrate-ammonium tropospheric particles on global aerosol direct radiative forcing is assessed. A global three-dimensional chemical transport model predicts sulfate, nitrate, and ammonium aerosol mass. An aerosol thermodynamics model is called twice, once for the upper side (US) and once for lower side (LS) of the hysteresis loop of particle phase. On the LS, the sulfate mass budget is 40% solid ammonium sulfate, 12% letovicite, 11% ammonium bisulfate, and 37% aqueous. The LS nitrate mass budget is 26% solid ammonium nitrate, 7% aqueous, and 67% gas-phase nitric acid release due to increased volatility upon crystallization. The LS ammonium budget is 45% solid ammonium sulfate, 10% letovicite, 6% ammonium bisulfate, 4% ammonium nitrate, 7% ammonia release due to increased volatility, and 28% aqueous. LS aerosol water mass partitions as 22% effloresced to the gas-phase and 78% remaining as aerosol mass. The predicted US/LS global fields of aerosol mass are employed in a Mie scattering model to generate global US/LS aerosol optical properties, including scattering efficiency, single scattering albedo, and asymmetry parameter. Global annual average LS optical depth and mass scattering efficiency are, respectively, 0.023 and 10.7 m² (g SO₄^-2)^-1, which compare to US values of 0.030 and 13.9 m² (g SO₄^-2)^-1. Radiative transport is computed, first for a base case having no aerosol and then for the two global fields corresponding to the US and LS of the hysteresis loop. Regional, global, seasonal, and annual averages of top-of-the-atmosphere aerosol radiative forcing on the LS and US (<i>F_L </i> and <i>F_U</i>, respectively, in W m^-2) are calculated. Including both anthropogenic and natural emissions, we obtain global annual averages of <i>F_L</i>=-0.750, <i>F_U</i>=-0.930, and <font face='Symbol'>D</font><i>F_U,L</i>=24% for full sky calculations without clouds and <i>F_L</i>=-0.485, <i>F_U</i>=-0.605, and <font face='Symbol'>D</font><i>F_U,L</i>=25% when clouds are included. Regionally, <font face='Symbol'>D</font><i>F_U,L</i>=48% over the USA, 55% over Europe, and 34% over East Asia. Seasonally, <font face='Symbol'>D</font><i>F_U,L</i>varies from 18% in DJF to 75% in SON over the USA. The global annual average contribution from anthropogenic aerosol is <i>F_L</i>=-0.314 and <i>F_U</i>=-0.404, which yield normalized direct radiative forcings (<i>G</i>) of <i>G_L</i>=-205 W (g SO₄^-2)^-1 and <i>G_U</i>=-264 W (g SO₄^-2)^-1

Preliminary Findings from an Interventional Study using Network Analysis to Support Management in Local Health Departments in Florida

Management is the core service that integrates and coordinates essential public health services. Managers of local health departments (LHDs) are experts in practice but may not have expertise in organizational management. We conducted an evidence-based training intervention in 10 LHDs in Florida to support managers’ decision-making on organizational integration and coordination. We deployed a standard survey to collect organizational network measurements pre and post intervention. We presented results as evidence-based performance feedback and interviewed managers to document how they used the results in the context of each organization. Post intervention we found unexpected, significantly higher network centralization in daily work. We attributed this increase in hierarchical communication to preparations for a statewide accreditation initiative. When QI initiatives are undertaken globally within a state, managers and leaders need to be alert for possible impact on autonomous decision-making of professionals at the point of service which could affect service delivery

Epigenetic suppression of hippocampal calbindin-D28k by ΔFosB drives seizure-related cognitive deficits.

The calcium-binding protein calbindin-D28k is critical for hippocampal function and cognition, but its expression is markedly decreased in various neurological disorders associated with epileptiform activity and seizures. In Alzheimer\u27s disease (AD) and epilepsy, both of which are accompanied by recurrent seizures, the severity of cognitive deficits reflects the degree of calbindin reduction in the hippocampal dentate gyrus (DG). However, despite the importance of calbindin in both neuronal physiology and pathology, the regulatory mechanisms that control its expression in the hippocampus are poorly understood. Here we report an epigenetic mechanism through which seizures chronically suppress hippocampal calbindin expression and impair cognition. We demonstrate that ΔFosB, a highly stable transcription factor, is induced in the hippocampus in mouse models of AD and seizures, in which it binds and triggers histone deacetylation at the promoter of the calbindin gene (Calb1) and downregulates Calb1 transcription. Notably, increasing DG calbindin levels, either by direct virus-mediated expression or inhibition of ΔFosB signaling, improves spatial memory in a mouse model of AD. Moreover, levels of ΔFosB and calbindin expression are inversely related in the DG of individuals with temporal lobe epilepsy (TLE) or AD and correlate with performance on the Mini-Mental State Examination (MMSE). We propose that chronic suppression of calbindin by ΔFosB is one mechanism through which intermittent seizures drive persistent cognitive deficits in conditions accompanied by recurrent seizures

Effects of the physical state of tropospheric ammonium-sulfate-nitrate particles on global aerosol direct radiative forcing

International audienceThe effect of aqueous versus crystalline sulfate-nitrate-ammonium tropospheric particles on global aerosol direct radiative forcing is assessed. A global three-dimensional chemical transport model predicts sulfate, nitrate, and ammonium aerosol mass. An aerosol thermodynamics model is called twice, once for the upper side (US) and once for lower side (LS) of the hysteresis loop of particle phase. On the LS, the sulfate mass budget is 40% solid ammonium sulfate, 12% letovicite, 11% ammonium bisulfate, and 37% aqueous. The LS nitrate mass budget is 26% solid ammonium nitrate, 7% aqueous, and 67% gas-phase nitric acid release due to increased volatility upon crystallization. The LS ammonium budget is 45% solid ammonium sulfate, 10% letovicite, 6% ammonium bisulfate, 4% ammonium nitrate, 7% ammonia release due to increased volatility, and 28% aqueous. LS aerosol water mass partitions as 22% effloresced to the gas-phase and 78% remaining as aerosol mass. The predicted US/LS global fields of aerosol mass are employed in a Mie scattering model to generate global US/LS aerosol optical properties, including scattering efficiency, single scattering albedo, and asymmetry parameter. Global annual average LS optical depth and mass scattering efficiency are, respectively, 0.023 and 10.7 m2 (g SO42?)?1, which compare to US values of 0.030 and 13.9 m2 (g SO42?)?1. Radiative transport is computed, first for a base case having no aerosol and then for the two global fields corresponding to the US and LS of the hysteresis loop. Regional, global, seasonal, and annual averages of top-of-the-atmosphere aerosol radiative forcing on the LS and US (FL and FU, respectively, in W m2?) are calculated. Including both anthropogenic and natural emissions, we obtain global annual averages of FL = ?0.750, FU = ?0.930, and ?FU,L = 24% for full sky calculations without clouds and FL = ?0.485, FU = ?0.605, and ?FU,L = 25% when clouds are included. Regionally, ?FU,L = 48% over the USA, 55% over Europe, and 34% over East Asia. Seasonally, ?FU,L varies from 18% in DJF to 75% in SON over the USA. The global annual average contribution from anthropogenic aerosol is FL = ?0.314 and FU = ?0.404, which yield normalized direct radiative forcings (G) of GL = ?205 W (g SO42?)?1 and GU = ?264 W (g SO42?)?1

Effects of the physical state of tropospheric ammonium-sulfate-nitrate particles on global aerosol direct radiative forcing

International audienceThe effect of aqueous versus crystalline sulfate-nitrate-ammonium tropospheric particles on global aerosol direct radiative forcing is assessed. A global three-dimensional chemical transport model predicts sulfate, nitrate, and ammonium aerosol mass. An aerosol thermodynamics model is called twice, once for the upper side (US) and once for lower side (LS) of the hysteresis loop of particle phase. On the LS, the sulfate mass budget is 40% solid ammonium sulfate, 12% letovicite, 11% ammonium bisulfate, and 37% aqueous. The LS nitrate mass budget is 26% solid ammonium nitrate, 7% aqueous, and 67% gas-phase nitric acid release due to increased volatility upon crystallization. The LS ammonium budget is 45% solid ammonium sulfate, 10% letovicite, 6% ammonium bisulfate, 4% ammonium nitrate, 7% ammonia release due to increased volatility, and 28% aqueous. LS aerosol water mass partitions as 22% effloresced to the gas-phase and 78% remaining as aerosol mass. The predicted US/LS global fields of aerosol mass are employed in a Mie scattering model to generate global US/LS aerosol optical properties, including scattering efficiency, single scattering albedo, and asymmetry parameter. Global annual average LS optical depth and mass scattering efficiency are, respectively, 0.023 and 10.7 m2 (g SO4-2)-1, which compare to US values of 0.030 and 13.9 m2 (g SO4-2)-1. Radiative transport is computed, first for a base case having no aerosol and then for the two global fields corresponding to the US and LS of the hysteresis loop. Regional, global, seasonal, and annual averages of top-of-the-atmosphere aerosol radiative forcing on the LS and US (FL and FU, respectively, in W m-2) are calculated. Including both anthropogenic and natural emissions, we obtain global annual averages of FL=-0.750, FU=-0.930, and DFU,L=24% for full sky calculations without clouds and FL=-0.485, FU=-0.605, and DFU,L=25% when clouds are included. Regionally, DFU,L=48% over the USA, 55% over Europe, and 34% over East Asia. Seasonally, DFU,L varies from 18% in DJF to 75% in SON over the USA. The global annual average contribution from anthropogenic aerosol is FL=-0.314 and FU=-0.404, which yield normalized direct radiative forcings (G) of GL=-205 W (g SO4-2)-1 and GU=-264 W (g SO4-2)-1

Mono-anionic phosphopeptides produced by unexpected histidine alkylation exhibit high plk1 polo-box domain-binding affinities and enhanced antiproliferative effects in hela cells

Binding of polo-like kinase 1 (Plk1) polo-box domains (PBDs) to phosphothreonine (pThr)/phosphoserine (pSer)-containing sequences is critical for the proper function of Plk1. Although high-affinity synthetic pThr-containing peptides provide starting points for developing PBD-directed inhibitors, to date the efficacy of such peptides in whole cell assays has been poor. This potentially reflects limited cell membrane permeability arising, in part, from the di-anionic nature of the phosphoryl group or its mimetics. In our current article we report the unanticipated on-resin N(τ)-alkylation of histidine residues already bearing a N(π)- alkyl group. This resulted in cationic imidazolium-containing pThr peptides, several of which exhibit single-digit nanomolar PBD-binding affinities in extracellular assays and improved antimitotic efficacies in intact cells. We enhanced the cellular efficacies of these peptides further by applying bio-reversible pivaloyloxymethyl (POM) phosphoryl protection. New structural insights presented in our current study, including the potential utility of intramolecular charge masking, may be useful for the further development of PBD-binding peptides and peptide mimetics.National Institutes of Health (U.S.) (Grants ES015339 and GM104047

Nonparametric nonlinear model predictive control

Model Predictive Control (MPC) has recently found wide acceptance in industrial applications, but its potential has been much impeded by linear models due to the lack of a similarly accepted nonlinear modeling or databased technique. Aimed at solving this problem, the paper addresses three issues: (i) extending second-order Volterra nonlinear MPC (NMPC) to higher-order for improved prediction and control; (ii) formulating NMPC directly with plant data without needing for parametric modeling, which has hindered the progress of NMPC; and (iii) incorporating an error estimator directly in the formulation and hence eliminating the need for a nonlinear state observer. Following analysis of NMPC objectives and existing solutions, nonparametric NMPC is derived in discrete-time using multidimensional convolution between plant data and Volterra kernel measurements. This approach is validated against the benchmark van de Vusse nonlinear process control problem and is applied to an industrial polymerization process by using Volterra kernels of up to the third order. Results show that the nonparametric approach is very efficient and effective and considerably outperforms existing methods, while retaining the original data-based spirit and characteristics of linear MPC