Zebrafish behavioural profiling identifies GABA and serotonin receptor ligands related to sedation and paradoxical excitation.

Anesthetics are generally associated with sedation, but some anesthetics can also increase brain and motor activity-a phenomenon known as paradoxical excitation. Previous studies have identified GABAA receptors as the primary targets of most anesthetic drugs, but how these compounds produce paradoxical excitation is poorly understood. To identify and understand such compounds, we applied a behavior-based drug profiling approach. Here, we show that a subset of central nervous system depressants cause paradoxical excitation in zebrafish. Using this behavior as a readout, we screened thousands of compounds and identified dozens of hits that caused paradoxical excitation. Many hit compounds modulated human GABAA receptors, while others appeared to modulate different neuronal targets, including the human serotonin-6 receptor. Ligands at these receptors generally decreased neuronal activity, but paradoxically increased activity in the caudal hindbrain. Together, these studies identify ligands, targets, and neurons affecting sedation and paradoxical excitation in vivo in zebrafish

Inter-annual carbon isotope analysis of tree-rings by laser ablation

The stable carbon isotopic analysis of tree-rings for environmental, plant physiological and archaeological applications using conventional methods is occasionally limited by physical constraints (narrow rings) or administrative concerns (requirement for non-destructive sampling) that prevent researcher access to scientifically valuable wood samples. Analysis of such archives by laser-ablation can potentially address these issues and facilitate access to restricted archives. Smaller quantities of wood are required for analysis by laser ablation, hence the approach may be considered less-invasive and is virtually non-destructive compared to standard preparation methods. High levels of intra-annual isotopic variability reported elsewhere mean that a single measurement may not faithfully represent the inter-annual isotopic signal, so before such an approach can be used with confidence it is necessary to compare the stable carbon isotopic data produced using these two methods. This paper presents stable carbon isotope (δ13C) data from the resin-extracted wood of dated Scots Pine (Pinus sylvestris L.) tree-rings analysed using a modified Schulze-type laser-ablation system with results obtained using conventional manual sampling and analysis of α-cellulose prepared from the same tree-ring groups. The laser sampling system is found to perform very well against established more invasive methods. High correlations are observed between the methods for both raw and Suess corrected data (r > 0.90 n =50). These results highlight the potential for using laser-sampling to support the development of long isotope chronologies, for sampling narrow rings or for pre-screening cores prior to analysis using more detailed or labour intensive methods.201

The Impact of Waves and Tides on Residual Sand Transport on a Sediment‐Poor, Energetic, and Macrotidal Continental Shelf

©2019. The Authors. The energetic, macrotidal shelf off South West England was used to investigate the influence of different tide and wave conditions and their interactions on regional sand transport patterns using a coupled hydrodynamic, wave, and sediment transport model. Residual currents and sediment transport patterns are important for the transport and distribution of littoral and shelf-sea sediments, morphological evolution of the coastal and inner continental shelf zones, and coastal planning. Waves heavily influence sand transport across this macrotidal environment. Median (50% exceedance) waves enhance transport in the tidal direction. Extreme (1% exceedance) waves can reverse the dominant transport path, shift the dominant transport phase from flood to ebb, and activate sand transport below 120-m depth. Wave-tide interactions (encompassing radiation stresses, Stoke's drift, enhanced bottom-friction and bed shear stress, refraction, current-induced Doppler shift, and wave blocking) significantly and nonlinearly enhance sand transport, determined by differencing transport between coupled, wave-only, and tide-only simulations. A new continental shelf classification scheme is presented based on sand transport magnitude due to wave-forcing, tide-forcing, and nonlinear wave-tide interactions. Classification changes between different wave/tide conditions have implications for sand transport direction and distribution across the shelf. Nonlinear interactions dominate sand transport during extreme waves at springs across most of this macrotidal shelf. At neaps, nonlinear interactions drive a significant proportion of sand transport under median and extreme waves despite negligible tide-induced transport. This emphasizes the critical need to consider wave-tide interactions when considering sand transport in energetic environments globally, where previously tides alone or uncoupled waves have been considered

Post-Prior discrepancies in CDW-EIS calculations for ion impact ionization fully differential cross sections

In this work we present fully differential cross sections (FDCSs) calculations using post and prior version of CDW--EIS theory for helium single ionization by 100 MeV C$^{6+}$ amu$^{-1}$ and 3.6 MeV amu$^{-1}$ Au$^{24+}$ and Au$^{53+}$ ions. We performed our calculations for different momentum transfer and ejected electron energies. The influence of internuclear potential on the ejected electron spectra is taken into account in all cases. We compare our calculations with absolute experimental measurements. It is shown that prior version calculations give better agreement with experiments in almost all studied cases.Comment: 9 pages, 7 figure

Polymorphic Allele of Human IRGM1 Is Associated with Susceptibility to Tuberculosis in African Americans

An ancestral polymorphic allele of the human autophagy-related gene IRGM1 is associated with altered gene expression and a genetic risk for Crohn's Disease (CD). We used the single nucleotide polymorphism rs10065172C/T as a marker of this polymorphic allele and genotyped 370 African American and 177 Caucasian tuberculosis (TB) cases and 180 African American and 110 Caucasian controls. Among African Americans, the TB cases were more likely to carry the CD-related T allele of rs10065172 (odds ratio of 1.54; 95% confidence interval, 1.17–2.02; P<0.01) compared to controls. Our finding suggests that this CD-related IRGM1 polymorphic allele is also associated with human susceptibility to TB disease among African Americans

The relationships between golf and health:A scoping review

OBJECTIVE: To assess the relationships between golf and health. DESIGN: Scoping review. DATA SOURCES: Published and unpublished reports of any age or language, identified by searching electronic databases, platforms, reference lists, websites and from consulting experts. REVIEW METHODS: A 3-step search strategy identified relevant published primary and secondary studies as well as grey literature. Identified studies were screened for final inclusion. Data were extracted using a standardised tool, to form (1) a descriptive analysis and (2) a thematic summary. RESULTS AND DISCUSSION: 4944 records were identified with an initial search. 301 studies met criteria for the scoping review. Golf can provide moderate intensity physical activity and is associated with physical health benefits that include improved cardiovascular, respiratory and metabolic profiles, and improved wellness. There is limited evidence related to golf and mental health. The incidence of golfing injury is moderate, with back injuries the most frequent. Accidental head injuries are rare, but can have serious consequences. CONCLUSIONS: Practitioners and policymakers can be encouraged to support more people to play golf, due to associated improved physical health and mental well-being, and a potential contribution to increased life expectancy. Injuries and illnesses associated with golf have been identified, and risk reduction strategies are warranted. Further research priorities include systematic reviews to further explore the cause and effect nature of the relationships described. Research characterising golf's contribution to muscular strengthening, balance and falls prevention as well as further assessing the associations and effects between golf and mental health are also indicated

Role of Atmospheric Indices in Describing Inshore Directional Wave Climate in the United Kingdom and Ireland

Improved understanding of how our coasts will evolve over a range of time scales (years‐decades) is critical for effective and sustainable management of coastal infrastructure. A robust knowledge of the spatial, directional and temporal variability of the inshore wave climate is required to predict future coastal evolution and hence vulnerability. However, the variability of the inshore directional wave climate has received little attention, and an improved understanding could drive development of skillful seasonal or decadal forecasts of coastal response. We examine inshore wave climate at 63 locations throughout the United Kingdom and Ireland (1980–2017) and show that 73% are directionally bimodal. We find that winter‐averaged expressions of six leading atmospheric indices are strongly correlated (r = 0.60–0.87) with both total and directional winter wave power (peak spectral wave direction) at all studied sites. Regional inshore wave climate classification through hierarchical cluster analysis and stepwise multi‐linear regression of directional wave correlations with atmospheric indices defined four spatially coherent regions. We show that combinations of indices have significant skill in predicting directional wave climates (R2 = 0.45–0.8; p<0.05). We demonstrate for the first time the significant explanatory power of leading winter‐averaged atmospheric indices for directional wave climates, and show that leading seasonal forecasts of the NAO skillfully predict wave climate in some regions. Plain Language Summary Understanding the seasonal variability in wave climate around our coasts is fundamental for improving our understanding of how coasts will respond to climate change and sea‐level rise. Recent research has highlighted the importance of wave direction on coastal response. In this study we specifically explore the seasonal variability in wave direction throughout the inshore regions of the United Kingdom and Ireland at 63 locations between 1980 and 2017. We find that 73% of sites examined are directionally bimodal. We also find that combinations of six of the regions leading climate indices (NAO, AO, WEPA, EA, SCAND, EA/WR) are strongly correlated with both total and directional winter wave power at all the studied sites. We show that regression models using combinations of these climate indices have significant skill in predicting directional wave climates over the period 1980‐2017. For the first time we show that 'seasonal ahead' forecasts of the NAO can skilfully predict wave climate in some regions of the United Kingdom and Ireland, which could be used as tool to support coastal hazard mitigation