Despite advances in cancer genomics and the increased use of genomic medicine, metastatic cancer is still mostly an incurable and fatal disease. With diminishing returns from traditional drug discovery strategies, and high clinical failure rates, more emphasis is being placed on alternative drug discovery platforms, such as ex vivo approaches. Ex vivo approaches aim to embed biological relevance and inter-patient variability at an earlier stage of drug discovery, and to offer more precise treatment stratification for patients. However, these techniques also have a high potential to offer personalised therapies to patients, complementing and enhancing genomic medicine. Although an array of approaches are available to researchers, only a minority of techniques have made it through to direct patient treatment within robust clinical trials. Within this review, we discuss the current challenges to ex vivo approaches within clinical practice and summarise the contemporary literature which has directed patient treatment. Finally, we map out how ex vivo approaches could transition from a small-scale, predominantly research based technology to a robust and validated predictive tool. In future, these pre-clinical approaches may be integrated into clinical cancer pathways to assist in the personalisation of therapy choices and to hopefully improve patient experiences and outcomes.

Increasing interest in three-dimensional nanostructures adds impetus to electron microscopy techniques capable of imaging at or below the nanoscale in three dimensions. We present a reconstruction algorithm that takes as input a focal series of four-dimensional scanning transmission electron microscopy (4D-STEM) data. We apply the approach to a lead iridate, Pb$_2$Ir$_2$O$_7$, and yttrium-stabilized zirconia, Y$_{0.095}$Zr$_{0.905}$O$_2$, heterostructure from data acquired with the specimen in a single plan-view orientation, with the epitaxial layers stacked along the beam direction. We demonstrate that Pb–Ir atomic columns are visible in the uppermost layers of the reconstructed volume. We compare this approach to the alternative techniques of depth sectioning using differential phase contrast scanning transmission electron microscopy (DPC-STEM) and multislice ptychographic reconstruction.

High-throughput grain mapping with sub-nanometer spatial resolution is demonstrated using scanning nanobeam electron diffraction (also known as 4D scanning transmission electron microscopy, or 4D-STEM) combined with high-speed direct-electron detection. An electron probe size down to 0.5 nm in diameter is used and the sample investigated is a gold–palladium nanoparticle catalyst. Computational analysis of the 4D-STEM data sets is performed using a disk registration algorithm to identify the diffraction peaks followed by feature learning to map the individual grains. Two unsupervised feature learning techniques are compared: principal component analysis (PCA) and non-negative matrix factorization (NNMF). The characteristics of the PCA versus NNMF output are compared and the potential of the 4D-STEM approach for statistical analysis of grain orientations at high spatial resolution is discussed.

Single-particle reconstruction can be used to perform three-dimensional (3D) imaging of homogeneous populations of nano-sized objects, in particular viruses and proteins. Here, it is demonstrated that it can also be used to obtain 3D reconstructions of heterogeneous populations of inorganic nanoparticles. An automated acquisition scheme in a scanning transmission electron microscope is used to collect images of thousands of nanoparticles. Particle images are subsequently semi-automatically clustered in terms of their properties and separate 3D reconstructions are performed from selected particle image clusters. The result is a 3D dataset that is representative of the full population. The study demonstrates a methodology that allows 3D imaging and analysis of inorganic nanoparticles in a fully automated manner that is truly representative of large particle populations.

Information on performance of sequential treatments of quizalofop-P-ethyl with florpyrauxifen-benzyl on rice is lacking. Field studies were conducted in 2017 and 2018 in Stoneville, MS, to evaluate sequential timings of quizalofop-P-ethyl with florpyrauxifen-benzyl included in preflood treatments of rice. Quizalofop-P-ethyl treatments were no quizalofop-P-ethyl; sequential applications of quizalofop-P-ethyl at 120 g ha−1 followed by (fb) 120 g ai ha−1 applied to rice in the 2- to 3-leaf (EPOST) fb the 4-leaf to 1-tiller (LPOST) growth stages or LPOST fb 10 d after flooding (PTFLD); quizalofop-P-ethyl at 100 g ha−1 fb 139 g ha−1 EPOST fb LPOST or LPOST fb PTFLD; quizalofop-P-ethyl at 139 g ha−1 fb 100 g ha−1 EPOST fb LPOST and LPOST fb PTFLD; and quizalofop-P-ethyl at 85 g ha−1 fb 77 g ha−1 fb 77 g ha−1 EPOST fb LPOST fb PTFLD. Quizalofop-P-ethyl was applied alone and in mixture with florpyrauxifen-benzyl at 29 g ai ha−1 LPOST. Visible rice injury 14 d after PTFLD (DA-PTFLD) was no more than 3%. Visible control of volunteer rice (‘CL151’ and ‘Rex’) 7 DA-PTFLD was similar and at least 95% for each quizalofop-P-ethyl treatment. Barnyardgrass control with quizalofop-P-ethyl at 120 fb 120 g ha−1 LPOST fb PTFLD was greater (88%) in mixture with florpyrauxifen-benzyl. The addition of florpyrauxifen-benzyl to quizalofop-P-ethyl increased rough rice yield when quizalofop-P-ethyl was applied at 100 g ha−1 fb 139 g ha−1 EPOST fb LPOST. Sequential applications of quizalofop-P-ethyl at 120 g ha−1 fb 120 g ha−1 EPOST fb LPOST, 100 g ha−1 fb 139 g ha−1 EPOST fb LPOST, or 139 g ha−1 fb 100 g ha−1 EPOST fb LPOST controlled grass weed species. The addition of florpyrauxifen-benzyl was not beneficial for grass weed control. However, because quizalofop-P-ethyl does not control broadleaf weeds, florpyrauxifen-benzyl could provide broad-spectrum weed control in acetyl coenzyme A carboxylase–resistant rice.

Florpyrauxifen-benzyl and quizalofop were available for POST applications in 2018; however, little is known about the response of acetyl-CoA carboxylase (ACCase)–resistant rice cultivars and advanced lines to POST herbicides. A field study was conducted in 2017 and 2018 at Stoneville, MS, to characterize the response of ACCase-resistant rice cultivars and advanced lines to POST applications of florpyrauxifen-benzyl. The imidazolinone-resistant (IR) rice cultivars ‘CL163’ and ‘CLXL 745’, and ACCase-resistant rice cultivars ‘PVL01’, ‘PVL013’, ‘PVL024-B’, ‘PVL038’, ‘PVL080’, and ‘PVL081’were treated with florpyrauxifen-benzyl at 0 (nontreated control for each cultivar) and 58 g ai ha–1 at the four-leaf to one-tiller (LPOST) growth stage. At 14 d after treatment (DAT), PVL01 was injured 5% to 6% greater than CLXL 745, PVL013, and PVL081; however, injury was ≤10% at that evaluation for all cultivars. Similarly, injury was ≤13% for all cultivars 28 DAT. Mature heights were reduced for all cultivars except PVL013 and PVL081. Rough rice yield was ≥100% of the control for all cultivars except PVL081, PVL013, and CL163. Results suggest that florpyrauxifen-benzyl can safely be applied POST to rice cultivars grown in Mississippi as well as ACCase-resistant cultivars that are currently under development.

Off-target paraquat movement to rice has become a major problem in recent years for rice producers in the midsouthern United States. Nitrogen (N) fertilizer is applied to rice in greater quantity and frequency than all other nutrients to optimize rice yield. Two separate field studies were conducted from 2015 to 2018 in Stoneville, MS, to assess whether starter N fertilizer can aid rice recovery from exposure to a sub-lethal concentration of paraquat and to evaluate rice response to different N fertilizer management strategies following exposure to a sub-lethal concentration of paraquat. In both studies, paraquat treatments consisted of paraquat at 0 and 84 g ai ha–1 applied to rice in the two- to three-leaf (EPOST) growth stage. In the starter fertilizer study, N fertilizer at 24 kg ha–1 as ammonium sulfate (AMS) was applied to rice at spiking- to one-leaf (VEPOST), two- to three-leaf (EPOST), or three- to four-leaf (MPOST) growth stages before and after paraquat treatment. In the N fertilizer timing study, N fertilizer at 168 kg N ha–1 was applied in a single four-leaf to one-tiller (LPOST) application or two-, three-, and two four-way split applications. Despite starter N fertilizer applications, paraquat injured rice ≥41%, reduced height 57%, reduced dry weight prior to flooding 77%, delayed maturity 10 d, reduced dry weight at maturity 33%, and reduced rough rice yield 35% in the starter fertilizer study. Similarly, in the N fertilizer timing study, paraquat injured rice ≥45%, reduced height 14%, delayed maturity 10 d, reduced dry weight at maturity 44%, and reduced rough rice yield 50% for all N fertilizer management strategies. Both studies indicate that severe complications in growth and development can occur from rice exposure to a sub-lethal concentration of paraquat. In both studies, manipulation of N fertilizer management did not facilitate rice recovery from early-season exposure to paraquat.

In glyphosate-resistant (GR) cropping systems, paraquat applied in mixtures with residual herbicides prior to crop emergence offers an alternative herbicide mode of action (MOA) to aid in GR weed management. Rice is sensitive to off-target herbicide movement; however, severity of injury can vary with herbicide, rate, and formulation. Therefore, research was conducted from 2015 to 2017 in Stoneville, MS, to characterize rice response to a sublethal concentration of paraquat applied at 84 g ai ha–1 in combination with common residual herbicides. Paraquat plus metribuzin injured rice 68% to 69% 14 and 28 d after treatment (DAT), which was 10% to 13% greater than injury following paraquat alone or paraquat plus fomesafen. Pooled across metribuzin and fomesafen treatments, paraquat reduced rough rice yields 23%. Paraquat plus 10 different residual herbicides injured rice ≥51% 28 DAT and reduced rough rice yields ≥21%. These studies indicate a severe negative impact on rice growth and development following exposure to a sublethal concentration of paraquat alone or in mixture with common residual herbicides. Therefore, applications of paraquat plus residual herbicides to fields in proximity to rice should be avoided if conditions are conducive for off-target movement.

Rice with enhanced tolerance to herbicides that inhibit acetyl coA carboxylase (ACCase) allows POST application of quizalofop, an ACCase-inhibiting herbicide. Two concurrent field studies were conducted in 2017 and 2018 near Stoneville, MS, to evaluate control of grass (Grass Study) and broadleaf (Broadleaf Study) weeds with sequential applications of quizalofop alone and in mixtures with auxinic herbicides applied in the first or second application. Sequential treatments of quizalofop were applied at 119 g ai ha−1 alone and in mixtures with labeled rates of auxinic herbicides to rice at the two- to three-leaf (EPOST) or four-leaf to one-tiller (LPOST) growth stages. In the Grass Study, no differences in rice injury or control of volunteer rice (‘CL151’ and ‘Rex’) were detected 14 and 28 d after last application (DA-LPOST). Barnyardgrass control at 14 and 28 DA-LPOST with quizalofop applied alone or with auxinic herbicides EPOST was ≥93% for all auxinic herbicide treatments except penoxsulam plus triclopyr. Barnyardgrass control was ≥96% with quizalofop applied alone and with auxinic herbicides LPOST. In the Broadleaf Study, quizalofop plus florpyrauxifen-benzyl controlled more Palmer amaranth 14 DA-LPOST than other mixtures with auxinic herbicides, and control with this treatment was greater EPOST compared with LPOST. Hemp sesbania control 14 DA-LPOST was ≤90% with quizalofop plus quinclorac LPOST, orthosulfamuron plus quinclorac LPOST, and triclopyr EPOST or LPOST. All mixtures except quinclorac and orthosulfamuron plus quinclorac LPOST controlled ivyleaf morningglory ≥91% 14 DA-LPOST. Florpyrauxifen-benzyl or triclopyr were required for volunteer soybean control >63% 14 DA-LPOST. To optimize barnyardgrass control and rice yield, penoxsulam plus triclopyr and orthosulfamuron plus quinclorac should not be mixed with quizalofop. Quizalofop mixtures with auxinic herbicides are safe and effective for controlling barnyardgrass, volunteer rice, and broadleaf weeds in ACCase-resistant rice, and the choice of herbicide mixture could be adjusted based on weed spectrum in the treated field.

The development of laser wakefield accelerators (LWFA) over the past several years has led to an interest in very compact sources of X-ray radiation – such as “table-top” free electron lasers. However, the use of conventional undulators using permanent magnets also implies system sizes which are large. In this work, we assess the possibilities for the use of novel mini-undulators in conjunction with a LWFA so that the dimensions of the undulator become comparable with the acceleration distances for LWFA experiments (i.e., centimeters). The use of a prototype undulator using laser machining of permanent magnets for this application is described and the emission characteristics and limitations of such a system are determined. Preliminary electron propagation and X-ray emission measurements are taken with a LWFA electron beam at the University of Michigan.