Intercomparison of bidirectional reflectance distribution function measurements at in- and out-of-plane geometries.

In recent years, there has been a growing interest in the measurements of the bidirectional reflectance distribution function (BRDF) in industry and research and development. However, there is currently no dedicated key comparison to demonstrate the scale conformity. To date, scale conformity has been proved only for classical in-plane geometries, in comparisons between different national metrology institutes (NMIs) and designated institutes (DIs). This study aims at expanding that with nonclassical geometries, including, for the first time, to the best of our knowledge, two out-of-plane geometries. A total of four NMIs and two DIs participated in a scale comparison of the BRDF measurements of three achromatic samples at 550 nm in five measurement geometries. The realization of the scale of BRDF is a well-understood procedure, as explained in this paper, but the comparison of the measured values presents slight inconsistencies in some geometries, most likely due to the underestimation of measurement uncertainties. This underestimation was revealed and indirectly quantified using the Mandel-Paule method, which provides the interlaboratory uncertainty. The results from the presented comparison allow the present state of the BRDF scale realization to be evaluated, not only for classical in-plane geometries, but also for out-of-plane geometries.

Imaging x-ray spectrometer at the high energy density instrument of the European x-ray free electron laser.

A multipurpose imaging x-ray crystal spectrometer is developed for the high energy density instrument of the European X-ray Free Electron Laser. The spectrometer is designed to measure x rays in the energy range of 4-10 keV, providing high-resolution, spatially resolved spectral measurements. A toroidally bent germanium (Ge) crystal is used, allowing x-ray diffraction from the crystal to image along a one-dimensional spatial profile while spectrally resolving along the other. A detailed geometrical analysis is performed to determine the curvature of the crystal. The theoretical performance of the spectrometer in various configurations is calculated by ray-tracing simulations. The key properties of the spectrometer, including the spectral and spatial resolution, are demonstrated experimentally on different platforms. Experimental results prove that this Ge spectrometer is a powerful tool for spatially resolved measurements of x-ray emission, scattering, or absorption spectra in high energy density physics.

Preliminary measurement scales for sparkle and graininess.

Large effect pigments, widely used in various fields of industrial applications, produce characteristic visual textures known as sparkle and graininess, which need to be quantified by objective or subjective methods. The development of preliminary measurement scales for sparkle and graininess, whose recommendation is now under discussion in the International Commission on Illumination (CIE), is described in this article. These scales are absolute, linear and traceable to standards of optical radiation metrology. The main purpose of this article is to justify the convenience of adopting these preliminary measurements scales, showing clear evidence that they correlate well with subjective evaluations. Before standardization, these scales need to be validated with more experimental data, including different specimens and experimental systems from other research groups.

Microstructured layered targets for improved laser-induced x-ray backlighters.

We present the usage of two-layer targets with laser-illuminated front-side microstructures for x-ray backlighter applications. The targets consisted of a silicon front layer and copper back side layer. The structured layer was irradiated by the 500-fs PHELIX laser with an intensity above 10^{20}Wcm^{-2}. The total emission and one-dimensional extent of the copper Kα x-ray emission as well as a wide spectral range between 7.9 and 9.0 keV were recorded with an array of crystal spectrometers. The measurements show that the front-side modifications of the silicon in the form of conical microstructures maintain the same peak brightness of the Kα emission as flat copper foils while suppressing the thermal emission background significantly. The observed Kα source sizes can be influenced by tilting the conical microstructures with respect to the laser axis. Overall, the recorded copper Kα photon yields were in the range of 10^{11}sr^{-1}, demonstrating the suitability of these targets for probing applications without subjecting the probed material to additional heating from thermal line emission.

Mirror to measure small angle x-ray scattering signal in high energy density experiments.

Small angle x-ray scattering (SAXS) is a well established technique to detect nanometer scale structures in matter. In a typical setup, this diagnostic uses a detector with a direct line of sight to the scattering target. However, in the harsh environment of high intensity laser interaction, intense secondary radiation and high-energy particles are generated. Such a setup would therefore suffer a significant increase of noise due to this background, which could eventually prevent such measurements. In this paper, we present a novel tool consisting of a mosaic graphite crystal that works as a mirror for the SAXS signal and allows us to position the detector behind appropriate shielding. This paper studies the performance of this mirror both by experiment at the European XFEL (X-Ray Free-Electron Laser Facility) laboratory and by simulations.

Interconnectivity between molecular subtypes and tumor stage in colorectal cancer.

BACKGROUND: There are profound individual differences in clinical outcomes between colorectal cancers (CRCs) presenting with identical stage of disease. Molecular stratification, in conjunction with the traditional TNM staging, is a promising way to predict patient outcomes. We investigated the interconnectivity between tumor stage and tumor biology reflected by the Consensus Molecular Subtypes (CMSs) in CRC, and explored the possible value of these insights in patients with stage II colon cancer. METHODS: We performed a retrospective analysis using clinical records and gene expression profiling in a meta-cohort of 1040 CRC patients. The interconnectivity of tumor biology and disease stage was assessed by investigating the association between CMSs and TNM classification. In order to validate the clinical applicability of our findings we employed a meta-cohort of 197 stage II colon cancers. RESULTS: CMS4 was significantly more prevalent in advanced stages of disease (stage I 9.8% versus stage IV 38.5%, p < 0.001). The observed differential gene expression between cancer stages is at least partly explained by the biological differences as reflected by CMS subtypes. Gene signatures for stage III-IV and CMS4 were highly correlated (r = 0.77, p < 0.001). CMS4 cancers showed an increased progression rate to more advanced stages (CMS4 compared to CMS2: 1.25, 95% CI: 1.08-1.46). Patients with a CMS4 cancer had worse survival in the high-risk stage II tumors compared to the total stage II cohort (5-year DFS 41.7% versus 100.0%, p = 0.008). CONCLUSIONS: Considerable interconnectivity between tumor biology and tumor stage in CRC exists. This implies that the TNM stage, in addition to the stage of progression, might also reflect distinct biological disease entities. These insights can potentially be utilized to optimize identification of high-risk stage II colon cancers.

Nature of fiber-coupled detector responsivity measurements at 0.1% using a primary standard.

We demonstrate the capability to measure the absolute power responsivity of optical fiber-coupled detectors at an expanded uncertainty of 0.1%, by direct comparison with a cryogenic primary standard. To facilitate synchronous power measurements, commercial all-fiber beam-splitters direct laser diode light simultaneously to the device under test and the primary standard. We investigate the use of single-mode, polarisation maintaining, and photonic crystal fibers to access the cryogenic standard, and report a reduction in the temperature dependent effective refractive index of these fibers of 0.1%, 0.15% and 0.3% respectively in going from room temperature to 5 K. We also evaluate the polarisation dependent loss of the beam-splitters, the stability of the beam-splitter ratio between the cryogenic detector and the device under test and the temporal and modal stability of the Fabry-Pérot laser diode sources. It is shown that the stability of the optical fiber beam-splitters limits the overall performance of the measurement system to an expanded uncertainty of 0.1%.

Erratum: Measurement of Preheat Due to Nonlocal Electron Transport in Warm Dense Matter [Phys. Rev. Lett. 120, 025002 (2018)].

This corrects the article DOI: 10.1103/PhysRevLett.120.025002.

Author Correction: Laser-wakefield accelerators for high-resolution X-ray imaging of complex microstructures.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Characterization of suprathermal electrons inside a laser accelerated plasma via highly-resolved K⍺-emission.

Suprathermal electrons are routinely generated in high-intensity laser produced plasmas via instabilities driven by non-linear laser-plasma interaction. Their accurate characterization is crucial for the performance of inertial confinement fusion as well as for performing experiments in laboratory astrophysics and in general high-energy-density physics. Here, we present studies of non-thermal atomic states excited by suprathermal electrons in kJ-ns-laser produced plasmas. Highly spatially and spectrally resolved X-ray emission from the laser-deflected part of the warm dense Cu foil visualized the hot electrons. A multi-scale two-dimensional hydrodynamic simulation including non-linear laser-plasma interactions and hot electron propagation has provided an input for ab initio non-thermal atomic simulations. The analysis revealed a significant delay between the maximum of laser pulse and presence of suprathermal electrons. Agreement between spectroscopic signatures and simulations demonstrates that combination of advanced high-resolution X-ray spectroscopy and non-thermal atomic physics offers a promising method to characterize suprathermal electrons inside the solid density matter.

Laser-wakefield accelerators for high-resolution X-ray imaging of complex microstructures.

Laser-wakefield accelerators (LWFAs) are high acceleration-gradient plasma-based particle accelerators capable of producing ultra-relativistic electron beams. Within the strong focusing fields of the wakefield, accelerated electrons undergo betatron oscillations, emitting a bright pulse of X-rays with a micrometer-scale source size that may be used for imaging applications. Non-destructive X-ray phase contrast imaging and tomography of heterogeneous materials can provide insight into their processing, structure, and performance. To demonstrate the imaging capability of X-rays from an LWFA we have examined an irregular eutectic in the aluminum-silicon (Al-Si) system. The lamellar spacing of the Al-Si eutectic microstructure is on the order of a few micrometers, thus requiring high spatial resolution. We present comparisons between the sharpness and spatial resolution in phase contrast images of this eutectic alloy obtained via X-ray phase contrast imaging at the Swiss Light Source (SLS) synchrotron and X-ray projection microscopy via an LWFA source. An upper bound on the resolving power of 2.7 ± 0.3 µm of the LWFA source in this experiment was measured. These results indicate that betatron X-rays from laser wakefield acceleration can provide an alternative to conventional synchrotron sources for high resolution imaging of eutectics and, more broadly, complex microstructures.

Single-Shot Multi-keV X-Ray Absorption Spectroscopy Using an Ultrashort Laser-Wakefield Accelerator Source.

Single-shot absorption measurements have been performed using the multi-keV x rays generated by a laser-wakefield accelerator. A 200 TW laser was used to drive a laser-wakefield accelerator in a mode which produced broadband electron beams with a maximum energy above 1 GeV and a broad divergence of ≈15 mrad FWHM. Betatron oscillations of these electrons generated 1.2±0.2×10^{6} photons/eV in the 5 keV region, with a signal-to-noise ratio of approximately 300∶1. This was sufficient to allow high-resolution x-ray absorption near-edge structure measurements at the K edge of a titanium sample in a single shot. We demonstrate that this source is capable of single-shot, simultaneous measurements of both the electron and ion distributions in matter heated to eV temperatures by comparison with density functional theory simulations. The unique combination of a high-flux, large bandwidth, few femtosecond duration x-ray pulse synchronized to a high-power laser will enable key advances in the study of ultrafast energetic processes such as electron-ion equilibration.

Association of microRNA-7 and its binding partner CDR1-AS with the prognosis and prediction of 1st-line tamoxifen therapy in breast cancer.

The large number of non-coding RNAs (ncRNAs) and their breadth of functionalities has fuelled many studies on their roles in cancer. We previously linked four microRNAs to breast cancer prognosis. One of these microRNAs, hsa-miR-7, was found to be regulated by another type of ncRNA, the circular non-coding RNA (circRNA) CDR1-AS, which contains multiple hsa-miR-7 binding sites. Based on this finding, we studied the potential clinical value of this circRNA on breast cancer prognosis in a cohort based on a cohort that was previously analysed for hsa-miR-7 and in an adjuvant hormone-naïve cohort for 1st-line tamoxifen treatment outcomes, in which we also analysed hsa-miR-7. A negative correlation was observed between hsa-miR-7 and CDR1-AS in both cohorts. Despite associations with various clinical metrics (e.g., tumour grade, tumour size, and relapse location), CDR1-AS was neither prognostic nor predictive of relevant outcomes in our cohorts. However, we did observe stromal CDR1-AS expression, suggesting a possible cell-type specific interaction. Next to the known association of hsa-miR-7 expression with poor prognosis in primary breast cancer, we found that high hsa-miR-7 expression was predictive of an adverse response to tamoxifen therapy and poor progression-free and post-relapse overall survival in patients with recurrent disease.

Measurement of Preheat Due to Nonlocal Electron Transport in Warm Dense Matter.

This Letter presents a novel approach to study electron transport in warm dense matter. It also includes the first x-ray Thomson scattering (XRTS) measurement from low-density CH foams compressed by a strong laser-driven shock at the OMEGA laser facility. The XRTS measurement is combined with velocity interferometry (VISAR) and optical pyrometry (SOP) providing a robust measurement of thermodynamic conditions in the shock. Evidence of significant preheat contributing to elevated temperatures reaching 17.5-35 eV in shocked CH foam is measured by XRTS. These measurements are complemented by abnormally high shock velocities observed by VISAR and early emission seen by SOP. These results are compared to radiation hydrodynamics simulations that include first-principles treatment of nonlocal electron transport in warm dense matter with excellent agreement. Additional simulations confirm that the x-ray contribution to this preheat is negligible.

Breast cancer genomics and immuno-oncological markers to guide immune therapies.

There is an increasing awareness of the importance of tumor - immune cell interactions to the evolution and therapy responses of breast cancer (BC). Not surprisingly, numerous studies are currently assessing the clinical value of immune modulation for BC patients. However, till now durable clinical responses are only rarely observed. It is important to realize that BC is a heterogeneous disease comprising several histological and molecular subtypes, which cannot be expected to be equally immunogenic and therefore not equally sensitive to single immune therapies. Here we review the characteristics of infiltrating leukocytes in healthy and malignant breast tissue, the prognostic and predictive values of immune cell subsets across different BC subtypes and the various existing immune evasive mechanisms. Furthermore, we describe the presence of certain groups of antigens as putative targets for treatment, evaluate the outcomes of current clinical immunotherapy trials, and finally, we propose a strategy to better implement immuno-oncological markers to guide future immune therapies in BC.

Use of prophylactic antibiotics in women with previable prelabor rupture of membranes.

OBJECTIVE: To measure the effect of prophylactic antibiotics given at time of previable prelabor rupture of membranes (PROM) on latency. METHODS: Single center, retrospective cohort study of singleton pregnancies with previable (<23 0/7weeks) PROM. Antibiotics were given at clinician discretion. The primary outcome was latency, defined as duration of time between previable PROM and delivery. Secondary outcomes included delivery at ≥ 23weeks, infant survival, and maternal morbidity. Bivariate analysis compared maternal covariates between women who did and did not receive antibiotics. Antibiotic effect on latency was modeled using a Cox proportional hazards ratio. RESULTS: 213 women with previable PROM were identified; 77 (36%) remained pregnant and thus were included in this analysis. Forty (52%) of 77 received antibiotics. Compared to women who did not receive antibiotics, those who did had PROM at a later median (IQR) estimated gestational age, EGA, (22.2weeks [20.7, 22.5] vs. 19.3weeks [18, 20.7], p < 0.01). Median (IQR) latency was not different between women who did and did not receive antibiotics (2.2 [0.7, 3.9] vs. 1.5 [0.5, 4.6] weeks, p = 0.49). More infants survived to discharge among women who received antibiotics compared to those who did not [17(43%) vs. 3(8%), p < 0.01]. When adjusted for EGA at PROM, antibiotics were associated with longer latency (HR 0.57 [95% CI 0.33, 0.97], p = 0.01). Antibiotic use was not associated with differences in maternal morbidity. CONCLUSION: After adjusting for EGA at PROM, antibiotic receipt was associated with longer latency. Larger prospective studies are needed to define the utility of prophylactic antibiotics in previable PROM.

Highly efficient angularly resolving x-ray spectrometer optimized for absorption measurements with collimated sources.

Highly collimated betatron radiation from a laser wakefield accelerator is a promising tool for spectroscopic measurements. Therefore, there is a requirement to create spectrometers suited to the unique properties of such a source. We demonstrate a spectrometer which achieves an energy resolution of <5 eV at 9 keV (E∕ΔE>1800) and is angularly resolving the x-ray emission allowing the reference and spectrum to be recorded at the same time. The single photon analysis is used to significantly reduce the background noise. Theoretical performance of various configurations of the spectrometer is calculated by a ray-tracing algorithm. The properties and performance of the spectrometer including the angular and spectral resolution are demonstrated experimentally on absorption above the K-edge of a Cu foil backlit by a laser-produced betatron radiation x-ray beam.

mRNA expression profiles of colorectal liver metastases as a novel biomarker for early recurrence after partial hepatectomy.

BACKGROUND: Identification of specific risk groups for recurrence after surgery for isolated colorectal liver metastases (CRLM) remains challenging due to the heterogeneity of the disease. Classical clinicopathologic parameters have limited prognostic value. The aim of this study was to identify a gene expression signature measured in CRLM discriminating early from late recurrence after partial hepatectomy. METHODS: CRLM from two patient groups were collected: I) with recurrent disease ≤12 months after surgery (N = 33), and II) without recurrences and disease free for ≥36 months (N = 30). The patients were clinically homogeneous; all had a low clinical risk score (0-2) and did not receive (neo-) adjuvant chemotherapy. Total RNA was hybridised to Illumina arrays, and processed for analysis. A leave-one-out cross validation (LOOCV) analysis was performed to identify a prognostic gene expression signature. RESULTS: LOOCV yielded an 11-gene profile with prognostic value in relation to recurrent disease ≤12 months after partial hepatectomy. This signature had a sensitivity of 81.8%, with a specificity of 66.7% for predicting recurrences (≤12 months) versus no recurrences for at least 36 months after surgery (X2 P < 0.0001). CONCLUSION: The current study yielded an 11-gene signature at mRNA level in CRLM discriminating early from late or no relapse after partial hepatectomy.

Potential causative agents of acute gastroenteritis in households with preschool children: prevalence, risk factors, clinical relevance and household transmission.

Acute gastroenteritis (AGE) morbidity remains high amongst preschool children, posing a significant societal burden. Empirical data on AGE-causing agents is needed to gauge their clinical relevance and identify agent-specific targets for control. We assessed the prevalence, risk factors and association with symptoms for enteropathogens in households with preschool children. A monthly-repeated cross-sectional survey of enteropathogens in households with preschool children was performed. A parent-child pair per household (n = 907 households) provided faecal samples and reported their symptoms and potential risk exposures. Samples were tested by multiplex reverse transcription polymerase chain reaction (RT-PCR) for 19 enteropathogens. Associations were assessed using logistic regression. 28.3 % of children (n = 981) and 15.6 % of parents (n = 971) carried pathogenic bacteria and/or Escherichia coli-associated pathogenicity genes, and 6.5 % and 3.3 % carried viruses, respectively. Giardia lamblia (4.6 % of children, 2.5 % of parents) and Dientamoeba fragilis (36 %, 39 %, respectively) were the main parasites, and were associated with pet exposure. Living in rural areas was associated with carriage of pathogenic E. coli, norovirus I and D. fragilis. Pathogenic E. coli was associated with summertime and livestock exposure. Attending day-care centres increased the risk of carrying norovirus, sapovirus and G. lamblia. Viruses occurred mainly in winter and were associated with AGE symptoms. Child-parent associations were found for bacterial pathogenicity genes, viruses, G. lamblia and D. fragilis. Enteropathogens spread widely in households with preschool children, particularly viruses, which more often cause symptoms. While bacteria predominate during summer and in those exposed to livestock, viruses predominate in wintertime and, like G. lamblia, are widespread amongst day-care centre attendees.