We extend the twist-bend nematic (N(TB)) model to describe the electro-optics of this novel phase. We predict an electroclinic effect (ECE) subject to a dc electric field E applied perpendicular to ...the helix axis or wave vector q, with rotation of the N(TB) optic axis around E. This linear effect, with its flexoelectric origin, is a close analog to the electro-optic effects observed for chiral liquid crystals. However, in nematics composed of achiral molecules having a bent shape, it is the electro-optic signature of the N(TB) phase. We test our model experimentally in the low-temperature nematic phase of the odd liquid crystal dimer, CB7CB, with its molecules having, on average, a bent shape. The ECE measurements confirm the previously proposed twist-bend nematic structure of this phase, with its broken chiral symmetry, extremely short (<10 nm) doubly degenerate pitch and ultrafast, submicrosecond response times.
At least 5 per cent of the massive stars are moving supersonically through the interstellar medium (ISM) and are expected to produce a stellar wind bow shock. We explore how the mass-loss and space ...velocity of massive runaway stars affect the morphology of their bow shocks. We run two-dimensional axisymmetric hydrodynamical simulations following the evolution of the circumstellar medium of these stars in the Galactic plane from the main sequence to the red supergiant phase. We find that thermal conduction is an important process governing the shape, size and structure of the bow shocks around hot stars, and that they have an optical luminosity mainly produced by forbidden lines, e.g. O III. The Hα emission of the bow shocks around hot stars originates from near their contact discontinuity. The Hα emission of bow shocks around cool stars originates from their forward shock, and is too faint to be observed for the bow shocks that we simulate. The emission of optically thin radiation mainly comes from the shocked ISM material. All bow shock models are brighter in the infrared, i.e. the infrared is the most appropriate waveband to search for bow shocks. Our study suggests that the infrared emission comes from near the contact discontinuity for bow shocks of hot stars and from the inner region of shocked wind for bow shocks around cool stars. We predict that, in the Galactic plane, the brightest, i.e. the most easily detectable bow shocks are produced by high-mass stars moving with small space velocities.
Lung disease accounts for every sixth death globally. Profiling the molecular state of all lung cell types in health and disease is currently revolutionizing the identification of disease mechanisms ...and will aid the design of novel diagnostic and personalized therapeutic regimens. Recent progress in high-throughput techniques for single-cell genomic and transcriptomic analyses has opened up new possibilities to study individual cells within a tissue, classify these into cell types, and characterize variations in their molecular profiles as a function of genetics, environment, cell-cell interactions, developmental processes, aging, or disease. Integration of these cell state definitions with spatial information allows the in-depth molecular description of cellular neighborhoods and tissue microenvironments, including the tissue resident structural and immune cells, the tissue matrix, and the microbiome. The Human Cell Atlas consortium aims to characterize all cells in the healthy human body and has prioritized lung tissue as one of the flagship projects. Here, we present the rationale, the approach, and the expected impact of a Human Lung Cell Atlas.
Quantitative real‐time PCR (qPCR) has become one of the most used techniques to measure gene expression. However, normalization of gene expression data against reference genes is essential, although ...these are usually used without any kind of validation. The expression of seven genes was compared in organs of Rhodnius prolixus under diverse conditions, using published software to test gene expression stability. Rp18S and elongation factor 1 (RpEF ‐1) were the most reliable genes for normalization in qPCR when gene expression in different organs was compared. Moreover, both genes were found to be the best references when transcript levels were compared in the posterior midgut of insects infected with Trypanosoma cruzi. Rp18S was also the best reference gene in the fat bodies of unfed and fed insects. By contrast, RpEF‐1 was found to be the best reference gene for comparison between posterior midguts, and RpMIP or RpActin should be used to compare gene expression in the ovaries. Although Rp18S is indicated here as the best reference in most cases, reports from the literature show that it is difficult to find an optimum reference gene. Nevertheless, validation of candidate genes to be taken as references is important when new experimental conditions are tested to avoid incorrect data interpretation.
Fms-like tyrosine kinase 3 internal tandem duplication (FLT3-ITD)–positive acute myeloid leukaemia (AML) relapsing after allogeneic stem cell transplantation (allo-SCT) has a dismal prognosis with ...limited therapeutic options. FLT3-ITD kinase inhibition is a reasonable but palliative experimental treatment alternative in this situation. Information on long-term outcome is not available.
We performed a long-term follow-up analysis of a previously reported cohort of 29 FLT3-ITD–positive AML patients, which were treated in relapse after allo-SCT with sorafenib monotherapy.
With a median follow-up of 7.5 years, 6 of 29 patients (21%) are still alive. Excluding one patient who received a second allo-SCT, five patients (17%) achieved sustained complete remissions with sorafenib. Four of these patients are in treatment-free remission for a median of 4.4 years.
Sorafenib may enable cure of a proportion of very poor risk FLT3-ITD–positive AML relapsing after allo-SCT.
•Sorafenib induces long-term survival in Fms-like tyrosine kinase 3 internal tandem duplication (FLT3-ITD)+ acute myeloid leukaemia (AML) relapsing after allogeneic stem cell transplantation (allo-SCT).•Sorafenib cures a minority of FLT3-ITD+ AML relapsing after allo-SCT.•Achievement of molecular negativity is strongly associated with cure.
Preliminary evidence suggests that the multikinase inhibitor sorafenib has clinical activity in FLT3-ITD-positive (FLT3-ITD) acute myeloid leukemia (AML). However, the quality and sustainability of ...achievable remissions and clinical variables that influence the outcome of sorafenib monotherapy are largely undefined. To address these questions, we evaluated sorafenib monotherapy in 65 FLT3-ITD AML patients treated at 23 centers. All but two patients had relapsed or were chemotherapy-refractory after a median of three prior chemotherapy cycles. Twenty-nine patients (45%) had undergone prior allogeneic stem cell transplantation (allo-SCT). The documented best responses were: hematological remission in 24 patients (37%), bone marrow remission in 5 patients (8%), complete remission (with and without normalization of peripheral blood counts) in 15 patients (23%) and molecular remission with undetectable FLT3-ITD mRNA in 10 patients (15%), respectively. Seventeen of the patients without prior allo-SCT (47%) developed sorafenib resistance after a median treatment duration of 136 days (range, 56-270 days). In contrast, allo-SCT patients developed sorafenib resistance less frequently (38%) and significantly later (197 days, range 38-225 days; P=0.03). Sustained remissions were seen exclusively in the allo-SCT cohort. Thus, sorafenib monotherapy has significant activity in FLT3-ITD AML and may synergize with allogeneic immune effects to induce durable remissions.
The Galaxy and Mass Assembly (GAMA) survey has been operating since 2008 February on the 3.9-m Anglo-Australian Telescope using the AAOmega fibre-fed spectrograph facility to acquire spectra with a ...resolution of R≈ 1300 for 120 862 Sloan Digital Sky Survey selected galaxies. The target catalogue constitutes three contiguous equatorial regions centred at 9h (G09), 12h (G12) and 14.5h (G15) each of 12 × 4 deg2 to limiting fluxes of r
pet < 19.4, r
pet < 19.8 and r
pet < 19.4 mag, respectively (and additional limits at other wavelengths). Spectra and reliable redshifts have been acquired for over 98 per cent of the galaxies within these limits. Here we present the survey footprint, progression, data reduction, redshifting, re-redshifting, an assessment of data quality after 3 yr, additional image analysis products (including ugrizYJHK photometry, Sérsic profiles and photometric redshifts), observing mask and construction of our core survey catalogue (GamaCore). From this we create three science-ready catalogues: GamaCoreDR1 for public release, which includes data acquired during year 1 of operations within specified magnitude limits (2008 February to April); GamaCoreMainSurvey containing all data above our survey limits for use by the GAMA Team and collaborators; and GamaCoreAtlasSV containing year 1, 2 and 3 data matched to Herschel-ATLAS science demonstration data. These catalogues along with the associated spectra, stamps and profiles can be accessed via the GAMA website: http://www.gama-survey.org/
Summary
Background
The increasing prevalence of food allergy (FA) is a growing clinical and public health problem. The contribution of genetic factors to FA remains largely unknown.
Objective
This ...study examined the pattern of familial aggregation and the degree to which genetic factors contribute to FA and sensitization to food allergens.
Methods
This study included 581 nuclear families (2,004 subjects) as part of an ongoing FA study in Chicago, IL, USA. FA was defined by a set of criteria including timing, clinical symptoms obtained via standardized questionnaire interview and corroborative specific IgE cut‐offs for 95% positive predictive value (PPV) for food allergens measured by Phadia ImmunoCAP. Familial aggregation of FA as well as sensitization to food allergens was examined using generalized estimating equation (GEE) models, with adjustment for important covariates including age, gender, ethnicity and birth order. Heritability was estimated for food‐specific IgE measurements.
Results
FA in the index child was a significant and independent predictor of FA in other siblings (OR=2.6, 95% CI: 1.2–5.6, P=0.01). There were significant and positive associations among family members (father–offspring, mother–offspring, index–other siblings) for total IgE and specific IgE to all the nine major food allergens tested in this sample (sesame, peanut, wheat, milk, egg white, soy, walnut, shrimp and cod fish). The estimated heritability of food‐specific IgE ranged from 0.15 to 0.35 and was statistically significant for all the nine tested food allergens.
Conclusion
This family‐based study demonstrates strong familial aggregation of FA and sensitization to food allergens, especially, among siblings. The heritability estimates indicate that food‐specific IgE is likely influenced by both genetic and environmental factors. Together, this study provides strong evidence that both host genetic susceptibility and environmental factors determine the complex trait of IgE‐mediated FA.
Abstract
Background
Adequate MRI-based staging of early rectal cancers is essential for decision-making in an era of organ-conserving treatment approaches. The aim of this population-based study was ...to determine the accuracy of routine daily MRI staging of early rectal cancer, whether or not combined with endorectal ultrasonography (ERUS).
Methods
Patients with cT1–2 rectal cancer who underwent local excision or total mesorectal excision (TME) without downsizing (chemo)radiotherapy between 1 January 2011 and 31 December 2018 were selected from the Dutch ColoRectal Audit. The accuracy of imaging was expressed as sensitivity, specificity, and positive predictive value (PPV) and negative predictive value.
Results
Of 7382 registered patients with cT1–2 rectal cancer, 5539 were included (5288 MRI alone, 251 MRI and ERUS; 1059 cT1 and 4480 cT2). Among patients with pT1 tumours, 54·7 per cent (792 of 1448) were overstaged by MRI alone, and 31·0 per cent (36 of 116) by MRI and ERUS. Understaging of pT2 disease occurred in 8·2 per cent (197 of 2388) and 27·9 per cent (31 of 111) respectively. MRI alone overstaged pN0 in 17·3 per cent (570 of 3303) and the PPV for assignment of cN0 category was 76·3 per cent (2733 of 3583). Of 834 patients with pT1 N0 disease, potentially suitable for local excision, tumours in 253 patients (30·3 per cent) were staged correctly as cT1 N0, whereas 484 (58·0 per cent) and 97 (11·6 per cent) were overstaged as cT2 N0 and cT1–2 N1 respectively.
Conclusion
This Dutch population-based analysis of patients who underwent local excision or TME surgery for cT1–2 rectal cancer based on preoperative MRI staging revealed substantial overstaging, indicating the weaknesses of MRI and missed opportunities for organ preservation strategies.
Graphical Abstract
This population-based study determined the accuracy of routine daily MRI staging of early rectal cancer, whether or not combined with endorectal ultrasonography. The results showed that preoperative MRI led to substantial overstaging in patients who underwent local excision or total mesorectal incision surgery for cT1–2 rectal cancer, indicating the weaknesses of MRI and missed opportunities for organ preservation strategies.
Graphical Abstract
Imaging weakness
Context. Radio-loud active galactic nuclei with powerful relativistic jets are thought to be associated with rapidly spinning black holes (BHs). BH spin-up may result from a number of processes, ...including accretion of matter onto the BH itself, and catastrophic events such as BH-BH mergers. Aims. We study the intriguing properties of the powerful (Lbol ~ 1047 erg s-1) radio-loud quasar 3C 186. This object shows peculiar features both in the images and in the spectra. Methods. We utilize near-IR Hubble Space Telescope (HST) images to study the properties of the host galaxy, and HST UV and Sloan Digital Sky Survey optical spectra to study the kinematics of the source. Chandra X-ray data are also used to better constrain the physical interpretation. Results. HST imaging shows that the active nucleus is offset by 1.3 ± 0.1 arcsec (i.e. ~11 kpc) with respect to the center of the host galaxy. Spectroscopic data show that the broad emission lines are offset by −2140 ± 390 km s-1 with respect to the narrow lines. Velocity shifts are often seen in QSO spectra, in particular in high-ionization broad emission lines. The host galaxy of the quasar displays a distorted morphology with possible tidal features that are typical of the late stages of a galaxy merger. Conclusions. A number of scenarios can be envisaged to account for the observed features. While the presence of a peculiar outflow cannot be completely ruled out, all of the observed features are consistent with those expected if the QSO is associated with a gravitational wave (GW) recoiling BH. Future detailed studies of this object will allow us to confirm this type of scenario and will enable a better understanding of both the physics of BH-BH mergers and the phenomena associated with the emission of GW from astrophysical sources.
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