Challenges in the care of familial hypercholesterolemia: a community care perspective

Familial hyperchoelsterolaemia (FH) remains under-diagnosed and under-treated in the community setting. Earlier evidence suggested prevalence of 1:500 worldwide but newer evidence suggests it is more common. Less than 15% of FH patients are ever diagnosed with children and young adults rarely tested despite having most to gain given their lifetime exposure. Increasing awareness among primary care teams is critical to improve detection profile for FH. Cascade testing in the community setting needs a sustainable approach to be developed to facilitate family tracing of index cases. The use of the Dutch Lipid Clinic Network Criteria score to facilitate a phenotypic diagnosis is the preferred approach adopted in Australia and eliminates the need to undertake genetic testing for all suspected FH cases

The relative contribution of climate to changes in lesser prairie-chicken abundance

Citation: Ross, B. E., Haukos, D., Hagen, C., & Pitman, J. (2016). The relative contribution of climate to changes in lesser prairie-chicken abundance. Ecosphere, 7(6), 11. doi:10.1002/ecs2.1323Managing for species using current weather patterns fails to incorporate the uncertainty associated with future climatic conditions; without incorporating potential changes in climate into conservation strategies, management and conservation efforts may fall short or waste valuable resources. Understanding the effects of climate change on species in the Great Plains of North America is especially important, as this region is projected to experience an increased magnitude of climate change. Of particular ecological and conservation interest is the lesser prairie-chicken (Tympanuchus pallidicinctus), which was listed as "threatened" under the U.S. Endangered Species Act in May 2014. We used Bayesian hierarchical models to quantify the effects of extreme climatic events (extreme values of the Palmer Drought Severity Index [PDSI]) relative to intermediate (changes in El Nino Southern Oscillation) and long-term climate variability (changes in the Pacific Decadal Oscillation) on trends in lesser prairie-chicken abundance from 1981 to 2014. Our results indicate that lesser prairie-chicken abundance on leks responded to environmental conditions of the year previous by positively responding to wet springs (high PDSI) and negatively to years with hot, dry summers (low PDSI), but had little response to variation in the El Nino Southern Oscillation and the Pacific Decadal Oscillation. Additionally, greater variation in abundance on leks was explained by variation in site relative to broad-scale climatic indices. Consequently, lesser prairie-chicken abundance on leks in Kansas is more strongly influenced by extreme drought events during summer than other climatic conditions, which may have negative consequences for the population as drought conditions intensify throughout the Great Plains

Symmetry breaking in crossed magnetic and electric fields

We present the first observations of cylindrical symmetry breaking in highly excited diamagnetic hydrogen with a small crossed electric field, and we give a semiclassical interpretation of this effect. As the small perpendicular electric field is added, the recurrence strengths of closed orbits decrease smoothly to a minimum, and revive again. This phenomenon, caused by interference among the electron waves that return to the nucleus, can be computed from the azimuthal dependence of the classical closed orbits.Comment: 4 page REVTeX file including 5 postscript files (using psfig) Accepted for publication in Physical Review Letters. Difference from earlier preprint: we have discovered the cause of the earlier apparent discrepancy between experiment and theory and now achieve excellent agreemen

Unresolved issues and new challenges in teaching English to young learners:the case of South Korea

The introduction of languages, especially English, into the primary curriculum around the world has been one of the major language-in-education policy developments in recent years. In countries where English has been compulsory for a number of years, the question arises as to what extent the numerous and well-documented challenges faced by the initial implementation of early language learning policies have been overcome and whether new challenges have arisen as policies have become consolidated. This article therefore focuses on South Korea, where English has been compulsory in primary school since 1997. The issues raised by the introduction of English into the primary curriculum are reviewed and the current situation in South Korea is investigated. The results of a mixed methods study using survey data from 125 Korean primary school teachers, together with data from a small-scale case study of one teacher are presented. The study shows that, while some of the initial problems caused by the introduction of early language learning appear to have been addressed, other challenges persist. Moreover, the data reveal the emergence of a number of new challenges faced by primary school teachers of English as they seek to implement government policy

Patterns in Greater Sage-grouse population dynamics correspond with public grazing records at broad scales

Human land use, such as livestock grazing, can have profound yet varied effects on wildlife interacting within common ecosystems, yet our understanding of land-use effects is often generalized from short-term, local studies that may not correspond with trends at broader scales. Here we used public land records to characterize livestock grazing across Wyoming, USA, and we used Greater Sage-grouse (Centrocercus urophasianus) as a model organism to evaluate responses to livestock management. With annual counts of male Sage-grouse from 743 leks (breeding display sites) during 2004-2014, we modeled population trends in response to grazing level (represented by a relative grazing index) and timing across a gradient in vegetation productivity as measured by the Normalized Vegetation Difference Index (NDVI). We found grazing can have both positive and negative effects on Sage-grouse populations depending on the timing and level of grazing. Sage-grouse populations responded positively to higher grazing levels after peak vegetation productivity, but populations declined when similar grazing levels occurred earlier, likely reflecting the sensitivity of cool-season grasses to grazing during peak growth periods. We also found support for the hypothesis that effects of grazing management vary with local vegetation productivity. These results illustrate the importance of broad-scale analyses by revealing patterns in Sage-grouse population trends that may not be inferred from studies at finer scales, and could inform sustainable grazing management in these ecosystems

Integrating Machine Learning for Planetary Science: Perspectives for the Next Decade

Machine learning (ML) methods can expand our ability to construct, and draw insight from large datasets. Despite the increasing volume of planetary observations, our field has seen few applications of ML in comparison to other sciences. To support these methods, we propose ten recommendations for bolstering a data-rich future in planetary science.Comment: 10 pages (expanded citations compared to 8 page submitted version for decadal survey), 3 figures, white paper submitted to the Planetary Science and Astrobiology Decadal Survey 2023-203

Resonant nonlinear magneto-optical effects in atoms

In this article, we review the history, current status, physical mechanisms, experimental methods, and applications of nonlinear magneto-optical effects in atomic vapors. We begin by describing the pioneering work of Macaluso and Corbino over a century ago on linear magneto-optical effects (in which the properties of the medium do not depend on the light power) in the vicinity of atomic resonances, and contrast these effects with various nonlinear magneto-optical phenomena that have been studied both theoretically and experimentally since the late 1960s. In recent years, the field of nonlinear magneto-optics has experienced a revival of interest that has led to a number of developments, including the observation of ultra-narrow (1-Hz) magneto-optical resonances, applications in sensitive magnetometry, nonlinear magneto-optical tomography, and the possibility of a search for parity- and time-reversal-invariance violation in atoms.Comment: 51 pages, 23 figures, to appear in Rev. Mod. Phys. in Oct. 2002, Figure added, typos corrected, text edited for clarit

Functional characterisation of the amyotrophic lateral sclerosis risk locus GPX3/TNIP1

Background Amyotrophic lateral sclerosis (ALS) is a complex, late-onset, neurodegenerative disease with a genetic contribution to disease liability. Genome-wide association studies (GWAS) have identified ten risk loci to date, including the TNIP1/GPX3 locus on chromosome five. Given association analysis data alone cannot determine the most plausible risk gene for this locus, we undertook a comprehensive suite of in silico, in vivo and in vitro studies to address this. Methods The Functional Mapping and Annotation (FUMA) pipeline and five tools (conditional and joint analysis (GCTA-COJO), Stratified Linkage Disequilibrium Score Regression (S-LDSC), Polygenic Priority Scoring (PoPS), Summary-based Mendelian Randomisation (SMR-HEIDI) and transcriptome-wide association study (TWAS) analyses) were used to perform bioinformatic integration of GWAS data (Ncases = 20,806, Ncontrols = 59,804) with ‘omics reference datasets including the blood (eQTLgen consortium N = 31,684) and brain (N = 2581). This was followed up by specific expression studies in ALS case-control cohorts (microarray Ntotal = 942, protein Ntotal = 300) and gene knockdown (KD) studies of human neuronal iPSC cells and zebrafish-morpholinos (MO). Results SMR analyses implicated both TNIP1 and GPX3 (p < 1.15 × 10−6), but there was no simple SNP/expression relationship. Integrating multiple datasets using PoPS supported GPX3 but not TNIP1. In vivo expression analyses from blood in ALS cases identified that lower GPX3 expression correlated with a more progressed disease (ALS functional rating score, p = 5.5 × 10−3, adjusted R2 = 0.042, Beffect = 27.4 ± 13.3 ng/ml/ALSFRS unit) with microarray and protein data suggesting lower expression with risk allele (recessive model p = 0.06, p = 0.02 respectively). Validation in vivo indicated gpx3 KD caused significant motor deficits in zebrafish-MO (mean difference vs. control ± 95% CI, vs. control, swim distance = 112 ± 28 mm, time = 1.29 ± 0.59 s, speed = 32.0 ± 2.53 mm/s, respectively, p for all < 0.0001), which were rescued with gpx3 expression, with no phenotype identified with tnip1 KD or gpx3 overexpression. Conclusions These results support GPX3 as a lead ALS risk gene in this locus, with more data needed to confirm/reject a role for TNIP1. This has implications for understanding disease mechanisms (GPX3 acts in the same pathway as SOD1, a well-established ALS-associated gene) and identifying new therapeutic approaches. Few previous examples of in-depth investigations of risk loci in ALS exist and a similar approach could be applied to investigate future expected GWAS findings

Functional characterisation of the amyotrophic lateral sclerosis risk locus GPX3/TNIP1

Background: Amyotrophic lateral sclerosis (ALS) is a complex, late-onset, neurodegenerative disease with a genetic contribution to disease liability. Genome-wide association studies (GWAS) have identified ten risk loci to date, including the TNIP1/GPX3 locus on chromosome five. Given association analysis data alone cannot determine the most plausible risk gene for this locus, we undertook a comprehensive suite of in silico, in vivo and in vitro studies to address this. // Methods: The Functional Mapping and Annotation (FUMA) pipeline and five tools (conditional and joint analysis (GCTA-COJO), Stratified Linkage Disequilibrium Score Regression (S-LDSC), Polygenic Priority Scoring (PoPS), Summary-based Mendelian Randomisation (SMR-HEIDI) and transcriptome-wide association study (TWAS) analyses) were used to perform bioinformatic integration of GWAS data (Ncases = 20,806, Ncontrols = 59,804) with ‘omics reference datasets including the blood (eQTLgen consortium N = 31,684) and brain (N = 2581). This was followed up by specific expression studies in ALS case-control cohorts (microarray Ntotal = 942, protein Ntotal = 300) and gene knockdown (KD) studies of human neuronal iPSC cells and zebrafish-morpholinos (MO). // Results: SMR analyses implicated both TNIP1 and GPX3 (p < 1.15 × 10−6), but there was no simple SNP/expression relationship. Integrating multiple datasets using PoPS supported GPX3 but not TNIP1. In vivo expression analyses from blood in ALS cases identified that lower GPX3 expression correlated with a more progressed disease (ALS functional rating score, p = 5.5 × 10−3, adjusted R2 = 0.042, Beffect = 27.4 ± 13.3 ng/ml/ALSFRS unit) with microarray and protein data suggesting lower expression with risk allele (recessive model p = 0.06, p = 0.02 respectively). Validation in vivo indicated gpx3 KD caused significant motor deficits in zebrafish-MO (mean difference vs. control ± 95% CI, vs. control, swim distance = 112 ± 28 mm, time = 1.29 ± 0.59 s, speed = 32.0 ± 2.53 mm/s, respectively, p for all < 0.0001), which were rescued with gpx3 expression, with no phenotype identified with tnip1 KD or gpx3 overexpression. // Conclusions: These results support GPX3 as a lead ALS risk gene in this locus, with more data needed to confirm/reject a role for TNIP1. This has implications for understanding disease mechanisms (GPX3 acts in the same pathway as SOD1, a well-established ALS-associated gene) and identifying new therapeutic approaches. Few previous examples of in-depth investigations of risk loci in ALS exist and a similar approach could be applied to investigate future expected GWAS findings