Summary Background Patients with locally advanced rectal cancer who achieve a pathological complete response to neoadjuvant chemoradiation have an improved prognosis. The need for surgery in these ...patients has been questioned, but the proportion of patients achieving a pathological complete response is small. We aimed to assess whether adding cycles of mFOLFOX6 between chemoradiation and surgery increased the proportion of patients achieving a pathological complete response. Methods We did a phase 2, non-randomised trial consisting of four sequential study groups of patients with stage II–III locally advanced rectal cancer at 17 institutions in the USA and Canada. All patients received chemoradiation (fluorouracil 225 mg/m2 per day by continuous infusion throughout radiotherapy, and 45·0 Gy in 25 fractions, 5 days per week for 5 weeks, followed by a minimum boost of 5·4 Gy). Patients in group 1 had total mesorectal excision 6–8 weeks after chemoradiation. Patients in groups 2–4 received two, four, or six cycles of mFOLFOX6, respectively, between chemoradiation and total mesorectal excision. Each cycle of mFOLFOX6 consisted of racemic leucovorin 200 mg/m2 or 400 mg/m2 , according to the discretion of the treating investigator, oxaliplatin 85 mg/m2 in a 2-h infusion, bolus fluorouracil 400 mg/m2 on day 1, and a 46-h infusion of fluorouracil 2400 mg/m2 . The primary endpoint was the proportion of patients who achieved a pathological complete response, analysed by intention to treat. This trial is registered with ClinicalTrials.gov , number NCT00335816. Findings Between March 24, 2004, and Nov 16, 2012, 292 patients were registered, 259 of whom (60 in group 1, 67 in group 2, 67 in group 3, and 65 in group 4) met criteria for analysis. 11 (18%, 95% CI 10–30) of 60 patients in group 1, 17 (25%, 16–37) of 67 in group 2, 20 (30%, 19–42) of 67 in group 3, and 25 (38%, 27–51) of 65 in group 4 achieved a pathological complete response (p=0·0036). Study group was independently associated with pathological complete response (group 4 compared with group 1 odds ratio 3·49, 95% CI 1·39–8·75; p=0·011). In group 2, two (3%) of 67 patients had grade 3 adverse events associated with the neoadjuvant administration of mFOLFOX6 and one (1%) had a grade 4 adverse event; in group 3, 12 (18%) of 67 patients had grade 3 adverse events; in group 4, 18 (28%) of 65 patients had grade 3 adverse events and five (8%) had grade 4 adverse events. The most common grade 3 or higher adverse events associated with the neoadjuvant administration of mFOLFOX6 across groups 2–4 were neutropenia (five in group 3 and six in group 4) and lymphopenia (three in group 3 and four in group 4). Across all study groups, 25 grade 3 or worse surgery-related complications occurred (ten in group 1, five in group 2, three in group 3, and seven in group 4); the most common were pelvic abscesses (seven patients) and anastomotic leaks (seven patients). Interpretation Delivery of mFOLFOX6 after chemoradiation and before total mesorectal excision has the potential to increase the proportion of patients eligible for less invasive treatment strategies; this strategy is being tested in phase 3 clinical trials. Funding National Institutes of Health National Cancer Institute.
It is likely that nanofabrication will underpin many technologies in the 21st century. Synthetic chemistry is a powerful approach to generate molecular structures that are capable of assembling into ...functional nanoscale architectures. There has been intense interest in self‐assembling low‐molecular‐weight gelators, which has led to a general understanding of gelation based on the self‐assembly of molecular‐scale building blocks in terms of non‐covalent interactions and packing parameters. The gelator molecules generate hierarchical, supramolecular structures that are macroscopically expressed in gel formation. Molecular modification can therefore control nanoscale assembly, a process that ultimately endows specific material function. The combination of supramolecular chemistry, materials science, and biomedicine allows application‐based materials to be developed. Regenerative medicine and tissue engineering using molecular gels as nanostructured scaffolds for the regrowth of nerve cells has been demonstrated in vivo, and the prospect of using self‐assembled fibers as one‐dimensional conductors in gel materials has captured much interest in the field of nanoelectronics.
Starting to gel: Recent developments in self‐assembling low‐molecular‐weight gelators has led to rationally designed materials with increasingly advanced and specialized applications. Recent demonstrations of molecular gels in diverse technological fields are reviewed, including tissue engineering, regenerative medicine, and nanoelectronics.
Oxygen heterocycles are the second most common type of heterocycles that appear as structural components of U.S. Food and Drug Administration (FDA) approved pharmaceuticals. Analysis of our database ...of drugs approved through 2017 reveals 311 distinct pharmaceuticals containing at least one oxygen heterocycle. Most prevalent among these are pyranoses, with furanoses, macrolactones, morpholines, and dioxolanes rounding off the top five. The main body of this Perspective is organized according to ring size, commencing with three- and four-membered rings and ending with macrocycles, polymers, and unusual oxygen-containing heterocycles. For each section, all oxygen heterocycle-containing drugs are presented along with a brief discussion about structural and drug application patterns.
Using a novel data set that covers individual debt claims against 136 bankrupt US companies and includes information on a subset of claims transfers, we provide new empirical insight regarding how a ...firm’s debt ownership relates to bankruptcy outcomes. Firms with higher debt concentration at the start of the case are more likely to file prearranged bankruptcy plans, to move quickly through the restructuring process, and to emerge successfully as independent going concerns. Moreover, higher ownership concentration within a debt class is associated with higher recovery rates to that class. Trading of claims during bankruptcy concentrates ownership further, but this trading is not associated with subsequent improvements in bankruptcy outcomes and could, at the margin, increase the likelihood of liquidation.
Sampling rare and clustered populations is challenging because of the effort required to find rare units. Heuristically, a practitioner would prefer to discontinue sampling in areas where rare units ...of interest are apparently extremely sparse or absent. We take advantage of the characteristics of inverse sampling to adaptively inform practitioners when it is efficient to move on to sample new areas. We introduce Adaptive Two-stage Inverse Sampling (ATIS), which is designed to leave a selected area after observation of an a priori number of only non-rare units and to continue sampling in the area when rare units are observed. ATIS is efficient in many cases and yields more rare units than conventional sampling for a rare and clustered population. We derive unbiased estimators of population total and variance. We also introduce an easy-to-compute estimator, which is nearly as efficient as the unbiased estimator. A simulation study on a rare plant population of buttercups (Ranunculus) shows that ATIS even with the easy-to-compute estimator is more efficient than its conventional sampling counterparts and is more efficient than Two-stage Adaptive Cluster Sampling (TACS) for small and moderate final sample sizes. Additional simulations reveal that ATIS is efficient for binary data (e.g., presence or absence) whereas TACS is inefficient for binary data. The overall results indicate that ATIS is consistently efficient compared to conventional sampling and to adaptive cluster sampling in some important cases.
The method of regularized stokeslets is extensively used in biological fluid dynamics due to its conceptual simplicity and meshlessness. This simplicity carries a degree of cost in computational ...expense and accuracy because the number of degrees of freedom used to discretise the unknown surface traction is generally significantly higher than that required by boundary element methods. We describe a meshless method based on nearest-neighbour interpolation that significantly reduces the number of degrees of freedom required to discretise the unknown traction, increasing the range of problems that can be practically solved, without excessively complicating the task of the modeller. The nearest-neighbour technique is tested against the classical problem of rigid body motion of a sphere immersed in very viscous fluid, then applied to the more complex biophysical problem of calculating the rotational diffusion timescales of a macromolecular structure modelled by three closely-spaced non-slender rods. A heuristic for finding the required density of force and quadrature points by numerical refinement is suggested. Matlab/GNU Octave code for the key steps of the algorithm is provided, which predominantly use basic linear algebra operations, with a full implementation being provided on github. Compared with the standard Nyström discretisation, more accurate and substantially more efficient results can be obtained by de-refining the force discretisation relative to the quadrature discretisation: a cost reduction of over 10 times with improved accuracy is observed. This improvement comes at minimal additional technical complexity. Future avenues to develop the algorithm are then discussed.
•A numerical method for biological flow which combines ease-of-use with efficiency.•Efficiency is improved by a factor of 10 or more, while giving improved accuracy.•No true mesh generation (i.e. connectivity table) is required.•The rotational diffusion timescale of a novel macromolecule is calculated.•Matlab codes are provided which implement the method via vectorised operations.
This article covers recent advances in the fusion of metasurface antenna design and computational imaging (CI) concepts for the realization of imaging systems that are planar, fast, and low cost. We ...start by explaining the operation of metamaterial antennas which can generate diverse radiation patterns. Their advantages and distinctions from previous antennas are elucidated. We then provide an intuitive overview of the CI framework and argue that metamaterial antennas are a near ideal platform for implementing such schemes at microwave frequencies. We describe two metamaterial antenna implementations: frequency diverse and electronically reconfigurable. The tradeoffs governing the design and operation of each architecture are examined. We conclude by examining the outlook of metamaterial antennas for microwave imaging and propose various future directions.
In the late nineteenth century, Heinrich Hertz demonstrated that the electromagnetic properties of materials are intimately related to their structure at the subwavelength scale by using wire grids ...with centimetre spacing to manipulate metre-long radio waves. More recently, the availability of nanometre-scale fabrication techniques has inspired scientists to investigate subwavelength-structured metamaterials with engineered optical properties at much shorter wavelengths, in the infrared and visible regions of the spectrum. Here we review how optical metamaterials are expected to enhance the performance of the next generation of integrated photonic devices, and explore some of the challenges encountered in the transition from concept demonstration to viable technology.
Metamaterial Apertures for Computational Imaging Hunt, John; Driscoll, Tom; Mrozack, Alex ...
Science (American Association for the Advancement of Science),
01/2013, Letnik:
339, Številka:
6117
Journal Article
Recenzirano
By leveraging metamaterials and compressive imaging, a low-profile aperture capable of microwave imaging without lenses, moving parts, or phase shifters is demonstrated. This designer aperture allows ...image compression to be performed on the physical hardware layer rather than in the postprocessing stage, thus averting the detector, storage, and transmission costs associated with full diffraction-limited sampling of a scene. A guided-wave metamaterial aperture is used to perform compressive image reconstruction at 10 frames per second of two-dimensional (range and angle) sparse still and video scenes at K-band (18 to 26 gigahertz) frequencies, using frequency diversity to avoid mechanical scanning. Image acquisition is accomplished with a 40:1 compression ratio.
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