The Univariate Marginal Distribution Algorithm Copes Well With Deception and Epistasis

In their recent work, Lehre and Nguyen (FOGA 2019) show that the univariate marginal distribution algorithm (UMDA) needs time exponential in the parent populations size to optimize the DeceptiveLeadingBlocks (DLB) problem. They conclude from this result that univariate EDAs have difficulties with deception and epistasis. In this work, we show that this negative finding is caused by an unfortunate choice of the parameters of the UMDA. When the population sizes are chosen large enough to prevent genetic drift, then the UMDA optimizes the DLB problem with high probability with at most $\lambda(\frac{n}{2} + 2 e \ln n)$ fitness evaluations. Since an offspring population size $\lambda$ of order $n \log n$ can prevent genetic drift, the UMDA can solve the DLB problem with $O(n^2 \log n)$ fitness evaluations. In contrast, for classic evolutionary algorithms no better run time guarantee than $O(n^3)$ is known (which we prove to be tight for the ${(1+1)}$ EA), so our result rather suggests that the UMDA can cope well with deception and epistatis. From a broader perspective, our result shows that the UMDA can cope better with local optima than evolutionary algorithms; such a result was previously known only for the compact genetic algorithm. Together with the lower bound of Lehre and Nguyen, our result for the first time rigorously proves that running EDAs in the regime with genetic drift can lead to drastic performance losses

Experience in hepatic resection for metastatic colorectal cancer: Analysis of clinical and pathologic risk factors

Background. The selection of patients for resective therapy of hepatic colorectal metastases remains controversial. A number of clinical and pathologic prognostic risk factors have been variably reported to influence survival. Methods. Between January 1981 and December 1991, 204 patients underwent curative hepatic resection for metastatic colorectal cancer. Fourteen clinical and pathologic determinants previously reported to influence outcome were examined retrospectively. This led to a proposed TNM staging system for metastatic colorectal cancer (mTNM). Results. No operative deaths occurred (death within 1 month). Overall 1-, 3-, and 5-year survivals were 91%, 43%, and 32%, respectively. Gender, Dukes' classification, site of primary colorectal cancer, histologic differentiation, size of metastatic tumor, and intraoperative blood transfusion requirement were not statistically significant prognostic factors (p > 0.05). Age of 60 years or more, interval of 24 months or less between colorectal and hepatic resection, four or more gross tumors, bilobar involvement, positive resection margin, lymph node involvement, and direct invasion to adjacent organs were significant poor prognostic factors (p < 0.05). In the absence of nodal disease or direct invasion, patients with unilobar solitary tumor of any size, or unilobar multiple tumors of 2 cm or smaller (stages I and II) had the highest survival rates of 93% at 1 year, 68% at 3 years, and 61% at 5 years. Unilobar disease with multiple lesions greater than 2 cm (stage III) resulted in 1-, 3-, and 5-year survivals of 98%, 45%, and 28%, respectively. Patients with bilobar involvement (multiple tumors, any size, or a single large metastasis) (stage IVA) had survival rates of 88% at 1 year, 28% at 3 years, and 20% at 5 years (p < 0.00001). Patients with nodal involvement or extrahepatic disease (stage IVB) experienced the poorest outcome with 1-, 3- , and 5-year survivals of 80%, 12%, and 0%, respectively (p < 0.00001). Conclusions. The proposed mTNM staging system appears to be useful in predicting the outcomes after hepatic resection of metastatic colorectal tumors

Clinical Space Medicine Products as Developed by the Medical Operations Support Team (MOST)

Medical Operations Support Team (MOST) is introducing/integrating teaching practices associated with high fidelity human patient simulation into the NASA culture, in particular, into medical training sessions and medical procedure evaluations. Current/Future Products iclude: a) Development of Sub-optimal Airway Protocols for the International Space Station (ISS) using the ILMA; b) Clinical Core Competency Training for NASA Flight Surgeons (FS); c) Post-Soyuz Landing Clinical Training for NASA FS; d) Experimental Integrated Training for Astronaut Crew Medical Officers and NASA FS; and e) Private Clinical Refresher Training

Comparison of in vitro and in vivo models for the elucidation of metabolic patterns of 7-azaindole-derived synthetic cannabinoids exemplified using cumyl-5F-P7AICA

Due to the dynamic market involving synthetic cannabinoids (SCs), the determination of analytical targets is challenging in clinical and forensic toxicology. SCs usually undergo extensive metabolism, and therefore their main metabolites must be identified for the detection in biological matrices, particularly in urine. Controlled human studies are usually not possible for ethical reasons; thus, alternative models must be used. The aim of this work was to predict the in vitro and in vivo metabolic patterns of 7‐azaindole‐derived SCs using 1‐(5‐fluoropentyl)‐N‐(2‐phenylpropan‐2‐yl)‐1H‐pyrollo[2,3‐b]pyridin‐3‐carboxamide (cumyl‐5F‐P7AICA) as an example. Different in vitro (pooled human liver S9 fraction, pooled human liver microsomes, and pig liver microsomes) and in vivo (rat and pig) systems were compared. Monooxygenase isoenzymes responsible for the most abundant phase I steps, namely oxidative defluorination (OF) followed by carboxylation, monohydroxylation, and ketone formation, were identified. In both in vivo models, OF/carboxylation and N‐dealkylation/monohydroxylation/sulfation could be detected. Regarding pHS9 and pig urine, monohydroxylation/sulfation or glucuronidation was also abundant. Furthermore, the parent compound could still be detected in all models. Initial monooxygenase activity screening revealed the involvement of CYP2C19, CYP3A4, and CYP3A5. Therefore, in addition to the parent compound, the OF/carboxylated and monohydroxylated (and sulfated or glucuronidated) metabolites can be recommended as urinary targets. In comparison to literature, the pig model predicts best the human metabolic pattern of cumyl‐5F‐P7AICA. Furthermore, the pig model should be suitable to mirror the time‐dependent excretion pattern of parent compounds and metabolites

Toxicokinetics of U-47700, tramadol, and their main metabolites in pigs following intravenous administration: is a multiple species allometric scaling approach useful for the extrapolation of toxicokinetic parameters to humans?

New synthetic opioids (NSOs) pose a public health concern since their emergence on the illicit drug market and are gaining increasing importance in forensic toxicology. Like many other new psychoactive substances, NSOs are consumed without any preclinical safety data or any knowledge on toxicokinetic (TK) data. Due to ethical reasons, controlled human TK studies cannot be performed for the assessment of these relevant data. As an alternative animal experimental approach, six pigs per drug received a single intravenous dose of 100 µg/kg body weight (BW) of U-47700 or 1000 µg/kg BW of tramadol to evaluate whether this species is suitable to assess the TK of NSOs. The drugs were determined in serum and whole blood using a fully validated method based on solid-phase extraction and LC–MS/MS. The concentration–time profiles and a population (pop) TK analysis revealed that a three-compartment model best described the TK data of both opioids. Central volumes of distribution were 0.94 L/kg for U-47700 and 1.25 L/kg for tramadol and central (metabolic) clearances were estimated at 1.57 L/h/kg and 1.85 L/h/kg for U-47700 and tramadol, respectively. The final popTK model parameters for pigs were upscaled via allometric scaling techniques. In comparison to published human data, concentration–time profiles for tramadol could successfully be predicted with single species allometric scaling. Furthermore, possible profiles for U-47700 in humans were simulated. The findings of this study indicate that unlike a multiple species scaling approach, pigs in conjunction with TK modeling are a suitable tool for the assessment of TK data of NSOs and the prediction of human TK data

On the Runtime Analysis of the Clearing Diversity-Preserving Mechanism

Clearing is a niching method inspired by the principle of assigning the available resources among a niche to a single individual. The clearing procedure supplies these resources only to the best individual of each niche: the winner. So far, its analysis has been focused on experimental approaches that have shown that clearing is a powerful diversity-preserving mechanism. Using rigorous runtime analysis to explain how and why it is a powerful method, we prove that a mutation-based evolutionary algorithm with a large enough population size, and a phenotypic distance function always succeeds in optimising all functions of unitation for small niches in polynomial time, while a genotypic distance function requires exponential time. Finally, we prove that with phenotypic and genotypic distances clearing is able to find both optima for Twomax and several general classes of bimodal functions in polynomial expected time. We use empirical analysis to highlight some of the characteristics that makes it a useful mechanism and to support the theoretical results

The second flight of the SUNRISE balloon-borne solar observatory: overview of instrument updates, the flight, the data and first results

The SUNRISE balloon-borne solar observatory, consisting of a 1~m aperture telescope that provided a stabilized image to a UV filter imager and an imaging vector polarimeter, carried out its second science flight in June 2013. It provided observations of parts of active regions at high spatial resolution, including the first high-resolution images in the Mg~{\sc ii}~k line. The obtained data are of very high quality, with the best UV images reaching the diffraction limit of the telescope at 3000~\AA\ after Multi-Frame Blind Deconvolution reconstruction accounting for phase-diversity information. Here a brief update is given of the instruments and the data reduction techniques, which includes an inversion of the polarimetric data. Mainly those aspects that evolved compared with the first flight are described. A tabular overview of the observations is given. In addition, an example time series of a part of the emerging active region NOAA AR~11768 observed relatively close to disk centre is described and discussed in some detail. The observations cover the pores in the trailing polarity of the active region, as well as the polarity inversion line where flux emergence was ongoing and a small flare-like brightening occurred in the course of the time series. The pores are found to contain magnetic field strengths ranging up to 2500~G and, while large pores are clearly darker and cooler than the quiet Sun in all layers of the photosphere, the temperature and brightness of small pores approach or even exceed those of the quiet Sun in the upper photosphere.Comment: Accepted for publication in The Astrophysical Journa

Cumulant expansion for studying damped quantum solitons

The quantum statistics of damped optical solitons is studied using cumulant-expansion techniques. The effect of absorption is described in terms of ordinary Markovian relaxation theory, by coupling the optical field to a continuum of reservoir modes. After introduction of local bosonic field operators and spatial discretization pseudo-Fokker-Planck equations for multidimensional s-parameterized phase-space functions are derived. These partial differential equations are equivalent to an infinite set of ordinary differential equations for the cumulants of the phase-space functions. Introducing an appropriate truncation condition, the resulting finite set of cumulant evolution equations can be solved numerically. Solutions are presented in Gaussian approximation and the quantum noise is calculated, with special emphasis on squeezing and the recently measured spectral photon-number correlations [Spaelter et al., Phys. Rev. Lett. 81, 786 (1998)].Comment: 17 pages, 13 figures, revtex, psfig, multicols, published in Phys.Rev.

The Wave-Front Correction System for the Sunrise Balloon-Borne Solar Observatory

This paper describes the wave-front correction system developed for the Sunrise balloon telescope, and it provides information about its in-flight performance. For the correction of low-order aberrations, a Correlating Wave-Front Sensor (CWS) was used. It consisted of a six-element Shack - Hartmann wave-front sensor (WFS), a fast tip-tilt mirror for the compensation of image motion, and an active telescope secondary mirror for focus correction. The CWS delivered a stabilized image with a precision of 0.04 arcsec (rms), whenever the coarse pointing was better than ± 45 arcsec peak-to-peak. The automatic focus adjustment maintained a focus stability of 0.01 waves in the focal plane of the CWS. During the 5.5 day flight, good image quality and stability were achieved during 33 hours, containing 45 sequences, which lasted between 10 and 45 min. © 2010 The Author(s)

Rich Magnetic Phase Diagram of Putative Helimagnet Sr3_3Fe2_2O7_7

The cubic perovskite SrFeO$_3$ was recently reported to host hedgehog- and skyrmion-lattice phases in a highly symmetric crystal structure which does not support the Dzyaloshinskii-Moriya interactions commonly invoked to explain such magnetic order. Hints of a complex magnetic phase diagram have also recently been found in powder samples of the single-layer Ruddlesden-Popper analog Sr$_2$FeO$_4$, so a reinvestigation of the bilayer material Sr$_3$Fe$_2$O$_7$, believed to be a simple helimagnet, is called for. Our magnetization and dilatometry studies reveal a rich magnetic phase diagram with at least 6 distinct magnetically ordered phases and strong similarities to that of SrFeO$_3$. In particular, at least one phase is apparently multiple-$\mathbf{q}$, and the $\mathbf{q}$s are not observed to vary among the phases. Since Sr$_3$Fe$_2$O$_7$ has only two possible orientations for its propagation vector, some of the phases are likely exotic multiple-$\mathbf{q}$ order, and it is possible to fully detwin all phases and more readily access their exotic physics.Comment: 14 pages, 13 figure