Real-Time Evolutionary Learning of Cooperative Predator-Prey Strategies

Despite games often being used as a testbed for new computational intelligence techniques, the majority of artificial intelligence in commercial games is scripted. This means that the computer agents are non-adaptive and often inherently exploitable because of it. In this paper, we describe a learning system designed for team strategy development in a real time multi-agent domain. We test our system in a prey and predators domain, evolving adaptive team strategies for the predators in real time against a single prey opponent. Our learning system works by continually training and updating the predator strategies, one at a time for a designated length of time while the game us being played. We test the performance of the system for real-time learning of strategies in the prey and predators domain against a hand-coded prey opponent. We show that the resulting real-time team strategies are able to capture hand-coded prey of varying degrees of difficulty without any prior learning. The system is highly adaptive to change, capable of handling many different situations, and quickly learning to function in situations that it has never seen before

Safety of tubal ligation by minilaparotomy provided by clinical officers versus assistant medical officers: study protocol for a noninferiority randomized controlled trial in Tanzanian women.

BACKGROUND: Female sterilization by tubal ligation is a safe, extremely effective, and permanent way to limit childbearing. It is the most popular modern contraceptive method worldwide. The simplest way to provide tubal ligation is by a procedure called minilaparotomy, generally performed with the client under local anesthesia with systemic sedation and analgesia. In Tanzania, unmet need for family planning is high and has declined little in the past decade. Access to tubal ligation is limited throughout the country, in large part because of a lack of trained providers. Clinical officers (COs) are midlevel health workers who provide diagnosis, treatment, and minor surgeries. They are more prevalent than physicians in poorer and rural communities. Task shifting-the delegation of some tasks to less-specialized health workers, including task shifting of surgical procedures to midlevel cadres-has improved access to lifesaving interventions in resource-limited settings. It is a cost-effective way to address shortages of physicians, increasing access to services. The primary objective of this trial is to establish whether the safety of tubal ligation by minilaparotomy provided by COs is noninferior to the safety of tubal ligation by minilaparotomy provided by physicians (assistant medical officers [AMOs]), as measured by rates of major adverse events (AEs) during the procedure and through 42 days of follow-up. METHODS/DESIGN: In this facility-based, multicenter, noninferiority randomized controlled trial, we are comparing the safety of tubal ligation by minilaparotomy performed by trained COs versus by trained AMOs. The primary outcome is safety, defined by the overall rate of major AEs occurring during the minilaparotomy procedure and through 42 days of follow-up. The trial will be conducted among 1970 women 18 years of age or older presenting for tubal ligation at 7 study sites in northern Tanzania. DISCUSSION: If no major safety issues are identified, the data from this trial may facilitate changes in the Tanzanian government's regulations, allowing appropriately trained COs to provide tubal ligation by minilaparotomy. Positive findings may have broader implications. Task shifting to provide long-acting contraceptives, if proven safe, may be an effective approach to increasing contraceptive access in low- and middle-income countries. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02944149 . Registered on 14 October 2016

Disruption of cerebellar maturation by an antimitotic agent impairs the ontogeny of eyeblink conditioning in rats

This study represents an attempt to establish a relationship between maturation of the cerebellum and the ontogeny of eyeblink conditioning in the rat. Experiments 1 and 2 examined the effects of disrupting cerebellar maturation by neonatal exposure to the antimitotic agent methylazoxymethanol (MAM) on the ontogeny of eyeblink conditioning in infant rats. Experiment 1 demonstrated that neonatal exposure to MAM on Postnatal Day 4 (PND4) and 7 severely disrupted cerebellar maturation. This effect appeared to be specific in that there was no overt dysmorphology in other brain regions. MAM treatment also severely disrupted associative eyeblink conditioning in rats given training on PND24 and 25. However, exposure to MAM had no effect on the unconditioned response, T-maze delayed alternation, or conditioned suppression of ongoing behavior. In Experiment 2, MAM was given on PND4 and 7 and pups were tested behaviorally on PND17-18, 20-21, or 31-32. Cerebellar hypoplasia was most dramatic shortly after exposure. The cerebellar cortex continued to mature after exposure to MAM, but development of morphological endpoints examined here were static from PND19 to 33. Eyeblink conditioning was impaired at all ages, indicating that there was no functional recovery following neonatal exposure to MAM over the age range tested. These experiments suggest that normal cerebellar maturation may be important for the ontogeny of eyeblink conditioning

Increased circulating levels and salivary gland expression of interleukin-18 in patients with Sjögren's syndrome: relationship with autoantibody production and lymphoid organization of the periductal inflammatory infiltrate

IL-18, an immunoregulatory and proinflammatory cytokine, has been shown to play an important pathogenic role in Th1-driven autoimmune disorders. In this study, we evaluated the circulating levels and salivary-gland expression of IL-18 in patients with Sjögren's syndrome (SS), a mainly Th1-mediated disease. IL-18 serum levels were measured by ELISA in 37 patients with primary SS, 42 with rheumatoid arthritis, and 21 normal controls. We demonstrated high IL-18 serum levels in SS, similar to those in rheumatoid arthritis patients and significantly higher than in controls (P < 0.01). In addition, IL-18 serum concentrations were significantly higher in anti-SSA/Ro(+ )and anti-SSB/La(+ )than in anti-SSA/Ro(- )and anti-SSB/La(- )SS patients (respectively, P = 0.01, P < 0.01). Serum IL-18 correlated strongly with anti-SSA/Ro (P = 0.004) and anti-SSB/La (P = 0.01) titers. Salivary gland IL-18 expression was investigated by single/double immunohistochemistry in 13 patients with primary SS and in 10 with chronic sialoadenitis, used as controls. The expression of IL-18 was also examined in periductal inflammatory foci in relation to the acquisition of features of secondary lymphoid organs such as T–B compartmentalization, formation of follicular dendritic cell networks, and presence of germinal-center-like structures. IL-18 expression in SS salivary glands was detected in 28 of 32 periductal foci of mononuclear cells (87.5%), while no IL-18 production by infiltrating cells was detected in patients with chronic sialoadenitis. Within the inflammatory foci, IL-18 immunoreactivity co-localized almost exclusively with CD68(+ )macrophages. In addition, IL-18 was found in 15 of 19 foci (78.9%) with no evidence of T–B cell compartmentalization (nonsegregated) but in 100% of the segregated aggregates, both in T- and B-cell-rich areas. Strikingly, IL-18 was strongly expressed by CD68(+ )tingible body macrophages in germinal-centre-like structures both in SS salivary glands and in normal lymph nodes. IL-18 expression was observed in the ducts of all SS biopsies but in only 4 of 10 patients with nonspecific chronic sialoadenitis (P < 0.01). This study provides the first evidence of increased circulating levels and salivary gland expression of IL-18 in SS, suggesting an important contribution of this cytokine to the modulation of immune inflammatory pathways in this condition

A Call to Clarify the Intensity and Classification of Standing Behavior

Public health guidelines for physical activity now include recommendations to break up prolonged sitting with light-intensity activities. Concurrently, interventions to increase standing have emerged, especially within the workplace in the form of sit–stand or standing workstations. Moreover, in short-duration studies, breaking up prolonged sitting with standing has been associated improved cardiometabolic outcomes. Publicly available estimates of the intensity of standing range from 1.5 to 2.3 metabolic equivalents (METs), neatly classifying standing as a light-intensity activity (>1.5 to 2.0 METs and ≤2.0 METs, respectively. However, this study reviews data suggesting that some standing (e.g., while performing deskwork) is substantially below the minimum light intensity activity threshold of 1.5 METs. These data bring into question whether standing should be universally classified as a light-intensity behavior. The objectives of this study are to (i) highlight discrepancies in classifying standing behavior in the human movement spectrum continuum, and (ii) to propose a realignment of the ‘active’ vs. ‘passive’ standing threshold to match the light intensity threshold to help provide a clearer research framework and subsequent public health messaging for the expected health benefits from standing.N/

Safety of Tubal Occlusion by Minilaparotomy Provided by Trained Clinical Officers Versus Assistant Medical Officers in Tanzania: A Randomized, Controlled, Noninferiority Trial.

BACKGROUND: Tubal occlusion by minilaparotomy is a safe, highly effective, and permanent way to limit childbearing. We aimed to establish whether the safety of the procedure provided by trained clinical officers (COs) was not inferior to the safety when provided by trained assistant medical officers (AMOs), as measured by major adverse event (AE) rates. METHODS: In this randomized, controlled, open-label noninferiority trial, we enrolled participants at 7 health facilities in Arusha region, Tanzania, as well as during outreach activities conducted in Arusha and neighboring regions. Consenting, eligible participants were randomly allocated by a research assistant at each site to minilaparotomy performed by a trained CO or by a trained AMO, in a 1:1 ratio. We asked participants to return at 3, 7, and 42 days postsurgery. The primary outcome was the rate of major AEs following minilaparotomy performed by COs versus AMOs, during the procedure and through 42 days follow-up. The noninferiority margin was 2%. The trial is registered with ClinicalTrials.gov, Identifier NCT02944149. RESULTS: We randomly allocated 1,970 participants between December 2016 and June 2017, 984 to the CO group and 986 to the AMO group. Most (87%) minilaparotomies were conducted during outreach services. In the intent-to-treat analysis, 0 of 978 participants had a major AE in the CO group compared with 1 (0.1%) of 984 in the AMO group (risk difference: -0.1% [95% confidence interval: -0.3% to 0.1%]), meeting the criteria for noninferiority. We saw no evidence of differences in measures of procedure performance, participant satisfaction, or provider self-efficacy between the groups. CONCLUSIONS: Tubal occlusion by minilaparotomy performed by trained COs is safe, effective, and acceptable to women, and the procedure can be safely and effectively provided in outreach settings. Our results provide evidence to support policy change in resource-limited settings to allow task shifting of minilaparotomy to properly trained and supported COs, increasing access to female sterilization and helping to meet the rising demand for the procedure among women wanting to avoid pregnancy. They also suggest high demand for these services in Tanzania, given the large number of women recruited in a relatively short time period

Molecular structures and vibrations of neutral and anionic CuOx (x = 1-3,6) clusters

We report equilibrium geometric structures of CuO2, CuO3, CuO6, and CuO clusters obtained by an all-electron linear combination of atomic orbitals scheme within the density-functional theory with generalized gradient approximation to describe the exchange-correlation effects. The vibrational stability of all clusters is examined on the basis of the vibrational frequencies. A structure with Cs symmetry is found to be the lowest-energy structure for CuO2, while a -shaped structure with C2v symmetry is the most stable structure for CuO3. For the larger CuO6 and CuO clusters, several competitive structures exist with structures containing ozonide units being higher in energy than those with O2 units. The infrared and Raman spectra are calculated for the stable optimal geometries. ~Comment: Uses Revtex4, (Better quality figures can be obtained from authors

All-atom Molecular Dynamics simulations of spin labelled double and single-strand DNA for EPR studies

We report the first application of fully atomistic molecular dynamics (MD) simulations to the prediction of electron paramagnetic resonance (EPR) spectra of spin labelled DNA. Models for two structurally different DNA spin probes with either rigid or flexible position of the nitroxide group in the base pair, employed in experimental studies previously, have been developed. By the application of the combined MD-EPR simulation methodology we aimed at the following. Firstly, to provide a test bed against a sensitive spectroscopic technique for the recently developed an improved version of the parmbsc1 force field for MD modelling of DNA. The predicted EPR spectra show good agreement with the experimental ones available form the literature, thus confirming the accuracy of the currenly employed DNA force fields. Secondly, to provide quantative interpretation of the motional contributions into the dynamics of spin probes in both duplex and single-strand DNA fragments and to analyse their perturbing effects on the local DNA structure. Finally, a combination of MD and EPR allowed us to test the validity of the application of the Model-Free (M-F) approach coupled with partial averaging of magnetic tensors to the simulation of EPR spectra of DNA systems by comparing the resulting EPR spectra with those simulated directly from MD trajectories. The advantage of the M-F based EPR simulation approach over the direct propagation techniques is that it requires motional and order parameters that can be calculated from shorter MD trajectories. The reported MD-EPR methodology is transferable to the prediction and interpretation of EPR spectra of higher order DNA structures with novel types of spin labels

A Prospective Case-Control Study

Background: Few studies have assessed the effect of prothrombotic blood abnormalities on the risk of deep vein thrombosis (DVT) with hormone replacement therapy (HRT). Methods: We studied postmenopausal women with suspected DVT in whom HRT use and prothrombotic blood abnormalities were sought. Cases had unprovoked DVT and controls had no DVT and without DVT risk factors. The risk of DVT was determined in women with and without prothrombotic abnormalities. Results: A total of 510 postmenopausal women with suspected DVT were assessed; 57 cases and 283 controls were identified. Compared to HRT, nonusers without the factor V Leiden mutation, the risk of DVT was increased in estrogen-progestin HRT users (odds ratio [OR], 3.2; 95% confidence interval [CI]: 1.2-8.6) and in nonusers with the factor V Leiden mutation (OR, 5.3; 1.9-15.4) and appears multiplied in users of estrogen-progestin HRT with the factor V Leiden mutation (OR, 17.1; 3.7-78). Compared to HRT, nonusers with normal factor VIII, the risk of DVT was increased in estrogen-progestin HRT users with normal factor VIII (OR, 2.8; 1.0-7.9) and in HRT nonusers with the highest factor VIII quartile (OR, 6.0; 2.1-17), and appears to be multiplied in women who are users of estrogen-progestin HRT with the highest factor VIII quartile (OR, 17.0; 3.6-80). Conclusions: In postmenopausal women who are estrogen-progestin HRT users, the presence of the factor V Leiden mutation or an elevated factor VIII level appears to have a multiplicative effect on their overall risk of DVT, increasing it 17-fold compared to women without these blood abnormalities who are HRT nonusers