bluuebunny/crossref_metadata_2025 huggingface dataset:
Regional Assessment of Herbicide Sorption and Degradation in Two Sampling Years
Authors: Gaultier Jeanette , Farenhorst Annemieke , Cathcart Jason , Goddard Tom
Published: August 2008

Sorption and degradation of the herbicide 2,4‐D [2,4‐dichlorophenoxyacetic acid] were determined for 123 surface soils (0 to 15 cm) collected in 2002 and in 2004 between 49° to 60° north longitude and 110° to 120° west latitude in Alberta, Canada. The soils were characterized by soil organic carbon content (SOC), pH, electrical conductivity, soil texture, cation exchange capacity, carbonate content, and total soil microbial activity. The 2,4‐D sorption coefficients,KdandKoc, were highly variable with coefficients of variation of 89 and 59%, respectively, at the provincial scale. BothKdandKocwere well described by regression models with SOC and soil pH as variables, regardless of scale. Surprisingly, variations in 2,4‐D mineralization were much smaller than variations in sorption. Variability in total 2,4‐D mineralization was particularly low, with a coefficient of variation of only 7% at the provincial scale. Average 2,4‐D half‐lives in ecoregions ranged from 1.7 to 3.5 d, much lower than the field dissipation half‐life of 10 d reported for 2,4‐D in general pesticide property databases. Regression models describing degradation parameters were generally poor or not significant because 2,4‐D mineralization was only weakly associated with measured 2,4‐D sorption parameters and soil properties. As such, regional variations in herbicide sorption coefficients should be measured or calculated based on soil properties, to assign distinct pesticide fate model input parameters when estimating 2,4‐D off‐site transport at the provincial scale. Spatial variations in herbicide degradation appear less important for Alberta as 2,4‐D half‐lives were similar in soils across the province. The rapid mineralization of 2,4‐D is noteworthy because 2,4‐D is widely used in Alberta and perhaps adaptation of soil microbial communities allowed for accelerated degradation regardless of soil properties or the extent of 2,4‐D sorption by soil.
Comparison of DAYCENT‐Simulated and Measured Nitrous Oxide Emissions from a Corn Field
Authors: Jarecki Marek K. , Parkin Timothy B. , Chan Alvarus S. K. , Hatfield Jerry L. , Jones Raymond
Published: August 2008

Accurate assessment of N2O emission from soil requires continuous year‐round and spatially extensive monitoring or the use of simulation that accurately and precisely predict N2O fluxes based on climatic, soil, and agricultural system input data. DAYCENT is an ecosystem model that simulates, among other processes, N2O emissions from soils. The purpose of the study was to compare N2O fluxes predicted by the DAYCENT model to measured N2O fluxes from an experimental corn field in central Iowa. Soil water content temperature and inorganic N, simulated by DAYCENT were compared to measured values of these variables. Field N2O emissions were measured using four replicated automated chambers at 6‐h intervals, from day of year (DOY) 42 through DOY 254 of 2006. We observed that DAYCENT generally accurately predicted soil temperature, with the exception of winter when predicted temperatures tended to be lower than measured values. Volumetric water contents predicted by DAYCENT were generally lower than measured values during most of the experimental period. Daily N2O emissions simulated by DAYCENT were significantly correlated to field measured fluxes; however, time series analyses indicate that the simulated fluxes were out of phase with the measured fluxes. Cumulative N2O emission calculated from the simulations (3.29 kg N2O‐N ha−1) was in range of the measured cumulative N2O emission (4.26 ± 1.09 kg N2O‐N ha−1).
Need for protein supplementation in the diet of growing dairy bulls fed total mixed ration based on moderate digestible grass silage and barley
Authors: HUUSKONEN A. , KHALILI H. , JOKI-TOKOLA E.
Published: August 2008

The objective of the present experiment was to study the need for the protein supplementation in the diet of growing dairy bulls (initial live weight 272 ± 28.5 kg and final live weight 666 ± 31.2 kg, on average) fed total mixed ration based on moderate digestible grass silage and barley. The experiment comprised 24 Finnish Ayrshire bulls and 8 Holstein-Friesian bulls and included four treatments. The control diet (C) consisted of moderate digestible (653 g digestible organic matter in dry matter (DM) grass silage (450 g kg-1 DM), barley grain (275) and barley fibre (275) without protein supplementation. Three isonitrogenous experimental diets included also extra protein, i.e. (1) rapeseed meal (RSM) (supplementation 530 g DM per animal day-1), (2) wet distillers solubles (WDS) (600 g) and (3) a mixture of barley protein (90% of fresh weight) and wet distillers solubles (10) (BPWDS) (480 g). In all isonitrogenous diets the crude protein content of concentrate increased from 137 to 150 g kg-1 DM (9%) compared with the C diet. All bulls were fed total mixed ration ad libitum. The energy content of all diets was 11.6 MJ kg-1 DM. The live weight gain of the bulls tended to be higher with the BPWDS diet than with the C diet (C 1214 vs. BPWDS 1301 g d-1; p = 0.10), but the treatments had no significant effect on carcass gain, feed conversion or slaughter parameters. Only the BPWDS diet differed significantly from the C diet in DM (C 9.69 vs. BPWDS 10.38 kg DM d-1; p < 0.01) and energy intake (C 112.4 vs. BPWDS 120.3 MJ d-1; p < 0.05). The apparent organic matter digestibility (OMD) was 5% higher in the BPWDS diet than in the C diet (p < 0.001), but the RSM and WDS diets did not differ from the C diet in OMD. The results indicate that the supply of protein in dairy bulls is most probably adequate with moderate digestible, well-preserved grass silage and barley-based concentrates when intake of digestible organic matter is high enough to support microbial protein synthesis in the rumen.;
The effects of selenate and sulphate supply on the accumulation and volatilization of Se by cabbage, kohlrabi and alfalfa plants grown hydroponically
Authors: HAJIBOLAND R. , AMJAD L.
Published: August 2008

The effect of Selenium (Se) supplementation at five levels of 0 (control), 5, 10, 15, 20 ìM in plants supplied with one of four concentrations of sulphur (S) including 0.05, 0.25, 0.5 and 1.0 mM was investigated in two varieties of Brassica oleracea (cabbage and kohlrabi) and alfalfa (Medicago sativa L.) in a hydroponic experiment. In severely S deficient plants (0.05 mM), Se acted as a toxic element, alfalfa was the most susceptible plant that died at this treatment. However, in plants supplied with near adequate (0.5 mM) or adequate (1.0 mM) S, Se acted as a growth promoting element. The most pronounced stimulation of growth was observed in cabbage and the lowest in alfalfa. Increasing S concentration in the medium, reduced Se uptake and transport. In contrast, S uptake and transport increased in response to Se addition. Se volatilization was higher in alfalfa than cabbage and kohlrabi when expressed on unit shoot dry weight or leaf area basis, but not when expressed per plant. Results suggested that Se supplementation of plants supplied with adequate S, not only had beneficial effects on plants growth but also can have application in enrichment of livestock fodder and human food.;
Stormwater Runoff Quality from Different Surfaces in an Urban Catchment in Beijing, China
Authors: Yufen Ren , Xiaoke Wang , Zhiyun Ouyang , Hua Zheng , Xiaonan Duan , Hong Miao
Published: August 2008

Urban stormwater runoff quality, widely investigated around the world, has been monitored less in Beijing, China, which impedes the municipal government to use best management practices to protect surface water. In this study, rainwater and stormwater runoff samples from roofs, roads, and a lawn on the campus of the Research Center for Eco‐Environmental Sciences (RCEES) (Beijing, China) and from a ring road, with heavy traffic, have been sampled and analyzed for 31 storm events from June 2004 to August 2005. Total suspended solids (TSS), chemical oxygen demand (COD), 5‐day biochemical oxygen demand (BOD 5), total nitrogen, and total phosphorus concentrations in rainwater and runoff ranged over 2 or more orders of magnitude, meaning that the highest concentration of a certain pollutant did not always occur in a certain kind of runoff. Runoff contained significantly higher concentrations of pollutants than rainwater. On the campus of RCEES, TSS and total phosphorus in runoff samples from the lawn and roads were significantly higher than those from roofs, while the COD, BOD 5, and total nitrogen concentrations were not significantly different in runoff among surfaces. Compared with runoff from the roads on campus, runoff from the ring road contained more COD and total nitrogen, but less TSS, BOD 5, and total phosphorus. All pollutants measured in runoff from roofs on campus and from the ring road showed a peak concentration in starting runoff, which then decreased sharply. The peak concentrations of COD, BOD 5, total nitrogen, and total phosphorus in the roof runoff increased with the increase in time of the antecedent dry period. Thus, urban stormwater pollution control, especially for first‐flush control, is of great importance for the full use of rainwater and prevention of water pollution.
The Polyacetylenes Falcarinol and Falcarindiol Affect Stress Responses in Myotube Cultures in a Biphasic Manner
Authors: Young Jette F. , Christensen Lars P. , Theil Peter K. , Oksbjerg Niels
Published: August 2008

The effects of the bioactive polyacetylenes, falcarinol and falcarindiol, present in carrots, celery, celeriac and other umbelliferous vegetables, on the stress responses in primary myotube cultures, were studied. Biphasic responses on cellular stress responses in myotube cultures were investigated by exposing them to various concentrations of falcarinol and falcarindiol for 24 h before testing effects of 100 μM H2O2 on the intracellular formation of reactive oxygen species (ROS), transcription of the antioxidative enzyme cytosolic glutathione peroxidase (cGPx), and the heat shock proteins (HSP) HSP70 and HO1. At low concentrations (1.6 to 25 μM) polyacetylenes caused a slightly accelerated intracellular ROS formation, increased cGPx transcription and decreased HSP70 and HO1 transcription. The increased cGPx transcription may be interpreted as an adaptive response to the increased ROS formation and may have caused a reduced demand for the protective functions of the HSPs. ROS formation, however, was substantially decreased after pre-incubation with both polyacetylenes at 50 and 100 μM, the cGPx transcription was reduced and the HSP70 and HO1 transcription increased, indicating a need for the protective and repairing functions of the HSPs. In conclusion, pre-incubation with low concentrations of both polyacetylenes prior to H2O2 exposure induced a cytoprotective effect whereas higher concentrations had adverse effects.
The comparison of cultures, widal agglutination test and polymerase chain reaction as a diagnostic tool in typhoid fever
Authors: Devrim Ilker , Ergünay Koray , Kara Ates , Tezer Hasan , Yiğitkanl Inci , Bülent Cengiz Ali , Ceyhan Mehmet , Gür Deniz , Seçmeer Gülten , Ustaçelebi Şemsettin
Published: August 2008

Typhoid fever caused by Salmonella typhi, paratyphi A and B, is an important cause of morbidity and mortality in many developing countries. A rapid and sensitive method for the detection of S. typhi is essential for early diagnosis of typhoid fever and effective therapy. In this study 45 febrile patients who were suspected to have enteric fever were enrolled, and the results of blood cultures, widal agglutination tests and Polymerase Chain Reaction in these cases were evaluated. Group I consisted of 11 patients with diseases other than salmonella infections, group II represented 6 patients with positive cultures, and group III represented 28 patients with negative blood cultures negative but who were clinically suspected cases that had a medical history of using variable antimicrobial agents. Two positive PCR results were present; one of them was in culture positive group (16,6%) and the other was in culture negative group (3,5%). In our study widal agglutination tests and cultures were found not to be helpful in differential dignosis. Although PCR based detection of S. typhi is reported to be a sensitive and specific test for the diagnosis of enteric fever, in our study the benefit of this method in the diagnosis of especially patients who were treated with antimicrobial therapy was not clearly determined. Other methods to increase sensitiviy and specificity to levels such as those of real time PCR should be developed and large-scaled studies should be done in endemic and non-epidemic regions.
The influence of plastic instabilities on the mechanical properties of a high-manganese austenitic FeMnC steel
Authors: Allain Sébastien , Cugy Philippe , Scott Colin , Chateau Jean-Philippe , Rusinek Alexis , Deschamps Alexis
Published: August 2008

The serrations observed on the stress–strain curves of a Fe-22Mn-0.6C wt.% steel present all the phenomenological features associated with dynamic strain ageing, including negative strain rate sensitivity and thermal activation. We show that the activation energy is, however, inexplicably low and that the dynamic strain ageing contribution to work-hardening is limited, i. e. mechanical twinning is the dominant strain hardening mechanism. Finally, novel in-situ experiments are used to study the dynamic behaviour of intense strain localisation bands which form on tensile samples. In spite of the localisation behaviour seen in tensile tests, stamped parts do not present any surface defects.
Experimental study of the phase equilibria of the Ni – Zr system
Authors: Wang Na , Li Changrong , Du Zhenmin , Li Jingbo , Wang Fenge , Wang Fuming
Published: August 2008

The eutectic reaction between the NiZr and NiZr2 compounds in the Ni – Zr binary phase diagram was evaluated according to the previous experimental measurements and thermodynamic calculations. A discrepancy between the calculations and the measurements exists. In order to determine definitely this eutectic temperature, Ni – Zr alloys of the compositions 65, 68, 72 and 74 wt.% Zr were prepared by melting in an arc furnace under a purified argon atmosphere. The phase transformation temperature was measured by Differential Scanning Calorimetry using both alumina and zirconia crucibles. At heating rates of 5, 10 and 20 K min− 1, the eutectic temperature between the NiZr and NiZr2 compounds was determined consistently to be 1022 ± 5 °C. Zirconia crucibles can be used in Differential Scanning Calorimetry measurements of zirconium-containing alloys but only below 1170 °C.
Role of surface texture and roughness parameters in friction and transfer layer formation under dry and lubricated sliding conditions
Authors: Menezes Pradeep L. , Kishore  , Kailas Satish V.
Published: August 2008

Surface texture influences friction and transfer layer formation during sliding. In the present paper three well-defined surface textures, namely unidirectional, 8-ground, and random, were employed on steel plates. Experiments were conducted on a tribological couple – zinc pin against steel plate – using an inclined pin-on-plate sliding tester. It was observed that the occurrence of stick-slip motion, the transfer layer formation and the value of coefficient of friction as well as its two components, namely adhesion and plowing, depend primarily on surface texture. The effect of surface texture on coefficient of friction was attributed to the variation of the plowing component of friction for different surfaces. The plowing component of friction was highest for the surface texture that promotes plane strain conditions while it was lowest for the texture that favors plane stress conditions at the interface. Dimensionless quantifiable roughness parameters were formulated to describe the degree of plowing and hence the plane strain/stress type deformations taking place at the asperity level.
Diffusion bonding of the Mo-base alloy TZM with interlayers
Authors: Bhanumurthy Karanam , Schmid-Fetzer Rainer
Published: August 2008

Molybdenum-base alloys have excellent high temperature mechanical properties and joining of these alloys as heat sink materials is envisaged in many structural applications of fusion reactors. TZM is an important Mo-base alloy and diffusion bonding experiments were carried out in a hot vacuum press by sandwiching interlayers, Ti, Ni, Mo and Ta between two pieces of the TZM alloy in the temperature range 900 to 1200 °C. Detailed metallurgical analysis was carried out using optical microscopy, scanning electron microscopy and by electron probe microanalyser. All the sandwiched diffusion couples consisting of TZM/X/TZM, (X = Ti, Ni, Mo, Ti) showed defect-free microstructures at the bonded interface at the optimised bonding conditions. Ti seems to be a more suitable interlayer compared to other interlayers in terms of bonding temperature and applied pressure. The TZM/Ni interface was marked by the presence of the intermetallic compound NiMo. The concentration profiles for diffusion couples TZM/Ti were asymmetric, whilst TZM/Mo and TZM/Ta were symmetric about the Matano Interface. The interdiffusion coefficients calculated using the Boltzmann–Matano method for TZM/Ti diffusion couples showed decreases in the values with increase in the Mo concentration.
Effect of trace Ti on the microstructure and mechanical properties of AM50 alloy
Authors: Wang Q. D. , Lin J. B. , Liu M. P. , Ding W. J.
Published: August 2008

The effect of trace additions (0 – 0.1 wt.%) of titanium on the microstructure, mechanical properties and creep resistance of an AM50 alloy have been studied. The microstructure was examined using optical microscopy and scanning electron microscopy. Results showed that the microstructures of AM50 alloy were obviously refined by trace Ti addition, although the actual content of Ti was only about 0.0025 – 0.0079 wt.%. The refining ability of titanium was ascribed to its large growth restriction factor, and it can be described as a constitutional undercooling driven mechanism. As-cast samples were subjected to tensile tests at room temperature, 150 °C and 200 °C. A considerable increase in tensile properties was observed due to grain refinement, especially the ultimate tensile strength and elongation. In addition, the creep resistance of AM50 alloy was dramatically increased by Ti addition.
Relating viscoelastic nanoindentation creep and load relaxation experiments
Authors: Oyen Michelle L.
Published: August 2008

Nanoindentation characterization of polycarbonate is considered for load-controlled creep testing and displacement-controlled load-relaxation testing using a pyramidal Berkovich tip. An elastic – viscoelastic correspondence approach is used to obtain closed-form analytical solutions for fitting experimental data to deconvolute spring coefficients and viscosity values independently from creep and from relaxation tests. The a priori assumption of linear viscoelasticity is tested by varying the peak load and displacement levels by a factor of twenty. Results demonstrate surprisingly good agreement between parameters computed from relaxation and creep tests and little variation with load or depth. This result supports a linearly viscoelastic analysis under the conditions utilized in the current experiment, namely a Berkovich indenter tip and a glassy polymer. Plastic deformation is not explicitly considered in the current analysis, as all time-independent elastic and plastic deformation was lumped into a single effective deformation resistance term with a quadratic dependence of load on displacement. As such, obtained numerical values of the shear modulus are not representative of the material's elastic modulus. However, the technique demonstrates predictive capability across the interface between load-control and displacement-control, motivating further research on displacement-controlled nanoindentation relaxation for polymeric and biological material characterization.
Identification of viscoelastic model parameters by means of cyclic nanoindentation testing
Authors: Jäger Andreas , Lackner Roman
Published: August 2008

A method for the identification of model parameters describing the time-dependent material behavior by means of cyclic nanoindentation is presented. The complex shear modulus of the material sample is determined from the prescribed amplitude in the load history, the measured amplitude in the penetration history, and the phase shift between the peak values for the load and the penetration. The parameters for a specific viscoelastic model are obtained by comparing the experimentally-obtained storage and loss moduli – both depending on the frequency used during cyclic testing – with the analytical expressions for the respective viscoelastic model. The presented method is applied to low-density polyethylene, giving access to the parameters of the fractional dash-pot which is used to describe the viscoelastic behavior. The results are compared with results from nanoindentation (static) creep tests, considering different maximum loads. Finally, the performance of the presented method is assessed by comparing the creep-compliance functions corresponding to the model parameters identified by nanoindentation with the macroscopic creep-compliance function obtained from bending-beam-rheometer tests.
Effect of the indentation depth on the evaluation of mechanical properties of thin films
Authors: Calabri Lorenzo , Mantovani Sara , Rettighieri Leonardo , Valeri Sergio
Published: August 2008

Hardness measurement of thin films is a major topic. At the nanoscale the interplay between substrate and coating during the indentation process is not well known. Atomic force microscopy nanoindentation has been used to address this problem. We prepared a set of five chromium nitride films (100 – 500 nm thick) deposited on a steel substrate. Using nanoindentation we measured the hardness of these coatings, varying the depth of indentation and thus observing the effect of the substrate – coating interaction on the hardness evaluation. The results show that in this case (hard film on soft substrate) it is not trivial to have measurements not affected by the substrate even at very small depths of indentation. Focused ion beam cross-sections on the indentation and numerical simulations confirm these results showing a relevant contribution of the substrate to the hardness evaluation.
Mechanical properties of a-C, SiC and Ti-C: H films
Authors: Čtvrtlík Radim , Stranyánek Martin , Boháčv Petr , Kulikovsky Valeriy , Suchánek Jan
Published: August 2008

a-C, a-SiC and Ti-C: H coatings were deposited on two steel substrates with different hardness by magnetron sputtering. Their mechanical properties were investigated by depth sensing indentation and dry sliding testing. Load – displacement curves were obtained using a NanoTest™ NT600 instrument equipped with a Berkovich indenter. The depth profiles of the mechanical properties (indentation hardness H, effective modulus Eeff, and also H/E
eff and H
3/E
2
eff ratios) on both substrates are presented. The goal of this article is to compare the dependence of the real response of a coating/substrate system on the substrate. Regardless of substrate type the highest and the lowest values of hardness and modulus belong to a-C and Ti-C: H films, respectively.
Influence of the mathematical model on the evaluation of nanomechanical properties of ultrathin polymer layers studied by AFM
Authors: Koszewski Adam , Gorski Tomasz , Rymuza Zygmunt
Published: August 2008

The major research topic presented in this study concerns nanoindentation experiments of thin soft films, showing high adhesion forces. The aim of this research was to evaluate the nanomechanical properties of a 200 nm thick thermoplastic polymer layer mr-I 7000E devoted to nanoimprint lithography. The experiments were carried out using an atomic force microscopy instrument equipped with a modified 14 N m− 1 silicon cantilever tip (5 μm in diameter). The forces exerted during film indentation varied from 0 up to 2.5 μN. The Hertz and Johnson – Kendall – Roberts (JKR) models were used for analysis of the force – distance curves in order to extract the Young's modulus value. Contrary to the Hertz model, in the JKR model the adhesion force between tip and sample was considered as an additional load during the nanoindentation. The final results of these estimations were 0.20 and 0.25 GPa for the Hertz and JKR models, respectively. It shows that neglect of the adhesion force may cause an error of 20 %.
Phase equilibria in the system “MnO” – CaO – SiO2 – Al2O3 – K2O relevant to manganese smelting slags
Authors: Zhao B. , Jak E. , Hayes P. C.
Published: August 2008

K2O introduced with manganese ore is redistributed by evaporation and condensation within submerged arc ferromanganese smelting furnaces. To characterise the phase equilibria relevant to these slags experimental studies have been carried out to determine pseudo-ternary sections of the form “MnO” – CaO – (SiO2 + Al2O3) with a fixed Al2O3/SiO2 weight ratio of 0.65 and 6.0 wt.% K2O for temperatures in the range 1523 – 1673 K.

It was found that the presence of K2O in the slag decreases liquidus temperatures relative to those of K2O-free slags in the anorthite and gehlenite primary phase fields at low MnO concentration; at higher MnO concentration however the KAlSiO4 and KAlSi2O6 phases are formed maintaining the liquidus above 1500 K. The manganosite primary phase field is expanded in the direction of increased (Al2O3 + SiO2) and the liquidus temperatures in the manganosite primary phase field are increased significantly with the presence of K2O in the slag.
Transcripts Associated with Non‐Acclimated Freezing Response in Two Barley Cultivars
Authors: Koo B.C. , Bushman B.S. , Mott I.W.
Published: August 2008

Plants subjected to spring freezes are usually not acclimated sufficiently long to confer tolerance to sub‐zero freezing stress in contrast to fall‐grown plants which experience an acclimation period. Barley (Hordeum vulgare L.) periodically suffers from late spring freezes in areas throughout the world, with significant yield loss. We examined the response of ‘Dicktoo’ and ‘Keunal’ barley varieties to non‐acclimated freezing (NAF) (−3°C) at the jointing stage using the barley22K Affymetrix GeneChip to measure transcript abundances. Dicktoo was tolerant of NAF freezing for a longer period of time than Keunal, and had substantially more variable microarray probesets under the NAF treatment. Three hundred and thirteen probesets were selected as responsive genes to NAF based on their differential response in Dicktoo vs. Keunal. Seventy‐one of these probesets had homology‐based annotations, with 49 of them showing reduced transcript levels in Dicktoo NAF vs. Dicktoo control, Keunal control, and Keunal NAF treatments, and 22 showing increased transcript levels. Transcription factors, circadian related genes, and other genes involved in photoperiod response were represented among the probesets upregulated in Dicktoo NAF compared to Keunal NAF, while genes involved in RNA metabolism and water and sugar transport were downregulated. The transcriptome response of both Dicktoo and Keunal to NAF also differed from acclimation‐based freezing treatments, with 43% of Dicktoo NAF and 37% of Keunal NAF probesets unique.
Clinical Benefit and Regulatory Outcomes of Cancer Drugs Receiving Accelerated Approval
Authors: Liu Ian T. T. , Kesselheim Aaron S. , Cliff Edward R. Scheffer
Published: April 2024

Importance

The US Food and Drug Administration’s (FDA) accelerated approval pathway allows approval of investigational drugs treating unmet medical needs based on changes to surrogate measures considered “reasonably likely” to predict clinical benefit. Postapproval clinical trials are then required to confirm whether these drugs offer clinical benefit.

Objective

To determine whether cancer drugs granted accelerated approval ultimately demonstrate clinical benefit and to evaluate the basis of conversion to regular approval.

Design, Setting, and Participants

In this cohort study, publicly available FDA data were used to identify cancer drugs granted accelerated approval from 2013 to 2023.

Main Outcomes and Measures

Demonstrated improvement in quality of life or overall survival in accelerated approvals with more than 5 years of follow-up, as well as confirmatory trial end points and time to conversion for drug-indication pairs converted to regular approval.

Results

A total of 129 cancer drug–indication pairs were granted accelerated approval from 2013 to 2023. Among 46 indications with more than 5 years of follow-up (approved 2013-2017), approximately two-thirds (29, 63%) were converted to regular approval, 10 (22%) were withdrawn, and 7 (15%) remained ongoing after a median of 6.3 years. Fewer than half (20/46, 43%) demonstrated a clinical benefit in confirmatory trials. Time to withdrawal decreased from 9.9 years to 3.6 years, and time to regular approval increased from 1.6 years to 3.6 years. Among 48 drug-indication pairs converted to regular approval, 19 (40%) were converted based on overall survival, 21 (44%) on progression-free survival, 5 (10%) on response rate plus duration of response, 2 (4%) on response rate, and 1 (2%) despite a negative confirmatory trial. Comparing accelerated and regular approval indications, 18 of 48 (38%) were unchanged, while 30 of 48 (63%) had different indications (eg, earlier line of therapy).

Conclusions and Relevance

Most cancer drugs granted accelerated approval did not demonstrate benefit in overall survival or quality of life within 5 years of accelerated approval. Patients should be clearly informed about the cancer drugs that use the accelerated approval pathway and do not end up showing benefits in patient-centered clinical outcomes.
Cancer Stage Compared With Mortality as End Points in Randomized Clinical Trials of Cancer Screening
Authors: Feng Xiaoshuang , Zahed Hana , Onwuka Justina , Callister Matthew E. J. , Johansson Mattias , Etzioni Ruth , Robbins Hilary A.
Published: April 2024

Importance

Randomized clinical trials of cancer screening typically use cancer-specific mortality as the primary end point. The incidence of stage III-IV cancer is a potential alternative end point that may accelerate completion of randomized clinical trials of cancer screening.

Objective

To compare cancer-specific mortality with stage III-IV cancer as end points in randomized clinical trials of cancer screening.

Design, Setting, and Participants

This meta-analysis included 41 randomized clinical trials of cancer screening conducted in Europe, North America, and Asia published through February 19, 2024. Data extracted included numbers of participants, cancer diagnoses, and cancer deaths in the intervention and comparison groups. For each clinical trial, the effect of screening was calculated as the percentage reduction between the intervention and comparison groups in the incidence of participants with cancer-specific mortality and stage III-IV cancer.

Exposures

Randomization to a cancer screening test or to a comparison group in a clinical trial of cancer screening.

Main Outcomes and Measures

End points of cancer-specific mortality and incidence of stage III-IV cancer were compared using Pearson correlation coefficients with 95% CIs, linear regression, and fixed-effects meta-analysis.

Results

The included randomized clinical trials tested benefits of screening for breast (n = 6), colorectal (n = 11), lung (n = 12), ovarian (n = 4), prostate (n = 4), and other cancers (n = 4). Correlation between reductions in cancer-specific mortality and stage III-IV cancer varied by cancer type (I2 = 65%; P = .02). Correlation was highest for trials that screened for ovarian (Pearson ρ = 0.99 [95% CI, 0.51-1.00]) and lung (Pearson ρ = 0.92 [95% CI, 0.72-0.98]) cancers, moderate for breast cancer (Pearson ρ = 0.70 [95% CI, −0.26 to 0.96]), and weak for colorectal (Pearson ρ = 0.39 [95% CI, −0.27 to 0.80]) and prostate (Pearson ρ = −0.69 [95% CI, −0.99 to 0.81]) cancers. Slopes from linear regression were estimated as 1.15 for ovarian cancer, 0.75 for lung cancer, 0.40 for colorectal cancer, 0.28 for breast cancer, and −3.58 for prostate cancer, suggesting that a given magnitude of reduction in incidence of stage III-IV cancer produced different magnitudes of change in incidence of cancer-specific mortality (P for heterogeneity = .004).

Conclusions and Relevance

In randomized clinical trials of cancer screening, incidence of late-stage cancer may be a suitable alternative end point to cancer-specific mortality for some cancer types, but is not suitable for others. These results have implications for clinical trials of multicancer screening tests.
3D Printed Elastomer‐Hydrogel Composite Meniscal Scaffolds with Biomimetic Gradient Structure and Robust Interface for Preventing Osteoarthritis and Repairing Meniscal Injuries
Authors: Yan Wenqiang , He Yangyang , Zhang Manwen , Zhao Lingyu , Tian Feng , Hu Xiaoqing , Cheng Jin , Huang Wei , Ao Yingfang , Yu Ran
Published: April 2024

Meniscal implants with biomimetic 3D architecture, gradient mechanical properties, and excellent biocompatibility are urgently required due to the increasing incidence of meniscus injuries. Inspired by the microstructure of the meniscus, which consists of a meshwork interwoven with collagen fibers and a hydrophilic matrix filled with glycosaminoglycans and chondrocytes, here a type of structurally and functionally optimized meniscal scaffolds is prepared. Direct‐ink‐writing 3D printing technology is utilized to construct an elastomeric skeleton with a biomimetic 3D and gradient microstructure, and then hydrogel resin is infiltrated into the skeleton, resulting in an elastomer‐reinforced hydrogel composite meniscal scaffold through co‐curing of the elastomer and hydrogel resins. The composite meniscal scaffolds exhibit a highly porous structure and biomimetic gradient mechanical properties by controlling the ratio of elastomer and hydrogel materials. The co‐curing of the two materials creates robust interfaces through strong covalent bonding, ensuring their reliable long‐term mechanical performance. Furthermore, the coexistence of aqueous and oily phases of the emulsion‐type hydrogel resin allows the loading of both water‐soluble and lipid‐soluble drugs, endowing the composite scaffolds with a diphasic drug‐release capacity. The composite scaffolds are then implanted in the knee joints of beagle canines, successfully promoting the repair of meniscal injury and tissue regeneration.
Boosted Second Harmonic Generation and Cascaded Sum Frequency Generation from a Surface Crystallized Glass Ceramic Microcavity
Authors: Chen Jianhao , Huang Xiongjian , Yang Dandan , Li Yantong , Wu Jiachang , Yu Huakang , Liu Xiaofeng , Qiu Jianrong , Yang Zhongmin , Dong Guoping
Published: April 2024

The development of novel materials and structures for efficient second‐order nonlinear micro/nano devices remains a significant challenge. In this study, the remarkable enhancement of second‐harmonic generation (SHG) and cascaded sum frequency generation in whispering gallery mode microspheres made of surface‐crystallized glass with a 6‐µm Ba2TiSi2O8 crystal layer are demonstrated. Attributed to the core–shell design, the Ba2TiSi2O8 located on the surface can be efficiently coupled with whispering gallery modes, resulting in a highly efficient micron‐scale cavity‐enhanced second‐order optical nonlinearity. Greatly enhanced SHG of the microcavity is observed, which is up to 80 times stronger than that of a non‐resonant sample. Furthermore, owing to the wavelength non‐selectivity of random quasi‐phase matching, ultra‐wideband SHG with a strong response ranging from 860 to 1600 nm and high‐contrast polarization characteristics is demonstrated. The glass‐ceramic‐based microsphere cavity also boosts the cascading optical nonlinearity, manifested by a two‐magnitude enhancement of cascaded sum frequency generation. This work delineates an efficient strategy for boosting nonlinear optical response in glass ceramics, which will open up new opportunities for applications in photonics and optical communications.
Self‐Lubricating, Living Contact Lenses
Authors: Puertas‐Bartolomé María , Gutiérrez‐Urrutia Izabook , Teruel‐Enrico Lara Luana , Duong Cao Nguyen , Desai Krupansh , Trujillo Sara , Wittmann Christoph , del Campo Aránzazu
Published: April 2024

The increasing prevalence of dry eye syndrome in aging and digital societies compromises long‐term contact lens (CL) wear and forces users to regular eye drop instillation to alleviate discomfort. Here a novel approach with the potential to improve and extend the lubrication properties of CLs is presented. This is achieved by embedding lubricant‐secreting biofactories within the CL material. The self‐replenishable reservoirs autonomously produce and release hyaluronic acid (HA), a natural lubrication and wetting agent, long term. The hydrogel matrix regulates the growth of the biofactories and the HA production, and allows the diffusion of nutrients and HA for at least 3 weeks. The continuous release of HA sustainably reduces the friction coefficient of the CL surface. A self‐lubricating CL prototype is presented, where the functional biofactories are contained in a functional ring at the lens periphery, outside of the vision area. The device is cytocompatible and fulfils physicochemical requirements of commercial CLs. The fabrication process is compatible with current manufacturing processes of CLs for vision correction. It is envisioned that the durable‐by‐design approach in living CL could enable long‐term wear comfort for CL users and minimize the need for lubricating eye drops.
A Biohybrid Self‐Dispersing Miniature Machine Using Wild Oat Fruit Awns for Reforestation and Precision Agriculture
Authors: Fiorello Isabella , Ronzan Marilena , Speck Thomas , Sinibaldi Edoardo , Mazzolai Barbara
Published: April 2024

Advances in bioinspired and biohybrid robotics are enabling the creation of multifunctional systems able to explore complex unstructured environments. Inspired by Avena fruits, a biohybrid miniaturized autonomous machine (HybriBot) composed of a biomimetic biodegradable capsule as cargo delivery system and natural humidity‐driven sister awns as biological motors is reported. Microcomputed tomography, molding via two‐photon polymerization and casting of natural awns into biodegradable materials is employed to fabricate multiple HybriBots capable of exploring various soil and navigating soil irregularities, such as holes and cracks. These machines replicate the dispersal movements and biomechanical performances of natural fruits, achieving comparable capsule drag forces up to ≈0.38 N and awns torque up to ≈100 mN mm−1. They are functionalized with fertilizer and are successfully utilized to germinate selected diaspores. HybriBots function as self‐dispersed systems with applications in reforestation and precision agriculture.
Programmable, High‐resolution Printing of Spatially Graded Perovskites for Multispectral Photodetectors
Authors: Duan Yongqing , Yu Rui , Zhang Hanyuan , Yang Weili , Xie Wenshuo , Huang YongAn , Yin Zhouping
Published: April 2024

Micro/nanostructured perovskites with spatially graded compositions and bandgaps are promising in filter‐free, chip‐level multispectral, and hyperspectral detection. However, achieving high‐resolution patterning of perovskites with controlled graded compositions is challenging. Here, a programmable mixed electrohydrodynamic printing (M‐ePrinting) technique is presented to realize the one‐step direct‐printing of arbitrary spatially graded perovskite micro/nanopatterns for the first time. M‐ePrinting enables in situ mixing and ejection of solutions with controlled composition/bandgap by programmatically varying driving voltage applied to a multichannel nozzle. Composition can be graded over a single dot, line or complex pattern, and the printed feature size is down to 1 µm, which is the highest printing resolution of graded patterns to the knowledge. Photodetectors based on micro/nanostructured perovskites with halide ions gradually varying from Br to I are constructed, which successfully achieve multispectral detection and full‐color imaging, with a high detectivity and responsivity of 3.27 × 1015 Jones and 69.88 A W−1, respectively. The presented method provides a versatile and competitive approach for such miniaturized bandgap‐tunable perovskite spectrometer platforms and artificial vision systems, and also opens new avenues for the digital fabrication of composition‐programmable structures.
Orbital Electrowetting‐on‐Dielectric for Droplet Manipulation on Superhydrophobic Surfaces
Authors: Tan Jie , Fan Zeng , Zhou Mingfei , Liu Tong , Sun Shulan , Chen Guijun , Song Yongchen , Wang Zuankai , Jiang Dongyue
Published: April 2024

Electrowetting‐on‐dielectric (EWOD), recognized as the most successful electrical droplet actuation method, is essential in diverse applications, ranging from thermal management to microfluidics and water harvesting. Despite significant advances, it remains challenging to achieve repeatability, high speed, and simple circuitry in EWOD‐based droplet manipulation on superhydrophobic surfaces. Moreover, its efficient operation typically requires electrode arrays and sophisticated circuit control. Here, a newly observed droplet manipulation phenomenon on superhydrophobic surfaces with orbital EWOD (OEW) is reported. Due to the asymmetric electrowetting force generated on the orbit, flexible and versatile droplet manipulation is facilitated with OEW. It is demonstrated that OEW droplet manipulation on superhydrophobic surfaces exhibits higher speed (up to 5 times faster), enhanced functionality (antigravity), and manipulation of diverse liquids (acid, base, salt, organic, e.g., methyl blue, artificial blood) without contamination, and good durability after 1000 tests. It is envisioned that this robust droplet manipulation strategy using OEW will provide a valuable platform for various processes involving droplets, spanning from microfluidic devices to controllable chemical reactions. The previously unreported droplet manipulation phenomenon and control strategy shown here can potentially upgrade EWOD‐based microfluidics, antifogging, anti‐icing, dust removal, and beyond.
Revolutionizing Neurocare: Biomimetic Nanodelivery Via Cell Membranes
Authors: Liao Jun , Gong Lidong , Xu Qingqiang , Wang Jingya , Yang Yuanyuan , Zhang Shiming , Dong Junwei , Lin Kerui , Liang Zichao , Sun Yuhan , Mu Yongxu , Chen Zhengju , Lu Ying , Zhang Qiang , Lin Zhiqiang
Published: April 2024

Brain disorders represent a significant challenge in medical science due to the formidable blood–brain barrier (BBB), which severely limits the penetration of conventional therapeutics, hindering effective treatment strategies. This review delves into the innovative realm of biomimetic nanodelivery systems, including stem cell‐derived nanoghosts, tumor cell membrane‐coated nanoparticles, and erythrocyte membrane‐based carriers, highlighting their potential to circumvent the BBB's restrictions. By mimicking native cell properties, these nanocarriers emerge as a promising solution for enhancing drug delivery to the brain, offering a strategic advantage in overcoming the barrier's selective permeability. The unique benefits of leveraging cell membranes from various sources is evaluated and advanced technologies for fabricating cell membrane‐encapsulated nanoparticles capable of masquerading as endogenous cells are examined. This enables the targeted delivery of a broad spectrum of therapeutic agents, ranging from small molecule drugs to proteins, thereby providing an innovative approach to neurocare. Further, the review contrasts the capabilities and limitations of these biomimetic nanocarriers with traditional delivery methods, underlining their potential to enable targeted, sustained, and minimally invasive treatment modalities. This review is concluded with a perspective on the clinical translation of these biomimetic systems, underscoring their transformative impact on the therapeutic landscape for intractable brain diseases.
Super‐Ionic Conductor Soft Filler Promotes Li+ Transport in Integrated Cathode–Electrolyte for Solid‐State Battery at Room Temperature
Authors: Yang Binbin , Deng Chenglong , Chen Nan , Zhang Fengling , Hu Kaikai , Gui Boshun , Zhao Liyuan , Wu Feng , Chen Renjie
Published: April 2024

Composite polymer solid electrolytes (CPEs), possessing good rigid flexible, are expected to be used in solid‐state lithium‐metal batteries. The integration of fillers into polymer matrices emerges as a dominant strategy to improve Li+ transport and form a Li+‐conducting electrode–electrolyte interface. However, challenges arise as traditional fillers: 1) inorganic fillers, characterized by high interfacial energy, induce agglomeration; 2) organic fillers, with elevated crystallinity, impede intrinsic ionic conductivity, both severely hindering Li+ migration. Here, a concept of super‐ionic conductor soft filler, utilizing a Li+ conductivity nanocellulose (Li‐NC) as a model, is introduced which exhibits super‐ionic conductivity. Li‐NC anchors anions, and enhances Li+ transport speed, and assists in the integration of cathode–electrolyte electrodes for room temperature solid‐state batteries. The tough dual‐channel Li+ transport electrolyte (TDCT) with Li‐NC and polyvinylidene fluoride (PVDF) demonstrates a high Li+ transfer number (0.79) due to the synergistic coordination mechanism in Li+ transport. Integrated electrodes’ design enables stable performance in LiNi0.5Co0.2Mn0.3O2|Li cells, with 720 cycles at 0.5 C, and 88.8% capacity retention. Furthermore, the lifespan of Li|TDCT|Li cells over 4000 h and Li‐rich Li1.2Ni0.13Co0.13Mn0.54O2|Li cells exhibits excellent performance, proving the practical application potential of soft filler for high energy density solid‐state lithium‐metal batteries at room temperature.
Smart Solid‐State Interphases Enable High‐Safety and High‐Energy Practical Lithium Batteries
Authors: Wu Yu , Liu Yuan , Feng Xuning , Ma Zhuang , Xu Xiaodong , Ren Dongsheng , Han Xuebing , Li Yalun , Lu Languang , Wang Li , He Xiangming , Ouyang Minggao
Published: April 2024

With the electrochemical performance of batteries approaching the bottleneck gradually, it is increasingly urgent to solve the safety issue. Herein, all‐in‐one strategy is ingeniously developed to design smart, safe, and simple (3S) practical pouch‐type LiNi0.8Co0.1Mn0.1O2||Graphite@SiO (NCM811||Gr@SiO) cell, taking full advantage of liquid and solid‐state electrolytes. Even under the harsh thermal abuse and high voltage condition (100 °C, 3–4.5 V), the pouch‐type 3S NCM811||Gr@SiO cell can present superior capacity retention of 84.6% after 250 cycles (based pouch cell: 47.8% after 250 cycles). More surprisingly, the designed 3S NCM811||Gr@SiO cell can efficiently improve self‐generated heat T1 by 45 °C, increase TR triggering temperature T2 by 40 °C, and decrease the TR highest T3 by 118 °C. These superior electrochemical and safety performances of practical 3S pouch‐type cells are attributed to the robust and stable anion‐induced electrode‐electrolyte interphases and local solid‐state electrolyte protection layer. All the fundamental findings break the conventional battery design guidelines and open up a new direction to develop practical high‐performance batteries.