Christian Albert Theodor Billroth, M.D., founding father of abdominal surgery (1829-1894).

In the 1800s, the field of surgery was in its infancy, somewhat primitive and embryonic. The technical nature of surgery was the basis for the dividing line between the disciplines of surgery and internal medicine. Sterilization was not a common practice. Radical surgical resections and experimentation in medicine were shunned. With his boldness equaled only by his innovation and resourcefulness, Theodor Billroth would become a pioneer not only in the development of modern surgery, but also in the advancement of its cultural and historical significance

Emil Theodor Kocher, M.D., and his Nobel Prize (1841-1917).

Major contributions to the advancement of surgery occurred at the turn of the 20th century. Theodor Billroth was in the midst of revolutionizing abdominal surgery, whereas Louis Pasteur and Joseph Lister were making landmark strides in antisepsis, forever changing the foundations of surgical thinking. Undoubtedly, Theodor Kocher’s (Fig. 1) exposure to these and other giants had a major influence on his career and contributed to his success and ascent as the first, and one of only 10, surgeons ever to be awarded the Nobel Prize in Medicine

Picosecond electric-field-induced threshold switching in phase-change materials

Many chalcogenide glasses undergo a breakdown in electronic resistance above a critical field strength. Known as threshold switching, this mechanism enables field-induced crystallization in emerging phase-change memory. Purely electronic as well as crystal nucleation assisted models have been employed to explain the electronic breakdown. Here, picosecond electric pulses are used to excite amorphous Ag$_4$In$_3$Sb$_{67}$Te$_{26}$. Field-dependent reversible changes in conductivity and pulse-driven crystallization are observed. The present results show that threshold switching can take place within the electric pulse on sub-picosecond time-scales - faster than crystals can nucleate. This supports purely electronic models of threshold switching and reveals potential applications as an ultrafast electronic switch.Comment: 6 pages manuscript with 3 figures and 8 pages supplementary materia

A non-repeating fast radio burst in a dwarf host galaxy

We present the discovery of as-of-yet non-repeating Fast Radio Burst (FRB), FRB 20210117A, with the Australian Square Kilometer Array Pathfinder (ASKAP) as a part of the Commensal Real-time ASKAP Fast Transients (CRAFT) Survey. The sub-arcsecond localization of the burst led to the identification of its host galaxy at a $z=0.214(1)$. This redshift is much lower than what would be expected for a source dispersion measure (DM) of 729 pc cm$^{-3}$, given typical contributions from the intergalactic medium and the host galaxy. Optical observations reveal the host to be a dwarf galaxy with little on-going star formation, very different to the dwarf host galaxies of known repeating FRBs 20121102A, and 20190520B. We find an excess DM contribution from the host and attribute it to the FRB's local environment. We do not find any radio emission from the FRB site or host galaxy. The low magnetized environment and lack of a persistent radio source (PRS) indicate that the FRB source is older than those found in other dwarf host galaxies, and establish the diversity of FRB sources in dwarf galaxy environments. We find our observations to be fully consistent with the hypernebula model, where the FRB is powered by accretion-jet from a hyper-accreting black hole. Finally, our high-time resolution analysis reveals burst characteristics similar to those seen in repeating FRBs. We encourage follow-up observations of FRB 20210117A to establish any repeating nature.Comment: 15 pages, 9 figures, 2 Table

A gene expression-based model predicts outcome in children with intermediate-risk classical Hodgkin lymphoma

Classical Hodgkin lymphoma (cHL) is a common malignancy in children and adolescents. Although cHL is highly curable, treatment with chemotherapy and radiation often come at the cost of long-term toxicity and morbidity. Effective risk-stratification tools are needed to tailor therapy. Here, we used gene expression profiling (GEP) to investigate tumor microenvironment (TME) biology, to determine molecular correlates of treatment failure, and to develop an outcome model prognostic for pediatric cHL. A total of 246 formalin-fixed, paraffin-embedded tissue biopsies from patients enrolled in the Children’s Oncology Group trial AHOD0031 were used for GEP and compared with adult cHL data. Eosinophil, B-cell, and mast cell signatures were enriched in children, whereas macrophage and stromal signatures were more prominent in adults. Concordantly, a previously published model for overall survival prediction in adult cHL did not validate in pediatric cHL. Therefore, we developed a 9-cellular component model reflecting TME composition to predict event-free survival (EFS). In an independent validation cohort, we observed a significant difference in weighted 5-year EFS between high-risk and low-risk groups (75.2% vs 90.3%; log-rank P = .0138) independent of interim response, stage, fever, and albumin. We demonstrate unique disease biology in children and adolescents that can be harnessed for risk-stratification at diagnosis. This trial was registered at www.clinicaltrials.gov as #NCT00025259

Development of the Resource Prospector Planetary Rover

The Resource Prospector (RP) is an In-Situ Resource Utilization (ISRU) lunar rover mission under study by NASA. RP is planned to launch in 2020 to prospect for subsurface volatiles and to extract oxygen from lunar regolith. The mission will address several of NASA's "Strategic Knowledge Gaps" for lunar exploration. The mission will also address the Global Exploration Roadmap's strategic goal of using local resources for human exploration. The distribution of lunar subsurface volatiles drives the mission requirement for mobility. The spatial distribution is hypothesized to be governed by impact cratering with the top 0.5 m being patchy at scales of 100 m. The mixing time scale increases with depth (less frequent larger impacts). Consequently, increased mobility reduces the depth requirement for sampling. The target RP traverse will extend 1 km radially from the landing site to sample craters of varying sizes. Sampling craters with different ages will reveal possible volatile emplacement history. In 1 Ga, approximately 60-70 craters of 10 m diameter form per km2. Thus, the rover will need to sample at least ten of these craters, which may require a total traverse path length of 2-3 km. During 2014-2015, we developed an initial prototype rover for RP. The current design is a solar powered, four-wheeled vehicle, with hub motor drive, offset four wheel steering, and active suspension. Active suspension provides capabilities including changing vehicle ride height, traversing comparatively large obstacles, and controlling load on the wheels. All-wheel steering enables the vehicle to point arbitrarily while roving, e.g., to keep the solar array pointed at the sun while in motion. The offset steering combined with active suspension improves driving in soft soil. The rover's on-board software utilizes NASA's Core Flight Software, which is a reusable flight software environment. During 2015, we completed the initial rover software build, which provides low-level hardware interfaces, basic mobility control, waypoint driving, odometry, basic error checking, and camera services. Development of the prototype rover has enabled maturation of many of the subsystems to TRL 5. During the next year, we will conduct integrated testing of concepts of operation, navigation, and remote driving tools. In addition, we will perform environmental tests including radiation (avionics), thermal and thermal/vacuum (mechanisms), and gravity offload (mobility)

Rucaparib maintenance treatment for recurrent ovarian carcinoma after response to platinum therapy (ARIEL3): a randomised, double-blind, placebo-controlled, phase 3 trial

Background: Rucaparib, a poly(ADP-ribose) polymerase inhibitor, has anticancer activity in recurrent ovarian carcinoma harbouring a BRCA mutation or high percentage of genome-wide loss of heterozygosity. In this trial we assessed rucaparib versus placebo after response to second-line or later platinum-based chemotherapy in patients with high-grade, recurrent, platinum-sensitive ovarian carcinoma. Methods: In this randomised, double-blind, placebo-controlled, phase 3 trial, we recruited patients from 87 hospitals and cancer centres across 11 countries. Eligible patients were aged 18 years or older, had a platinum-sensitive, high-grade serous or endometrioid ovarian, primary peritoneal, or fallopian tube carcinoma, had received at least two previous platinum-based chemotherapy regimens, had achieved complete or partial response to their last platinum-based regimen, had a cancer antigen 125 concentration of less than the upper limit of normal, had a performance status of 0–1, and had adequate organ function. Patients were ineligible if they had symptomatic or untreated central nervous system metastases, had received anticancer therapy 14 days or fewer before starting the study, or had received previous treatment with a poly(ADP-ribose) polymerase inhibitor. We randomly allocated patients 2:1 to receive oral rucaparib 600 mg twice daily or placebo in 28 day cycles using a computer-generated sequence (block size of six, stratified by homologous recombination repair gene mutation status, progression-free interval after the penultimate platinum-based regimen, and best response to the most recent platinum-based regimen). Patients, investigators, site staff, assessors, and the funder were masked to assignments. The primary outcome was investigator-assessed progression-free survival evaluated with use of an ordered step-down procedure for three nested cohorts: patients with BRCA mutations (carcinoma associated with deleterious germline or somatic BRCA mutations), patients with homologous recombination deficiencies (BRCA mutant or BRCA wild-type and high loss of heterozygosity), and the intention-to-treat population, assessed at screening and every 12 weeks thereafter. This trial is registered with ClinicalTrials.gov, number NCT01968213; enrolment is complete. Findings: Between April 7, 2014, and July 19, 2016, we randomly allocated 564 patients: 375 (66%) to rucaparib and 189 (34%) to placebo. Median progression-free survival in patients with a BRCA-mutant carcinoma was 16·6 months (95% CI 13·4–22·9; 130 [35%] patients) in the rucaparib group versus 5·4 months (3·4–6·7; 66 [35%] patients) in the placebo group (hazard ratio 0·23 [95% CI 0·16–0·34]; p<0·0001). In patients with a homologous recombination deficient carcinoma (236 [63%] vs 118 [62%]), it was 13·6 months (10·9–16·2) versus 5·4 months (5·1–5·6; 0·32 [0·24–0·42]; p<0·0001). In the intention-to-treat population, it was 10·8 months (8·3–11·4) versus 5·4 months (5·3–5·5; 0·36 [0·30–0·45]; p<0·0001). Treatment-emergent adverse events of grade 3 or higher in the safety population (372 [99%] patients in the rucaparib group vs 189 [100%] in the placebo group) were reported in 209 (56%) patients in the rucaparib group versus 28 (15%) in the placebo group, the most common of which were anaemia or decreased haemoglobin concentration (70 [19%] vs one [1%]) and increased alanine or aspartate aminotransferase concentration (39 [10%] vs none). Interpretation: Across all primary analysis groups, rucaparib significantly improved progression-free survival in patients with platinum-sensitive ovarian cancer who had achieved a response to platinum-based chemotherapy. ARIEL3 provides further evidence that use of a poly(ADP-ribose) polymerase inhibitor in the maintenance treatment setting versus placebo could be considered a new standard of care for women with platinum-sensitive ovarian cancer following a complete or partial response to second-line or later platinum-based chemotherapy. Funding: Clovis Oncology

The nuclear receptors of Biomphalaria glabrata and Lottia gigantea: Implications for developing new model organisms

© 2015 Kaur 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 creditedNuclear receptors (NRs) are transcription regulators involved in an array of diverse physiological functions including key roles in endocrine and metabolic function. The aim of this study was to identify nuclear receptors in the fully sequenced genome of the gastropod snail, Biomphalaria glabrata, intermediate host for Schistosoma mansoni and compare these to known vertebrate NRs, with a view to assessing the snail's potential as a invertebrate model organism for endocrine function, both as a prospective new test organism and to elucidate the fundamental genetic and mechanistic causes of disease. For comparative purposes, the genome of a second gastropod, the owl limpet, Lottia gigantea was also investigated for nuclear receptors. Thirty-nine and thirty-three putative NRs were identified from the B. glabrata and L. gigantea genomes respectively, based on the presence of a conserved DNA-binding domain and/or ligand-binding domain. Nuclear receptor transcript expression was confirmed and sequences were subjected to a comparative phylogenetic analysis, which demonstrated that these molluscs have representatives of all the major NR subfamilies (1-6). Many of the identified NRs are conserved between vertebrates and invertebrates, however differences exist, most notably, the absence of receptors of Group 3C, which includes some of the vertebrate endocrine hormone targets. The mollusc genomes also contain NR homologues that are present in insects and nematodes but not in vertebrates, such as Group 1J (HR48/DAF12/HR96). The identification of many shared receptors between humans and molluscs indicates the potential for molluscs as model organisms; however the absence of several steroid hormone receptors indicates snail endocrine systems are fundamentally different.The National Centre for the Replacement, Refinement and Reduction of Animals in Research, Grant Ref:G0900802 to CSJ, LRN, SJ & EJR [www.nc3rs.org.uk]

The Demographics, Stellar Populations, and Star Formation Histories of Fast Radio Burst Host Galaxies: Implications for the Progenitors

We present a comprehensive catalog of observations and stellar population properties for 23 highly secure host galaxies of fast radio bursts (FRBs). Our sample comprises 6 repeating FRBs and 17 apparent nonrepeaters. We present 82 new photometric and 8 new spectroscopic observations of these hosts. Using stellar population synthesis modeling and employing nonparametric star formation histories (SFHs), we find that FRB hosts have a median stellar mass of ≈109.9M⊙, mass-weighted age ≈5.1 Gyr, and ongoing star formation rate ≈1.3 M⊙ yr−1 but span wide ranges in all properties. Classifying the hosts by degree of star formation, we find that 87% (20 of 23 hosts) are star-forming, two are transitioning, and one is quiescent. The majority trace the star-forming main sequence of galaxies, but at least three FRBs in our sample originate in less-active environments (two nonrepeaters and one repeater). Across all modeled properties, we find no statistically significant distinction between the hosts of repeaters and nonrepeaters. However, the hosts of repeating FRBs generally extend to lower stellar masses, and the hosts of nonrepeaters arise in more optically luminous galaxies. While four of the galaxies with the clearest and most prolonged rises in their SFHs all host repeating FRBs, demonstrating heightened star formation activity in the last ≲100 Myr, one nonrepeating host shows this SFH as well. Our results support progenitor models with short delay channels (i.e., magnetars formed via core-collapse supernova) for most FRBs, but the presence of some FRBs in less-active environments suggests a fraction form through more delayed channels