Building more accurate decision trees with the additive tree.

The expansion of machine learning to high-stakes application domains such as medicine, finance, and criminal justice, where making informed decisions requires clear understanding of the model, has increased the interest in interpretable machine learning. The widely used Classification and Regression Trees (CART) have played a major role in health sciences, due to their simple and intuitive explanation of predictions. Ensemble methods like gradient boosting can improve the accuracy of decision trees, but at the expense of the interpretability of the generated model. Additive models, such as those produced by gradient boosting, and full interaction models, such as CART, have been investigated largely in isolation. We show that these models exist along a spectrum, revealing previously unseen connections between these approaches. This paper introduces a rigorous formalization for the additive tree, an empirically validated learning technique for creating a single decision tree, and shows that this method can produce models equivalent to CART or gradient boosted stumps at the extremes by varying a single parameter. Although the additive tree is designed primarily to provide both the model interpretability and predictive performance needed for high-stakes applications like medicine, it also can produce decision trees represented by hybrid models between CART and boosted stumps that can outperform either of these approaches

Effect of solar particle event radiation and hindlimb suspension on gastrointestinal tract bacterial translocation and immune activation.

The environmental conditions that could lead to an increased risk for the development of an infection during prolonged space flight include: microgravity, stress, radiation, disturbance of circadian rhythms, and altered nutritional intake. A large body of literature exists on the impairment of the immune system by space flight. With the advent of missions outside the Earth's magnetic field, the increased risk of adverse effects due to exposure to radiation from a solar particle event (SPE) needs to be considered. Using models of reduced gravity and SPE radiation, we identify that either 2 Gy of radiation or hindlimb suspension alone leads to activation of the innate immune system and the two together are synergistic. The mechanism for the transient systemic immune activation is a reduced ability of the GI tract to contain bacterial products. The identification of mechanisms responsible for immune dysfunction during extended space missions will allow the development of specific countermeasures

Leukocyte activity is altered in a ground based murine model of microgravity and proton radiation exposure.

Immune system adaptation during spaceflight is a concern in space medicine. Decreased circulating leukocytes observed during and after space flight infer suppressed immune responses and susceptibility to infection. The microgravity aspect of the space environment has been simulated on Earth to study adverse biological effects in astronauts. In this report, the hindlimb unloading (HU) model was employed to investigate the combined effects of solar particle event-like proton radiation and simulated microgravity on immune cell parameters including lymphocyte subtype populations and activity. Lymphocytes are a type of white blood cell critical for adaptive immune responses and T lymphocytes are regulators of cell-mediated immunity, controlling the entire immune response. Mice were suspended prior to and after proton radiation exposure (2 Gy dose) and total leukocyte numbers and splenic lymphocyte functionality were evaluated on days 4 or 21 after combined HU and radiation exposure. Total white blood cell (WBC), lymphocyte, neutrophil, and monocyte counts are reduced by approximately 65%, 70%, 55%, and 70%, respectively, compared to the non-treated control group at 4 days after combined exposure. Splenic lymphocyte subpopulations are altered at both time points investigated. At 21 days post-exposure to combined HU and proton radiation, T cell activation and proliferation were assessed in isolated lymphocytes. Cell surface expression of the Early Activation Marker, CD69, is decreased by 30% in the combined treatment group, compared to the non-treated control group and cell proliferation was suppressed by approximately 50%, compared to the non-treated control group. These findings reveal that the combined stressors (HU and proton radiation exposure) result in decreased leukocyte numbers and function, which could contribute to immune system dysfunction in crew members. This investigation is one of the first to report on combined proton radiation and simulated microgravity effects on hematopoietic, specifically immune cells

Broad-spectrum antibiotic or G-CSF as potential countermeasures for impaired control of bacterial infection associated with an SPE exposure during spaceflight.

A major risk for astronauts during prolonged space flight is infection as a result of the combined effects of microgravity, situational and confinement stress, alterations in food intake, altered circadian rhythm, and radiation that can significantly impair the immune system and the body's defense systems. We previously reported a massive increase in morbidity with a decrease in the ability to control a bacterial challenge when mice were maintained under hindlimb suspension (HS) conditions and exposed to solar particle event (SPE)-like radiation. HS and SPE-like radiation treatment alone resulted in a borderline significant increase in morbidity. Therefore, development and testing of countermeasures that can be used during extended space missions in the setting of exposure to SPE radiation becomes a serious need. In the present study, we investigated the efficacy of enrofloxacin (an orally bioavailable antibiotic) and Granulocyte colony stimulating factor (G-CSF) (Neulasta) on enhancing resistance to Pseudomonas aeruginosa infection in mice subjected to HS and SPE-like radiation. The results revealed that treatment with enrofloxacin or G-CSF enhanced bacterial clearance and significantly decreased morbidity and mortality in challenged mice exposed to suspension and radiation. These results establish that antibiotics, such as enrofloxacin, and G-CSF could be effective countermeasures to decrease the risk of bacterial infections after exposure to SPE radiation during extended space flight, thereby reducing both the risk to the crew and the danger of mission failure

The splenic T lymphocyte population is decreased at 21 days post-proton radiation exposure +/− HU, compared to the No treatment group (*) and/or the HU group (#).

<p>The average percentage of CD3+ splenocytes is shown +/− SD, n = 4–6.</p

Total blood cell counts are decreased in the irradiated (2 Gy) groups +/− HU treatment WBCs (A) and lymphocytes (B) at 4 days post-proton radiation exposure are significantly decreased, compared to the No treatment group (*).

<p>The WBC and lymphocyte results indicated statistically significant differences between the 2 Gy + HU group and the No treatment group (*), as well as between the 2 Gy + HU group and the HU group (#). Average counts +/− SD are expressed as a fraction of the control, n = 3–5. The neutrophil count at 4 days post-proton radiation exposure + HU treatment are significantly decreased, compared to the neutrophil counts observed for the No treatment group (*) and the HU group (#). HU treatment results in a statistically significant increase in neutrophil counts, compared to the No treatment group (*) (C); however, the differences between the neutrophil counts for the 2 Gy group are not statistically significant when compared to the neutrophil counts from the mice in the No treatment group. Monocytes are decreased in the combined treatment group (2 Gy + HU) compared to the No treatment group (*) (D).</p

Cytotoxic T cells are decreased in the irradiated and HU animals.

<p>At 4 days post-proton irradiation exposure + HU treatment, the population of splenic cytotoxic T cells (expressing CD3+ CD8+ surface markers) is significantly decreased when compared to the HU group, by approximately 50%. The average percent of antigen expressing cells are shown +/− SD, n = 4–6.</p

SPE-like radiation and hindlimb suspension increase the acute-phase reactant LPS binding protein.

<p>Mice were hindlimb suspended and/or irradiated with 2 Gy protons at 50 cGy/min. One (A) and 4 (B) days later, serum was obtained and analyzed for LPS binding protein content by ELISA. Data shown are the averages for five mice per group run in duplicate; error bars are SEM. Statistically significant differences between groups is noted in the inset table with C = control, R = radiation, S = suspension as calculated with ANOVA analyses with post-hoc group comparisons using Bonferroni correction. Data shown are from a single experiment representative of three experiments.</p