One health in the U.S. military: a review of existing systems and recommendations for the future

2014 Summer.Includes bibliographical references.Background: The merging of the former U.S. Army Veterinary Command (VETCOM) with the former U.S. Army Center for Health Promotion and Preventive Medicine (USACHPPM) into the U.S. Army Public Health Command (USAPHC) in 2011 created an opportunity for the military to fully embrace the One Health concept. That same year, the USAPHC began work on a Zoonotic Disease Report (ZDR) aimed at supporting critical zoonotic disease risk assessments by combining zoonotic disease data from human, entomological, laboratory, and animal data sources. The purpose of this dissertation is to facilitate the creation of a military Zoonotic Disease Surveillance program that combines disease data from both military human and animal sources. Methods: Five of the most commonly used human military medical data systems were systematically reviewed using a standardized template based on Centers for Disease Control and Preventive Medicine (CDC) guidelines. The systems were then compared to each other in order to recommend the one(s) best suited for use in the USAPHC ZDR. The first stage of the comparison focused on each system's ability to meet the specific goals and objectives of the ZDR, whereas the second stage applied capture-recapture methodology to data system queries in order to evaluate each system's data quality (completeness). A pilot study was conducted using Lyme borreliosis to investigate the utility of military pet dogs as sentinel surveillance for zoonotic disease in military populations. Canine data came from 3996 surveys collected from 15 military veterinary facilities from 1 November 2012 through 31 October 2013. Surveys simultaneously collected Borrelia burgdorferi (Bb) seroprevalence and canine risk factor data for each participating pet dog. Human data were obtained by querying the Defense Medical Surveillance System for the same 15 military locations and the same time period. The correlation of military pet dog Bb seroprevalence and military human Lyme disease (borreliosis) data was estimated using the Spearman Rank Correlation. The difference between military pet dog data and civilian pet dog data was examined through the use of the chi-squared test for proportions. Multivariable logistic regression was then used to investigate the potential for identified risk factors to impact the observed association. Results: The comparison of human military medical data systems found the Military Health System Management Analysis and Reporting Tool (M2) data system most completely met the specific goals and objects of the ZDR. In addition, completeness calculation showed the M2 data source to be the most complete source of human data; 55% of total captured cases coming from the M2 system alone. The pilot study found a strong positive correlation between military human borreliosis data and military pet dog Bb seroprevalence data by location (rs = 0.821). The study showed reassuring similarities in pet dog seroprevalence by location for the majority of sites, but also showed meaningful differences between two locations, potentially indicating military pet dogs as more appropriate indicators of Lyme disease risk for military populations than civilian pet dog data. Unfortunately, whether canine Bb seroprevalence is influenced by the distribution of identified risk factors could not be determined due to limited study power. Conclusions: Based on this study M2 was recommended as the primary source of military human medical data for use in the Public Health Command Zoonotic Disease Report. In addition, it was recommended that Service member pet dog data be incorporated as a sensitive and convenient measure of zoonotic disease risk in human military populations. The validity of the data, however, should be evaluated further with either larger sample sizes and/or a zoonotic disease with higher prevalence

Structure of an anti-blood group A Fv and improvement of its binding affinity without loss of specificity.

The specificity of antibody recognition of the ABO blood group trisaccharide antigens has been explored by crystal structure analysis and mutation methods. The crystal structure of the Fv corresponding to the anti-blood group A antibody AC1001 has been determined to 2.2-A resolution and reveals a binding pocket that is complementary to the blood group A-trisaccharide antigen. The effect of mutating specific residues lining this pocket on binding to the A and B blood group oligosaccharide antigens was investigated through a panel of single point mutations and through a phage library of mutations in complementarity determining region H3. Both approaches gave several mutants with improved affinity for antigen. Surface plasmon resonance indicated up to 8-fold enhancement in affinity for the A-pentasaccharide with no observable binding to the blood group B antigen. This is the first example of single point mutations in a carbohydrate-binding antibody resulting in significant increases in binding affinity without loss of specificity

Increased matrix synthesis following adenoviral transfer of a transforming growth factor beta1 gene into articular chondrocytes

Monolayer cultures of lapine articular chondrocytes were transduced with first-generation adenoviral vectors carrying lacZ or transforming growth factor β1 genes under the transcriptional control of the human cytomegalovirus early promoter. High concentrations of transforming growth factor β1 were produced by chondrocytes following transfer of the transforming growth factor β1 gene but not the lacZ gene. Transduced chondrocytes responded to the elevated endogenous production of transforming growth factor β1 by increasing their synthesis of proteoglycan, collagen, and noncollagenous proteins in a dose-dependent fashion. The increases in collagen synthesis were not accompanied by alterations in the collagen phenotype; type-II collagen remained the predominant collagen. Transforming growth factor β1 could not, however, rescue the collagen phenotype of cells that had undergone phenotypic modulation as a result of serial passaging. These data demonstrate that chondrocytes can be genetically manipulated to produce and respond to the potentially therapeutic cytokine transforming growth factor β1. This technology has a number of experimental and therapeutic applications, including those related to the study and treatment of arthritis and cartilage repair

Simple Process-Led Algorithms for Simulating Habitats (SPLASH v.1.0): Robust Indices of Radiation, Evapotranspiration and Plant-Available Moisture

Bioclimatic indices for use in studies of ecosystem function, species distribution, and vegetation dynamics under changing climate scenarios depend on estimates of surface fluxes and other quantities, such as radiation, evapotranspi- ration and soil moisture, for which direct observations are sparse. These quantities can be derived indirectly from me- teorological variables, such as near-surface air temperature, precipitation and cloudiness. Here we present a consolidated set of simple process-led algorithms for simulating habitats (SPLASH) allowing robust approximations of key quantities at ecologically relevant timescales. We specify equations, derivations, simplifications, and assumptions for the estima- tion of daily and monthly quantities of top-of-the-atmosphere solar radiation, net surface radiation, photosynthetic photon flux density, evapotranspiration (potential, equilibrium, and actual), condensation, soil moisture, and runoff, based on analysis of their relationship to fundamental climatic drivers. The climatic drivers include a minimum of three meteoro- logical inputs: precipitation, air temperature, and fraction of bright sunshine hours. Indices, such as the moisture index, the climatic water deficit, and the Priestley–Taylor coeffi- cient, are also defined. The SPLASH code is transcribed in C++, FORTRAN, Python, and R. A total of 1 year of results are presented at the local and global scales to exemplify the spatiotemporal patterns of daily and monthly model outputs along with comparisons to other model results

Changing mothers' perception of infant emotion:a pilot study

Cognitive Bias Modification (CBM) techniques, which experimentally retrain abnormal processing of affective stimuli, are becoming established for various psychiatric disorders. Such techniques have not yet been applied to maternal processing of infant emotion, which is affected by various psychiatric disorders. MATERIALS AND METHODS: In a pilot study, mothers of children under 3 years old (n = 32) were recruited and randomly allocated to one of three training exercises, aiming either to increase or decrease their threshold of perceiving distress in a morphed continuum of 15 infant facial images. Differences between pre- and post-training threshold were analysed between and within subjects. RESULTS: Compared to baseline thresholds, the threshold for perceiving infant distress decreased in the lowered threshold group (mean difference -1.7 frames, 95% confidence intervals (CI) -3.1 to -0.3 p=0.02), increased in the raised threshold group (1.3 frames, 95% CI 0.6 to 2.1 p<0.01), and was unchanged in the control group (0.1 frames, 95% CI -0.8 to 1.1 p=0.80). Between group differences were similarly robust in regression models, and were not attenuated by potential confounders. CONCLUSIONS: The findings suggest that it is possible to change the threshold at which mothers perceive ambiguous infant faces as distressed, either to increase or decrease sensitivity to distress. This small study was intended to provide proof of concept (i.e., that it is possible to alter a mother’s perception of infant distress.) Questions remain as to whether the effects persist beyond the immediate experimental session, have an impact on maternal behaviour, and could be used in clinical samples to improve maternal sensitivity and child outcomes

Threat-sensitive anti-predator defence in precocial wader, the northern lapwing Vanellus vanellus

Birds exhibit various forms of anti-predator behaviours to avoid reproductive failure, with mobbing—observation, approach and usually harassment of a predator—being one of the most commonly observed. Here, we investigate patterns of temporal variation in the mobbing response exhibited by a precocial species, the northern lapwing (Vanellus vanellus). We test whether brood age and self-reliance, or the perceived risk posed by various predators, affect mobbing response of lapwings. We quantified aggressive interactions between lapwings and their natural avian predators and used generalized additive models to test how timing and predator species identity are related to the mobbing response of lapwings. Lapwings diversified mobbing response within the breeding season and depending on predator species. Raven Corvus corax, hooded crow Corvus cornix and harriers evoked the strongest response, while common buzzard Buteo buteo, white stork Ciconia ciconia, black-headed gull Chroicocephalus ridibundus and rook Corvus frugilegus were less frequently attacked. Lapwings increased their mobbing response against raven, common buzzard, white stork and rook throughout the breeding season, while defence against hooded crow, harriers and black-headed gull did not exhibit clear temporal patterns. Mobbing behaviour of lapwings apparently constitutes a flexible anti-predator strategy. The anti-predator response depends on predator species, which may suggest that lapwings distinguish between predator types and match mobbing response to the perceived hazard at different stages of the breeding cycle. We conclude that a single species may exhibit various patterns of temporal variation in anti-predator defence, which may correspond with various hypotheses derived from parental investment theory

Maternal postnatal depressive symptoms and offspring emotional and behavioral development at age 7 years in a U.K. birth cohort: The role of paternal involvement

There is considerable variability in developmental outcomes of children whose mothers experience depression. Few longitudinal studies have examined contributions of paternal involvement in the association between maternal postnatal depression (PND) and offspring development. We examined pathways from maternal PND at 8 weeks (Edinburgh Postnatal Depression Scale; total score) to offspring emotional and behavioral development at 7 years (Strengths and Difficulties Questionnaire; total score) through behavioral, affective, and cognitive dimensions of paternal involvement in a U.K.-based birth cohort (Avon Longitudinal Study of Parents and Children; n = 3,434). Analyses were adjusted for baseline confounders and paternal PND (Edinburgh Postnatal Depression Scale; total score) as an intermediate confounder. Maternal PND was strongly associated with offspring development, but this association was not mediated by the combination of all indirect pathways through various dimensions of paternal involvement. Only father–child conflict emerged as a risk factor for adverse offspring development and as a mediator in the association between maternal PND and offspring development (albeit the effect size was small). If found causal, interventions that reduce father–child conflict may reduce the risk of adverse development in offspring of mothers with PND

CSF1R+ Macrophages Sustain Pancreatic Tumor Growth through T Cell Suppression and Maintenance of Key Gene Programs that Define the Squamous Subtype.

Pancreatic ductal adenocarcinoma (PDAC) is resistant to most therapies including single-agent immunotherapy and has a dense desmoplastic stroma, and most patients present with advanced metastatic disease. We reveal that macrophages are the dominant leukocyte population both in human PDAC stroma and autochthonous models, with an important functional contribution to the squamous subtype of human PDAC. We targeted macrophages in a genetic PDAC model using AZD7507, a potent selective inhibitor of CSF1R. AZD7507 caused shrinkage of established tumors and increased mouse survival in this difficult-to-treat model. Malignant cell proliferation diminished, with increased cell death and an enhanced T cell immune response. Loss of macrophages rewired other features of the TME, with global changes in gene expression akin to switching PDAC subtypes. These changes were markedly different to those elicited when neutrophils were targeted via CXCR2. These results suggest targeting the myeloid cell axis may be particularly efficacious in PDAC, especially with CSF1R inhibitors