A Capability Approach to Understand the Scarring Effects of Unemployment and Job Insecurity: Developing the Research Agenda

Having a poor start in the labour market has a ‘scarring’ effect on future employment and well-being. Indeed, unemployment at any point of the life-course can scar. While there is extensive quantitative research examining scarring effects at the macro- and meso-levels, evidence regarding scarring from the micro-level that provides insights into individual perceptions, values, attitudes and capabilities, and how they shape employment trajectories is lacking. A qualitative approach which avoids the imposition of values and choices onto individuals’ employment trajectories, and accounts more fully for the contextual constraints which shape available options and choices, is argued for. In emphasising people’s substantive freedom of choice, which may be enabled or constrained by contextual conditions, the Capability Approach is proposed as providing a valuable lens to examine complex and insecure labour market transitions. Such an approach stands in contrast to the supply-side focused active labour market policies characteristic of neo-liberal welfare states

Implementation of 3D spatial indexing and compression in a large-scale molecular dynamics simulation database for rapid atomic contact detection

<p>Abstract</p> <p>Background</p> <p>Molecular dynamics (MD) simulations offer the ability to observe the dynamics and interactions of both whole macromolecules and individual atoms as a function of time. Taken in context with experimental data, atomic interactions from simulation provide insight into the mechanics of protein folding, dynamics, and function. The calculation of atomic interactions or contacts from an MD trajectory is computationally demanding and the work required grows exponentially with the size of the simulation system. We describe the implementation of a spatial indexing algorithm in our multi-terabyte MD simulation database that significantly reduces the run-time required for discovery of contacts. The approach is applied to the Dynameomics project data. Spatial indexing, also known as spatial hashing, is a method that divides the simulation space into regular sized bins and attributes an index to each bin. Since, the calculation of contacts is widely employed in the simulation field, we also use this as the basis for testing compression of data tables. We investigate the effects of compression of the trajectory coordinate tables with different options of data and index compression within MS SQL SERVER 2008.</p> <p>Results</p> <p>Our implementation of spatial indexing speeds up the calculation of contacts over a 1 nanosecond (ns) simulation window by between 14% and 90% (i.e., 1.2 and 10.3 times faster). For a 'full' simulation trajectory (51 ns) spatial indexing reduces the calculation run-time between 31 and 81% (between 1.4 and 5.3 times faster). Compression resulted in reduced table sizes but resulted in no significant difference in the total execution time for neighbour discovery. The greatest compression (~36%) was achieved using page level compression on both the data and indexes.</p> <p>Conclusions</p> <p>The spatial indexing scheme significantly decreases the time taken to calculate atomic contacts and could be applied to other multidimensional neighbor discovery problems. The speed up enables on-the-fly calculation and visualization of contacts and rapid cross simulation analysis for knowledge discovery. Using page compression for the atomic coordinate tables and indexes saves ~36% of disk space without any significant decrease in calculation time and should be considered for other non-transactional databases in MS SQL SERVER 2008.</p

The efficacy of lenvatinib plus everolimus in patients with metastatic renal cell carcinoma exhibiting primary resistance to front-line targeted therapy or immunotherapy

BACKGROUND: Patients with primary refractory metastatic renal cell carcinoma (mRCC) have a dismal prognosis and poor response to subsequent treatments. While there are several approved second-line therapies, it remains critical to choose the most effective treatment regimen. PATIENTS AND METHODS: We identified 7 patients with clear cell mRCC who had primary resistance to vascular endothelial growth factor (VEGF)-targeted tyrosine kinase inhibitors (TKIs) or immune checkpoint inhibitor (ICI) combination therapy. The patients were treated with lenvatinib (a multitargeted TKI) plus everolimus (a mammalian target of rapamycin inhibitor). Among these 7 patients, 2 had prior TKI therapy, 3 had prior ICI therapy, and 2 had prior TKI and ICI therapy. We collected the patients\u27 clinical characteristics, molecular profiles, treatment durations, and toxicity outcomes. RESULTS: The median time to progression on prior therapies was 1.5 months. Lenvatinib plus everolimus was used either as a second-line (n = 4) or third-line (n = 3) therapy. As best responses, 3 patients had partial responses and 3 achieved stable disease. Patients were followed for ≥17 months; progression-free survival ranged from 3 to 15 months, and overall survival ranged from 4 to 17 months. CONCLUSION: These 7 cases provide real-world data for the use of lenvatinib plus everolimus in patients with mRCC with primary resistance to first-line VEGF-targeted TKIs or ICI combination therapy

IRVE-3 Post-Flight Reconstruction

The Inflatable Re-entry Vehicle Experiment 3 (IRVE-3) was conducted from the NASA Wallops Flight Facility on July 23, 2012. Launched on a Black Brant XI sounding rocket, the IRVE-3 research vehicle achieved an apogee of 469 km, deployed and inflated a Hypersonic Inflatable Aerodynamic Decelerator (HIAD), re-entered the Earth's atmosphere at Mach 10 and achieved a peak deceleration of 20 g's before descending to splashdown roughly 20 minutes after launch. This paper presents the filtering methodology and results associated with the development of the Best Estimated Trajectory of the IRVE-3 flight test. The reconstructed trajectory is compared against project requirements and pre-flight predictions of entry state, aerodynamics, HIAD flexibility, and attitude control system performance

Quantifying the Coastal Hazard Risk Reduction Benefits of Coral Reef Restoration in the U.S. Virgin Islands

Coastal habitat restoration, especially of coral reef ecosystems, can significantly reduce the exposure of coastal communities to natural hazards and, consequently, the risk of wave-driven flooding. Likewise, reef degradation can increase coastal flood risks to people and property. In this study, the valuation of coral reefs in the United States Virgin Islands (USVI), along the coasts of St. Croix, St. John, and St. Thomas, demonstrated the social and economic benefits provided by these natural defenses. Across the territory, more than 481 people and 31.2 million of infrastructure were estimated to receive protection from coral reefs per year (2010 U.S. dollars). In 2017, Hurricanes Irma and Maria significantly damaged coral reefs throughout the archipelago. By combining engineering, ecological, geospatial, social, and economic data and tools, this study provided a rigorous valuation of where potential coral reef restoration projects could help rebuild these damaged habitats and decrease the risks from coastal hazards faced by USVI’s reef-fronted communities. Multiple restoration scenarios were considered in the analysis, two of which are detailed in this report. These include (1) ‘Ecological’ restoration, where restoration creates a structure that is 0.25 m high and 25-m-wide reef, and (2) ‘Hybrid’ restoration, where restoration creates a structure that is 1.25 m high and 5 m wide. There are many ways that such structures could be developed. In the hydrodynamic analyses, there are no assumptions about how the restoration is developed. Many practitioners of both coral (and oyster reef) restoration consider that a reef height of 0.25 m might be delivered from planting corals alone and that 1.25 m might require a combination of artificial structures and coral planting. In a third scenario, the analysis investigated the reduction of protection benefits that would occur through the reduction of 1 meter of naturally occurring reef height due to reef degradation. The reduction of protection due to the loss of reefs can also be interpreted as the protection value of the existing reefs. In all studied restoration scenarios, it was assumed that the planting of corals would enhance hydrodynamic roughness, effectively dissipating incident wave energy and reducing the potential for coastal flooding. A standardized approach was employed to strategically locate potential restoration projects along the entire linear extent of existing reefs bordering the USVI, and to identify where coral reef restoration could offer valuable benefits in flood reduction. Potential restoration projects were only located within the existing distribution of reefs across the region, even though numerous sites were positioned far offshore (2-3 km), and some were at relatively deep depths (up to 7 m). Risk-based valuation approaches were followed to delineate flood zones at a 10 m2 resolution along the entire region's reef-lined shorelines for all the potential coral reef restoration scenarios. These were subsequently compared to flood zones without coral reef restoration. The potential reduction in coastal flood risk provided by coral reef restoration, and the protection value of existing reefs, were quantified utilizing the latest information available at the time of analysis from the U.S. Census Bureau, Federal Emergency Management Agency (FEMA), and Bureau of Economic Analysis for return-interval storm events. The change in Expected Annual Damages (EAD), a metric indicating the annual protection gained due to coral reef restoration, was calculated based on the damages associated with each storm probability. The findings suggest that the benefits of reef restoration are spatially variable within the USVI. In some areas, the analysis showed limited benefits from reef restoration, which may be attributed to the depth or offshore distances of proposed restoration sites. However, there were a number of key areas where reef restoration could have substantial benefits for flood risk reduction. The annual flood risk reduction attributed to potential ‘ecological’ coral reef restoration in the USVI was 99 people and 6.1 million (2010 U.S. dollars). The Benefit-to-Cost Ratio (BCR) for this restoration approach was found to be larger than 1 (i.e., cost-effective) along 11% of the St. Croix coastline, 4.9% of the St. John coastline, and 8.7% of the St. Thomas coastline. This analysis offers stakeholders and decision-makers a spatially explicit and rigorous evaluation that illustrates how, where, and when potential coral reef restoration efforts in St. Croix, St. John, and St. Thomas could be instrumental to reducing coastal storm-induced flooding. Understanding areas where reef management, recovery, and restoration could effectively reduce climate hazard-related risks is crucial to protect and enhance the resilience of coastal communities in USVI

Return on investment for mangrove and reef flood protection

There is a growing need for coastal and marine restoration, but it is not clear how to pay for it given that environmental funding is low, and national budgets are stretched in response to natural hazards. We use risk-industry methods and find that coral reef and mangrove restoration could yield strong Return on Investment (ROI) for flood risk reduction on shorelines across more than 20 Caribbean countries. These results are robust to changes in discount rates and the timing of restoration benefits. Data on restoration costs are sparse, but the Present Value (PV) of restored natural infrastructure shows that ROI would be positive in many locations even if restoration costs are in the hundreds of thousand per hectare for mangroves and millions per km for reefs. Based on these benefits, we identify significant sources of funding for restoring these natural defenses.This work was supported in part by the Kingfisher Foundation, the World Bank, AXA XL, AXA Research Fund, The Nature Conservancy, and the Federal Ministry for the Environment, Nature Conservation and Nuclear Safety (BMU) on the basis of a decision adopted by the German Bundestag. We thank Chris Lowrie for help with the figures

The Effects of Acute Δ⁹-Tetrahydrocannabinol on Striatal Glutamatergic Function:A Proton Magnetic Resonance Spectroscopy Study

Background: Cannabis and its main psychoactive component, Δ9-tetrahydrocannabinol (THC), can elicit transient psychotic symptoms. A key candidate biological mechanism of how THC induces psychotic symptoms is the modulation of glutamate in the brain. We sought to investigate the effects of acute THC administration on striatal glutamate levels and its relationship to the induction of psychotic symptoms. Methods: We used proton magnetic resonance spectroscopy to measure glutamate levels in the striatum in 20 healthy participants after THC (15 mg, oral) and matched placebo administration in a randomized, double-blind, placebo-controlled design. Psychotic symptoms were measured using the Psychotomimetic States Inventory. Results: We found that THC administration did not significantly change glutamate (glutamate plus glutamine relative to creatine) concentration in the striatum (p =.58; scaled Jeffreys-Zellner-Siow Bayes factor = 4.29). THC increased psychotic symptoms, but the severity of these symptoms was not correlated with striatal glutamate levels. Conclusions: These findings suggest that oral administration of 15 mg of THC does not result in altered striatal glutamate levels. Further work is needed to clarify the effects of THC on striatal glutamate.</p

Impaired decisional impulsivity in pathological videogamers

Abstract Background Pathological gaming is an emerging and poorly understood problem. Impulsivity is commonly impaired in disorders of behavioural and substance addiction, hence we sought to systematically investigate the different subtypes of decisional and motor impulsivity in a well-defined pathological gaming cohort. Methods Fifty-two pathological gaming subjects and age-, gender- and IQ-matched healthy volunteers were tested on decisional impulsivity (Information Sampling Task testing reflection impulsivity and delay discounting questionnaire testing impulsive choice), and motor impulsivity (Stop Signal Task testing motor response inhibition, and the premature responding task). We used stringent diagnostic criteria highlighting functional impairment. Results In the Information Sampling Task, pathological gaming participants sampled less evidence prior to making a decision and scored fewer points compared with healthy volunteers. Gaming severity was also negatively correlated with evidence gathered and positively correlated with sampling error and points acquired. In the delay discounting task, pathological gamers made more impulsive choices, preferring smaller immediate over larger delayed rewards. Pathological gamers made more premature responses related to comorbid nicotine use. Greater number of hours played also correlated with a Motivational Index. Greater frequency of role playing games was associated with impaired motor response inhibition and strategy games with faster Go reaction time. Conclusions We show that pathological gaming is associated with impaired decisional impulsivity with negative consequences in task performance. Decisional impulsivity may be a potential target in therapeutic management

Comparisons and contrasts of the impact of the crisis on euro area labour markets

The global financial and economic crisis – including two euro area recessions in 2008-2009 and 2011-2013 – has had a heavy impact on euro area labour markets. A notable feature throughout the crisis has been the considerable degree of cross-country heterogeneity of labour market adjustments – with some economies emerging relatively unscathed, while others have seen steep and persisting increases in unemployment. This paper analyses the impacts of the crisis on euro area labour markets, paying particular attention to the differential impact of the two euro area recessions of the crisis and the interplay of sectoral and institutional features driving labour market outcomes. Despite ongoing structural reforms in some euro area countries, progress has been partial and uneven across the euro area. Further reductions in labour market rigidities are necessary to increase and accelerate the adjustment capacity of euro area labour markets and help reduce the current high levels of structural unemployment