The Ally Principle and Bureaucratic Structure

Abstract Existing theories of legislative delegation feature various spatial models in which a principal chooses a single agent to whom to delegate authority and …nd that the ally principle holds-the principal picks the ideologically closest agent. However, Congress typically decides whether to delegate not to an individual but to an institution, which consists of many individuals with di¤ering preferences. To improve on existing models, I design models of delegation without assuming that bureaucracies are unitary actors. Results show that the ally principle does not hold when bureaucratic structure is incorporated. The principal is often better o¤ by delegating to non-allies rather than allies. And delegation is not necessarily more likely to occur when the ideological distance between the principal and the agency head is smaller. Internal structures of bureaucracies, which are ignored in existing literature, should be taken into account in studies of delegation

Fecal Pharmacokinetics and Gut Microbiome Effects of oral Omadacycline Versus Vancomycin in Healthy Volunteers

BACKGROUND: Clostridioides difficile infection (CDI) is a common healthcare-associated infection with limited treatment options. Omadacycline, an aminomethylcycline tetracycline, has potent in vitro activity against C difficile and a low propensity to cause CDI in clinical trials. We aimed to assess fecal pharmacokinetics and gut microbiome effects of oral omadacycline compared to oral vancomycin in healthy adults. METHODS: This was a phase 1, nonblinded, randomized clinical trial conducted in healthy volunteers aged 18-40 years. Subjects received a 10-day course of omadacycline or vancomycin. Stool samples were collected at baseline, daily during therapy, and at follow-up visits. Omadacycline and vancomycin stool concentrations were assessed, and microbiome changes were compared. RESULTS: Sixteen healthy volunteers with a mean age of 26 (standard deviation [SD], 5) years were enrolled; 62.5% were male, and participants\u27 mean body mass index was 23.5 (SD, 4.0) kg/m2. Omadacycline was well tolerated with no safety signal differences between the 2 antibiotics. A rapid initial increase in fecal concentrations of omadacycline was observed compared to vancomycin, with maximum concentrations achieved within 48 hours. A significant difference in alpha diversity was observed following therapy in both the omadacycline and vancomycin groups (P \u3c .05). Bacterial abundance and beta diversity analysis showed differing microbiome changes in subjects who received omadacycline versus vancomycin. CONCLUSIONS: Subjects given omadacycline had high fecal concentrations with a distinct microbiome profile compared to vancomycin. CLINICAL TRIALS REGISTRATION: NCT06030219

Childhood adversity and late-life depression: moderated mediation model of stress and social support

BackgroundAs life expectancy increases, understanding the mechanism for late-life depression and finding a crucial moderator becomes more important for mental health in older adults. Childhood adversity increases the risk of clinical depression even in old age. Based on the stress sensitivity theory and stress-buffering effects, stress would be a significant mediator, while social support can be a key moderator in the mediation pathways. However, few studies have tested this moderated mediation model with a sample of older adults. This study aims to reveal the association between childhood adversity and late-life depression in older adults, taking into consideration the effects of stress and social support.MethodsThis study used several path models to analyze the data from 622 elderly participants who were never diagnosed with clinical depression.ResultsWe found that childhood adversity increases the odds ratio of depression by approximately 20% in older adults. Path model with mediation demonstrates that stress fully mediates the pathway from childhood adversity to late-life depression. Path model with moderated mediation also illustrates that social support significantly weakens the association between childhood adversity and perceived stress.ConclusionThis study provides empirical evidence to reveal a more detailed mechanism for late-life depression. Specifically, this study identifies one crucial risk factor and one protective factor, stress and social support, respectively. This brings insight into prevention of late-life depression among those who have experienced childhood adversity

Real-world, Multicenter Experience With Meropenem-Vaborbactam for Gram-Negative Bacterial Infections Including Carbapenem-Resistant Enterobacterales and Pseudomonas Aeruginosa

Background: We aimed to describe the clinical characteristics and outcomes of patients treated with meropenem-vaborbactam (MEV) for a variety of gram-negative infections (GNIs), primarily including carbapenem-resistant Enterobacterales (CRE). Methods: This is a real-world, multicenter, retrospective cohort within the United States between 2017 and 2020. Adult patients who received MEV for ≥72 hours were eligible for inclusion. The primary outcome was 30-day mortality. Classification and regression tree analysis (CART) was used to identify the time breakpoint (BP) that delineated the risk of negative clinical outcomes (NCOs) and was examined by multivariable logistic regression analysis (MLR). Results: Overall, 126 patients were evaluated from 13 medical centers in 10 states. The most common infection sources were respiratory tract (38.1%) and intra-abdominal (19.0%) origin, while the most common isolated pathogens were CRE (78.6%). Thirty-day mortality and recurrence occurred in 18.3% and 11.9%, respectively. Adverse events occurred in 4 patients: nephrotoxicity (n = 2), hepatoxicity (n = 1), and rash (n = 1). CART-BP between early and delayed treatment was 48 hours (P = .04). MEV initiation within 48 hours was independently associated with reduced NCO following analysis by MLR (adusted odds ratio, 0.277; 95% CI, 0.081-0.941). Conclusions: Our results support current evidence establishing positive clinical and safety outcomes of MEV in GNIs, including CRE. We suggest that delaying appropriate therapy for CRE significantly increases the risk of NCOs

The effect of sex and physical frailty on incident disability after 2 years among community-dwelling older adults: KFACS study

Background : This study investigated the impact of physical frailty on the development of disabilities in mobility, activities of daily living (ADL), and instrumental activities of daily living (IADL) according to sex among community-dwelling Korean older adults. Methods : We used data of 2,905 older adults aged 70-84 years from the Korean Frailty and Aging Cohort Study (KFACS) at baseline (2016-2017) and Wave 2 (2018-2019). Fried’s physical frailty phenotype was used to identify frailty. Results : After adjustment, frailty showed a higher impact for women than men on developing mobility disability (odds ratio [OR]=14.00, 95% confidence interval [CI]=4.8–40.78 vs. OR=9.89, 95% CI=4.28–22.86) and IADL disability after two years (OR=7.22, 95% CI=2.67–19.56 vs. OR=3.19, 95% CI=1.17–8.70). Pre-frailty led to mobility disability for women and men (OR=2.77, 95% CI=1.93–3.98 vs. OR=2.49, 95% CI=1.66–3.72, respectively), and IADL disability only for women (OR=3.01, 95% CI=1.28–7.09). Among the IADL components, both men and women who were prefrail or frail showed increased disability in ‘using transportation’. Among men, pre-frailty was significantly associated with disability in “going out” and “shopping”. In women, frailty was significantly associated with disability in “doing laundry,” “performing household chores,” “shopping,” and “managing money”. Conclusions : Physical frailty increased disability over 2 years for women more than men. Physical frailty increased disability in outdoor activity-related IADL components in men and household work-related IADL components in women. This study highlights the need for gender-specific policies and preventative programs for frailty, particularly restorative interventions that focus on women who are physically frail.This research was supported by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), which is funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HI15C3153), and the Research Program funded by the National Institute of Health, Korea Disease Control and Prevention Agency (2021-ER060500). The funding bodies had no role in the study design the collection, analysis and interpretation of the data; the writing of the report; or the decision to submit this article for publication

Replication data for: Non-uniqueness of the Equilibrium in Lewis and Schultz's Model

The source code below is used for the simulations reported in Jo (2011, Non-uniqueness of the Equilibrium in Lewis and Schultz's Model). The simulation is intended to show that when there are multiple equilibria, the parameter estimates may not get closer to their true values even if the number of observations increases

Replication Data for: Anchors Away: A New Approach for Estimating Ideal Points Comparable across Time and Chambers

Replication Data and Code for "Anchors Away: A New Approach for Estimating Ideal Points Comparable across Time and Chambers

Spatially controlled silica coating in poly(dimethylsiloxane) microchannels with the sol-gel process

This study presents spatially controlled silica coating in poly(dimethylsiloxane) (PDMS) microchannels using the well-known sol-gel process. First, the corona discharge between two Pt electrodes inserted into the microchannels generated silanol groups at the desired location for further modifications. Next, the cross-linking of the silanol groups with silica sol produced a chemically bonded silica surface in the PDMS microchannels. After any remaining unreacted silica sol was removed from the channels with organic solvents, a spatially patterned glass-like surface was observed on the PDMS microchannels. The introduced hydrophilicity and chemical stability of the silica coated PDMS was characterized with various analytical techniques including contact angle analysis, charge-coupled device (CCD) imaging, scanning electron microscopy (SEM), electro-osmotic flow (EOF) mobility measurement, neutral dye BODIPY/organic solvents absorption test and capillary gel electrophoresis. The water contact angle of the silica coated PDMS decreased, and the absorption of BODIPY was substantially suppressed in the silica coated PDMS microchannels while the native ones exhibited an increased fluorescent background signal within 10 min after BODIPY injection. The EOF of the silica coated surface was one order of magnitude higher than the ones with the native PDMS surface for a wide range of pHs. Polyacrylamide gel was immobilized in the silica coated PDMS microchannels, and a DNA ladder was successfully separated in the microchannel. PDMS microfluidic devices with enhanced wettability and stability can be used in multistep chemical syntheses and in various bio- and medical technologies. © 2016 Elsevier B.V. All rights reserved.1

H2O2 biosensor consisted of hemoglobin-DNA conjugate on nanoporous gold thin film electrode with electrochemical signal enhancement

Abstract In this research, we developed electrochemical biosensor which was composed of hemoglobin (Hb)-DNA conjugate on nanoporous gold thin film (NPGF) for hydrogen peroxide (H2O2) detection. For the first time, Hb and DNA was conjugated as a sensing platform for uniform orientation of Hb on electrode. The newly developed Hb-DNA conjugate was designed to prevent Hb from aggregation on electrode. DNA hybridization of Hb-DNA conjugate and complementary DNA (cDNA) on NPGF electrode induced uniformly assembled biosensor. Furthermore, NPGF electrode fabrication method was introduced to the increment of the surface area. To confirm the conjugation of Hb-DNA conjugate, sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and ultraviolet–visible spectroscopy (UV–VIS) were used. Formation of the NPGF electrode was verified by scanning electron microscope (SEM). Atomic force microscopy (AFM) was operated for the confirmation of Hb-DNA immobilization on electrode. The electrochemical property of fabricated electrode was investigated by cyclic voltammetry (CV). Also, H2O2 sensing performance of fabricated electrode was investigated by amperometric i-t curve technique. This sensor showed a wide linear range from 0.00025 to 5.00 mM and a correlation coefficient of R2 = 0.9986. The detection limit was 250 nM. Proposed biosensor can be utilized as a sensing platform for development of biosensor