LSD: An Analysis of the Literature Concerning its Use in the Therapy of Alcoholism

It will be the concern of this paper to explore the use of the chemical d-lysergic acid diethylamide-25 in therapeutic regimes for alcoholics

Quantifying the impacts of uncertainties in coastal hazard modelling

This thesis applies coupled regional models to address coastal flood risk management needs in hyper-tidal estuaries. The project aims to understand how tide-surge-wind-waves combine to increase flood and wave hazard at the coast, using the Severn Estuary, southwest England as an extreme example. Little previous research has considered the impact of tide-surge-wind-wave interaction on total water level in a hyper-tidal estuary. Numerical modelling tools can be used to predict the individual contributions of physical factors to total water levels and forms a key component of flood hazard assessment. However uncertainty can be introduced into model predictions due to inaccurate boundary forcing or representation of the physical processes which control the volume and rate water moves through a model domain. Uncertainties in model predictions lead to a wide spread of results within which exposure or impacts could occur. Similarly, a range of possible values exist for a single parameter which may cause errors in the definition of critical thresholds or presents challenges to emergency response planners. Sources of uncertainty in flood hazard assessments should be identified and quantified as sustainable coastal management requires confidence in the knowledge of any possible future changes to flood and wave hazard. The thesis utilises wave, ocean and meteorological observation and model hindcast data to simulate total water level and significant wave height using the Delft3D-FLOW-WAVE modelling package. The validated Severn Estuary model domain is used to investigate the sensitivity of extreme water levels to changes in event severity, timing of the peak of a storm surge relative to tidal high water and the temporal distribution of the storm surge component, and wave heights to changes in wind-wave direction, model coupling and forcing processes. Model outputs from Delft3D-FLOW-WAVE are viewed in the context of the source-pathway-receptor-consequence model to better understand the influence of coastal hazard uncertainty on flood and wave hazard. Event severity is the most important control on flood hazard, and concurrence of the sources of flood hazard generate greatest water levels along the coastline of the estuary. Estuarine morphology acts as a pathway for flood hazard, as funnelling effects control the spatial variability of flood hazard and amplify surge magnitude up to 255% up-estuary. Surge predictions from forecasting systems at tide gauge locations could under-predict the magnitude and duration of surge contribution to up-estuary water levels. Wave height and wave period controls the response of wave generation and propagation to other factors. Wind speed generates greatest wave hazard, and uncertainty in wind and wave direction generate a large spread of results. Stronger, opposing winds steepen high amplitude, low period waves in the outer estuary and stronger, following winds enhance propagation of low amplitude high period waves up-estuary. The inclusion of locally generated winds is most important in regional models to continue to add momentum to the estuarine system, and model coupling processes (the representation of interaction between wave and currents) improve accuracy of flood and wave hazard predictions. Exclusion of locally generated winds can generate up to 1.45 m error in high water significant wave heights in the outer estuary, and 1.13 m error in the upper estuary. Coastal hazard uncertainty due to model coupling and forcing processes is propagated through the modelling chain to the two-dimensional inundation model LISFLOOD-FP to understand how changes in boundary condition and boundary position influences depth, extent and volume of inundation over a storm event. The exclusion of local atmospheric forcing increases coastal hazard uncertainty in the boundary forcing and under-predicts damage by up to £26.2 M at Oldbury-on-Severn. Once the threshold for flooding is exceeded, a few centimetres increase in coastal hazard conditions increases both the inundation and consequent damage costs for suburbia and arable land. The results of this thesis identify optimum model setups for simulating coastal flood hazard, which includes incorporating local atmospheric forcing and representing two-way interaction between waves and currents. Coastal hazard uncertainty can cause large variability in simulated total water level and wave heights, which has implications for flood damage assessments, shoreline management plans and emergency response plans. The research findings can aid long-term coastal defence and management strategies for improved public safety, and improve the timing and accuracy of early warning systems. Key sources of coastal hazard uncertainty have been identified here, e.g. the importance of storm surge timing relative to tidal high water and sensitivity of wave propagation to winds speeds, and these can be accounted for in future management plans. Utilising optimal model setups when predicting water level and wave height under current and future climate conditions can also help to increase confidence in results. Further to this, if the key sources of uncertainty which contribute to a large spread of results are known, e.g. exclusion of local atmospheric forcing, then this can be resolved in predictions which are used to inform early warning systems. The spread of model results can therefore be minimised to more accurately know who or what is in a flood or wave hazard zone

The impact of tidal lagoons on future flood risk on the North Wirral and Conwy coastline, UK

This report considers the viability of tidal lagoons in the North Wirral and Conwy coastlines, to mitigate future flood risk and reduce the cost of damage in these areas. The report is aims to provide information on the feasibility and benefits of tidal lagoons as mitigation and adaptation strategies to future sea-level rise, as part of the RISES-AM project. Sea-level has been rising since instrumental records began in the 1700s, and has been rising at a rate of 3.0 ± 0.7 mm / yr-1 since 1990 (Hay et al., 2015). Low probability, plausible high-end sea-level rise scenarios, where global average warming exceeds 2oC in respect to the pre-industrial level, estimate up to 0.98 m sea-level rise (SLR) by 2100 (Church et al., 2013). There is a move away from hard defences in favour of strategies which can mitigate flood risk benefit and allow coastal communities to adapt to and benefit from high-end SLR scenarios (Linham and Nicholls, 2010). Tidal lagoons could be one such innovative option. The report aims to assess the impact of the construction of tidal lagoons on flood risk on the North Wirral and Conwy coastline, under future high-end sea-level rise scenarios. Computer simulations of extreme flood events, using a 2D hydrodynamic model called LISFLOOD, will estimate changes in the extent and depth of flooding following the construction of a lagoon under both present day and future extreme climate conditions. The results of LISFLOOD suggest that: • Colwyn Bay and the North Wirral coastline are not areas at increased flood risk under baseline future high-end SLR, due to steep topography and existing defences. • Infrastructure at Stanlow oil refinery and Connah’s Quay in the North Wirral domain and residential areas in the Colwyn Bay domain at Llandudno, Rhyl and Prestatyn experience increased flood risk under RCP 4.5 (0.72 m SLR) and RCP 8.5 (0.98 m SLR) with no tidal lagoon. This is due to low-lying topography. • The presence of a tidal lagoon on the North Wirral provides flood risk benefit to infrastructure at Stanlow and Connah’s Quay as the magnitude of tidal currents is limited through the Dee and Mersey Estuary. However the size of the lagoon and the bathymetry of Liverpool Bay may mean the lagoon in this study may not be financially feasible. • The construction of a tidal lagoon at Colwyn Bay increases extent and depth of inundation at Llandudno, Rhyl and Prestatyn under all sea-level rise scenarios. Increased flood risk in these areas following the construction of a tidal lagoon is reason enough not to build a lagoon in this location. Tidal lagoons have the potential to offer flood risk benefit and become part of integrated strategies to minimise flood risk in coastal areas. The benefits of tidal lagoons are dependent on their shape, size and location, and feasibility studies should consider impacts in the near- and far-field

Researcher Training in Spreadsheet Curation

Spreadsheets are commonly used across most academic discplines, however their use has been associated with a number of issues that affect the accuracy and integrity of research data. In 2016, new training on spreadsheet curation was introduced at the University of Sydney to address a gap between practical software skills training and generalised research data management training. The approach to spreadsheet curation behind the training was defined and the training's distinction from other spreadsheet curation training offering described.\parThe uptake of and feedback on the training were evaluated. Training attendance was analysed by discipline and by role. Quantitative and qualitative feedback were analysed and discussed. Feedback revealed that many attendees had been expecting and desired practical spreadsheet software skills training. Issues relating to whether or not practical skills training should and can be integrated with curation training were discussed. While attendees were found to be predominantly from science disciplines, qualitative feedback suggests that humanities attendees have specific needs in relation to managing data with spreadsheets that are currently not being met. Feedback also suggested that some attendees would prefer the curation training to be delivered as a longer, more in depth, hands on workshop.\parThe impact of the training was measured using data collected from the University's Research Data Management Planning (RDMP) tool and the Sydney eScholarship Repository. RDMP descriptions of spreadsheet data and records of tabular datasets published in the repository were analysed and assessed for quality and for accompanying data documentation. No significant improvements in data documentation or quality were found, however it is likely too soon after the launch of the training program to have seen much in the way of impact.\parIdentified next steps include clarifying the marketing material promoting to the training to better communicate the curation focus, investigating the needs of humanities researchers working with qualitative data in spreadsheets, and incorporating new material into the training in order to address those needs. Integrating curation training with practical skills training and modifying the training to be more hands on are changes that may be considered in future, but will not be implemented at this stage

Peritoneal fluid haptoglobin from women with endometriosis differentially regulates macrophage cytokine production [abstract]

Abstract only availableThe objective of this study was to define mechanisms by which haptoglobin from endometriotic lesions (eHp) which binds to macrophages modulates immune surveillance and inflammation in the peritoneal cavity by characterizing macrophage products regulated by eHp. To eliminate human macrophage variation, the established THP-1 monocyte cell line (1.0 x106 cells/mL/well, 24-well plates, RPMI 1640+L-glutamine, FBS, and antibiotics) was routinely differentiated into macrophage-like cells with low dose PMA (20 ng/mL) and concurrently treated with media only (M), serum haptoglobin (sHp) or haptoglobin purified from peritoneal fluid of women without (cHp) or with (eHp) endometriosis (10 μg/mL, 24 h). The RayBio Inflammatory Antibody Array III was used per instructions and chemiluminescene signal intensity was quantified by densitometry. Differences were evaluated by ANOVA and post hoc tests.Variation in 8 control spots per and between membranes was sHp, cHp, M. P=0.002), TNF-α (eHp>sHp, cHp, M. P=0.045), TNF-β (eHp>sHp, cHp, M. P=0.043), PDGF-BB (eHp>sHp, cHp, M. P=0.016), IL-6sR (eHp>cHp, M. PsHp>cHp, M. P=0.072), IP-10 (eHp, sHp> cHp, M. P=0.017), RANTES (eHp, sHp>cHp, M. P=0.004) and TGF-β (eHp, sHp>M, cHp. P=0.008). Unexpectedly, cHp differentially decreased IL-2 (cHp<eHp, sHp, M. P=0.001) and MCP-1 (cHp<eHp, sHp, M. P=0.023). Twenty substances were similar in all treatments; the _expression range was divided into quartiles: High: IL-8. Moderate: IL-1β, MIP-1β. Slight: IL-10, TNFsRII, TIMP-2. Minimal: ICAM, INF-gamma, I-309; IL-1α, IL-3, IL-6, IL-11, IL-12p40, IL-12p70, IL-15, M-CSF, MIP-1α, MIP-1δ and TNFsRI. Nine were not detected in any treatment: Eotaxin-1, GCSF, GM-CSF, IL-4, IL-7, IL-13, IL-17, MCP-2, MIG. Differential eHp up-regulation and cHp down-regulation of macrophage inflammatory substances indicates that the function of eHp, hence the function of macrophages in women with endometriosis is skewed compared to controls. We postulate that peritoneal macrophages interaction with eHp contributes to endometrioisis persistence and/or pathophysiologies.National Institutes of Healt