Restoration and Management of High-Use Urban Missouri Woodlands and Forests in St. Louis

St. Louis City’s urban woodland and forested natural areas were modified, degraded, and/or overly-mature habitats requiring management intervention for ecological health, species diversity, and public safety. To accomplish long-term success in Forest Park’s woodlands and forests, restorations and management strategies seeking to “treat the problem not the symptom” was implemented. The most important best management practices for Forest Park’s woodlands and forests included forest stand improvement, prescribed burns, invasive and non-native species management, creation of public stewards, and plant material supplementation

Natural Resource Monitoring Progression of Forest Park’s Forested Natural Areas in St. Louis, Missouri

St. Louis City, MO had 121 acres managed as woodland or forested natural areas: 98 acres in Forest Park and 13 acres in O’Fallon Park. In Forest Park, standardized Missouri forest vegetation monitoring plots were started in 1993 to develop and guide habitat management such as thinning, species richness development, etc. In 2018 and 2019, a holistic Natural Resources Management Plan (NRMP) for Forest Park provided additional recommended metrics and monitoring, some of which have already begun implementation

The Importance of Nebular Continuum and Line Emission in Observations of Young Massive Star Clusters

In this spectroscopic study of infant massive star clusters, we find that continuum emission from ionized gas rivals the stellar luminosity at optical wavelengths. In addition, we find that nebular line emission is significant in many commonly used broad-band HST filters including the F814W I-band, the F555W V-band and the F435W B-band. Two young massive clusters (YMCs) in NGC 4449 were targeted for spectroscopic observations after Reines et al. (2008a) discovered an F814W I-band excess in their photometric study of radio-detected clusters in the galaxy. The spectra were obtained with the Dual Imaging Spectrograph on the 3.5 m APO telescope. We supplement these data with HST and SDSS photometry. By comparing our data to the Starburst99 and GALEV models, we find that nebular continuum emission competes with the stellar light in our observations and that the relative contribution is largest in the U- and I-bands, where the Balmer and Paschen jumps are located. The spectra also exhibit strong line emission including the [SIII] 9069,9532 lines in the HST F814W I-band. We find that the combination of nebular continuum and line emission can account for the F814W I-band excess found by Reines et al. (2008a). In an effort to provide a benchmark for estimating the impact of ionized gas emission on photometric observations of YMCs, we compute the relative contributions of the stellar continuum, nebular continuum, and emission lines to the total flux of a 3 Myr-old cluster through various HST filter/instrument combinations, including filters in the WFC3. We urge caution when comparing observations of YMCs to evolutionary synthesis models since nebular emission can have a large impact on magnitudes and colors of young (< 5 Myr) clusters, significantly affecting inferred properties such as ages, masses and extinctions. (Abridged)Comment: 13 pages, 11 figures, Accepted for Publication in Ap

Reducing recurrent stroke: Methodology of the motivational interviewing in stroke (MIST) randomized clinical trial

Rationale Recurrent stroke is prevalent in both developed and developing countries, contributing significantly to disability and death. Recurrent stroke rates can be reduced by adequate risk factor management. However, adherence to prescribed medications and lifestyle changes recommended by physicians at discharge after stroke is poor, leading to a large number of preventable recurrent strokes. Using behavior change methods such as Motivational Interviewing early after stroke occurrence has the potential to prevent recurrent stroke. Aims and/or hypothesis The overall aim of the study is to determine the effectiveness of motivational interviewing in improving adherence to medication and lifestyle changes recommended by treating physicians at and after hospital discharge in stroke patients 12 months poststroke to reduce risk factors for recurrent stroke. Design Recruitment of 430 first-ever stroke participants will occur in the Auckland and Waikato regions. Randomization will be to intervention or usual care groups. Participants randomized to intervention will receive four motivational interviews and five follow-up assessments over 12 months. Nonintervention participants will be assessed at the same time points. Study outcomes Primary outcome measures are changes in systolic blood pressure and low-density lipoprotein levels 12 months poststroke. Secondary outcomes include self-reported adherence and barriers to prescribed medications, new cardiovascular events (including stroke), changes in quality of life, and mood. Discussion The results of the motivational interviewing in stroke trial will add to our understanding of whether motivational interviewing may be potentially beneficial in the management of stroke and other diseases where similar lifestyle factors or medication adherence are relevant

Corneal Alterations during Combined Therapy with Cyclodextrin/Allopregnanolone and Miglustat in a Knock-Out Mouse Model of NPC1 Disease

BACKGROUND: Niemann Pick disease type C1 is a neurodegenerative disease caused by mutations in the NPC1 gene, which result in accumulation of unesterified cholesterol and glycosphingolipids in the endosomal-lysosomal system as well as limiting membranes. We have previously shown the corneal involvement in NPC1 pathology in form of intracellular inclusions in epithelial cells and keratocytes. The purpose of the present study was to clarify if these inclusions regress during combined substrate reduction- and by-product therapy (SRT and BPT). METHODOLOGY/PRINCIPAL FINDINGS: Starting at postnatal day 7 (P7) and thereafter, NPC1 knock-out mice (NPC1(-/-)) and wild type controls (NPC1(+/+)) were injected with cyclodextrin/allopregnanolone weekly. Additionally, a daily miglustat injection started at P10 until P23. Starting at P23 the mice were fed powdered chow with daily addition of miglustat. The sham group was injected with 0.9% NaCl at P7, thereafter daily starting at P10 until P23, and fed powdered chow starting at P23. For corneal examination, in vivo confocal laser-scanning microscopy (CLSM) was performed one day before experiment was terminated. Excised corneas were harvested for lipid analysis (HPLC/MS) and electron microscopy. In vivo CLSM demonstrated a regression of hyperreflective inclusions in all treated NPC1(-/-)mice. The findings varied between individual mice, demonstrating a regression, ranging from complete absence to pronounced depositions. The reflectivity of inclusions, however, was significantly lower when compared to untreated and sham-injected NPC1(-/-) mice. These confocal findings were confirmed by lipid analysis and electron microscopy. Another important CLSM finding revealed a distinct increase of mature dendritic cell number in corneas of all treated mice (NPC1(-/-) and NPC1(+/+)), including sham-treated ones. CONCLUSIONS/SIGNIFICANCE: The combined substrate reduction- and by-product therapy revealed beneficial effects on the cornea. In vivo CLSM is a non-invasive tool to monitor disease progression and treatment effects in NPC1 disorder

Improving Genetic Prediction by Leveraging Genetic Correlations Among Human Diseases and Traits

Genomic prediction has the potential to contribute to precision medicine. However, to date, the utility of such predictors is limited due to low accuracy for most traits. Here theory and simulation study are used to demonstrate that widespread pleiotropy among phenotypes can be utilised to improve genomic risk prediction. We show how a genetic predictor can be created as a weighted index that combines published genome-wide association study (GWAS) summary statistics across many different traits. We apply this framework to predict risk of schizophrenia and bipolar disorder in the Psychiatric Genomics consortium data, finding substantial heterogeneity in prediction accuracy increases across cohorts. For six additional phenotypes in the UK Biobank data, we find increases in prediction accuracy ranging from 0.7 for height to 47 for type 2 diabetes, when using a multi-trait predictor that combines published summary statistics from multiple traits, as compared to a predictor based only on one trait. © 2018 The Author(s)

Genome-wide association study identifies 30 Loci Associated with Bipolar Disorder

This paper is dedicated to the memory of Psychiatric Genomics Consortium (PGC) founding member and Bipolar disorder working group co-chair Pamela Sklar. We thank the participants who donated their time, experiences and DNA to this research, and to the clinical and scientific teams that worked with them. We are deeply indebted to the investigators who comprise the PGC. The views expressed are those of the authors and not necessarily those of any funding or regulatory body. Analyses were carried out on the NL Genetic Cluster Computer (http://www.geneticcluster.org ) hosted by SURFsara, and the Mount Sinai high performance computing cluster (http://hpc.mssm.edu).Bipolar disorder is a highly heritable psychiatric disorder. We performed a genome-wide association study including 20,352 cases and 31,358 controls of European descent, with follow-up analysis of 822 variants with P<1x10-4 in an additional 9,412 cases and 137,760 controls. Eight of the 19 variants that were genome-wide significant (GWS, p < 5x10-8) in the discovery GWAS were not GWS in the combined analysis, consistent with small effect sizes and limited power but also with genetic heterogeneity. In the combined analysis 30 loci were GWS including 20 novel loci. The significant loci contain genes encoding ion channels, neurotransmitter transporters and synaptic components. Pathway analysis revealed nine significantly enriched gene-sets including regulation of insulin secretion and endocannabinoid signaling. BDI is strongly genetically correlated with schizophrenia, driven by psychosis, whereas BDII is more strongly correlated with major depressive disorder. These findings address key clinical questions and provide potential new biological mechanisms for BD.This work was funded in part by the Brain and Behavior Research Foundation, Stanley Medical Research Institute, University of Michigan, Pritzker Neuropsychiatric Disorders Research Fund L.L.C., Marriot Foundation and the Mayo Clinic Center for Individualized Medicine, the NIMH Intramural Research Program; Canadian Institutes of Health Research; the UK Maudsley NHS Foundation Trust, NIHR, NRS, MRC, Wellcome Trust; European Research Council; German Ministry for Education and Research, German Research Foundation IZKF of Münster, Deutsche Forschungsgemeinschaft, ImmunoSensation, the Dr. Lisa-Oehler Foundation, University of Bonn; the Swiss National Science Foundation; French Foundation FondaMental and ANR; Spanish Ministerio de Economía, CIBERSAM, Industria y Competitividad, European Regional Development Fund (ERDF), Generalitat de Catalunya, EU Horizon 2020 Research and Innovation Programme; BBMRI-NL; South-East Norway Regional Health Authority and Mrs. Throne-Holst; Swedish Research Council, Stockholm County Council, Söderström Foundation; Lundbeck Foundation, Aarhus University; Australia NHMRC, NSW Ministry of Health, Janette M O'Neil and Betty C Lynch

Using psychological theory and qualitative methods to develop a new evidence-based website about acupuncture for back pain.

INTRODUCTION: Potential acupuncture patients seek out information about acupuncture from various sources including websites, many of which are unreliable. We aimed to create an informative, scientifically accurate and engaging website to educate patients about acupuncture for back pain and modify their beliefs in a way that might enhance its clinical effects. METHODS: We used psychological theory and techniques to design an evidence-based website, incorporating multimedia elements. We conducted qualitative "think aloud" audio-recorded interviews to elicit user views of the website. A convenience sample of ten participants (4 male; aged 21-64 years from the local community) looked at the website in the presence of a researcher and spoke their thoughts out loud. Comments were categorised by topic. RESULTS: The website comprises 11 main pages and addresses key topics of interest to potential acupuncture patients, including beneficial and adverse effects, mechanisms of action, safety, practicalities, and patients' experiences of acupuncture. It provides information through text, evidence summaries and audio-clips of four patients' stories and two acupuncturists' descriptions of their practice, and three short films. Evidence from the think aloud study was used to identify opportunities to make the website more informative, engaging, and user-friendly. CONCLUSIONS: Using a combination of psychological theory and qualitative interviews enabled us to produce a user-friendly, evidence-based website that is likely to change patients' beliefs about acupuncture for back pain. Before using the website in clinical settings it is necessary to test its effects on key outcomes including patients' beliefs and capacity for making informed choices about acupuncture

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