Amphibians and Reptiles of United States Department of Defense Installations

The U.S. Department of Defense (DoD) occupies approximately 10.1 million ha of land within the U.S. spanning most ecosystems contained therein. To date, no comprehensive agency-wide inventory of amphibian and reptile species has been compiled. We developed an amphibian and reptile species inventory for 415 DoD installations/sites and evaluated species diversity. The amphibian and reptile species confirmed present on DoD sites represent 66% of the total native species documented in the continental U.S. Snakes are the most widespread group found on DoD lands. Of the military services, Army sites have the greatest number of confirmed species, federally listed, state-listed, and At-risk species. There are 24 federally listed (threatened or endangered), 55 state- listed, and 70 At-risk species confirmed present on DoD sites. Thirty non-native and native transplant amphibian and reptile species/subspecies are also confirmed present on DoD sites. Lastly, we verified that approximately half of the military sites evaluated in this study have at least one venomous snake species confirmed present. Our study results assist directly with ongoing management and conservation of amphibian and reptile species on DoD lands and confirm military lands comprise a significant contribution to biodiversity conservation

Amphibians and Reptiles of United States Department of Defense Installations

The U.S. Department of Defense (DoD) occupies approximately 10.1 million ha of land within the U.S. spanning most ecosystems contained therein. To date, no comprehensive agency-wide inventory of amphibian and reptile species has been compiled. We developed an amphibian and reptile species inventory for 415 DoD installations/sites and evaluated species diversity. The amphibian and reptile species confirmed present on DoD sites represent 66% of the total native species documented in the continental U.S. Snakes are the most widespread group found on DoD lands. Of the military services, Army sites have the greatest number of confirmed species, federally listed, state-listed, and At-risk species. There are 24 federally listed (threatened or endangered), 55 state- listed, and 70 At-risk species confirmed present on DoD sites. Thirty non-native and native transplant amphibian and reptile species/subspecies are also confirmed present on DoD sites. Lastly, we verified that approximately half of the military sites evaluated in this study have at least one venomous snake species confirmed present. Our study results assist directly with ongoing management and conservation of amphibian and reptile species on DoD lands and confirm military lands comprise a significant contribution to biodiversity conservation

The role of molecular sizes of carbohydrates on mouth sensations

The effects of addition to sweet potatoes of varying amounts of dextrin, glucose, maltose, and starch on mouth sensations, apparent viscosity, and static yield were tested. Sensory evaluations were conducted a minimum of four times on each sweet potato-carbohydrate mixture, and mixtures were objectively evaluated by a Brookfield viscosimeter for static yield and a Haake Rotovisco Model RV-l Viscometer for apparent viscosity. A two-way analysis of variance was used to test for differences between mean sensory panel ranks, static yield values, and apparent viscosity values of different sweet potato mixtures. A regression technique was used to determine whether linear, quadratic, or cubic effects were found with increasing amounts of carbohydrates. To further test the effects of variations in starch, maltose, and dextrin on apparent viscosity and static yield, a model system approximating the protein, carbohydrate, fat, and water composition of a cured, uncooked sweet potato was prepared. Nine variations of the model system were made in which the dextrin, starch, and maltose content were varied; all other components remained constant. Mean static yield and apparent viscosity values were tested as a function of quantity of starch, maltose, and dextrin

An Economic Framework for Evaluating Personalized Medicine

Individual variation accounts for a wide range of medical and economic consequences, from inefficiencies in drug discovery and development to ineffectiveness of drug treatment to drug-induced morbidity and mortality. Addressing these consequences could benefit patients, health care providers and payers, and the pharmaceutical industry. When appropriate markers are known, diagnostic tests allow precise diagnosis and dosing, prediction of disease progression, prediction of treatment response and prediction of adverse drug reactions for individual patients. There may also be substantial savings realized by eliminating costs associated with failed treatment. We developed an analytical framework for analyzing the potential value of using a diagnostic test in clinical practice. Our framework determines the economic consequences of implementing pharmacogenomics in the clinic using a diagnostic test to predict drug response. We offer an empirical test of these ideas: we calculated the cost offset realized by predicting the likelihood of response to an alternative existing treatment using a hypothetical pharmacogenomic test in an asthma population. Because the diagnostic test is hypothetical, our framework is general and could be applied to other indications where diagnostic tests have not been developed. Our results could potentially guide future economic evaluation of new diagnostic tests. Importantly, they may also influence biomarker discovery strategies to ensure consistency between market priorities and the future stream of product introductions

The Capacity of Mycobacterium tuberculosis To Survive Iron Starvation Might Enable It To Persist in Iron-Deprived Microenvironments of Human Granulomas

ABSTRACT This study was conducted to investigate the role of iron deprivation in the persistence of Mycobacterium tuberculosis. We present evidence of iron restriction in human necrotic granulomas and demonstrate that under iron starvation M. tuberculosis persists, refractive to antibiotics and capable of restarting replication when iron is made available. Transcriptomics and metabolomic analyses indicated that the persistence of M. tuberculosis under iron starvation is dependent on strict control of endogenous Fe utilization and is associated with upregulation of pathogenicity and intrinsic antibiotic resistance determinants. M. tuberculosis mutants compromised in their ability to survive Fe starvation were identified. The findings of this study advance the understanding of the physiological settings that may underpin the chronicity of human tuberculosis (TB) and are relevant to the design of effective antitubercular therapies

Association studies of up to 1.2 million individuals yield new insights into the genetic etiology of tobacco and alcohol use.

Tobacco and alcohol use are leading causes of mortality that influence risk for many complex diseases and disorders1. They are heritable2,3 and etiologically related4,5 behaviors that have been resistant to gene discovery efforts6-11. In sample sizes up to 1.2 million individuals, we discovered 566 genetic variants in 406 loci associated with multiple stages of tobacco use (initiation, cessation, and heaviness) as well as alcohol use, with 150 loci evidencing pleiotropic association. Smoking phenotypes were positively genetically correlated with many health conditions, whereas alcohol use was negatively correlated with these conditions, such that increased genetic risk for alcohol use is associated with lower disease risk. We report evidence for the involvement of many systems in tobacco and alcohol use, including genes involved in nicotinic, dopaminergic, and glutamatergic neurotransmission. The results provide a solid starting point to evaluate the effects of these loci in model organisms and more precise substance use measures

Comprehensive Essentiality Analysis of the Mycobacterium tuberculosis Genome via Saturating Transposon Mutagenesis

For decades, identifying the regions of a bacterial chromosome that are necessary for viability has relied on mapping integration sites in libraries of random transposon mutants to find loci that are unable to sustain insertion. To date, these studies have analyzed subsaturated libraries, necessitating the application of statistical methods to estimate the likelihood that a gap in transposon coverage is the result of biological selection and not the stochasticity of insertion. As a result, the essentiality of many genomic features, particularly small ones, could not be reliably assessed. We sought to overcome this limitation by creating a completely saturated transposon library in Mycobacterium tuberculosis. In assessing the composition of this highly saturated library by deep sequencing, we discovered that a previously unknown sequence bias of the Himar1 element rendered approximately 9% of potential TA dinucleotide insertion sites less permissible for insertion. We used a hidden Markov model of essentiality that accounted for this unanticipated bias, allowing us to confidently evaluate the essentiality of features that contained as few as 2 TA sites, including open reading frames (ORF), experimentally identified noncoding RNAs, methylation sites, and promoters. In addition, several essential regions that did not correspond to known features were identified, suggesting uncharacterized functions that are necessary for growth. This work provides an authoritative catalog of essential regions of the M. tuberculosis genome and a statistical framework for applying saturating mutagenesis to other bacteria

A large-scale genome-wide association study meta-analysis of cannabis use disorder

Summary Background Variation in liability to cannabis use disorder has a strong genetic component (estimated twin and family heritability about 50–70%) and is associated with negative outcomes, including increased risk of psychopathology. The aim of the study was to conduct a large genome-wide association study (GWAS) to identify novel genetic variants associated with cannabis use disorder. Methods To conduct this GWAS meta-analysis of cannabis use disorder and identify associations with genetic loci, we used samples from the Psychiatric Genomics Consortium Substance Use Disorders working group, iPSYCH, and deCODE (20 916 case samples, 363 116 control samples in total), contrasting cannabis use disorder cases with controls. To examine the genetic overlap between cannabis use disorder and 22 traits of interest (chosen because of previously published phenotypic correlations [eg, psychiatric disorders] or hypothesised associations [eg, chronotype] with cannabis use disorder), we used linkage disequilibrium score regression to calculate genetic correlations. Findings We identified two genome-wide significant loci: a novel chromosome 7 locus (FOXP2, lead single-nucleotide polymorphism [SNP] rs7783012; odds ratio [OR] 1·11, 95% CI 1·07–1·15, p=1·84 × 10−9) and the previously identified chromosome 8 locus (near CHRNA2 and EPHX2, lead SNP rs4732724; OR 0·89, 95% CI 0·86–0·93, p=6·46 × 10−9). Cannabis use disorder and cannabis use were genetically correlated (rg 0·50, p=1·50 × 10−21), but they showed significantly different genetic correlations with 12 of the 22 traits we tested, suggesting at least partially different genetic underpinnings of cannabis use and cannabis use disorder. Cannabis use disorder was positively genetically correlated with other psychopathology, including ADHD, major depression, and schizophrenia. Interpretation These findings support the theory that cannabis use disorder has shared genetic liability with other psychopathology, and there is a distinction between genetic liability to cannabis use and cannabis use disorder. Funding National Institute of Mental Health; National Institute on Alcohol Abuse and Alcoholism; National Institute on Drug Abuse; Center for Genomics and Personalized Medicine and the Centre for Integrative Sequencing; The European Commission, Horizon 2020; National Institute of Child Health and Human Development; Health Research Council of New Zealand; National Institute on Aging; Wellcome Trust Case Control Consortium; UK Research and Innovation Medical Research Council (UKRI MRC); The Brain & Behavior Research Foundation; National Institute on Deafness and Other Communication Disorders; Substance Abuse and Mental Health Services Administration (SAMHSA); National Institute of Biomedical Imaging and Bioengineering; National Health and Medical Research Council (NHMRC) Australia; Tobacco-Related Disease Research Program of the University of California; Families for Borderline Personality Disorder Research (Beth and Rob Elliott) 2018 NARSAD Young Investigator Grant; The National Child Health Research Foundation (Cure Kids); The Canterbury Medical Research Foundation; The New Zealand Lottery Grants Board; The University of Otago; The Carney Centre for Pharmacogenomics; The James Hume Bequest Fund; National Institutes of Health: Genes, Environment and Health Initiative; National Institutes of Health; National Cancer Institute; The William T Grant Foundation; Australian Research Council; The Virginia Tobacco Settlement Foundation; The VISN 1 and VISN 4 Mental Illness Research, Education, and Clinical Centers of the US Department of Veterans Affairs; The 5th Framework Programme (FP-5) GenomEUtwin Project; The Lundbeck Foundation; NIH-funded Shared Instrumentation Grant S10RR025141; Clinical Translational Sciences Award grants; National Institute of Neurological Disorders and Stroke; National Heart, Lung, and Blood Institute; National Institute of General Medical Sciences.Peer reviewe

European Cystic Fibrosis Society standards of care: best practice guidelines

Specialised CF care has led to a dramatic improvement in survival in CF: in the last four decades, well above what was seen in the general population over the same period. With the implementation of newborn screening in many European countries, centres are increasingly caring for a cohort of patients who have minimal lung disease at diagnosis and therefore have the potential to enjoy an excellent quality of life and an even greater life expectancy than was seen previously. To allow high quality care to be delivered throughout Europe, a landmark document was published in 2005 that sets standards of care. Our current document builds on this work, setting standards for best practice in key aspects of CF care. The objective of our document is to give a broad overview of the standards expected for screening, diagnosis, pre-emptive treatment of lung disease, nutrition, complications, transplant/end of life care and psychological support. For comprehensive details of clinical care of CF, references to the most up to date European Consensus Statements, Guidelines or Position Papers are provided in Table 1. We hope that this best practice document will be useful to clinical teams both in countries where CF care is developing and those with established CF centres