Using Gaussian Processes to Optimise Concession in Complex Negotiations against Unknown Opponents

In multi-issue automated negotiation against unknown opponents, a key part of effective negotiation is the choice of concession strategy. In this paper, we develop a principled concession strategy, based on Gaussian processes predicting the opponent's future behaviour. We then use this to set the agent's concession rate dynamically during a single negotiation session. We analyse the performance of our strategy and show that it outperforms the state-of-the-art negotiating agents from the 2010 Automated Negotiating Agents Competition, in both a tournament setting and in self-play, across a variety of negotiation domains

Negotiating Concurrently with Unknown Opponents in Complex, Real-Time Domains

We propose a novel strategy to enable autonomous agents to negotiate concurrently with multiple, unknown opponents in real-time, over complex multi-issue domains. We formalise our strategy as an optimisation problem, in which decisions are based on probabilistic information about the opponents' strategies acquired during negotiation. In doing so, we develop the first principled approach that enables the coordination of multiple, concurrent negotiation threads for practical negotiation settings. Furthermore, we validate our strategy using the agents and domains developed for the International Automated Negotiating Agents Competition (ANAC), and we benchmark our strategy against the state-of-the-art. We find that our approach significantly outperforms existing approaches, and this difference improves even further as the number of available negotiation opponents and the complexity of the negotiation domain increases

A Synthetic Vesicle-to-Vesicle Communication System.

A molecular signal displayed on the external surface of one population of vesicles was used to trigger a catalytic process on the inside of a second population of vesicles. The key recognition event is the transfer of a protein (NeutrAvidin) bound to vesicles displaying desthiobiotin to vesicles displaying biotin. The desthiobiotin-protein complex was used to anchor a synthetic transducer in the outer leaflet of the vesicles, and when the protein was displaced, the transducer translocated across the bilayer to expose a catalytic headgroup to the internal vesicle solution. As a result, an ester substrate encapsulated on the inside of this second population of vesicles was hydrolyzed to give a fluorescence output signal. The protein has four binding sites, which leads to multivalent interactions with membrane-anchored ligands and very high binding affinities. Thus, biotin, which has a dissociation constant 3 orders of magnitude higher than desthiobiotin, did not displace the protein from the membrane-anchored transducer, and membrane-anchored biotin displayed on the surface of a second population of vesicles was required to generate an effective input signal.Herchel Smith Fun

Modeling the Alkaline Hydrolysis of Diaryl Sulfate Diesters: A Mechanistic Study

Phosphate and sulfate esters have important roles in regulating cellular processes. However, while there has been substantial experimental and computational investigation of the mechanisms and the transition states involved in phosphate ester hydrolysis, there is far less work on sulfate ester hydrolysis. Here, we report a detailed computational study of the alkaline hydrolysis of diaryl sulfate diesters, using different DFT functionals as well as mixed implicit/explicit solvation with varying numbers of explicit water molecules. We consider the impact of the computational model on computed linear free-energy relationships (LFER) and the nature of the transition states (TS) involved. We obtain good qualitative agreement with experimental LFER data when using a pure implicit solvent model and excellent agreement with experimental kinetic isotope effects for all models used. Our calculations suggest that sulfate diester hydrolysis proceeds through loose transition states, with minimal bond formation to the nucleophile and bond cleavage to the leaving group already initiated. Comparison to prior work indicates that these TS are similar in nature to those for the alkaline hydrolysis of neutral arylsulfonate monoesters or charged phosphate diesters and fluorophosphates. Obtaining more detailed insights into the transition states involved assists in understanding the selectivity of enzymes that hydrolyze these reactions

Fulfilling Community Health Assessment Requirements: Lessons Learned From Facilitating State-Wide Community Health Forums

Background: A prerequisite for National Public Health Accreditation is completion of a Community Health Assessment (CHA) that presents an exhaustive profile of the population served by a particular public health agency. Methods: The Georgia Department of Public Health (GA DPH) contracted with the Center for Public Health Practice and Research at Georgia Southern University to facilitate five state-wide community health forums. Results: Evaluation of the forums yielded qualitative data illustrating current challenges faced by Georgians, as well as assets that could be leveraged to improve health status. Conclusion: Lessons learned from these state-wide community health forums can be applied to improve the overall process of gathering data for a comprehensive CHA throughout Georgia or other areas interested in pursuing public health agency accreditation

Assessing Neurofilaments as Biomarkers of Neuroprotection in Progressive Multiple Sclerosis: From the MS-STAT Randomized Controlled Trial

BACKGROUND AND OBJECTIVES: Improved biomarkers of neuroprotective treatment are needed in progressive multiple sclerosis (PMS) to facilitate more efficient phase 2 trial design. The MS-STAT randomized controlled trial supported the neuroprotective potential of high-dose simvastatin in secondary progressive MS (SPMS). Here, we analyze serum from the MS-STAT trial to assess the extent to which neurofilament light (NfL) and neurofilament heavy (NfH), both promising biomarkers of neuroaxonal injury, may act as biomarkers of simvastatin treatment in SPMS. METHODS: The MS-STAT trial randomized patients to 80 mg simvastatin or placebo. Serum was analyzed for NfL and NfH using Simoa technology. We used linear mixed models to investigate the treatment effects of simvastatin compared with placebo on NfL and NfH. Additional models examined the relationships between neurofilaments and MRI and clinical measures of disease severity. RESULTS: A total of 140 patients with SPMS were included. There was no evidence for a simvastatin treatment effect on NfL or NfH: compared with placebo, NfL was 1.2% lower (95% CI 10.6% lower to 9.2% higher; p = 0.820) and NfH was 0.4% lower (95% CI 18.4% lower to 21.6% higher; p = 0.969) in the simvastatin treatment group. Secondary analyses suggested that higher NfL was associated with greater subsequent whole brain atrophy, higher T2 lesion volume, and more new/enlarging T2 lesions in the previous 12 months, as well as greater physical disability. There were no significant associations between NfH and MRI or clinical variables. DISCUSSION: We found no evidence of a simvastatin treatment effect on serum neurofilaments. While confirmation of the neuroprotective benefits of simvastatin is awaited from the ongoing phase 3 study (NCT03387670), our results suggest that treatments capable of slowing the rate of whole brain atrophy in SPMS, such as simvastatin, may act via mechanisms largely independent of neuroaxonal injury, as quantified by NfL. This has important implications for the design of future phase 2 clinical trials in PMS. TRIAL REGISTRATION INFORMATION: MS-STAT: NCT00647348. CLASSIFICATION OF EVIDENCE: This study provides class I evidence that simvastatin treatment does not have a large impact on either serum NfL or NfH, as quantified in this study, in SPMS

RSV in Young Children During and After the COVID-19 Pandemic – Implications for Delaying the Age of First Infection

Nonpharmaceutical interventions introduced in the United Kingdom’s response to the COVID-19 pandemic disrupted the transmission of other childhood infections. We report changes in seasonality, age dynamics and severity of respiratory syncytial virus infections between 2019 and 2023. These data show the potential effects of delaying respiratory syncytial virus exposure and may provide insights for the implementation of treatments preventing infection during early infancy

Fulfilling Community Health Assessment Requirements: Lessons Learned From Facilitating State-wide Community Health Forums

Background: A prerequisite for National Public Health Accreditation is completion of a Community Health Assessment (CHA) that presents an exhaustive profile of the population served by a particular public health agency. Methods: The Georgia Department of Public Health (GA DPH) contracted with the Center for Public Health Practice and Research at Georgia Southern University to facilitate five state-wide community health forums. Results: Evaluation of the forums yielded qualitative data illustrating current challenges faced by Georgians, as well as assets that could be leveraged to improve health status. Conclusion: Lessons learned from these state-wide community health forums can be applied to improve the overall process of gathering data for a comprehensive CHA throughout Georgia or other areas interested in pursuing public health agency accreditation

Manifold learning for coarse-graining atomistic simulations: Application to amorphous solids

We introduce a generalized machine learning framework to probabilistically parameterize upper-scale models in the form of nonlinear PDEs consistent with a continuum theory, based on coarse-grained atomistic simulation data of mechanical deformation and flow processes. The proposed framework utilizes a hypothesized coarse-graining methodology with manifold learning and surrogate-based optimization techniques. Coarse-grained high-dimensional data describing quantities of interest of the multiscale models are projected onto a nonlinear manifold whose geometric and topological structure is exploited for measuring behavioral discrepancies in the form of manifold distances. A surrogate model is constructed using Gaussian process regression to identify a mapping between stochastic parameters and distances. Derivative-free optimization is employed to adaptively identify a unique set of parameters of the upper-scale model capable of rapidly reproducing the system's behavior while maintaining consistency with coarse-grained atomic-level simulations. The proposed method is applied to learn the parameters of the shear transformation zone (STZ) theory of plasticity that describes plastic deformation in amorphous solids as well as coarse-graining parameters needed to translate between atomistic and continuum representations. We show that the methodology is able to successfully link coarse-grained microscale simulations to macroscale observables and achieve a high-level of parity between the models across scales.Comment: 34 pages, 12 figures, references added, Section 4 added, Section 2.1 update

Delayed Psychological Morbidity Associated with Snakebite Envenoming

Introduction The psychological impact of snakebite on its victims, especially possible late effects, has not been systematically studied. Objectives To assess delayed somatic symptoms, depressive disorder, post-traumatic stress disorder (PTSD), and impairment in functioning, among snakebite victims. Methods The study had qualitative and quantitative arms. In the quantitative arm, 88 persons who had systemic envenoming following snakebite from the North Central Province of Sri Lanka were randomly identified from an established research database and interviewed 12 to 48 months (mean 30) after the incident. Persons with no history of snakebite, matched for age, sex, geograpical location and occupation, acted as controls. A modified version of the Beck Depression Inventory, Post-Traumatic Stress Symptom Scale, Hopkins Somatic Symptoms Checklist, Sheehan Disability Inventory and a structured questionnaire were administered. In the qualitative arm, focus group discussions among snakebite victims explored common somatic symptoms attributed to envenoming. Results Previous snakebite victims (cases) had more symptoms than controls as measured by the modified Beck Depression Scale (mean 19.1 Vs 14.4; p<0.001) and Hopkins Symptoms Checklist (38.9 vs. 28.2; p<0.001). 48 (54%) cases met criteria for depressive disorder compared to 13 (15%) controls. 19 (21.6%) cases also met criteria for PTSD. 24 (27%) claimed that the snakebite caused a negative change in their employment; nine (10.2%) had stopped working and 15 (17%) claimed residual physical disability. The themes identified in the qualitative arm included blindness, tooth decay, body aches, headaches, tiredness and weakness. Conclusions Snakebite causes significant ongoing psychological morbidity, a complication not previously documented. The economic and social impacts of this problem need further investigation