Focusing laser light onto a very small target can produce the conditions for laboratory-scale nuclear fusion of hydrogen isotopes. The lack of accurate predictive models, which are essential for the ...design of high-performance laser-fusion experiments, is a major obstacle to achieving thermonuclear ignition. Here we report a statistical approach that was used to design and quantitatively predict the results of implosions of solid deuterium-tritium targets carried out with the 30-kilojoule OMEGA laser system, leading to tripling of the fusion yield to its highest value so far for direct-drive laser fusion. When scaled to the laser energies of the National Ignition Facility (1.9 megajoules), these targets are predicted to produce a fusion energy output of about 500 kilojoules-several times larger than the fusion yields currently achieved at that facility. This approach could guide the exploration of the vast parameter space of thermonuclear ignition conditions and enhance our understanding of laser-fusion physics.
The emulsion copolymerization of 2-(diethylamino)ethyl methacrylate (DEA) with a divinylbenzene cross-linker in the presence of monomethoxy-capped poly(ethylene glycol) methacrylate (PEGMA) at 70 °C ...afforded near-monodisperse, sterically stabilized PEGMA-PDEA latexes at 10% solids. Dynamic light scattering studies indicated intensity-average diameters of 190 to 240 nm for these latexes at pH 9. A latex-to-microgel transition occurred on lowering the solution pH to below the latex pK a of 6.9. When dilute HCl/KOH was used to adjust the aqueous pH, a systematic reduction in the cationic microgel hydrodynamic diameter of 80 nm was observed over ten pH cycles as a result of the gradual buildup of background salt. However, no such size reduction was observed when using CO2/N2 gases to regulate the aqueous pH because this protocol does not generate background salt. Thus, the latter approach offers better reversibility, albeit at the cost of slower response times. PEGMA-PDEA microgel does not stabilize Pickering emulsions when homogenized at pH 3 with n-dodecane, sunflower oil, isononyl isononanoate, or isopropyl myristate. In contrast, PEGMA-PDEA latex proved to be a ubiquitous Pickering emulsifier at pH 10, forming stable oil-in-water emulsions with each of these four model oils. Lowering the solution pH from 10 to 3 resulted in demulsification within seconds. This is because these pH-responsive particles undergo a latex-to-microgel transition, which leads to their interfacial desorption. Six successive demulsification/emulsification cycles were performed on these Pickering emulsions using HCl/KOH to adjust the solution pH. Demulsification could also be achieved by purging the emulsion solution with CO2 gas to lower the aqueous pH to 4.8. However, complete phase separation required CO2 purging for 4 h at 20 °C. A subsequent N2 purge raised the aqueous pH sufficiently to induce a microgel-to-latex transition, but rehomogenization did not produce a stable Pickering emulsion. Presumably, a higher pH is required, which cannot be achieved by a N2 purge alone.
Background: We demonstrated that circulating tumor cell (CTC) number at baseline and follow-up is an independent prognostic factor in metastatic colorectal cancer (mCRC). This analysis was undertaken ...to explore whether patient and treatment characteristics impact the prognostic value of CTCs.
Patients and methods: CTCs were enumerated with immunomagnetic separation from the blood of 430 patients with mCRC at baseline and on therapy. Patients were stratified into unfavorable and favorable prognostic groups based on CTC levels of ≥3 or <3 CTCs/7.5ml, respectively. Subgroups were analyzed by line of treatment, liver involvement, receipt of oxaliplatin, irinotecan, or bevacizumab, age, and Eastern Cooperative Oncology Group performance status (ECOG PS).
Results: Seventy-one percent of deaths have occurred. Median follow-up for living patients is 25.8 months. For all patients, progression-free survival (PFS) and overall survival (OS) for unfavorable compared with favorable baseline CTCs is shorter (4.4 versus 7.8 m, P=0.004 for PFS; 9.4 versus 20.6 m, P<0.0001 for OS). In all patient subgroups, unfavorable baseline CTC was associated with inferior OS (P<0.001). In patients receiving first- or second-line therapy (P=0.003), irinotecan (P=0.0001), having liver involvement (P=0.002), ≥65 years (P=0.0007), and ECOG PS of zero (P=0.04), unfavorable baseline CTC was associated with inferior PFS.
Conclusion: Baseline CTC count is an important prognostic factor within specific subgroups defined by treatment or patient characteristics.
Abstract The intervertebral disc annulus fibrosus (AF) is subjected to high circumferential tensile stresses resulting from nucleus pulposus pressurisation under axial compression. In other pressure ...containing tissues, such as blood vessel walls, residual compressive stresses along the inside surface of the tissues without pressurisation reduce peak tensile stresses under pressurisation. This study hypothesised that similar patterns of residual stress exist in the annulus fibrosus. Accurate characterisation of residual stresses is essential for both the incorporation of nonlinear material descriptions into models of the disc as well as the design of effective annulus repair strategies. By imaging nine bovine caudal discs before and after the release of residual stresses via incision, we measured a mean residual stretch of 0.86±0.13 at the inner AF and 1.02±0.08 at the outer AF. These stretch values were used to calculate a gradient of residual stress ranging from −230±22 kPa of compression at the inner AF to 54±0.2 kPa of tension at the outer AF. Material models of AF have assumed that the AF was in a stress free reference state when there are no external loads. However, this study documents that there are large residual stresses in the AF even without external loads. The release of residual tension in the outer AF by herniation, needle injection or incisions makes closure difficult and may accelerate degeneration of the surrounding tissue. Retention of these residual stresses may be essential to maintaining disc mechanical function and to producing viable AF repair techniques.
Emulsion copolymerization of 2-(tert-butylamino)ethyl methacrylate in the presence of divinylbenzene (DVB) cross-linker and monomethoxy-capped poly(ethylene glycol) methacrylate (PEGMA) ...macromonomer at 70 °C afforded sterically-stabilized latexes at approximately 10% solids at pH 9. Dynamic light scattering and scanning electron microscopy (SEM) confirmed that relatively narrow size distributions were obtained. SEM confirmed the formation of spherical particles in the absence of any DVB cross-linker using a simple batch protocol, but in the presence of DVB it was necessary to use seeded emulsion polymerization under monomer-starved conditions to prevent the formation of latexes with ill-defined non-spherical morphologies. Lightly cross-linked latexes acquired cationic microgel character upon lowering the solution pH due to protonation of the secondary amine groups. Increasing the degree of cross-linking led to a progressively lower effective pK a of the copolymer chains from 8.0 to 7.3, which implies a gradual reduction in their basicity. Poly(tert-butylamino)ethyl methacrylate latex proved to be an effective Pickering emulsifier at pH 10, forming stable oil-in-water emulsions when homogenized with either n-dodecane or sunflower oil at 12 000 rpm for 2 min. These Pickering emulsions exhibited pH-responsive behavior: lowering the solution pH to 3 resulted in immediate demulsification due to the spontaneous desorption of the cationic microgels from the oil/water interface. Following rehomogenization at high pH, four successive demulsification/emulsification pH cycles could be achieved without a discernible loss in performance. However, no demulsification occurred on acidification of the fifth cycle, due to the progressive build-up of background salt.
Familial primary pulmonary hypertension is a rare autosomal dominant disorder that has reduced penetrance and that has been mapped to a 3-cM region on chromosome 2q33 (locus
PPH1). The phenotype is ...characterized by monoclonal plexiform lesions of proliferating endothelial cells in pulmonary arterioles. These lesions lead to elevated pulmonary-artery pressures, right-ventricular failure, and death. Although primary pulmonary hypertension is rare, cases secondary to known etiologies are more common and include those associated with the appetite-suppressant drugs, including phentermine-fenfluramine. We genotyped 35 multiplex families with the disorder, using 27 microsatellite markers; we constructed disease haplotypes; and we looked for evidence of haplotype sharing across families, using the program TRANSMIT. Suggestive evidence of sharing was observed with markers GGAA19e07 and D2S307, and three nearby candidate genes were examined by denaturing high-performance liquid chromatography on individuals from 19 families. One of these genes (
BMPR2), which encodes bone morphogenetic protein receptor type II, was found to contain five mutations that predict premature termination of the protein product and two missense mutations. These mutations were not observed in 196 control chromosomes. These findings indicate that the bone morphogenetic protein–signaling pathway is defective in patients with primary pulmonary hypertension and may implicate the pathway in the nonfamilial forms of the disease.
As treatment options expand for metastatic colorectal cancer (mCRC), a blood marker with a prognostic and predictive role could guide treatment. We tested the hypothesis that circulating tumor cells ...(CTCs) could predict clinical outcome in patients with mCRC.
In a prospective multicenter study, CTCs were enumerated in the peripheral blood of 430 patients with mCRC at baseline and after starting first-, second-, or third-line therapy. CTCs were measured using an immunomagnetic separation technique.
Patients were stratified into unfavorable and favorable prognostic groups based on CTC levels of three or more or less than three CTCs/7.5 mL, respectively. Patients with unfavorable compared with favorable baseline CTCs had shorter median progression-free survival (PFS; 4.5 v 7.9 months; P = .0002) and overall survival (OS; 9.4 v 18.5 months; P < .0001). Differences persisted at 1 to 2, 3 to 5, 6 to 12, and 13 to 20 weeks after therapy. Conversion of baseline unfavorable CTCs to favorable at 3 to 5 weeks was associated with significantly longer PFS and OS compared with patients with unfavorable CTCs at both time points (PFS, 6.2 v 1.6 months; P = .02; OS, 11.0 v 3.7 months; P = .0002). Among nonprogressing patients, favorable compared with unfavorable CTCs within 1 month of imaging was associated with longer survival (18.8 v 7.1 months; P < .0001). Baseline and follow-up CTC levels remained strong predictors of PFS and OS after adjustment for clinically significant factors.
The number of CTCs before and during treatment is an independent predictor of PFS and OS in patients with metastatic colorectal cancer. CTCs provide prognostic information in addition to that of imaging studies.
There is accumulating evidence for decadal-scale regime shifts at the base of the food web on the Northeast US Continental Shelf. However, less evidence exists for regime shifts in fish recruitment ...success, particularly for synchronized regimes across multiple species. Here, we analyzed stock assessment output and survey data to test for regimes in the recruitment success of 18 commercially important marine species over a 29 yr timespan. We then tested whether recruitment regimes coincide with regimes in the zooplankton community, and whether the abundance of large spawners could explain the patterns in recruitment. We found evidence for 3 decadal-scale recruitment regimes: low recruitment success in the 1980s, high success in the 1990s, and a return to low recruitment success in the 2000s. This general pattern was found in all datasets of recruitment. The abundance of large spawners did not appear to be a broad-scale driver of recruitment success; however, recruitment regimes coincided with regimes in copepod abundance and size structure.
Amorphous solids lack long-range order. Therefore identifying structural defects -- akin to dislocations in crystalline solids -- that carry plastic flow in these systems remains a daunting ...challenge. By comparing many different structural indicators in computational models of glasses, under a variety of conditions we carefully assess which of these indicators are able to robustly identify the structural defects responsible for plastic flow in amorphous solids. We further demonstrate that the density of defects changes as a function of material preparation and strain in a manner that is highly correlated with the macroscopic material response. Our work represents an important step towards predicting how and when an amorphous solid will fail from its microscopic structure.
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