Neuroevolution of Self-Interpretable Agents

Inattentional blindness is the psychological phenomenon that causes one to miss things in plain sight. It is a consequence of the selective attention in perception that lets us remain focused on important parts of our world without distraction from irrelevant details. Motivated by selective attention, we study the properties of artificial agents that perceive the world through the lens of a self-attention bottleneck. By constraining access to only a small fraction of the visual input, we show that their policies are directly interpretable in pixel space. We find neuroevolution ideal for training self-attention architectures for vision-based reinforcement learning (RL) tasks, allowing us to incorporate modules that can include discrete, non-differentiable operations which are useful for our agent. We argue that self-attention has similar properties as indirect encoding, in the sense that large implicit weight matrices are generated from a small number of key-query parameters, thus enabling our agent to solve challenging vision based tasks with at least 1000x fewer parameters than existing methods. Since our agent attends to only task critical visual hints, they are able to generalize to environments where task irrelevant elements are modified while conventional methods fail. Videos of our results and source code available at https://attentionagent.github.io/Comment: To appear at the Genetic and Evolutionary Computation Conference (GECCO 2020) as a full pape

A bayesian meta-analysis of multiple treatment comparisons of systemic regimens for advanced pancreatic cancer

© 2014 Chan et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Background: For advanced pancreatic cancer, many regimens have been compared with gemcitabine (G) as the standard arm in randomized controlled trials. Few regimens have been directly compared with each other in randomized controlled trials and the relative efficacy and safety among them remains unclear

Meta-analysis of clodronate and breast cancer survival

Clinical trials have reported conflicting results on whether oral clodronate therapy improves survival in breast cancer patients. This study was undertaken to evaluate further the effect of oral clodronate therapy on overall survival, bone metastasis-free survival and nonskeletal metastasis-free survival among breast cancer patients. An extensive literature search was undertaken for the period 1966 to July 2006 to identify clinical trials examining survival in breast cancer patients who received 2 or 3 years of oral clodronate therapy at 1600 mg day−1 compared with those without therapy. Meta-analyses were carried out separately for patients diagnosed with advanced breast cancer and early breast cancer. Our meta-analysis found no evidence of any statistically significant difference in overall survival, bone metastasis-free survival or nonskeletal metastasis-free survival in advanced breast cancer patients receiving clodronate therapy or early breast cancer patients receiving adjuvant clodronate treatment compared with those who did not receive any active treatment

Vitamin D supplementation and breast cancer prevention : a systematic review and meta-analysis of randomized clinical trials

In recent years, the scientific evidence linking vitamin D status or supplementation to breast cancer has grown notably. To investigate the role of vitamin D supplementation on breast cancer incidence, we conducted a systematic review and meta-analysis of randomized controlled trials comparing vitamin D with placebo or no treatment. We used OVID to search MEDLINE (R), EMBASE and CENTRAL until April 2012. We screened the reference lists of included studies and used the “Related Article” feature in PubMed to identify additional articles. No language restrictions were applied. Two reviewers independently extracted data on methodological quality, participants, intervention, comparison and outcomes. Risk Ratios and 95% Confident Intervals for breast cancer were pooled using a random-effects model. Heterogeneity was assessed using the I2 test. In sensitivity analysis, we assessed the impact of vitamin D dosage and mode of administration on treatment effects. Only two randomized controlled trials fulfilled the pre-set inclusion criteria. The pooled analysis included 5372 postmenopausal women. Overall, Risk Ratios and 95% Confident Intervals were 1.11 and 0.74–1.68. We found no evidence of heterogeneity. Neither vitamin D dosage nor mode of administration significantly affected breast cancer risk. However, treatment efficacy was somewhat greater when vitamin D was administered at the highest dosage and in combination with calcium (Risk Ratio 0.58, 95% Confident Interval 0.23–1.47 and Risk Ratio 0.93, 95% Confident Interval 0.54–1.60, respectively). In conclusions, vitamin D use seems not to be associated with a reduced risk of breast cancer development in postmenopausal women. However, the available evidence is still limited and inadequate to draw firm conclusions. Study protocol code: FARM8L2B5L

Gravitationally redshifted absorption lines in the X-ray burst spectra of a neutron star

The fundamental properties of neutron stars provide a direct test of the equation of state of cold nuclear matter, a relationship between pressure and density that is determined by the physics of the strong interactions between the particles that constitute the star. The most straightforward method of determining these properties is by measuring the gravitational redshift of spectral lines produced in the neutron star photosphere. The equation of state implies a mass-radius relation, while a measurement of the gravitational redshift at the surface of a neutron star provides a direct constraint on the mass-to-radius ratio. Here we report the discovery of signficant absorption lines in the spectra of 28 bursts of the low-mass X-ray binary EXO 0748-676. We identify the most signficant features with the Fe XXVI and XXV n=2-3 and O VIII n=1-2 transitions, all with a redshift of z=0.35, identical within small uncertainties for the respective transitions. For an astrophysically plausible range of masses (M ~ 1.3-2.0 M_solar), this value is completely consistent with models of neutron stars composed of normal nuclear matter, while it excludes some models in which the neutron stars are made of more exotic matter.Comment: Published in Nature (Nov 7, 2002

Production of phi mesons at mid-rapidity in sqrt(s_NN) = 200 GeV Au+Au collisions at RHIC

We present the first results of meson production in the K^+K^- decay channel from Au+Au collisions at sqrt(s_NN) = 200 GeV as measured at mid-rapidity by the PHENIX detector at RHIC. Precision resonance centroid and width values are extracted as a function of collision centrality. No significant variation from the PDG accepted values is observed. The transverse mass spectra are fitted with a linear exponential function for which the derived inverse slope parameter is seen to be constant as a function of centrality. These data are also fitted by a hydrodynamic model with the result that the freeze-out temperature and the expansion velocity values are consistent with the values previously derived from fitting single hadron inclusive data. As a function of transverse momentum the collisions scaled peripheral.to.central yield ratio RCP for the is comparable to that of pions rather than that of protons. This result lends support to theoretical models which distinguish between baryons and mesons instead of particle mass for explaining the anomalous proton yield.Comment: 326 authors, 24 pages text, 23 figures, 6 tables, RevTeX 4. To be submitted to Physical Review C as a regular article. Plain text data tables for the points plotted in figures for this and previous PHENIX publications are (or will be) publicly available at http://www.phenix.bnl.gov/papers.htm

Meta-analysis of randomized trials: evaluation of benefit from gemcitabine-based combination chemotherapy applied in advanced pancreatic cancer

<p>Abstract</p> <p>Background</p> <p>Single-agent gemcitabine (GEM) is a standard treatment for advanced and metastatic pancreatic cancer. This study examines the question whether GEM-based combination chemotherapy can further improve treatment efficacy.</p> <p>Methods</p> <p>A meta-analysis was performed to evaluate randomized trials comparing GEM versus GEM+X (X = cytotoxic agent). Fifteen trials including 4465 patients were eligible for an analysis of overall survival, the primary end-point of this investigation.</p> <p>Results</p> <p>The meta-analysis revealed a significant survival benefit for GEM+X with a pooled hazard ratio (HR) of 0.91 (95% CI: 0.85 – 0.97, p = 0.004). The overall test for heterogeneity resulted in p = 0.82 (I²= 0%). The analysis of platinum-based combinations indicated a HR of 0.85 (95% CI: 0.76 – 0.96, p = 0.010), while for fluoropyrimidine-based combinations the HR was 0.90 (95% CI: 0.81 – 0.99, p = 0.030). No risk reduction was observed in the group of trials combining GEM with irinotecan, exatecan or pemetrexed (HR = 0.99). A meta-analysis of the trials with adequate information on baseline performance status (PS) was performed in five trials with 1682 patients. This analysis indicated that patients with a good PS had a marked survival benefit when receiving combination chemotherapy (HR = 0.76; 95% CI: 0.67 – 0.87; p < 0.0001). By contrast, application of combination chemotherapy to patients with an initially poor PS appeared to be ineffective (HR = 1.08; 95% CI: 0.90 – 1.29, p = 0.40).</p> <p>Conclusion</p> <p>The meta-analysis of randomized trials indicated a significant survival benefit when GEM was either combined with platinum analogs or fluoropyrimidines. Based on a preliminary subgroup analysis (representing 38% of all patients included in this meta-analysis), pancreatic cancer patients with a good PS appear to benefit from GEM-based cytotoxic combinations, whereas patients with a poor PS seem to have no survival benefit from combination chemotherapy.</p

SirT1 modulates the estrogen–insulin-like growth factor-1 signaling for postnatal development of mammary gland in mice

INTRODUCTION: Estrogen and insulin-like growth factor-1 (IGF-1) play important roles in mammary gland development and breast cancer. SirT1 is a highly conserved protein deacetylase that can regulate the insulin/IGF-1 signaling in lower organisms, as well as a growing number of transcription factors, including NF-κB, in mammalian cells. Whether SirT1 regulates the IGF-1 signaling for mammary gland development and function, however, is not clear. In the present study, this role of SirT1 was examined by studying SirT1-deficient mice. METHODS: SirT1-deficient (SirT1(ko/ko)) mice were generated by crossing a new strain of mice harboring a conditional targeted mutation in the SirT1 gene (SirT1(co/co)) with CMV-Cre transgenic mice. Whole mount and histology analyses, immunofluorescence staining, immunohistochemistry, and western blotting were used to characterize mammary gland development in virgin and pregnant mice. The effect of exogenous estrogen was also examined by subcutaneous implantation of a slow-releasing pellet in the subscapular region. RESULTS: Both male and female SirT1(ko/ko )mice can be fertile despite the growth retardation phenotype. Virgin SirT1(ko/ko )mice displayed impeded ductal morphogenesis, whereas pregnant SirT1(ko/ko )mice manifested lactation failure due to an underdeveloped lobuloalveolar network. Estrogen implantation was sufficient to rescue ductal morphogenesis. Exogenous estrogen reversed the increased basal level of IGF-1 binding protein-1 expression in SirT1(ko/ko )mammary tissues, but not that of IκBα expression, suggesting that increased levels of estrogen enhanced the production of local IGF-1 and rescued ductal morphogenesis. Additionally, TNFα treatment enhanced the level of the newly synthesized IκBα in SirT1(ko/ko )cells. SirT1 deficiency therefore affects the cellular response to multiple extrinsic signals. CONCLUSION: SirT1 modulates the IGF-1 signaling critical for both growth regulation and mammary gland development in mice. SirT1 deficiency deregulates the expression of IGF-1 binding protein-1 and attenuates the effect of IGF-1 signals, including estrogen-stimulated local IGF-1 signaling for the onset of ductal morphogenesis. These findings suggest that the enzymatic activity of SirT1 may influence both normal growth and malignant growth of mammary epithelial cells

Wall shear stress as measured in vivo: consequences for the design of the arterial system

Based upon theory, wall shear stress (WSS), an important determinant of endothelial function and gene expression, has been assumed to be constant along the arterial tree and the same in a particular artery across species. In vivo measurements of WSS, however, have shown that these assumptions are far from valid. In this survey we will discuss the assessment of WSS in the arterial system in vivo and present the results obtained in large arteries and arterioles. In vivo WSS can be estimated from wall shear rate, as derived from non-invasively recorded velocity profiles, and whole blood viscosity in large arteries and plasma viscosity in arterioles, avoiding theoretical assumptions. In large arteries velocity profiles can be recorded by means of a specially designed ultrasound system and in arterioles via optical techniques using fluorescent flow velocity tracers. It is shown that in humans mean WSS is substantially higher in the carotid artery (1.1–1.3 Pa) than in the brachial (0.4–0.5 Pa) and femoral (0.3–0.5 Pa) arteries. Also in animals mean WSS varies substantially along the arterial tree. Mean WSS in arterioles varies between about 1.0 and 5.0 Pa in the various studies and is dependent on the site of measurement in these vessels. Across species mean WSS in a particular artery decreases linearly with body mass, e.g., in the infra-renal aorta from 8.8 Pa in mice to 0.5 Pa in humans. The observation that mean WSS is far from constant along the arterial tree implies that Murray’s cube law on flow-diameter relations cannot be applied to the whole arterial system. Because blood flow velocity is not constant along the arterial tree either, a square law also does not hold. The exponent in the power law likely varies along the arterial system, probably from 2 in large arteries near the heart to 3 in arterioles. The in vivo findings also imply that in in vitro studies no average shear stress value can be taken to study effects on endothelial cells derived from different vascular areas or from the same artery in different species. The cells have to be studied under the shear stress conditions they are exposed to in real life