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Juan Marcos González,1 Sarika Ogale,2 Robert Morlock,2 Joshua Posner,1 Brett Hauber,1 Nicolas Sommer,2 Axel Grothey3 1Health Preference Assessment Department, RTI Health Solutions, Research Triangle Park, NC, 2Genentech, South San Francisco, CA, 3Division of Medical Oncology, Mayo Clinic, Rochester, MN, USA Objective: Many publications describe preferences for colorectal cancer (CRC) screening; however, few studies elicited preferences for anticancer-drug treatment for metastatic CRC (mCRC). This study was designed to elicit preferences and risk tolerance among patients and oncologists in the USA for anticancer drugs to treat mCRC. Materials and methods: Patients aged 18 years or older with a self-reported diagnosis of mCRC and board-certified (or equivalent) oncologists who had treated patients with mCRC were recruited by two survey research companies from existing online patient panels in the USA. Additional oncologists were recruited from a list of US physicians. Patients and oncologists completed a discrete-choice experiment (DCE) survey. DCEs offer a systematic method of eliciting preferences and quantifying both the relative importance of treatment attributes and the tradeoffs respondents are willing to make among benefits and risks. Treatment attributes in the DCE were progression-free survival (PFS) and risks of severe papulopustular rash, serious hemorrhage, cardiopulmonary arrest, and gastrointestinal perforation. Patients’ and physicians’ maximum levels of acceptable treatment-related risks for two prespecified increases in efficacy were estimated. Results: A total of 127 patients and 150 oncologists completed the survey. Relative preferences for the treatment attributes in the study were mostly consistent with the expectation that better clinical outcomes were preferred over worse clinical outcomes. Risk tolerance varied between patients and physicians. On average, physicians were willing to tolerate higher risks than patients, although these differences were mostly not statistically significant. Post hoc latent-class analyses revealed that some patients and physicians were unwilling to forgo any efficacy to avoid toxicities, while others were willing to make such tradeoffs. Conclusion: Differences in preferences between patients and physicians suggest that there is the potential for improvement in patients’ well-being. Initiating or enhancing discussions about patient tolerance for toxicities, such as skin rash and gastrointestinal perforations, may help prescribe treatments that entail more appropriate benefit–risk tradeoffs. Keywords: metastatic colorectal cancer, discrete-choice experiment, patient preferences, physician preferences, risk tolerance

Liver surgery is the cornerstone of the curative treatment of malignant liver tumors. However, the liver anatomy is very complex, and liver surgery is still associated with relevant morbidity despite many technical advances. The Brisbane nomenclature is used worldwide to classify liver resection. However, this nomenclature has several limitations as multiple terms are used for the same type of resection. Non-anatomical resections, multiple resections, and combined bilio-vascular resections were not mentioned. Therefore, new terminologies have been proposed for the precise and simple classification of liver resection. Furthermore, in recent years, many technical innovations have been introduced in liver surgery, such as 3D imaging systems and indocyanine green fluorescence, for better preoperative and intraoperative identification of tumor localization and critical vascular structures. Minimally invasive techniques are used more frequently in liver surgery. Potential benefits include less intraoperative blood loss, less pain, and a shorter hospital stay. The implementation of robotic systems also has an impact on liver surgery, and the number of cases reported in the literature is constantly increasing. The potential benefits of robotic liver resection over laparoscopic liver resection will be the subject of future studies.

Positions introduced into the Escherichia coli Ptac promoter make the mutant promoter responsive to Alt-ADP-ribosylated RNA polymerase, like T4 early promoters. The help with acceleration of transcription, the ADP-ribosylated enzyme must have integrity of several regions and also of position -33 and, more important, maintenance of the upstream promoter element at -42. To see which promoter elements help in increasing transcriptional activity directed at phage genes the very strong E. coli promoter, Ptac, was sequentially mutated toward the sequence of the T4 early promoter consensus.

Patients with myasthenia gravis (MG) have antibodies which react with an important part of their own bodies. Specifically, the autoantibodies in MG react with the acetylcholine receptor, which is a specialized structure in a muscle cell which receives the chemical stimulation from nerve endings. Because the chemical stimulation is interrupted, patients with myasthenia gravis have great muscle weakness and progressive fatigability. Although it is not known why some people develop antibodies against their own acetylcholine receptors and others do not, it is believed that T cells which react with the acetylcholine receptor are necessary to initiate the production of antibody. A study was conducted to evaluate the responsiveness of T cells from the blood of patients with MG to the acetylcholine receptor. T-cell reactivity with acetylcholine receptors could be identified in 23 of 114 patients tested. However, T-cell reactivity could also be identified in two of 25 normal healthy control patients. While the initial screening tests were conducted on acetylcholine receptors from the electric eel (which can be obtained cheaply in large amounts), further tests confirmed that the cells reacted with human acetylcholine receptor as well. Growing cell lines from some of these T cells were established in the laboratory to compare the T cells from the patients with those of the healthy controls. No obvious differences were found. The results of this study indicate that even a significant proportion of healthy individuals have T cells which react with human acetylcholine receptors. The cause of myasthenia gravis, therefore, lies not in the presence of such cells, but rather in some regulatory mechanism which normally keeps such cells in check. (Consumer Summary produced by Reliance Medical Information, Inc.)

We consider the effects of weak gravitational lensing on observations of 196 spectroscopically confirmed Type Ia Supernovae (SNe Ia) from years 1 to 3 of the Dark Energy Survey (DES). We simultaneously measure both the angular correlation function and the non-Gaussian skewness caused by weak lensing. This approach has the advantage of being insensitive to the intrinsic dispersion of SNe Ia magnitudes. We model the amplitude of both effects as a function of σ8, and find σ8 =1.2 |$^{+0.9}_{-0.8}$|⁠. We also apply our method to a subsample of 488 SNe from the Joint Light-curve Analysis (JLA; chosen to match the redshift range we use for this work), and find σ8 =0.8 |$^{+1.1}_{-0.7}$|⁠. The comparable uncertainty in σ8 between DES–SN and the larger number of SNe from JLA highlights the benefits of homogeneity of the DES–SN sample, and improvements in the calibration and data analysis. [ABSTRACT FROM AUTHOR]

A Co-Ni-Ga high-temperature shape memory alloy has been additively manufactured by directed energy deposition. Due to the highly anisotropic microstructure, i.e. columnar grains featuring a strong near-⟨001⟩ texture in build direction, the as-built material is characterized by a very low degree of constraints and, thus, shows excellent superelasticity without conducting a post-process heat treatment. As characterized by in situ deformation testing and post-mortem microstructural analysis, additive manufacturing employing directed energy deposition seems to be highly promising for processing of shape memory alloys, which often suffer difficult workability. The present work establishes a new pathway towards realization of high performance shape memory alloys by additive manufacturing and, thus, will stimulate further research in this field directed towards application. [ABSTRACT FROM AUTHOR]

Black hole mass measurements outside the local Universe are critically important to derive the growth of supermassive black holes over cosmic time, and to study the interplay between black hole growth and galaxy evolution. In this paper, we present two measurements of supermassive black hole masses from reverberation mapping (RM) of the broad C  iv emission line. These measurements are based on multiyear photometry and spectroscopy from the Dark Energy Survey Supernova Program (DES-SN) and the Australian Dark Energy Survey (OzDES), which together constitute the OzDES RM Program. The observed reverberation lag between the DES continuum photometry and the OzDES emission line fluxes is measured to be |$358^{+126}_{-123}$| and |$343^{+58}_{-84}$| d for two quasars at redshifts of 1.905 and 2.593, respectively. The corresponding masses of the two supermassive black holes are 4.4 × 109 and 3.3 × 109 M⊙, which are among the highest redshift and highest mass black holes measured to date with RM studies. We use these new measurements to better determine the C  iv radius−luminosity relationship for high-luminosity quasars, which is fundamental to many quasar black hole mass estimates and demographic studies. [ABSTRACT FROM AUTHOR]

The SkyMapper Transient survey (SMT) is exploring variability in the southern sky by performing (a) a rolling search to discover and study supernovæ, and (b) a Target of Opportunity programme that uses the robotic SkyMapper Telescope at Siding Spring Observatory. The supernova survey is obtaining a non-targeted sample of Type Ia supernovæ (SNe Ia) at low redshifts, z < 0.1, and studying other interesting transients found with the search strategy. We have a Target of Opportunity programme with an automatic response mechanism to search for optical counterparts to gravitational-wave and fast radio-burst events; it benefits from SkyMapper's large field of view of 5.7 sq. deg. and a rapid data reduction pipeline. We present first results of the SMT survey. The SMT pipeline can process and obtain potential candidates within 12 hours of observation. It disentangles real transients from processing artefacts using a machine-learning algorithm. To date, SMT has discovered over 60 spectroscopically confirmed supernovæ, several peculiar objects, and over 40 SNe Ia including one (SNIa 2016hhd) which was found within the first few days of explosion. We have also participated in searches for optical counterparts of gravitational waves, fast radio bursts and other transients, and have published observations of the optical counterpart of the gravitational-wave event GW170817. We also participate in coordinated observations with the Deeper Wider Faster programme, and the Kepler K2 cosmology project. [ABSTRACT FROM AUTHOR]

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Aims/Hypothesis: Low physical fitness (PF) is a risk factor for type 2 diabetes mellitus (T2D). Women with a history of gestational diabetes (GDM) are at risk for T2D at a young age, but the role of PF in this population is not clear. PF has also been found to correlate inversely with plasma leptin in previous studies. Here, we examine whether women who had GDM have lower PF than women after a normoglycemic pregnancy and, second, whether PF is associated with plasma leptin, independently of body fat mass. Methods: Cross-sectional analysis of 236 participants in the PPSDiab Study (cohort study of women 3–16 months after delivery, 152 after gestational diabetes (pGDM), 84 after normoglycemic pregnancy (control subjects); consecutively recruited 2011–16); medical history, physical examination with bioelectrical impedance analysis (BIA), whole body magnetic resonance imaging (MRI) (n = 154), 5-point oral glucose tolerance test, cardiopulmonary exercise testing, clinical chemistry including fasting plasma leptin; statistical analysis with Mann–Whitney U and t -test, Spearman correlation coefficient, multiple linear regression. Results: Women pGDM had lower maximally achieved oxygen uptake (VO2peak/kg: 25.7(21.3–29.9) vs. 30.0(26.6–34.1)ml/min/kg; total VO2peak: 1733(1552–2005) vs. 1970(1767–2238)ml/min; p<0.0001 for both), and maximum workload (122.5(105.5–136.5) vs. 141.0(128.5–159.5)W; p<0.0001). Fasting plasma leptin correlated inversely with PF (VO2peak/kg ρ = -0.72 p<0.0001; VO2peak ρ = -0.16 p = 0.015; max. load ρ = -0.35 p<0.0001). These associations remained significant with adjustment for body mass index, or for body fat mass (BIA and MRI). Conclusions/Interpretation: Women with a recent history of GDM were less fit than control subjects. Low PF may therefore contribute to the risk for T2D after GDM. This should be tested in intervention studies. Low PF also associated with increased leptin levels–independently of body fat. PF may therefore influence leptin levels and signaling. This hypothesis requires further investigation. [ABSTRACT FROM AUTHOR]