Summary
The visual deficiency symptoms developing on plants constitute the ultimate manifestation of suboptimal nutrient supply. In classical plant nutrition, these symptoms have been extensively ...used as a tool to characterise the nutritional status of plants and to optimise fertilisation. Here we expand this concept by bridging the typical deficiency symptoms for each of the six essential macronutrients to their molecular and physiological functionalities in higher plants. We focus on the most recent insights obtained during the last decade, which now allow us to better understand the links between symptom and function for each element. A deep understanding of the mechanisms underlying the visual deficiency symptoms enables us to thoroughly understand how plants react to nutrient limitations and how these disturbances may affect the productivity and biodiversity of terrestrial ecosystems. A proper interpretation of visual deficiency symptoms will support the potential for sustainable crop intensification through the development of new technologies that facilitate automatised management practices based on imaging technologies, remote sensing and in‐field sensors, thereby providing the basis for timely application of nutrients via smart and more efficient fertilisation.
The IMpower150 trial showed significant improvements in progression-free and overall survival with atezolizumab plus bevacizumab plus carboplatin plus paclitaxel (ABCP) versus the standard-of-care ...bevacizumab plus carboplatin plus paclitaxel (BCP) in chemotherapy-naive patients with non-squamous non-small-cell lung cancer. Here, we report the efficacy of ABCP or atezolizumab plus carboplatin plus paclitaxel (ACP) versus BCP in key patient subgroups.
IMpower150 was a randomised, open-label, phase 3 study done at 240 academic medical centres and community oncology practices across 26 countries worldwide. Patients with chemotherapy-naive metastatic non-small-cell lung cancer were randomly assigned (1:1:1) to receive ABCP, ACP, or BCP every three weeks. The co-primary endpoints were overall survival and investigator-assessed progression-free survival in intention-to-treat wild-type patients (patients with epidermal growth factor receptor EGFR or anaplastic lymphoma kinase ALK genetic alterations were excluded). Efficacy was assessed in key subgroups within the intention-to-treat population, including patients with EGFR mutations (both sensitising and non-sensitising; EGFR-positive) previously treated with one or more tyrosine kinase inhibitors and patients with baseline liver metastases. Overall survival in the intention-to-treat population was included among secondary efficacy endpoints. Exploratory endpoints included the proportion of patients achieving an objective response in the intention-to-treat population, including EGFR-positive patients and patients with baseline liver metastases. Data are reported as per the Jan 22, 2018, data cutoff date, at which the number of coprimary prespecified overall survival events was met in the ABCP versus BCP groups. This trial is registered with ClinicalTrials.gov, number NCT02366143, and is ongoing.
Between March 31, 2015, and Dec 30, 2016, 1202 patients were enrolled. 400 patients were randomly assigned to ABCP, 402 to ACP, and 400 to BCP. In EGFR-positive patients (124 of 1202), median overall survival was not estimable (NE; 95% CI 17·0-NE) with ABCP (34 of 400) and 18·7 months (95% CI 13·4-NE) with BCP (45 of 400; hazard ratio HR 0·61 95% CI 0·29-1·28). Improved overall survival with ABCP versus BCP was observed in patients with sensitising EGFR mutations (median overall survival NE 95% CI NE-NE with ABCP 26 of 400 vs 17·5 months 95% CI 11·7-NE with BCP 32 of 400; HR 0·31 95% CI 0·11-0·83) and in the intention-to-treat population (19·8 months 17·4-24·2 vs 14·9 months 13·4-17·1; HR 0·76 0·63-0·93). Improved median overall survival with ABCP versus BCP was seen in patients with baseline liver metastases (13·3 months 11·6-NE with ABCP 52 of 400 vs 9·4 months 7·9-11·7 with BCP 57 of 400; HR 0·52 0·33-0·82). Median overall survival was 21·4 months (95% CI 13·8-NE) with ACP versus 18·7 months (95% CI 13·4-NE) with BCP in EGFR-positive patients (HR 0·93 95% CI 0·51-1·68). No overall survival benefit was seen with ACP versus BCP in patients with sensitising EGFR mutations (HR 0·90 95% CI 0·47-1·74), in the intention-to-treat population (HR 0·85 0·71-1·03), or in patients with baseline liver metastases (HR 0·87 0·57-1·32). In the intention-to-treat safety-evaluable population, grade 3-4 treatment-related events occurred in 223 (57%) patients in the ABCP group, in 172 (43%) in the ACP group, and in 191 (49%) in the BCP group; 11 (3%) grade 5 adverse events occurred in the ABCP group, as did four (1%) in the ACP group, and nine (2%) in the BCP group.
Improved survival was noted for patients treated with ABCP compared with those given BCP in the intention-to-treat population, and in patients with baseline liver metastases. The overall survival signal in the subgroup of patients with EGFR sensitising mutations warrants further study.
F. Hoffmann-La Roche, Genentech.
Auger decay is a relaxation process of core-vacant states in atoms and molecules, in which one valence electron fills the core vacancy while a second one is emitted. These states pose a challenge to ...electronic-structure theory, because they are embedded in the ionisation continuum. Recently, we showed that molecular Auger decay can be described using complex-variable coupled-cluster (CC) methods and that partial widths and branching ratios can be computed based on a decomposition of the CC energy. Here, we introduce channel-specific core-valence projectors, dubbed Auger channel projectors, as a more general technique to evaluate partial widths from complex-variable treatments. We apply this new method to core-ionised states of neon, water, ammonia and methane using CC singles and doubles (CCSD), equation-of-motion ionisation potential CCSD and configuration interaction singles (CIS) wave functions. Even though a single CIS calculation can never describe all Auger decay channels at once, we show that a combination of CIS calculations based on different reference states is able to recover partial and total decay widths from CC calculations to an excellent degree.
We investigate the capability of several variants of the second-order approximate coupled-cluster singles and doubles (CC2) method to describe dipole-bound, quadrupole-bound, and correlation-bound ...molecular anions. The binding energy of anions formed by electron attachment to closed-shell molecules is computed using the electron attachment variant of CC2 (EA-CC2), whereas anions with a closed-shell ground state are treated with the standard CC2 method that preserves the number of particles. We find that EA-CC2 captures the binding energies of dipole-bound radical anions quite well, whereas results for other types of non-valence anions are less reliable. We also test the performance of semi-empirical spin-scaling factors for all types of non-valence anions and observe that the spin-scaled CC2 variants generally do not provide more accurate binding energies for dipole-bound anions, while the binding energies of quadrupole-bound and correlation-bound anions are improved. As exemplary applications of EA-CC2, we investigate the dipole-bound anions of the steroids cortisol, progesterone, and testosterone. In addition, we characterize electron attachment to
sym
-tetracyanonaphthalene, a molecule that supports five anionic states, two of which can be interpreted as hitherto unobserved π-type quadrupole-bound states.
The CC2 electronic-structure method is applied to dipole-bound, quadrupole-bound, and correlation-bound anions.
We report an implementation of a spin-flip variant of the second-order approximate coupled-cluster singles and doubles (CC2) method. The resolution-of-the-identity approximation or, alternatively, ...Cholesky decomposition are applied to the electron repulsion integrals. We illustrate the performance of the new method by constructing potential energy curves of H
2
and HF and by computing singlet-triplet splittings for various diradicals including some binuclear copper complexes that are of interest as molecular magnets. We find that spin-flip CC2 performs very similarly to the spin-flip variant of the algebraic diagrammatic construction scheme for the polarization propagator of second order (ADC(2)). Application to ozone shows that, depending on the reference state used, spin-flip CC2 erroneously predicts a barrierless symmetric dissociation of this molecule. A similar failure was observed in earlier work for spin-conserving CC2. In contrast, spin-flip ADC(2) and coupled-cluster singles and doubles yield qualitatively correct potential energy surfaces for ozone.
A spin-flip variant of the CC2 electronic-structure method is introduced and applied to various molecules.
After overexposure to loud music, we experience a decrease in our ability to hear (robustness), which usually recovers (resilience). Here, we exploited the amenable auditory system of the desert ...locust, Schistocerca gregaria, to measure how robustness and resilience depend on age. We found that gene expression changes are dominated by age as opposed to noise exposure. We measured sound-evoked nerve activity for young and aged locusts directly after 24 hours and 48 hours after noise exposure. We found that both young and aged locusts recovered their auditory nerve function over 48 hours. We also measured the sound-evoked transduction current in individual auditory neurons, and although the transduction current magnitude recovered in the young locusts after noise exposure, it failed to recover in the aged locusts. Our physiological data suggest a plastic mechanism that, in aged locusts, compensates for the decreased transduction current. We suggest key genes upregulated in young noise-exposed locusts that mediate robustness to noise exposure and find potential candidates responsible for compensatory mechanisms in the auditory neurons of aged noise-exposed locusts.
Ryan Kaufman—whose rich body of work often centers on video games adapted from movies or TV shows—has had a profound impact on video game designers, writers, and players alike ...
To further understand documented associations between obesity and urban sprawl, this research describes individuals’ trade-offs between health-related activities and commuting time. A cross-section ...of 24,861 working-age individuals employed full-time and residing in urban counties is constructed from the American Time Use Survey (2003–2010). Data are analyzed using seemingly unrelated regressions to quantify health-related activity decreases in response to additional time spent commuting. Outcomes are total daily minutes spent in physical activity at a moderate or greater intensity, preparing food, eating meals with family, and sleeping. Commuting time is measured as all travel time between home and work and vice versa. The mean commuting time is 62 min daily, the median is 55 min, and 10.1% of workers commute 120 min or more. Spending an additional 60 min daily commuting above average is associated with a 6% decrease in aggregate health-related activities and spending an additional 120 min is associated with a 12% decrease. The greatest percentage of commuting time comes from sleeping time reductions (28–35%). Additionally, larger proportions of commuting time are taken from physical activity and food preparation relative to the mean commuting length: of 60 min spent commuting, 16.1% is taken from physical activity and 4.1% is taken from food preparation; of 120 min commuting, 20.3% is taken from physical activity and 5.6% is taken from food preparation. The results indicate that longer commutes are associated with behavioral patterns which over time may contribute to obesity and other poor health outcomes. These findings will assist both urban planners and researchers wishing to understand time constraints’ impacts on health.
This article compares Ridley Scott’s film Alien (1979) with Creative Assembly’s video game Alien: Isolation (2014), which is based on Scott’s film. Guidance for academics who teach creative ...writing—as well as for working screenwriters and video game narrative designers—emerges in the comparison, particularly with regard to the importance of developing strong yet vulnerable main characters who put themselves in danger in order to protect other characters with whom they have meaningful relationships. Examples from other media, including Ira Levin’s Rosemary’s Baby (1967), James Cameron’s Aliens (1986), Telltale Games’ The Walking Dead (2012), and Naughty Dog’s The Last of Us (2013), are also discussed as they relate to larger principles involved in crafting sympathetic characters, realistic settings, and compelling gameplay for media within the horror and sci-fi genres.
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