Off-Duty and Under Arrest: An Exploratory Study of the Arrests of Off-Duty Police Officers, 2005-2017

Presentation at the Annual Meeting of the Academy of Criminal Justice Sciences in National Harbor, MD, on March 17, 2023

The role of central command in the increase in muscle sympathetic nerve activity to contracting muscle during high intensity isometric exercise

We previously demonstrated that muscle sympathetic nerve activity (MSNA) increases to contracting muscle as well as to non-contracting muscle, but this was only assessed during isometric exercise at ∼10% of maximum voluntary contraction (MVC). Given that high-intensity isometric contractions will release more metabolites, we tested the hypothesis that the metaboreflex is expressed in the contracting muscle during highintensity but not low-intensity exercise. MSNA was recorded continuously via a tungsten microelectrode inserted percutaneously into the right common peroneal nerve in 12 participants, performing isometric dorsiflexion of the right ankle at 10, 20, 30, 40, and 50% MVC for 2 min. Contractions were immediately followed by 6 min of post-exercise schemia (PEI); 6 min of recovery separated contractions. Cross-correlation analysis was performed between the negative-going sympathetic spikes of the raw neurogram and the ECG. MSNA increased as contraction intensity increased, reaching mean values (± SD) of 207 ± 210 spikes/min at 10% MVC (P = 0.04), 270 ± 189 spikes/min at 20% MVC (P < 0.01), 538 ± 329 spikes/min at 30% MVC (P < 0.01), 816 ± 551 spikes/min at 40% MVC (P < 0.01), and 1,097 ± 782 spikes/min at 50% MVC (P < 0.01). Mean arterial pressure also increased in an intensity-dependent manner from 76 ± 3 mmHg at rest to 90 ± 6 mmHg (P < 0.01) during contractions of 50% MVC. At all contraction intensities, blood pressure remained elevated during PEI, but MSNA returned to pre-contraction levels, indicating that the metaboreflex does not contribute to the increase in MSNA to contracting muscle even at these high contraction intensitie

A Comparison of Muscle Sympathetic Nerve Activity to Non-contracting Muscle During Isometric Exercise in the Upper and Lower Limbs

Previous research indicates that greater sympathetic vasoconstrictor drive to skeletal muscle occurs during isometric upper limb exercise compared to lower limb exercise. However, potential disparity between blood flow and metaboreflex activation in contracting upper and lower limbs could contribute to the augmented sympathetic response during upper limb exercise. Therefore, the aim of this study was to examine MSNA responses during ankle dorsiflexion and handgrip exercise under ischaemic conditions, in order to standardize the conditions in terms of perfusion and metaboreflex activation. Eight healthy male subjects performed 4-min contractions of ischaemic isometric handgrip and ankle dorsiflexion at ∼10% maximal voluntary contraction, followed by 6 min of post-exercise ischaemia. MSNA was recorded continuously by microneurography of the common peroneal nerve of the non-contracting leg and quantified from negative-going sympathetic spikes in the neurogram, synchronized with the cardiac cycle. The time-course of MSNA exhibited parallel increases during exercise of the upper and lower limbs, rising throughout the contraction to peak at 4 min. This represented an increase of 100% relative to resting levels for handgrip exercise (66 ± 24 vs. 33 ± 7 spikes/min at rest) and 103% for dorsiflexion (63 ± 25 vs. 31 ± 8 spikes/min at rest; P &lt; 0.01). In both conditions MSNA remained elevated during post-exercise ischaemia and returned to pre-contraction levels during recovery. These findings demonstrate that that the MSNA response to metaboreflex activation is similar for upper and lower limb exercise when perfusion is controlled for

Impact of acute stress, sex, and childhood maltreatment on fear learning and fear generalization in a fear-potentiated startle paradigm

Many researchers approach the etiology of trauma-, stressor-, and anxiety-related mental disorders from the perspective of classical conditioning processes gone awry. According to this view, abnormal associative relationships between conditioned and unconditioned stimuli may underlie pathological anxiety and result in unusually intense fear memories or fear memories that cannot be properly extinguished. Recent work has expanded on this view by showing that many psychological disorders involving pathological anxiety are associated with an exaggerated form of stimulus generalization, leading individuals with such disorders to respond with fear and anxiety to a variety of contexts and cues that should not be threatening. It is well-known that stress, biological sex, childhood maltreatment, and certain dispositional factors can increase one’s susceptibility for pathological anxiety and significantly impact fear learning; thus, it is possible that these factors, alone or in combination, contribute to clinical anxiety by influencing fear generalization processes. In the present study, 478 healthy undergraduate students were exposed to the socially-evaluated cold pressor test immediately or 30 min prior to learning to associate one geometrical shape, but not another, with an aversive stimulus in a fear-potentiated startle paradigm. The next day, participants were tested for fear generalization by measuring their fear responses to a variety of stimuli that were similar to, but different from, the shapes observed on Day 1. Objective and subjective measures of stress were collected on Day 1, and childhood maltreatment was quantified with the Childhood Trauma Questionnaire. The results revealed that, across both stress time points, greater heart rate and greater cortisol levels in response to stress were associated with weaker fear acquisition and a flatter generalization gradient. These effects were influenced by participant sex and trait anxiety. We also found evidence to suggest that greater childhood maltreatment was associated with impaired fear acquisition in males but enhanced fear acquisition in females. These findings reveal a complex interaction between acute stress, biological sex, childhood maltreatment, dispositional anxiety, and fear learning that may lend insight into the etiology of certain stress-related psychological disorders

Ring-fused 2-pyridones effective against multidrug-resistant Gram-positive pathogens and synergistic with standard-of-care antibiotics

The alarming rise of multidrug-resistant Gram-positive bacteria has precipitated a healthcare crisis, necessitating the development of new antimicrobial therapies. Here we describe a new class of antibiotics based on a ring-fused 2-pyridone backbone, which are active against vancomycin-resistant enterococci (VRE), a serious threat as classified by the Centers for Disease Control and Prevention, and other multidrug-resistant Gram-positive bacteria. Ring-fused 2-pyridone antibiotics have bacteriostatic activity against actively dividing exponential phase enterococcal cells and bactericidal activity against nondividing stationary phase enterococcal cells. The molecular mechanism of drug-induced killing of stationary phase cells mimics aspects of fratricide observed in enterococcal biofilms, where both are mediated by the Atn autolysin and the GelE protease. In addition, combinations of sublethal concentrations of ring-fused 2-pyridones and standard-of-care antibiotics, such as vancomycin, were found to synergize to kill clinical strains of VRE. Furthermore, a broad range of antibiotic resistant Gram-positive pathogens, including those responsible for the increasing incidence of antibiotic resistant healthcare-associated infections, are susceptible to this new class of 2-pyridone antibiotics. Given the broad antibacterial activities of ring-fused 2-pyridone compounds against Gram-positive (GmP) bacteria we term these compounds GmPcides, which hold promise in combating the rising tide of antibiotic resistant Gram-positive pathogens

Tunnel vision, false memories, and intrusive memories following exposure to the Trier Social Stress Test

Most research examining the impact of stress on learning and memory has exposed participants to a stressor and measured how it affects learning and memory for unrelated material (e.g., list of words). Such work has been helpful, but it has not been the most translational to the human condition. When considering phenomena such as intrusive memories in post-traumatic stress disorder (PTSD) or an eyewitness\u27s memory for a crime, it is most useful to know what an individual remembers about the stress experience itself, not unrelated information. In prior work, investigators used a modified version of the Trier Social Stress Test (TSST) to quantify participant memory for the stressor. We aimed to replicate this work by examining participant memory for the TSST and extend on it by quantifying false and intrusive memories that result from TSST exposure. Forty-six undergraduate students from Ohio Northern University were exposed to the TSST or the friendly-TSST (f-TSST). The TSST required participants to deliver a ten-minute speech in front of two lab panel members as part of a mock job interview; the f-TSST required participants to casually converse with the panel members about their interests and hobbies. In both conditions, the panel members interacted with (central) or did not interact with (peripheral) several objects sitting on a desk in front of them. Participants’ anxiety levels were assessed before and after the TSST or f-TSST, and saliva samples were collected to assay for cortisol. The next day, participants’ memory for the objects that were present on Day 1 was assessed with recall and recognition tests. We also quantified participants’ intrusive memories for each task by having them complete an intrusive memory questionnaire on Days 2, 4, 6, and 8. Participants exposed to the TSST exhibited greater recall of central objects than participants exposed to the f-TSST. There were no differences observed for the recall of peripheral objects or for recognition memory. Interestingly, TSST exposure increased false recall in males, but reduced it in females. Females exposed to the TSST also showed greater evidence of intrusive memories than males exposed to the TSST. Consistent with prior work, these findings show that stress enhances memory for the central details of a stressful experience. They also extend on prior work by showing that stressful experiences sex-dependently impact the manifestation of false and intrusive memories. This is the first study of which we are aware to quantify intrusive memory formation with the TSST; the modified TSST paradigm may be useful in understanding differential susceptibility to intrusive memory formation and the development of PTSD

BOWIE-ALIGN: A JWST comparative survey of aligned versus misaligned hot Jupiters to test the dependence of atmospheric composition on migration history

A primary objective of exoplanet atmosphere characterization is to learn about planet formation and evolution, however, this is challenged by degeneracies. To determine whether differences in atmospheric composition can be reliably traced to differences in evolution, we are undertaking a transmission spectroscopy survey with JWST to compare the compositions of a sample of hot Jupiters that have different orbital alignments around F stars above the Kraft break. Under the assumption that aligned planets migrate through the inner disc, while misaligned planets migrate after disc dispersal, the act of migrating through the inner disc should cause a measurable difference in the C/O between aligned and misaligned planets. We expect the amplitude and sign of this difference to depend on the amount of planetesimal accretion and whether silicates accreted from the inner disc release their oxygen. Here, we identify all known exoplanets that are suitable for testing this hypothesis, describe our JWST survey, and use noise simulations and atmospheric retrievals to estimate our survey’s sensitivity. With the selected sample of four aligned and four misaligned hot Jupiters, we will be sensitive to the predicted differences in C/O between aligned and misaligned hot Jupiters for a wide range of model scenarios

Cognitive dysfunction in naturally occurring canine idiopathic epilepsy

Globally, epilepsy is a common serious brain disorder. In addition to seizure activity, epilepsy is associated with cognitive impairments including static cognitive impairments present at onset, progressive seizure-induced impairments and co-morbid dementia. Epilepsy occurs naturally in domestic dogs but its impact on canine cognition has yet to be studied, despite canine cognitive dysfunction (CCD) recognised as a spontaneous model of dementia. Here we use data from a psychometrically validated tool, the canine cognitive dysfunction rating (CCDR) scale, to compare cognitive dysfunction in dogs diagnosed with idiopathic epilepsy (IE) with controls while accounting for age. An online cross-sectional study resulted in a sample of 4051 dogs, of which n = 286 had been diagnosed with IE. Four factors were significantly associated with a diagnosis of CCD (above the diagnostic cut-off of CCDR ≥50): (i) epilepsy diagnosis: dogs with epilepsy were at higher risk; (ii) age: older dogs were at higher risk; (iii) weight: lighter dogs (kg) were at higher risk; (iv) training history: dogs with more exposure to training activities were at lower risk. Impairments in memory were most common in dogs with IE, but progression of impairments was not observed compared to controls. A significant interaction between epilepsy and age was identified, with IE dogs exhibiting a higher risk of CCD at a young age, while control dogs followed the expected pattern of low-risk throughout middle age, with risk increasing exponentially in geriatric years. Within the IE sub-population, dogs with a history of cluster seizures and high seizure frequency had higher CCDR scores. The age of onset, nature and progression of cognitive impairment in the current IE dogs appear divergent from those classically seen in CCD. Longitudinal monitoring of cognitive function from seizure onset is required to further characterise these impairments

DNAm scores for serum GDF15 and NT-proBNP levels associate with a range of traits affecting the body and brain

Background: Plasma growth differentiation factor 15 (GDF15) and N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) are cardiovascular biomarkers that associate with a range of diseases. Epigenetic scores (EpiScores) for GDF15 and NT-proBNP may provide new routes for risk stratification.Results: In the Generation Scotland cohort (N ≥ 16,963), GDF15 levels were associated with incident dementia, ischaemic stroke and type 2 diabetes, whereas NT-proBNP levels were associated with incident ischaemic heart disease, ischaemic stroke and type 2 diabetes (all PFDR &lt; 0.05). Bayesian Epigenome-wide association studies (EWAS) identified 12 and 4 DNA methylation (DNAm) CpG sites associated (Posterior Inclusion Probability [PIP] &gt; 95%) with levels of GDF15 and NT-proBNP, respectively. EpiScores for GDF15 and NT-proBNP were trained in a subset of the population. The GDF15 EpiScore replicated protein associations with incident dementia, type 2 diabetes and ischaemic stroke in the Generation Scotland test set (Hazard Ratios (HR) range 1.36 – 1.41, PFDR &lt;0.03). The EpiScore for NT-proBNP replicated the protein association with type 2 diabetes, but failed to replicate an association with ischaemic stroke. EpiScores explained comparable variance in protein levels across both the Generation Scotland test set and the external LBC1936 test cohort (R2 range of 5.7-12.2%). In LBC1936, both EpiScores were associated with indicators of poorer brain health. Neither EpiScore was associated with incident dementia in the LBC1936 population.Conclusions: EpiScores for serum levels of GDF15 and Nt-proBNP associate with body and brain health traits. These EpiScores are provided as potential tools for disease risk stratification.<br/

Intestinal barrier disruption with Plasmodium falciparum infection in pregnancy and risk of preterm birth: a cohort study

Malaria in early pregnancy is a risk factor for preterm birth and is associated with sustained inflammation and dysregulated angiogenesis across gestation. This study investigated whether malaria is associated with increased gut leak and whether this contributes to systemic inflammation, altered angiogenesis, and preterm birth. We quantified plasma concentrations of gut leak markers, soluble CD14 (sCD14) and lipopolysaccharide binding protein (LBP) from 1339 HIV-negative pregnant Malawians at <24 weeks gestational age. We assessed the relationship of sCD14 and LBP concentrations with markers of inflammation, angiogenesis, and L-arginine bioavailability and compared them between participants with and without malaria, and with and without preterm birth. Plasma concentrations of sCD14 and LBP were significantly higher in participants with malaria and were associated with parasite burden (p <0.0001, both analyses and analytes). The odds ratio for preterm birth associated with one log sCD14 was 2.67 (1.33 to 5.35, p = 0.006) and 1.63 (1.07-2.47, p = 0.023) for LBP. Both gut leak analytes were positively associated with increases in proinflammatory cytokines CRP, sTNFR2, IL18-BP, CHI3L1 and Angptl3 (p <0.05, all analytes) and sCD14 was significantly associated with angiogenic proteins Angpt-2, sENG and the sFLT:PlGF ratio (p <0.05, all analytes). sCD14 was negatively associated with L-arginine bioavailability (p <0.001). Malaria in early pregnancy is associated with intestinal barrier dysfunction, which is linked to an increased risk of preterm birth. Open Philanthropy, Canadian Institutes of Health Research, Canada Research Chair program, European and Developing Countries Clinical Trials Partnership, Bill & Melinda Gates Foundation