Breaking up with the continuous exoplanet mass-radius relation

We use a carefully selected subsample of 1053 confirmed exoplanets from the NASA Exoplanet Archive to construct empirical power-law exoplanet mass-radius-temperature ($M$-$R$-$T$) relations. Using orthogonal distance regression to account for errors in both mass and radius, we allow the data to decide: 1) the number of distinct planetary regimes; 2) whether the boundaries of these regimes are best described by broken power laws joined at mass break points, or by discontinuous power laws motivated by changes in equations of state and temperature. We find strong support from the data for three distinct planetary $M$-$R$ regimes and for those regimes to be discontinuous. Our most successful model involves an $M$-$R$-$T$ relation in which ice/rock (rocky) and ice-giant (neptunian) planets are segregated by a pure-ice equation of state, whilst neptunes and gas giant (jovian) planets are segregated by a mass break at $M_{\rm br} = 115\pm19~M_{\oplus}$. The rocky planet regime is shown to follow $M \propto R^{0.34\pm0.01}$, whilst neptunes have $M\propto R^{0.55\pm0.02}$. Planets in both regimes are seen to extend to similar maximum masses. In the jovian regime, we find that $M \propto R^{0.00\pm0.01}T^{0.35\pm 0.02}$, where $T$ is the planet equilibrium temperature. This implies that, for jovian planets detected so far, equilibrium temperature alone provides a robust estimator of mass.Comment: 11 pages, 11 figures. For submission to The Open Journal of Astrophysic

Neutrophil-bead collision assay: Pharmacologically induced changes in membrane mechanics regulate the PSGL-1/P-selectin adhesion lifetime

Visualization of flowing neutrophils colliding with adherent 1-µm-diameter beads presenting P-selectin allowed the simultaneous measurement of collision efficiency (ε), membrane tethering fraction (f), membrane tether growth dynamics, and PSGL-1/P-selectin binding lifetime. For 1391 collisions analyzed over venous wall shear rates from 25 to 200 s-1 ε decreased from 0.17 to 0.004, whereas f increased from 0.15 to 0.70, and the average projected membrane tether length, ∠mtether, increased from 0.35 µm to ⋍2.0 µm over this shear range. At all shear rates tested, adhesive collisions lacking membrane tethers had average bond lifetimes less than those observed for collisions with tethers. For adhesive collisions that failed to form membrane tethers, the regressed Bell parameters (consistent with single bond Monte Carlo simulation) were zero-stress offrate, Koff(0) = 0.56 s-1and reactive compliance, r = 0.10 nm, similar to published atomic force microscopy (AFM) measurements. For all adhesion events (± tethers), the bond lifetime distributions were more similar to those obtained by rolling assay and best simulated by Monte Carlo with the above Bell parameters and an average of 1.48 bonds (n = 1 bond (67%), n = 2 (22%), and n = 3–5 (11%)). For collisions at 100 s-1, pretreatment of neutrophils with actin depolymerizing agents, latrunculin or cytochalasin D, had no effect on ε, but increased ∠mtether by 1.74- or 2.65-fold and prolonged the average tether lifetime by 1.41- or 1.65-fold, respectively. Jasplakinolide, an actin polymerizing agent known to cause blebbing, yielded results similar to the depolymerizing agents. Conversely, cholesterol-depletion with methyl-ß-cyclodextrin or formaldehyde fixation had no effect on ε, but reduced ∠mtether by 66% or 97% and reduced the average tether lifetime by 30% or 42%, respectively. The neutrophilbead collision assay combines advantages of atomic force microscopy (small contact zone), aggregometry (discrete interactions), micropipette manipulation (tether visualization), and rolling assays (physiologic flow loading). Membrane tether growth can be enhanced or reduced pharmacologically with consequent effects on PSGL-1/P-selectin lifetimes

Recruiting in surgical trial in the emergency setting: understanding clinician and patient perspectives: a mixed methods study

Background. Undertaking randomised controlled trials (RCT) in emergency surgical setting is associated with methodological and practical challenges. This study explored patients and clinicians’ perspectives associated with the conduct of a RCT comparing laparoscopic and open colorectal surgery in the acute setting.Method. All eligible patients screened/enrolled for the ‘Laparoscopic versus Open Colorectal Surgery in the Acute Setting multicentre, randomised controlled feasibility (LaCeS) trial’ in five NHS Trusts were invited to respond to a survey. Also, patients and healthcare professionals were invited to take part in semi-structured interviews. Survey and interviews explored acceptability of the feasibility trial. Interviews were audio-recorded, transcribed verbatim and analysed using thematic analysis. Survey data were analysed descriptively to assess patient views of the trial and intervention. Results. Out of 72 patients enrolled for the LaCeS RCT, survey data was collected from 28 patients (38.9%), and interviews were conducted with 16 patients and 14 healthcare professionals. Thirteen out of 28 patients (46%) had treatment preferences but these were not strong enough to deter participation. Twelve of the patients interviewed believed their surgeon preferred laparoscopic surgery, but this did not deter them from participating in the trial. Half of the surgeons interviewed expressed the view that laparoscopic surgery was of benefit in this setting, but recognised that the need for research evidence outweighed their personal treatment preferences. Eight of the 14 recruiters reported that the emergency setting affected recruitment, especially in centres with fewer recruiting surgeons. Interviewees reported that recruitment was helped significantly by using surgical trainees to consent patients. Conclusion. This study identified specific challenges for the LaCeS2 trial design to address, and adds to our understanding of recruiting to emergency surgical trials more broadly

Sites of vulnerability in HCV E1E2 identified by comprehensive functional screening

The E1 and E2 envelope proteins of hepatitis C virus (HCV) form a heterodimer that drives virus-host membrane fusion. Here, we analyze the role of each amino acid in E1E2 function, expressing 545 individual alanine mutants of E1E2 in human cells, incorporating them into infectious viral pseudoparticles, and testing them against 37 different monoclonal antibodies (MAbs) to ascertain full-length translation, folding, heterodimer assembly, CD81 binding, viral pseudoparticle incorporation, and infectivity. We propose a model describing the role of each critical residue in E1E2 functionality and use it to examine how MAbs neutralize infection by exploiting functionally critical sites of vulnerability on E1E2. Our results suggest that E1E2 is a surprisingly fragile protein complex where even a single alanine mutation at 92% of positions disrupts its function. The amino-acid-level targets identified are highly conserved and functionally critical and can be exploited for improved therapies and vaccines

RoSETZ: Roman Survey of the Earth Transit Zone -- a SETI-optimized survey for habitable-zone exoplanets

In this White Paper for Nancy Grace Roman Space Telescope (Roman) science, we propose the Roman Survey of the Earth Transit Zone (RoSETZ), a transit search for rocky planets within the habitable zones (HZs) of stars located within the Earth Transit Zone (ETZ). The ETZ holds special interest in the search for extra-terrestrial intelligence (SETI) - observers on planets within the ETZ can see Earth as a transiting planet. RoSETZ would augment the Roman Galactic Bulge Time Domain Survey (GBTDS) as an additional field located $\sim 5$~degrees away from other GBTDS fields. Our simulations show that RoSETZ alone can find from 120 to 630 Earth-sized HZ planets around K- and M-type hosts, with the range reflecting different survey design assumptions. These yields are 5-20 times the number currently known. Such a sample will transform our knowledge of ``Eta-Earth'' ($\eta_{\oplus}$) -- the occurrence of Earth-sized HZ planets -- and would be the first catalogue of exoplanets selected in a manner optimized according to the Mutual Detectability targetted-SETI strategy. If it can be accommodated alongside the existing GBTDS design, we favour a RoSETZ-Max design that is observed for the duration of the GBTDS. If not, we show that a slimmed-down RoSETZ-Lite design, occupying two GBTDS seasons, would not significantly impact overall GBTDS exoplanet yields, even if time allocated to it had to come from time allocations to other fields. We argue that the angular separation of RoSETZ from other GBTDS fields permits self-calibration of systematic uncertainties that would otherwise hamper exoplanet demographic modelling of both microlensing and transit datasets. Other science possible with RoSETZ data include studies of small solar system bodies and high resolution 3D extinction mapping.Comment: 20 pages. Submission to the NASA Roman Core Community Surveys White Paper Cal

CONNECT for quality: protocol of a cluster randomized controlled trial to improve fall prevention in nursing homes

<p>Abstract</p> <p>Background</p> <p>Quality improvement (QI) programs focused on mastery of content by individual staff members are the current standard to improve resident outcomes in nursing homes. However, complexity science suggests that learning is a social process that occurs within the context of relationships and interactions among individuals. Thus, QI programs will not result in optimal changes in staff behavior unless the context for social learning is present. Accordingly, we developed CONNECT, an intervention to foster systematic use of management practices, which we propose will enhance effectiveness of a nursing home Falls QI program by strengthening the staff-to-staff interactions necessary for clinical problem-solving about complex problems such as falls. The study aims are to compare the impact of the CONNECT intervention, plus a falls reduction QI intervention (CONNECT + FALLS), to the falls reduction QI intervention alone (FALLS), on fall-related process measures, fall rates, and staff interaction measures.</p> <p>Methods/design</p> <p>Sixteen nursing homes will be randomized to one of two study arms, CONNECT + FALLS or FALLS alone. Subjects (staff and residents) are clustered within nursing homes because the intervention addresses social processes and thus must be delivered within the social context, rather than to individuals. Nursing homes randomized to CONNECT + FALLS will receive three months of CONNECT first, followed by three months of FALLS. Nursing homes randomized to FALLS alone receive three months of FALLs QI and are offered CONNECT after data collection is completed. Complexity science measures, which reflect staff perceptions of communication, safety climate, and care quality, will be collected from staff at baseline, three months after, and six months after baseline to evaluate immediate and sustained impacts. FALLS measures including quality indicators (process measures) and fall rates will be collected for the six months prior to baseline and the six months after the end of the intervention. Analysis will use a three-level mixed model.</p> <p>Discussion</p> <p>By focusing on improving local interactions, CONNECT is expected to maximize staff's ability to implement content learned in a falls QI program and integrate it into knowledge and action. Our previous pilot work shows that CONNECT is feasible, acceptable and appropriate.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT00636675">NCT00636675</a></p

Identification of Lysine 37 of Histone H2B as a Novel Site of Methylation

Recent technological advancements have allowed for highly-sophisticated mass spectrometry-based studies of the histone code, which predicts that combinations of post-translational modifications (PTMs) on histone proteins result in defined biological outcomes mediated by effector proteins that recognize such marks. While significant progress has been made in the identification and characterization of histone PTMs, a full appreciation of the complexity of the histone code will require a complete understanding of all the modifications that putatively contribute to it. Here, using the top-down mass spectrometry approach for identifying PTMs on full-length histones, we report that lysine 37 of histone H2B is dimethylated in the budding yeast Saccharomyces cerevisiae. By generating a modification-specific antibody and yeast strains that harbor mutations in the putative site of methylation, we provide evidence that this mark exist in vivo. Importantly, we show that this lysine residue is highly conserved through evolution, and provide evidence that this methylation event also occurs in higher eukaryotes. By identifying a novel site of histone methylation, this study adds to our overall understanding of the complex number of histone modifications that contribute to chromatin function

Neutrophil adhesion dynamics during flow

Neutrophils have been observed to adhere activated endothelium, platelets and neutrophils in vivo. We investigated the dynamics of neutrophil adhesion through assays that surveyed of interactions between neutrophils and adherent neutrophils or surface-presented ligands. We designed experiments that allowed combined the advantages of aggregometry (discrete events), rolling assays (physiological shear environment), micropipette aspiration (tether visualization) and atomic force microscopy (small contact zone). During observation of interactions between flowing and adherent neutrophils, we observed hydrodynamic thresholding in primary collision efficiency (ϵ) and neutrophil string formation, with a maximum in adhesion in both cases at a wall shear rate of γ w = 100 sec−1. High resolution imaging revealed deformation of the neutrophil at venous shear rates. Strings of neutrophils formed on ICAM-1, but not fibrinogen-coated surfaces, and analysis of collision lifetimes between neutrophils and the β2 integrin ligands revealed that poor capture to fibrinogen was the root cause of poor string formation on this substrate. We observed that both static adhesion and the subsequent onset of flow caused calcium mobilization in the neutrophil. When neutrophils were perfused over P-selectin presenting beads from γw = 25 to 200 sec−1, ϵ, was observed to decrease, while the membrane tethering fraction (f) and the average membrane tether length, Lmtether, increased. For adhesive collisions that failed to form membrane tethers, the regressed Bell parameters were: zero-stress off-rate, koff(0) = 0.56 sec −1 and reactive compliance, r = 0.10 nm, similar to published values for AFM experiments. For all adhesion events, with and without membrane tethers, the bond-lifetime distributions were more similar to those obtained in neutrophil rolling assays, and best simulated by Monte Carlo with the above Bell parameters and an average of 1.36 bonds. Pretreatment of neutrophils with actin depolymerizing agents had no effect on ϵ, but increased L mtether, and prolonged the average tether lifetime. Conversely, cholesterol-depletion with methyl-β-cyclodextrin or formaldehyde fixation had no effect on ϵ, but reduced Lmtether and average tether lifetime. These several results demonstrate a role for cellular processes in mediating neutrophil adhesion dynamics under flow, and provide useful assays for the development of diagnostic tools and therapeutics targeting cross-talk between inflammatory and coagulation pathways

Crumb rubber used in concrete to provide freeze–thaw protection (optimal particle size)

This research has examined the optimum particle size of crumb rubber, used as an additive to concrete that would provide maximum freeze-thaw protection whilst minimising the compressive strength loss. The crumb rubber as used in the paper was divided into five batches, with increasing particle size, graded in increments of 0.5mm, from <0.5 to 2.5mm. The primary properties of the concrete investigated were; air content, freeze-thaw durability and compressive strength. These were tested using standard test methods. The range of tests used were conclusive in that the <0.5mm crumb rubber particle size, provided the greater degree of air entrainment. The freeze-thaw cycle results suggested that crumb rubber provided freeze-thaw protection, as the plain concrete deteriorated compared to the concrete with crumb rubber additions. There was no definitive correlation between the compressive strength and the crumb rubber particles size, although the rubberised concrete had an average strength loss of 5.24% after 28 days. This research indicates that crumb rubber graded up to <0.5mm is the optimum size to use, when crumb rubber granules are used to provide freeze-thaw protection in concrete