Estimating Density Dependence, Environmental Variance, and Long-Term Selection on a Stage-Structured Life History.

AbstractA method for analyzing long-term demographic data on density-dependent stage-structured populations in a stochastic environment is derived to facilitate comparison of populations and species with different life histories. We assume that a weighted sum of stage abundances, N, exerts density dependence on stage-specific vital rates of survival and reproduction and that N has a small or moderate coefficient of variation. The dynamics of N are approximated as a univariate stochastic process governed by three key parameters: the density-independent growth rate, the net density dependence, and environmental variance in the life history. We show how to estimate the relative weighs of stages in N and the key parameters. Life history evolution represents a stochastic maximization of a simple function of the key parameters. The long-term selection gradient on the life history can be expressed as a vector of sensitivities of this function with respect to density-independent, density-dependent, and stochastic components of the vital rates. To illustrate the method, we analyze 38 years of demographic data on a great tit population, estimating the key parameters, which accurately predict the observed mean, coefficient of variation, and fluctuation rate of N; we also evaluate the long-term selection gradient on the life history.

American Civil War medical practice, the post-bellum opium crisis and modern comparisons.

The American Civil War resulted in massive numbers of injured and ill soldiers. Throughout the conflict, medical doctors relied on opium to treat these conditions, giving rise to claims that the injudicious use of the narcotic caused America's post-bellum opium crisis. Similar claims of medical misuse of opioids are now made as America confronts the modern narcotic crisis. A more nuanced thesis based on a broader base of Civil War era research suggests a more complex set of interacting factors that collectively contributed to America's post-war opium crisis.

Native/citrullinated LL37-specific T-cells help autoantibody production in Systemic Lupus Erythematosus.

LL37 exerts a dual pathogenic role in psoriasis. Bound to self-DNA/RNA, LL37 licenses autoreactivity by stimulating plasmacytoid dendritic cells-(pDCs)-Type I interferon (IFN-I) and acts as autoantigen for pathogenic Th17-cells. In systemic lupus erythematosus (SLE), LL37 also triggers IFN-I in pDCs and is target of pathogenic autoantibodies. However, whether LL37 activates T-cells in SLE and how the latter differ from psoriasis LL37-specific T-cells is unknown. Here we found that 45% SLE patients had circulating T-cells strongly responding to LL37, which correlate with anti-LL37 antibodies/disease activity. In contrast to psoriatic Th17-cells, these LL37-specific SLE T-cells displayed a T-follicular helper-(TFH)-like phenotype, with CXCR5/Bcl-6 and IL-21 expression, implicating a role in stimulation of pathogenic autoantibodies. Accordingly, SLE LL37-specific T-cells promoted B-cell secretion of pathogenic anti-LL37 antibodies in vitro. Importantly, we identified abundant citrullinated LL37 (cit-LL37) in SLE tissues (skin and kidney) and observed very pronounced reactivity of LL37-specific SLE T-cells to cit-LL37, compared to native-LL37, which was much more occasional in psoriasis. Thus, in SLE, we identified LL37-specific T-cells with a distinct functional specialization and antigenic specificity. This suggests that autoantigenic specificity is independent from the nature of the autoantigen, but rather relies on the disease-specific milieu driving T-cell subset polarization and autoantigen modifications.

Toll-like receptors in mediating pathogenesis in systemic sclerosis.

Toll-like receptors (TLRs) are evolutionarily conserved receptors essential for the host defence against pathogens. Both immune and non-immune cells can express TLRs, although at different levels. Systemic sclerosis (SSc) is a chronic disease in which autoimmunity, dysregulated profibrotic mediator release and activation of fibroblasts lead to dysregulated collagen deposition and fibrosis. There is now increasing knowledge that the innate immune system and, in particular, TLRs take a part in SSc pathogenesis. The list of endogenous ligands that can stimulate TLRs in SSc is growing: these ligands represent specific danger-associated molecular patterns (DAMPs), involved either in the initiation or the perpetuation of inflammation, and in the release of factors that sustain the fibrotic process or directly stimulate the cells that produce collagen and the endothelial cells. This review reports evidences concerning TLR signalling involvement in SSc. We report the new DAMPs, as well as the TLR-linked pathways involved in disease, with emphasis on type I interferon signature in SSc, the role of plasmacytoid dendritic cells (pDCs) and platelets. The dissection of the contribution of all these pathways to disease, and their correlation with the disease status, as well as their values as prognostic tools, can help to plan timely intervention and design new drugs for more appropriate therapeutic strategies.

Nutraceutical Augmentation Strategies for Depression: A Narrative Review.

Context: Depression is one of the most commonly diagnosed psychiatric disorders, but antidepressant pharmacotherapy often fails to achieve remission, leading health care professionals and researchers to consider various augmentation strategies to improve clinical outcomes. Objective: To assess the safety, tolerability, and efficacy of nutraceutical augmentation for depression. Methods: Nutraceutical-focused systematic reviews and clinical practice guidelines identified the more commonly studied augmentation strategies for depression. Results: S-adenosylmethionine, l-methylfolate, omega-3 fatty acids, and hydroxyvitamin D have sufficient scientific evidence to support their clinical consideration in the stepped care approach to the management of depression. Conclusions: Clinical remission is the goal in the management of depression, and nutraceuticals may be part of an overall treatment approach to achieve that outcome.

Adaptive behavior impaired in children with low-grade glioma.

BACKGROUND: Adaptive behavior, i.e., the performance on daily activities required for personal and social independence, is essential to estimate in children with low-grade glioma (LGG) since most of them are long-term survivors. Our aim was to investigate adaptive behavior in children with LGG. METHODS: In a cross-sectional study, adaptive behavior was assessed using the paper pencil version of the Parent Form of the Vineland Adaptive Behavior Scales 2nd edition (VABS-II) testing communication, daily living skills, social skills, and motor skills. Scores of children with LGG, younger than 20 years, and diagnosed between 2004 and 2014 were compared with family controls. Correlations between clinical variables and adaptive behavior were explored. RESULTS: Fifty-six children with LGG (median age, 12.1 years; 52% male) and 46 controls (median age, 11.0 years; 43% male) were included in the analyses. Compared with controls, the LGG group was more impaired on total adaptive behavior, communication, and motor skills and in the subdomain gross motor skills (effect sizes d, 0.64-0.86, P < 0.003). Younger age at diagnosis (r = -0.357, P < 0.01) and chemotherapy (r = -0.342, P < 0.05) were associated with poorer motor skills. Residual disease was associated with poorer total adaptive behavior (r = -0.282, P < 0.05). No other significant correlations were found. CONCLUSION: At the group level, adaptive functioning of children with LGG is impaired compared with family controls. Regular structured monitoring of adaptive behavior is recommended to be able to define the needs for tailored rehabilitation in daily life at home as well as at school.

Prospective Study of Brain Wave Changes Associated With Cranial Electrotherapy Stimulation.

OBJECTIVE: To explore brain wave changes associated with cranial electrotherapy stimulation (CES) among subjects receiving psychiatric care. METHODS: Quantitative electroencephalogram data were obtained before and after a 20-minute session of CES. The investigators recruited active-duty military subjects from Walter Reed National Military Medical Center's Psychiatry Continuity Service, Bethesda, Maryland. Fifty subjects participated in this prospective, convenience sample study from August 2016 through March 2017. The main outcome measures were changes in brain wave activity and the Subjective Units of Distress Scale. RESULTS: The typical subject was mildly depressed and had severe trauma-related symptoms and sleep problems. There was a significant increase (P = .000) in the higher beta frequencies (18-21 Hz, 21-33 Hz, and 33-48 Hz) and a strong effect (with the Cohen d around 1.5) immediately following the 20-minute CES. Ten minutes after CES, slower wave activity (4-8 Hz and 8-12 Hz) significantly decreased (P < .05), while higher beta wave activity (13-15 Hz, 18-21 Hz, and 21-33 Hz) increased. A strong effect (with the Cohen d around 1.5) persisted in the beta brain wave bands 18-21 Hz and 21-33 Hz. CONCLUSIONS: Brain wave measurements taken immediately after the 20-minute CES session showed a significant and strong effect in the beta region, suggesting an increase in mental alertness, focus, and concentration. Ten minutes after the CES session, an even more marked change in brain wave activity occurred. The significant and strong effect in the beta region persisted but was joined by a reduction in slower wave activity, indicating an increase in mental alertness. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT03298308.

Alcohol Biomarkers Associated with Obstructive Sleep Apnea.

The views expressed in this presentation are those of the author and do not reflect the official policy of the Department of the Army/Navy/Air Force or the Department of Defense The identification of specific products or scientific instrumentation does not constitute an endorsement or implied endorsement on the part of the authors, DoD, or any component agency. While we generally excise references to products, companies, manufacturers, organizations, etc. in government produced works, the abstracts produced and other similarly situated researchers presents a special circumstance when such product inclusions become an integral part of the scientific endeavor.

The Reasons for Living Scale-Military Version: Assessing Protective Factors Against Suicide in a Military Sample.

INTRODUCTION: Military suicide rates have been rising over the past decade and continue to challenge military treatment facilities. Assessing suicide risk and improving treatments are a large part of the mission for clinicians who work with uniformed service members. This study attempts to expand the toolkit of military suicide prevention by focusing on protective factors over risk factors. In 1983, Marsha Linehan published a checklist called the Reasons for Living Scale, which asked subjects to check the reasons they choose to continue living, rather than choosing suicide. The authors of this article hypothesized that military service members may have different or additional reasons to live which may relate to their military service. They created a new version of Linehan's inventory by adding protective factors related to military life. The purpose of these additions was to make the inventory more acceptable and relevant to the military population, as well as to identify whether these items constitute a separate subscale as distinguished from previously identified factors. MATERIALS AND METHODS: A commonly used assessment tool, the Reasons for Living Inventory (RFL) designed by Marsha Linehan, was expanded to offer items geared to the military population. The RFL presents users with a list of items which may be reasons to not commit suicide (e.g., "I have a responsibility and commitment to my family"). The authors used focus groups of staff and patients in a military psychiatric partial hospitalization program to identify military-centric reasons to live. This process yielded 20 distinct items which were added to Linehan's original list of 48. This expanded list became the Reasons for Living-Military Version. A sample of 200 patients in the military partial hospitalization program completed the inventory at time of or close to admission. This study was approved by the Institutional Review Board at Walter Reed National Military Center for adhering to ethical principles related to pursuing research with human subjects. RESULTS: The rotated factor matrix revealed six factors that have been labeled as follows: Survival and Coping Beliefs, Military Values, Responsibility to Family, Fear of Suicide/Disability/Unknown, Moral Objections and Child-Related Concerns. The subscale of Military Values is a new factor reflecting the addition of military items to the original RFL. CONCLUSIONS: Results suggest that formally assessing protective factors in a military psychiatric population has potential as a useful tool in the prevention of military suicide and therefore warrants further research. The latent factor we have entitled "Military Values" may help identify those service members for whom military training or "esprit de corps" is a reason for living. Further research can focus on further validation, pre/post-treatment effects on scores, expanded clinical use to stimulate increased will to live, or evaluation of whether scores on this scale, or the subscale of Military Values, can predict future suicidal behavior by service members. Finally, a larger sample size may produce more robust results to support these findings.

Seeking Safety Pilot Outcome Study at Walter Reed National Military Medical Center.

Post-traumatic stress disorder (PTSD) and substance use disorder are two of the most prominent psychiatric disorders among military service members. Seeking Safety (SS) is an evidence-based behavioral therapy model for this comorbidity. This article reports results of a study of SS conducted in a military setting. Our pilot trial addressed outcomes, feasibility, and satisfaction. SS was conducted as is to evaluate its impact without adaptation for military culture. The sample was 24 outpatient service members (from the Army, Navy, Air Force, and Marines) with 33% minority representation. Inclusion criteria were current PTSD and/or SUD. Ten clinicians participated in this study after receiving SS training. Results showed significant improvements on most outcomes, including substance use on the Brief Addiction Monitor; PTSD symptoms on the PTSD Checklist-Military Version (total and criterion D); and the Trauma Symptom Checklist-40 (sexual abuse trauma index and anxiety subscale); functioning on the Sheehan Disability Scale (total and family subscale); psychopathology on the Zung Depression Scale total; the Behavior and Symptom Identification Scale (BASIS)-24 (total and subscales depression functioning, emotional liability, and psychosis); and the Brief Symptom Inventory-18 (total and anxiety subscale); and coping on the Coping Self-Efficacy Scale (total). Satisfaction was strong. Discussion includes methodology limitations and next steps.

Components and Characteristics of a Psychiatric Partial Hospital Military Program.

This article describes the components of a psychiatric partial hospital military program and the characteristics of referrals received over the 5-year period from 2009 to 2013. The 5-year study period included ongoing combat operations in Iraq and Afghanistan along with their subsequent troop withdrawals and change in mission. A total of 1,194 service members were referred for this level of care, and even with the changing battlefield conditions, the number of psychiatric referrals remained steady throughout the 5-year period, with a significant spike in admissions in 2013. The principal diagnoses were major depressive disorder and post-traumatic stress disorder. One-third of the admissions came from service members with 4 to 8 years' time in service and slightly more than one-third were employed in direct combat roles or medical support. In terms of gender, females accounted for one-quarter of the admissions.

Relationships between polypharmacy and the sleep cycle among active-duty service members.

CONTEXT: Sleep disorders are frequent clinical presentations, especially among active-duty service members. Medications are one factor that can affect sleep in many ways. OBJECTIVE: To determine the effect of increasing numbers of medications on the sleep cycle of active-duty service members. METHODS: Medical records for active-duty service members who completed enhanced sleep assessments at the Psychiatry Continuity Service at Walter Reed National Military Medical Center from October 1, 2010, through November 30, 2013, were retrospectively reviewed. Data were collected on home sleep study findings, sleep-related self-report instrument scores, and active medications. RESULTS: A total of 135 medical records were reviewed. One hundred patients (74.07%) had an active prescription for a psychoactive drug. Among all patients, the mean (SD) number of active medications per participant was 2.52 (2.09), with 118 patients (82.96%) having an active medication for depression or insomnia. As the number of prescribed medications increased, the percentage of the sleep cycle in deep sleep decreased (P=.049), the percentage of light sleep increased (P=.016), the percentage of rapid eye movement sleep decreased (P=.083), and the first episode of deep sleep was delayed (P=.056). An increased number of medications had no significant impact on total sleep time (P>.05). CONCLUSION: An increasing number of medications did not influence total sleep time but negatively affected the sleep cycle.

WITHDRAWN: Brain computer interface technology: Usability and applications in psychiatry.

Ahead of Print article withdrawn by publisher.

Stress in service members.

Military service differs from civilian jobs in the stressors that service members experience, including frequent deployments (eg, to an area of combat operations), obedience, regimentation, subordination of self to the group, integrity, and flexibility. The military culture emphasizes teamwork and peer support. In some cases, service members cannot adapt to military life, become overwhelmed by stress, or cannot overcome a traumatic experience. Clinicians should conduct a thorough evaluation guided by an understanding of the military culture. Every effort should be made to identify the stress and the maladaptive response and provide early clinical interventions to prevent progression.

Evolution of phenotypic plasticity and environmental tolerance of a labile quantitative character in a fluctuating environment.

Quantitative genetic models of evolution of phenotypic plasticity are used to derive environmental tolerance curves for a population in a changing environment, providing a theoretical foundation for integrating physiological and community ecology with evolutionary genetics of plasticity and norms of reaction. Plasticity is modelled for a labile quantitative character undergoing continuous reversible development and selection in a fluctuating environment. If there is no cost of plasticity, a labile character evolves expected plasticity equalling the slope of the optimal phenotype as a function of the environment. This contrasts with previous theory for plasticity influenced by the environment at a critical stage of early development determining a constant adult phenotype on which selection acts, for which the expected plasticity is reduced by the environmental predictability over the discrete time lag between development and selection. With a cost of plasticity in a labile character, the expected plasticity depends on the cost and on the environmental variance and predictability averaged over the continuous developmental time lag. Environmental tolerance curves derived from this model confirm traditional assumptions in physiological ecology and provide new insights. Tolerance curve width increases with larger environmental variance, but can only evolve within a limited range. The strength of the trade-off between tolerance curve height and width depends on the cost of plasticity. Asymmetric tolerance curves caused by male sterility at high temperature are illustrated. A simple condition is given for a large transient increase in plasticity and tolerance curve width following a sudden change in average environment.

Sleep problems, posttraumatic stress, and mood disorders among active-duty service members.

CONTEXT: Sleep problems among active-duty service members are pervasive and complicate the recovery from comorbid posttraumatic stress and mood disorders. OBJECTIVE: To better understand chronic sleep problems among active-duty service members. METHODS: Medical records for active-duty service members who completed enhanced sleep assessments during an 18-month period beginning in October 2010 at the Walter Reed National Military Medical Centers' Psychiatry Continuity Service were retrospectively reviewed. Sleep assessment measures included the Pittsburgh Insomnia Rating Scale, the Alcohol Use Disorders Identification Test, the Zung Self-Rating Depression Scale, the Zung Self-Rating Anxiety Scale, the Posttraumatic Stress Disorder Checklist - Military Version, the Epworth Sleepiness Scale, the Pre-Sleep Arousal Scale, and a home sleep study. RESULTS: A total of 76 records met the study criteria. Twenty-two participants (29%) had an apnea/hypopnea index that suggested mild to moderate sleep apnea. Service members with higher self-reported posttraumatic stress scores also reported a higher degree of both somatic and cognitive factors interfering with sleep initiation. Compared with those who had low self-reported posttraumatic stress scores, service members with high posttraumatic stress scores also had less total sleep time (mean difference, 38 minutes) and higher scores on the apnea/hypopnea index, the respiratory disturbance index, and the oxygen saturation index. CONCLUSION: Enhanced sleep assessments that include traditional self-report tests and a home sleep study can help identify previously undiscovered behavioral and respiratory problems among service members, particularly those with higher posttraumatic stress scores.

A comparison of two alcohol biomarkers in clinical practice: ethyl glucuronide versus ethyl sulfate.

This study compared the characteristics of two direct alcohol biomarkers, ethyl glucuronide and ethyl sulfate. Both biomarkers were analyzed from urine specimens submitted by 58 active duty service members at Walter Reed National Military Medical Center's Addiction Treatment Service. These 58 individuals, as a result of serial testing, submitted a total of 374 urine specimens for laboratory analysis. Of 374 specimens, the paired tests were most often negative (n = 295, 78.9%).The paired tests were both positive less frequently (n = 38, 10.2%). In an interesting development ethyl sulfate produced more positive results than ethyl glucuronide (n = 32, 8.6%).

United States military service members and their tattoos: a descriptive study.

To explore the characteristics of military service tattoos a descriptive study was conducted at Walter Reed Army Medical Center to collect information from a convenience sample. An investigator-developed questionnaire provided the data for this study. Over the ensuing 12 month-period the researchers collected 126 questionnaires. Typical respondents were enlisted men with at least one deployment to an area of combat operations. Among the respondents, 57% acquired their tattoos before their deployment. One-quarter of the respondents reported only one tattoo, leaving the majority with multiple tattoos. Men received their first tattoo at an earlier age than women. The most common tattoo listed a person's name. Respondents did not regret their tattoos and rarely acquired the body art under the influence of alcohol or drugs. Little evidence was found to support a connection between tattoos and deployment. Few regretted their decisions and most all approached the tattoo experience free of any mind-altering substance. All this seems to suggest that military tattoos are a well-accepted means of self-expression.

Sleep trends of active-duty service members referred for psychiatric care: a descriptive study.

CONTEXT: Military service members have unique experiences that may contribute to sleep problems in this patient population. OBJECTIVE: To gather sleep habits and chronic sleep complaints among active-duty service members to identify common characteristics. METHODS: The investigators administered a detailed sleep log, the Pittsburgh Insomnia Rating Scale, the Zung Self-Rating Depression Scale, the Epworth Sleepiness Scale, and the Pre-Sleep Arousal Scale to consenting service members referred to a military psychiatric partial hospitalization program. RESULTS: A total of 57 service members participated in this study. Participants reported a mean of less than 5 total hours of sleep and sleep latencies of 30 minutes or more. Tobacco users (n=22) reported nearly a full hour less of total time slept. Service members with combat experience (n=26) reported qualitatively poorer sleep with less total sleep time (P=.05), greater presleep arousal (P=.01), and a substantially greater number of troubling dreams (P=.06) compared with service members without combat experience. CONCLUSION: Chronic sleep issues are common complaints among military personnel, an anecdotal finding confirmed by the results of this study. These results lend support for more detailed sleep assessments, particularly among combat veterans.