Outreach Program to Develop And Implement Local Land Use Regulations to Protect the Remaining Undisturbed Natural Shoreland Buffers in the Towns of Candia and Deerfield, NH

The towns of Candia and Deerfield, New Hampshire, both situated within the Great Bay/Little Bay watershed and the Lamprey River subwatershed have agreed to participate with the Southern New Hampshire Regional Planning Commission (SNHPC) to develop and implement land use regulations to protect the remaining undisturbed natural shoreline buffers along the Lamprey and North Branch Rivers (2nd order or higher streams and tributaries) and other surface waters within these communities

Harmonic Morphisms on Lie groups and Minimal Conformal Foliations of Codimension two

Let G be a Lie group equipped with a left-invariant semi-Riemannian metric. Let K be a semisimple subgroup of G generating a left-invariant conformal foliation F of codimension two on G. We then show that the foliation F is minimal. This means that locally the leaves of F are fibres of a complex-valued harmonic morphism. In the Riemannian case, we prove that if the metric restricted to K is biinvariant then F is totally geodesic

Symmetric Spaces, Geometric Manifolds and Geodesic Completeness

This thesis explores topics related to the geodesic completeness of compact locally sym metric Lorentzian manifolds. In particular, it discusses some important results relating to locally and globally symmetric spaces as well as the theory of geometric manifolds. These results are used to present a proof of a key proposition in Klingler (1996), which proves the geodesic completeness of compact Lorentzian manifolds with constant curvature. We also prove a new result, that compact Lorentzian manifolds which are locally isometric to the product of Cahen-Wallach space and flat Riemannian space are geodesically complete by extending methods used in Leistner & Schliebner (2016). These results may be helpful in the study of geodesic completeness of compact locally symmetric Lorentzian manifolds more generally as they reduce the number of open cases.Thesis (MPhil) -- University of Adelaide, School of Mathematical Sciences, 202

Clinical effectiveness, cost effectiveness and acceptability of community-based treatment of Hepatitis C Virus infection: a mixed method systematic review

Several community-based models for treating Hepatitis C Virus (HCV) infection have been implemented to improve treatment accessibility and health outcomes. However, there is a lack of knowledge regarding how well these models achieve the desired goals. We conducted a mixed-method systematic review of quantitative and qualitative evidence about clinical effectiveness, cost effectiveness and acceptability of community-based HCV treatment models. Seventeen databases were researched for published and unpublished studies. Methodological quality was assessed using The Joanna Briggs Institute Critical Appraisal tools. Quantitative findings were synthesised in narrative form and qualitative findings were synthesised using meta-synthesis. Forty-two quantitative and six qualitative studies were included. No relevant cost effectiveness studies were found. Five categories of community-based models were identified: telehealth, integration of HCV and addiction services, integration of HCV and HIV services, integration of HCV and primary care, and implementation by a home care and health care management company. The range of reported outcomes included; end of treatment response: 48.7% to 96%, serious side effects: 3.3% to 27.8%, sustained virological response: 22·3% to 95·5%, relapse: 2·2% to 16·7%, and treatment completion: 33·4% to 100%. Inconsistent measures of uptake and adherence were used; uptake ranged from 8·3% to 92%, and 68·4% to 100% of patients received ≥80% of prescribed doses. Patient reported experiences included trusted and supportive care providers, safe and trusted services, easily accessible care, and positive psychological and behavioural changes. The clinical effectiveness and acceptability reported from the included studies are similar to or better than reported outcomes from systematic reviews of studies in tertiary settings. Studies of the cost-effectiveness of community-based models for treating HCV are needed. This article is protected by copyright. All rights reserved

The effects of integrated care: a systematic review of UK and international evidence

BACKGROUND: Healthcare systems around the world have been responding to the demand for better integrated models of service delivery. However, there is a need for further clarity regarding the effects of these new models of integration, and exploration regarding whether models introduced in other care systems may achieve similar outcomes in a UK national health service context. METHODS: The study aimed to carry out a systematic review of the effects of integration or co-ordination between healthcare services, or between health and social care on service delivery outcomes including effectiveness, efficiency and quality of care. Electronic databases including MEDLINE; Embase; PsycINFO; CINAHL; Science and Social Science Citation Indices; and the Cochrane Library were searched for relevant literature published between 2006 to March 2017. Online sources were searched for UK grey literature, and citation searching, and manual reference list screening were also carried out. Quantitative primary studies and systematic reviews, reporting actual or perceived effects on service delivery following the introduction of models of integration or co-ordination, in healthcare or health and social care settings in developed countries were eligible for inclusion. Strength of evidence for each outcome reported was analysed and synthesised using a four point comparative rating system of stronger, weaker, inconsistent or limited evidence. RESULTS: One hundred sixty seven studies were eligible for inclusion. Analysis indicated evidence of perceived improved quality of care, evidence of increased patient satisfaction, and evidence of improved access to care. Evidence was rated as either inconsistent or limited regarding all other outcomes reported, including system-wide impacts on primary care, secondary care, and health care costs. There were limited differences between outcomes reported by UK and international studies, and overall the literature had a limited consideration of effects on service users. CONCLUSIONS: Models of integrated care may enhance patient satisfaction, increase perceived quality of care, and enable access to services, although the evidence for other outcomes including service costs remains unclear. Indications of improved access may have important implications for services struggling to cope with increasing demand. TRIAL REGISTRATION: Prospero registration number: 42016037725

Exploration of Shared Genetic Architecture Between Subcortical Brain Volumes and Anorexia Nervosa

In MRI scans of patients with anorexia nervosa (AN), reductions in brain volume are often apparent. However, it is unknown whether such brain abnormalities are influenced by genetic determinants that partially overlap with those underlying AN. Here, we used a battery of methods (LD score regression, genetic risk scores, sign test, SNP effect concordance analysis, and Mendelian randomization) to investigate the genetic covariation between subcortical brain volumes and risk for AN based on summary measures retrieved from genome-wide association studies of regional brain volumes (ENIGMA consortium, n = 13,170) and genetic risk for AN (PGC-ED consortium, n = 14,477). Genetic correlations ranged from − 0.10 to 0.23 (all p > 0.05). There were some signs of an inverse concordance between greater thalamus volume and risk for AN (permuted p = 0.009, 95% CI: [0.005, 0.017]). A genetic variant in the vicinity of ZW10, a gene involved in cell division, and neurotransmitter and immune system relevant genes, in particular DRD2, was significantly associated with AN only after conditioning on its association with caudate volume (pFDR = 0.025). Another genetic variant linked to LRRC4C, important in axonal and synaptic development, reached significance after conditioning on hippocampal volume (pFDR = 0.021). In this comprehensive set of analyses and based on the largest available sample sizes to date, there was weak evidence for associations between risk for AN and risk for abnormal subcortical brain volumes at a global level (that is, common variant genetic architecture), but suggestive evidence for effects of single genetic markers. Highly powered multimodal brain- and disorder-related genome-wide studies are needed to further dissect the shared genetic influences on brain structure and risk for AN

Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity.

Global dispersal and increasing frequency of the SARS-CoV-2 spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the hypothesis for positive selection of spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequences. Despite the availability of a large dataset, well represented by both spike 614 variants, not all approaches showed a conclusive signal of positive selection. Population genetic analysis indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We do not find any indication that patients infected with the spike 614G variant have higher COVID-19 mortality or clinical severity, but 614G is associated with higher viral load and younger age of patients. Significant differences in growth and size of 614G phylogenetic clusters indicate a need for continued study of this variant

Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders

Genetic influences on psychiatric disorders transcend diagnostic boundaries, suggesting substantial pleiotropy of contributing loci. However, the nature and mechanisms of these pleiotropic effects remain unclear. We performed analyses of 232,964 cases and 494,162 controls from genome-wide studies of anorexia nervosa, attention-deficit/hyper-activity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, and Tourette syndrome. Genetic correlation analyses revealed a meaningful structure within the eight disorders, identifying three groups of inter-related disorders. Meta-analysis across these eight disorders detected 109 loci associated with at least two psychiatric disorders, including 23 loci with pleiotropic effects on four or more disorders and 11 loci with antagonistic effects on multiple disorders. The pleiotropic loci are located within genes that show heightened expression in the brain throughout the lifespan, beginning prenatally in the second trimester, and play prominent roles in neurodevelopmental processes. These findings have important implications for psychiatric nosology, drug development, and risk prediction.Peer reviewe

Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors

Background Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. Methods We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. Results Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. Conclusions Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.Peer reviewe