Importance of coastal change variables in determining vulnerability to sea- and lake-level change

This paper is not subject to U.S. copyright. The definitive version was published in Journal of Coastal Research 26 (2010): 176-183, doi:10.2112/08-1102.1.In 2001, the U.S. Geological Survey began conducting scientific assessments of coastal vulnerability to potential future sea- and lake-level changes in 22 National Park Service sea- and lakeshore units. Coastal park units chosen for the assessment included a variety of geological and physical settings along the U.S. Atlantic, Pacific, Gulf of Mexico, Gulf of Alaska, Caribbean, and Great Lakes shorelines. This research is motivated by the need to understand and anticipate coastal changes caused by accelerating sea-level rise, as well as lake-level changes caused by climate change, over the next century. The goal of these assessments is to provide information that can be used to make long-term (decade to century) management decisions. Here we analyze the results of coastal vulnerability assessments for several coastal national park units. Index-based assessments quantify the likelihood that physical changes may occur based on analysis of the following variables: tidal range, ice cover, wave height, coastal slope, historical shoreline change rate, geomorphology, and historical rate of relative sea- or lake-level change. This approach seeks to combine a coastal system's susceptibility to change with its natural ability to adapt to changing environmental conditions, and it provides a measure of the system's potential vulnerability to the effects of sea- or lake-level change. Assessments for 22 park units are combined to evaluate relationships among the variables used to derive the index. Results indicate that Atlantic and Gulf of Mexico parks have the highest vulnerability rankings relative to other park regions. A principal component analysis reveals that 99% of the index variability can be explained by four variables: geomorphology, regional coastal slope, water-level change rate, and mean significant wave height. Tidal range, ice cover, and historical shoreline change are not as important when the index is evaluated at large spatial scales (thousands of kilometers)

Seismic stratigraphic framework of the continental shelf offshore Delmarva, USA: implications for Mid-Atlantic Bight evolution since the Pliocene

© The Author(s), 2020. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Brothers, L. L., Foster, D. S., Pendleton, E. A., & Baldwin, W. E. Seismic stratigraphic framework of the continental shelf offshore Delmarva, USA: implications for Mid-Atlantic Bight evolution since the Pliocene. Marine Geology, 428, : (2020)106287, doi:10.1016/j.margeo.2020.106287.Understanding how past coastal systems have evolved is critical to predicting future coastal change. Using over 12,000 trackline kilometers of recently collected, co-located multi-channel boomer, sparker and chirp seismic reflection profile data integrated with previously collected borehole and vibracore data, we define the upper (< 115 m below mean lower low water) seismic stratigraphic framework offshore of the Delmarva Peninsula, USA. Twelve seismic units and 11 regionally extensive unconformities (U1-U11) were mapped over 5900 km2 of North America's Mid-Atlantic continental shelf. We interpret U3, U7, U9, U11 as transgressive ravinement surfaces, while U1,2,4,5,6,8,10 are subaerial unconformities illustrating distinct periods of lower sea-level. Based on areal distribution, stratigraphic relationships and dating results (Carbon 14 and amino acid racemization estimates) from earlier vibracore and borehole studies, we interpret the infilled channels as late Neogene and Quaternary courses of the Susquehanna, Potomac, Rappahannock, York, James rivers and tributaries, and a broad flood plain. These findings indicate that the region's geologic framework is more complex than previously thought and that Pleistocene paleochannels are abundant in the Mid-Atlantic. This study synthesizes and correlates the findings of other Atlantic Margin studies and establishes a large-scale Quaternary framework that enables more detailed stratigraphic analysis in the future. Such work has implications for inner continental shelf systems tract evolution, the relationship between antecedent geology and modern coastal systems, assessments of eustacy, glacial isostatic adjustment, and other processes and forcings that play a role in passive margin evolution.This work was supported by the U.S. Department of the Interior's Response to Hurricane Sandy

Critical Constraints on Chiral Hierarchies

We consider the constraints that critical dynamics places on models with a top quark condensate or strong extended technicolor (ETC). These models require that chiral-symmetry-breaking dynamics at a high energy scale plays a significant role in electroweak symmetry breaking. In order for there to be a large hierarchy between the scale of the high energy dynamics and the weak scale, the high energy theory must have a second order chiral phase transition. If the transition is second order, then close to the transition the theory may be described in terms of a low-energy effective Lagrangian with composite ``Higgs'' scalars. However, scalar theories in which there are more than one $\Phi^4$ coupling can have a {\it first order} phase transition instead, due to the Coleman-Weinberg instability. Therefore, top-condensate or strong ETC theories in which the composite scalars have more than one $\Phi^4$ coupling cannot always support a large hierarchy. In particular, if the Nambu--Jona-Lasinio model solved in the large-$N_c$ limit is a good approximation to the high-energy dynamics, then these models will not produce acceptable electroweak symmetry breaking.Comment: 10 pages, 1 postscript figure (appended), BUHEP-92-35, HUTP-92/A05

Changes in breast density and circulating estrogens in postmenopausal women receiving adjuvant anastrozole

Factors associated with an increased risk of breast cancer include prior breast cancer, high circulating estrogens, and increased breast density. Adjuvant aromatase inhibitors are associated with a reduction in incidence of contralateral breast cancer. We conducted a prospective, single-arm, single-institution study to determine whether use of anastrozole is associated with changes in contralateral breast density and circulating estrogens. Eligible patients included postmenopausal women with hormone receptor-positive early-stage breast cancer who had completed local therapy, had an intact contralateral breast, and were recommended an aromatase inhibitor as their only systemic therapy. Participants received anastrozole 1 mg daily for 12 months on study. We assessed contralateral breast density and serum estrogens at baseline, 6, and 12 months. The primary endpoint was change in contralateral percent breast density from baseline to 12 months. Secondary endpoints included change in serum estrone sulfate from baseline to 12 months. Fifty-four patients were accrued. At 12 months, compared with baseline, there was a nonstatistically significant reduction in breast density (mean change: -16%, 95% CI: -30 to 2, P = 0.08) and a significant reduction in estrone sulfate (mean change: -93%, 95% CI: -94 to -91, P < 0.001). Eighteen women achieved 20% or greater relative reduction in contralateral percent density at 12 months compared with baseline; however, no measured patient or disease characteristics distinguished these women from the overall population. Large trials are required to provide additional data on the relationship between aromatase inhibitors and breast density and, more importantly, whether observed changes in breast density correlate with meaningful disease-specific outcomes

The attitudes, beliefs and behaviours of GPs regarding exercise for chronic knee pain: a systematic review

<p>Abstract</p> <p>Background</p> <p>Joint pain, specifically chronic knee pain (CKP), is a frequent cause of chronic pain and limitation of function and mobility among older adults. Multiple evidence-based guidelines recommend exercise as a first-line treatment for all patients with CKP or knee osteoarthritis (KOA), yet healthcare practitioners' attitudes and beliefs may limit their implementation. This systematic review aims to identify the attitudes, beliefs and behaviours of General Practitioners (GPs) regarding the use of exercise for CKP/KOA.</p> <p>Methods</p> <p>We searched four electronic databases between inception and January 2008, using subject headings to identify studies examining the attitudes, beliefs or behaviours of GPs regarding the use of exercise for the treatment of CKP/KOA in adults aged over 45 years in primary care. Studies referring to patellofemoral pain syndrome or CKP secondary to other causes or that occurring in a prosthetic joint were excluded. Once inclusion and exclusion criteria were applied, study data were extracted and summarised. Study quality was independently reviewed using two assessment tools.</p> <p>Results</p> <p>From 2135 potentially relevant articles, 20 were suitable for inclusion. A variety of study methodologies and approaches to measuring attitudes beliefs and behaviours were used among the studies. Quality assessment revealed good reporting of study objective, type, outcome factors and, generally, the sampling frame. However, criticisms included use of small sample sizes, low response rates and under-reporting of non-responder factors. Although 99% of GPs agreed that exercise should be used for CKP/KOA and reported ever providing advice or referring to a physiotherapist, up to 29% believed that rest was the optimum management approach. The frequency of actual provision of exercise advice or physiotherapy referral was lower. Estimates of provision of exercise advice and physiotherapy referral were generally higher for vignette-based studies (exercise advice 9%-89%; physiotherapy referral 44%-77%) than reviews of actual practice (exercise advice 5%-52%; physiotherapy referral 13-63%). <it>A</it><it>dvice to exercise </it>and exercise <it>prescription </it>were not clearly differentiated.</p> <p>Conclusions</p> <p>Attitudes and beliefs of GPs towards exercise for CKP/KOA vary widely and exercise appears to be underused in the management of CKP/KOA. Limitations of the evidence base include the paucity of studies directly examining attitudes of GPs, poor methodological quality, limited generalisability of results and ambiguity concerning GPs' expected roles. Further investigation is required of the roles of GPs in using exercise as first-line management of CKP/KOA.</p

Pleiotropic meta-analysis of cognition, education, and schizophrenia differentiates roles of early neurodevelopmental and adult synaptic pathways

Susceptibility to schizophrenia is inversely correlated with general cognitive ability at both the phenotypic and the genetic level. Paradoxically, a modest but consistent positive genetic correlation has been reported between schizophrenia and educational attainment, despite the strong positive genetic correlation between cognitive ability and educational attainment. Here we leverage published genome-wide association studies (GWASs) in cognitive ability, education, and schizophrenia to parse biological mechanisms underlying these results. Association analysis based on subsets (ASSET), a pleiotropic meta-analytic technique, allowed jointly associated loci to be identified and characterized. Specifically, we identified subsets of variants associated in the expected (“concordant”) direction across all three phenotypes (i.e., greater risk for schizophrenia, lower cognitive ability, and lower educational attainment); these were contrasted with variants that demonstrated the counterintuitive (“discordant”) relationship between education and schizophrenia (i.e., greater risk for schizophrenia and higher educational attainment). ASSET analysis revealed 235 independent loci associated with cognitive ability, education, and/or schizophrenia at p < 5 × 10−8. Pleiotropic analysis successfully identified more than 100 loci that were not significant in the input GWASs. Many of these have been validated by larger, more recent single-phenotype GWASs. Leveraging the joint genetic correlations of cognitive ability, education, and schizophrenia, we were able to dissociate two distinct biological mechanisms—early neurodevelopmental pathways that characterize concordant allelic variation and adulthood synaptic pruning pathways—that were linked to the paradoxical positive genetic association between education and schizophrenia. Furthermore, genetic correlation analyses revealed that these mechanisms contribute not only to the etiopathogenesis of schizophrenia but also to the broader biological dimensions implicated in both general health outcomes and psychiatric illness

Identifying nootropic drug targets via large-scale cognitive GWAS and transcriptomics

Broad-based cognitive deficits are an enduring and disabling symptom for many patients with severe mental illness, and these impairments are inadequately addressed by current medications. While novel drug targets for schizophrenia and depression have emerged from recent large-scale genome-wide association studies (GWAS) of these psychiatric disorders, GWAS of general cognitive ability can suggest potential targets for nootropic drug repurposing. Here, we (1) meta-analyze results from two recent cognitive GWAS to further enhance power for locus discovery; (2) employ several complementary transcriptomic methods to identify genes in these loci that are credibly associated with cognition; and (3) further annotate the resulting genes using multiple chemoinformatic databases to identify "druggable" targets. Using our meta-analytic data set (N = 373,617), we identified 241 independent cognition-associated loci (29 novel), and 76 genes were identified by 2 or more methods of gene identification. Actin and chromatin binding gene sets were identified as novel pathways that could be targeted via drug repurposing. Leveraging our transcriptomic and chemoinformatic databases, we identified 16 putative genes targeted by existing drugs potentially available for cognitive repurposing.Peer reviewe

Genome-wide association meta-analysis in 269,867 individuals identifies new genetic and functional links to intelligence

Intelligence is highly heritable(1) and a major determinant of human health and well-being(2). Recent genome-wide meta-analyses have identified 24 genomic loci linked to variation in intelligence3-7, but much about its genetic underpinnings remains to be discovered. Here, we present a large-scale genetic association study of intelligence (n = 269,867), identifying 205 associated genomic loci (190 new) and 1,016 genes (939 new) via positional mapping, expression quantitative trait locus (eQTL) mapping, chromatin interaction mapping, and gene-based association analysis. We find enrichment of genetic effects in conserved and coding regions and associations with 146 nonsynonymous exonic variants. Associated genes are strongly expressed in the brain, specifically in striatal medium spiny neurons and hippocampal pyramidal neurons. Gene set analyses implicate pathways related to nervous system development and synaptic structure. We confirm previous strong genetic correlations with multiple health-related outcomes, and Mendelian randomization analysis results suggest protective effects of intelligence for Alzheimer's disease and ADHD and bidirectional causation with pleiotropic effects for schizophrenia. These results are a major step forward in understanding the neurobiology of cognitive function as well as genetically related neurological and psychiatric disorders.Peer reviewe

Basic science232. Certolizumab pegol prevents pro-inflammatory alterations in endothelial cell function

Background: Cardiovascular disease is a major comorbidity of rheumatoid arthritis (RA) and a leading cause of death. Chronic systemic inflammation involving tumour necrosis factor alpha (TNF) could contribute to endothelial activation and atherogenesis. A number of anti-TNF therapies are in current use for the treatment of RA, including certolizumab pegol (CZP), (Cimzia ®; UCB, Belgium). Anti-TNF therapy has been associated with reduced clinical cardiovascular disease risk and ameliorated vascular function in RA patients. However, the specific effects of TNF inhibitors on endothelial cell function are largely unknown. Our aim was to investigate the mechanisms underpinning CZP effects on TNF-activated human endothelial cells. Methods: Human aortic endothelial cells (HAoECs) were cultured in vitro and exposed to a) TNF alone, b) TNF plus CZP, or c) neither agent. Microarray analysis was used to examine the transcriptional profile of cells treated for 6 hrs and quantitative polymerase chain reaction (qPCR) analysed gene expression at 1, 3, 6 and 24 hrs. NF-κB localization and IκB degradation were investigated using immunocytochemistry, high content analysis and western blotting. Flow cytometry was conducted to detect microparticle release from HAoECs. Results: Transcriptional profiling revealed that while TNF alone had strong effects on endothelial gene expression, TNF and CZP in combination produced a global gene expression pattern similar to untreated control. The two most highly up-regulated genes in response to TNF treatment were adhesion molecules E-selectin and VCAM-1 (q 0.2 compared to control; p > 0.05 compared to TNF alone). The NF-κB pathway was confirmed as a downstream target of TNF-induced HAoEC activation, via nuclear translocation of NF-κB and degradation of IκB, effects which were abolished by treatment with CZP. In addition, flow cytometry detected an increased production of endothelial microparticles in TNF-activated HAoECs, which was prevented by treatment with CZP. Conclusions: We have found at a cellular level that a clinically available TNF inhibitor, CZP reduces the expression of adhesion molecule expression, and prevents TNF-induced activation of the NF-κB pathway. Furthermore, CZP prevents the production of microparticles by activated endothelial cells. This could be central to the prevention of inflammatory environments underlying these conditions and measurement of microparticles has potential as a novel prognostic marker for future cardiovascular events in this patient group. Disclosure statement: Y.A. received a research grant from UCB. I.B. received a research grant from UCB. S.H. received a research grant from UCB. All other authors have declared no conflicts of interes

Polygenic prediction of educational attainment within and between families from genome-wide association analyses in 3 million individuals

We conduct a genome-wide association study (GWAS) of educational attainment (EA) in a sample of ~3 million individuals and identify 3,952 approximately uncorrelated genome-wide-significant single-nucleotide polymorphisms (SNPs). A genome-wide polygenic predictor, or polygenic index (PGI), explains 12-16% of EA variance and contributes to risk prediction for ten diseases. Direct effects (i.e., controlling for parental PGIs) explain roughly half the PGI's magnitude of association with EA and other phenotypes. The correlation between mate-pair PGIs is far too large to be consistent with phenotypic assortment alone, implying additional assortment on PGI-associated factors. In an additional GWAS of dominance deviations from the additive model, we identify no genome-wide-significant SNPs, and a separate X-chromosome additive GWAS identifies 57