In a study involving men with castration-resistant prostate cancer and bone metastases, the alpha emitter radium-223 significantly prolonged survival, as compared with placebo, and was associated ...with fewer adverse events.
More than 90% of patients with metastatic castration-resistant prostate cancer have radiologic evidence of bone metastases, which are a major cause of death, disability, decreased quality of life, and increased treatment cost among these patients.
1
,
2
Unlike deaths from many other types of cancer, deaths from prostate cancer are often due to bone disease and its complications.
3
Current bone-targeted therapies have not been shown to improve survival, and the benefits derived from bisphosphonates, denosumab, and existing radioisotope treatments are primarily limited to pain relief and delay of skeletal events.
4
–
13
Radium-223 dichloride (radium-223) is a targeted alpha emitter that selectively . . .
The Cold Classical Kuiper Belt, a class of small bodies in undisturbed orbits beyond Neptune, is composed of primitive objects preserving information about Solar System formation. In January 2019, ...the New Horizons spacecraft flew past one of these objects, the 36-kilometer-long contact binary (486958) Arrokoth (provisional designation 2014 MU
). Images from the flyby show that Arrokoth has no detectable rings, and no satellites (larger than 180 meters in diameter) within a radius of 8000 kilometers. Arrokoth has a lightly cratered, smooth surface with complex geological features, unlike those on previously visited Solar System bodies. The density of impact craters indicates the surface dates from the formation of the Solar System. The two lobes of the contact binary have closely aligned poles and equators, constraining their accretion mechanism.
The duel, and the codes of honour that governed duelling,
functioned for decades in many European and Latin American
countries as a shadow legal system, regulating in practice what
legislators felt ...free to say and what journalists felt free to
write. Yet the duel was also an act of potentially deadly violence
and a challenge to the authority of statutory law. When duelling
became widespread in early twentieth-century Uruguay, legislators
facing this dilemma chose the unique and radical path of
legalization. The Pen, the Sword, and the Law explores how
the only country in the world to decriminalize duelling managed the
tension between these informal but widely accepted "gentlemanly
laws" and its own criminal code. The duel, which remained legal
until 1992, was meant to ensure civility in politics and decorum in
the press, but it often failed to achieve either. Drawing on rich
and detailed newspaper reports of duels and challenges,
parliamentary debates, legal records, private papers, and
interviews, David Parker examines the role of pistols and sabres in
shaping the everyday workings of a raucous public sphere.
Demonstrating that the duel was no simple throwback to archaic
conceptions of masculine honour and chivalry, The Pen, the
Sword, and the Law illustrates how duelling went hand in hand
with democracy and freedom of the press in one of South America's
most progressive nations.
In quantum magnets, magnetic moments fluctuate heavily and are strongly entangled with each other, a fundamental distinction from classical magnetism. Here, with inelastic neutron scattering ...measurements, we probe the spin correlations of the honeycomb lattice quantum magnet YbCl
. A linear spin wave theory with a single Heisenberg interaction on the honeycomb lattice, including both transverse and longitudinal channels of the neutron response, reproduces all of the key features in the spectrum. In particular, we identify a Van Hove singularity, a clearly observable sharp feature within a continuum response. The demonstration of such a Van Hove singularity in a two-magnon continuum is important as a confirmation of broadly held notions of continua in quantum magnetism and additionally because analogous features in two-spinon continua could be used to distinguish quantum spin liquids from merely disordered systems. These results establish YbCl
as a benchmark material for quantum magnetism on the honeycomb lattice.
The neuropeptide oxytocin (OXT) exerts anxiolytic and prosocial effects in the central nervous system of rodents. A number of recent studies have attempted to translate these findings by ...investigating the relationships between peripheral (e.g., blood, urinary and salivary) OXT concentrations and behavioral functioning in humans. Although peripheral samples are easy to obtain in humans, whether peripheral OXT measures are functionally related to central OXT activity remains unclear. To investigate a possible relationship, we quantified OXT concentrations in concomitantly collected cerebrospinal fluid (CSF) and blood samples from child and adult patients undergoing clinically indicated lumbar punctures or other CSF-related procedures. Anxiety scores were obtained in a subset of child participants whose parents completed psychometric assessments. Findings from this study indicate that plasma OXT concentrations significantly and positively predict CSF OXT concentrations (r=0.56, P=0.0064, N=27). Moreover, both plasma (r=-0.92, P=0.0262, N=10) and CSF (r=-0.91, P=0.0335, N=10) OXT concentrations significantly and negatively predicted trait anxiety scores, consistent with the preclinical literature. Importantly, plasma OXT concentrations significantly and positively (r=0.96, P=0.0115, N=10) predicted CSF OXT concentrations in the subset of child participants who provided behavioral data. This study provides the first empirical support for the use of blood measures of OXT as a surrogate for central OXT activity, validated in the context of behavioral functioning. These preliminary findings also suggest that impaired OXT signaling may be a biomarker of anxiety in humans, and a potential target for therapeutic development in individuals with anxiety disorders.
The Large Underground Xenon (LUX) experiment is a dual-phase xenon time-projection chamber operating at the Sanford Underground Research Facility (Lead, South Dakota). The LUX cryostat was filled for ...the first time in the underground laboratory in February 2013. We report results of the first WIMP search data set, taken during the period from April to August 2013, presenting the analysis of 85.3 live days of data with a fiducial volume of 118 kg. A profile-likelihood analysis technique shows our data to be consistent with the background-only hypothesis, allowing 90% confidence limits to be set on spin-independent WIMP-nucleon elastic scattering with a minimum upper limit on the cross section of 7.6 × 10(-46) cm(2) at a WIMP mass of 33 GeV/c(2). We find that the LUX data are in disagreement with low-mass WIMP signal interpretations of the results from several recent direct detection experiments.
Continental fold‐thrust belts display a variety of structural styles, ranging from thin‐skinned thrusts following weak lithologic contacts to thick‐skinned thrusts that deform mechanical basement. ...The common practice of splitting fold‐thrust belts into thin‐skinned and thick‐skinned map domains has not yielded a predictive model of the primary controls on structural style. Within the Mesozoic‐Paleogene Idaho‐Montana fold‐thrust belt (44°N‐45°N, 112°W‐114°W), we identify crosscutting thin‐skinned and thick‐skinned thrusts within an otherwise thin‐skinned map domain. This transition occurs within a thin (∼2.5 km) portion of the western Laurentian passive margin, where lower strata pinch out over a prominent basement high (Lemhi arch). Early fold‐thrust belt shortening of sedimentary cover rocks was accommodated through detachment folding, followed by east‐directed, thin‐skinned thrusting along regional‐scale faults (Thompson Gulch and Railroad Canyon thrusts). Later, basement and cover rocks were tilted toward the southeast and a basement‐involved normal fault was reactivated during thick‐skinned thrusting (Radio Tower‐Baby Joe Gulch‐Italian Gulch thrusts), which accommodated shortening at an oblique angle to and truncated the basal detachment of the older thin‐skinned thrusts. This progression from thin‐skinned to thick‐skinned thrusting occurred >50 km from the foreland, coincident with a regional basement high. Thus, the Idaho‐Montana fold‐thrust belt is a double‐decker system, with upper thin‐skinned and lower thick‐skinned domains. This double‐decker model is applicable to other fold‐thrust belts and predicts that the transition from thin‐skinned to thick‐skinned thrusting occurs where the growing critically tapered wedge can no longer fit within the sedimentary cover rocks and the basal detachment steps down into the structurally lower mechanical basement.
Key Points
Thin‐skinned and thick‐skinned thrusts record a progressive downward shift in the basal detachment of the Idaho‐Montana fold‐thrust belt
A transition from thin‐skinned to thick‐skinned thrusting occurred as the basal detachment encountered the basement high of the Lemhi arch
Thin‐skinned thrusts in the overlying cover and thick‐skinned thrusts below the basement/cover contact form a double‐decker fold‐thrust belt
Participation in sport carries an increased risk of sustaining dental trauma which can be reduced by the use of a mouthguard. Mouthguards work by dissipating the force of impact, thus reducing the ...force which is transferred to the dentition. There are different types of mouthguard available which vary in design, costs and the level of protection provided. This article aims to review the use of mouthguards in sport, the common barriers to their use and also the different types of mouthguards and their characteristics.
Objectives
To develop evidence-based recommendations for clinicians caring for children (including infants, school-aged children, and adolescents) with septic shock and other sepsis-associated organ ...dysfunction.
Design
A panel of 49 international experts, representing 12 international organizations, as well as three methodologists and three public members was convened. Panel members assembled at key international meetings (for those panel members attending the conference), and a stand-alone meeting was held for all panel members in November 2018. A formal conflict-of-interest policy was developed at the onset of the process and enforced throughout. Teleconferences and electronic-based discussion among the chairs, co-chairs, methodologists, and group heads, as well as within subgroups, served as an integral part of the guideline development process.
Methods
The panel consisted of six subgroups: recognition and management of infection, hemodynamics and resuscitation, ventilation, endocrine and metabolic therapies, adjunctive therapies, and research priorities. We conducted a systematic review for each Population, Intervention, Control, and Outcomes question to identify the best available evidence, statistically summarized the evidence, and then assessed the quality of evidence using the Grading of Recommendations Assessment, Development, and Evaluation approach. We used the evidence-to-decision framework to formulate recommendations as strong or weak, or as a best practice statement. In addition, “in our practice” statements were included when evidence was inconclusive to issue a recommendation, but the panel felt that some guidance based on practice patterns may be appropriate.
Results
The panel provided 77 statements on the management and resuscitation of children with septic shock and other sepsis-associated organ dysfunction. Overall, six were strong recommendations, 49 were weak recommendations, and nine were best-practice statements. For 13 questions, no recommendations could be made; but, for 10 of these, “in our practice” statements were provided. In addition, 52 research priorities were identified.
Conclusions
A large cohort of international experts was able to achieve consensus regarding many recommendations for the best care of children with sepsis, acknowledging that most aspects of care had relatively low quality of evidence resulting in the frequent issuance of weak recommendations. Despite this challenge, these recommendations regarding the management of children with septic shock and other sepsis-associated organ dysfunction provide a foundation for consistent care to improve outcomes and inform future research.
We report new, detailed, femtosecond time-resolved photoelectron spectroscopy experiments and calculations investigating the competition between ultrafast internal conversion and ultrafast ...intersystem crossing in electronically and vibrationally excited benzene at the onset of "channel 3". Using different probe energies to record the total photoelectron yield as a function of pump-probe delay we are able to confirm that S
1
, T
1
and T
2
electronic states are involved in the excited state dynamics. Time-resolved photoelectron spectroscopy measurements then allow us to unravel the evolution of the S
1
, T
1
and T
2
components of the excited state population and, together with complementary quantum chemistry and quantum dynamics calculations, support our earlier proposal that ultrafast intersystem crossing competes with internal conversion (
Chem. Phys. Lett.
, 2009,
469
, 43).
Time-resolved photoelectron spectroscopy experiments and quantum dynamics calculations reveal an ultrafast intersystem crossing in the "channel 3" region of benzene.
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