The Nasal Microbiome in ANCA-Associated Vasculitis:Picking the Nose for Clues on Disease Pathogenesis

PURPOSE OF REVIEW: The onset and progression of small vessel vasculitis associated with anti-neutrophil cytoplasmic antibodies has been linked to microbial infections. Here, we provide a brief overview of the association of nasal colonization of Staphylococcus aureus with ANCA-associated vasculitis (AAV) and discuss several recent studies mapping the nasal microbiome in AAV patients in particular. RECENT FINDINGS: Nasal microbiome studies revealed dysbiosis as a common trait in active AAV which tends to normalize upon immunosuppressive treatment and quiescent disease. However, due to differences in study design, patient selection, and methodology, the reported microbiome profiles differ considerably precluding conclusions on causal relationships. SUMMARY: The microbiome is an emerging area of research in AAV warranting further investigation. Ideally, such studies should be combined with mechanistic studies to unravel key elements related to host-microbe interactions and their relevance for AAV pathogenesis

Holistic corpus-based dialectology

This paper is concerned with sketching future directions for corpus-based dialectology. We advocate a holistic approach to the study of geographically conditioned linguistic variability, and we present a suitable methodology, 'corpusbased dialectometry', in exactly this spirit. Specifically, we argue that in order to live up to the potential of the corpus-based method, practitioners need to (i) abandon their exclusive focus on individual linguistic features in favor of the study of feature aggregates, (ii) draw on computationally advanced multivariate analysis techniques (such as multidimensional scaling, cluster analysis, and principal component analysis), and (iii) aid interpretation of empirical results by marshalling state-of-the-art data visualization techniques. To exemplify this line of analysis, we present a case study which explores joint frequency variability of 57 morphosyntax features in 34 dialects all over Great Britain

Decreased Expression of Negative Immune Checkpoint VISTA by CD4+T Cells Facilitates T Helper 1, T Helper 17, and T Follicular Helper Lineage Differentiation in GCA

Loss of immune checkpoint (IC) Programmed Death-1 (PD-1) and PD-Ligand1 (PD-L1) expression has been implicated in the immunopathology of Giant Cell Arteritis (GCA). The contribution of the negative immune checkpoint V-domain Immunoglobulin-containing suppressor of T cell activation (VISTA) to GCA pathology has not yet been studied. The aim of our study was to investigate if expression of VISTA and other IC molecules by peripheral blood (PB) immune cells is modulated in GCA and at the site of vascular inflammation. In addition, we assessed the effect of VISTA-Ig engagement on in vitro CD4+ T helper (Th) lineage differentiation. To this end, frequencies of monocytes expressing CD80/86, PD-L1, PD-L2, and VISTA were determined in blood samples from 30 GCA patients and 18 matched healthy controls by flow cytometry. In parallel, frequencies of CD4+ cells expressing CD28, Cytotoxic T-Lymphocyte-associated antigen-4 (CTLA-4), PD-1, and VISTA were determined. Immunohistochemistry was employed to detect VISTA, PD-1, and PD-L1-expressing cells in temporal artery biopsies (TABs) diagnostic of GCA. Furthermore, the effect of VISTA-Ig on in vitro CD4+ Th lineage differentiation in patients and controls was determined. Our study shows that frequencies of CD80/CD86+ and VISTA+ monocytes were decreased in treated GCA patients only. Moreover, proportions of PD-1+ and VISTA+ Th cells were significantly decreased in GCA patients. Clear infiltration of VISTA+, PD1+, and PD-L1+ cells was seen in GCA TABs. Finally, VISTA-Ig engagement failed to suppress Th1, Th17, and Tfh lineage development in GCA. Our results indicate that decreased expression of VISTA may facilitate development of pathogenic Th1 and Th17 cells in GCA

Design of the Army Study to Assess Risk and Resilience in Servicemembers (Army STARRS)

The Army Study to Assess Risk and Resilience in Servicemembers (Army STARRS) is a multi‐component epidemiological and neurobiological study designed to generate actionable evidence‐based recommendations to reduce US Army suicides and increase basic knowledge about the determinants of suicidality. This report presents an overview of the designs of the six components of the Army STARRS. These include: an integrated analysis of the Historical Administrative Data Study (HADS) designed to provide data on significant administrative predictors of suicides among the more than 1.6 million soldiers on active duty in 2004–2009; retrospective case‐control studies of suicide attempts and fatalities; separate large‐scale cross‐sectional studies of new soldiers (i.e. those just beginning Basic Combat Training [BCT], who completed self‐administered questionnaires [SAQs] and neurocognitive tests and provided blood samples) and soldiers exclusive of those in BCT (who completed SAQs); a pre‐post deployment study of soldiers in three Brigade Combat Teams about to deploy to Afghanistan (who completed SAQs and provided blood samples) followed multiple times after returning from deployment; and a platform for following up Army STARRS participants who have returned to civilian life. Department of Defense/Army administrative data records are linked with SAQ data to examine prospective associations between self‐reports and subsequent suicidality. The presentation closes with a discussion of the methodological advantages of cross‐component coordination. Copyright © 2013 John Wiley & Sons, Ltd .Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/102177/1/mpr1401.pd

Prognostic Indicators of Persistent Post-Concussive Symptoms after Deployment-Related Mild Traumatic Brain Injury: A Prospective Longitudinal Study in U.S. Army Soldiers

Mild traumatic brain injury (mTBI), or concussion, is prevalent in the military. The course of recovery can be highly variable. This study investigates whether deployment-acquired mTBI is associated with subsequent presence and severity of post-concussive symptoms (PCS) and identifies predictors of persistent PCS among US Army personnel who sustained mTBI while deployed to Afghanistan. We used data from a prospective longitudinal survey of soldiers assessed 1?2 months before a 10-month deployment to Afghanistan (T0), on redeployment to the United States (T1), approximately 3 months later (T2), and approximately 9 months later (T3). Outcomes of interest were PCS at T2 and T3. Predictors considered were: sociodemographic factors, number of previous deployments, pre-deployment mental health and TBI history, and mTBI and other military-related stress during the index deployment. The study sample comprised 4518 soldiers, 822 (18.2%) of whom experienced mTBI during the index deployment. After adjusting for demographic, clinical, and deployment-related factors, deployment-acquired mTBI was associated with nearly triple the risk of reporting any PCS and with increased severity of PCS when symptoms were present. Among those who sustained mTBI, severity of PCS at follow-up was associated with history of pre-deployment TBI(s), pre-deployment psychological distress, more severe deployment stress, and loss of consciousness or lapse of memory (versus being ?dazed? only) as a result of deployment-acquired mTBI. In summary, we found that sustaining mTBI increases risk for persistent PCS. Previous TBI(s), pre-deployment psychological distress, severe deployment stress, and loss of consciousness or lapse of memory resulting from mTBI(s) are prognostic indicators of persistent PCS after an index mTBI. These observations may have actionable implications for prevention of chronic sequelae of mTBI in the military and other settings.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140173/1/neu.2015.4320.pd

Neurocognitive Function and Suicide in U.S. Army Soldiers

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138894/1/sltb12307_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/138894/2/sltb12307.pd

Response bias, weighting adjustments, and design effects in the Army Study to Assess Risk and Resilience in Servicemembers (Army STARRS)

The Army Study to Assess Risk and Resilience in Servicemembers (Army STARRS) is a multi‐component epidemiological and neurobiological study designed to generate actionable recommendations to reduce US Army suicides and increase knowledge about determinants of suicidality. Three Army STARRS component studies are large‐scale surveys: one of new soldiers prior to beginning Basic Combat Training (BCT; n  = 50,765 completed self‐administered questionnaires); another of other soldiers exclusive of those in BCT ( n  = 35,372); and a third of three Brigade Combat Teams about to deploy to Afghanistan who are being followed multiple times after returning from deployment ( n  = 9421). Although the response rates in these surveys are quite good (72.0–90.8%), questions can be raised about sample biases in estimating prevalence of mental disorders and suicidality, the main outcomes of the surveys based on evidence that people in the general population with mental disorders are under‐represented in community surveys. This paper presents the results of analyses designed to determine whether such bias exists in the Army STARRS surveys and, if so, to develop weights to correct for these biases. Data are also presented on sample inefficiencies introduced by weighting and sample clustering and on analyses of the trade‐off between bias and efficiency in weight trimming. Copyright © 2013 John Wiley & Sons, Ltd .Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/102203/1/mpr1399.pd

Including information about co-morbidity in estimates of disease burden: results from the World Health Organization World Mental Health Surveys

Background The methodology commonly used to estimate disease burden, featuring ratings of severity of individual conditions, has been criticized for ignoring co-morbidity. A methodology that addresses this problem is proposed and illustrated here with data from the World Health Organization World Mental Health Surveys. Although the analysis is based on self-reports about one's own conditions in a community survey, the logic applies equally well to analysis of hypothetical vignettes describing co-morbid condition profiles. Method Face-to-face interviews in 13 countries (six developing, nine developed; n=31 067; response rate=69.6%) assessed 10 classes of chronic physical and nine of mental conditions. A visual analog scale (VAS) was used to assess overall perceived health. Multiple regression analysis with interactions for co-morbidity was used to estimate associations of conditions with VAS. Simulation was used to estimate condition-specific effects. Results The best-fitting model included condition main effects and interactions of types by numbers of conditions. Neurological conditions, insomnia and major depression were rated most severe. Adjustment for co-morbidity reduced condition-specific estimates with substantial between-condition variation (0.24-0.70 ratios of condition-specific estimates with and without adjustment for co-morbidity). The societal-level burden rankings were quite different from the individual-level rankings, with the highest societal-level rankings associated with conditions having high prevalence rather than high individual-level severity. Conclusions Plausible estimates of disorder-specific effects on VAS can be obtained using methods that adjust for co-morbidity. These adjustments substantially influence condition-specific rating

Field procedures in the Army Study to Assess Risk and Resilience in Servicemembers (Army STARRS)

The Army Study to Assess Risk and Resilience in Servicemembers (Army STARRS) is a multi‐component epidemiological and neurobiological study of unprecedented size and complexity designed to generate actionable evidence‐based recommendations to reduce US Army suicides and increase basic knowledge about determinants of suicidality by carrying out coordinated component studies. A number of major logistical challenges were faced in implementing these studies. The current report presents an overview of the approaches taken to meet these challenges, with a special focus on the field procedures used to implement the component studies. As detailed in the paper, these challenges were addressed at the onset of the initiative by establishing an Executive Committee, a Data Coordination Center (the Survey Research Center [SRC] at the University of Michigan), and study‐specific design and analysis teams that worked with staff on instrumentation and field procedures. SRC staff, in turn, worked with the Office of the Deputy Under Secretary of the Army (ODUSA) and local Army Points of Contact (POCs) to address logistical issues and facilitate data collection. These structures, coupled with careful fieldworker training, supervision, and piloting, contributed to the major Army STARRS data collection efforts having higher response rates than previous large‐scale studies of comparable military samples. Copyright © 2013 John Wiley & Sons, Ltd .Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/102238/1/mpr1400.pd