Linear endobronchial ultrasonography: a novelty turned necessity for mediastinal nodal assessment.

Linear endobronchial ultrasound was first described in 2003. Since then the technique has spread rapidly and has now become an established practice in many centres as the first-line mediastinal investigation for the diagnosis and staging of lung cancer. In combination with endoscopic ultrasound, the majority of the mediastinum can be assessed and this approach has been shown to have equivalent accuracy to surgical staging. This strategy is also cost-effective. New tissue processing techniques using liquid-based thin-layer cytology and cell blocks have increased diagnostic yield using immunohistochemical staining and molecular diagnostics. Several meta-analyses of case series and, more recently, randomised controlled trials have provided high-level evidence of efficacy leading to incorporation into national lung cancer staging guidelines. In addition, linear endobronchial ultrasound is increasingly used in the investigation of mediastinal lymphadenopathy for suspected sarcoidosis, tuberculosis and lymphoma. While undoubtedly endobronchial/endoscopic ultrasound has reduced the need for surgical staging in lung cancer, the latter still has an important role to play in certain scenarios. The challenge now facing clinicians is to learn to apply the appropriate test or sequence of tests in each patient while ensuring that operators are appropriately trained in order to ensure optimal outcomes

Spectrally tunable magnetic nanoparticles designed for distribution/recollection applications

The comprehensive goal of this research is the synthesis and characterization of nanomaterials that are spectrally tunable in terms of their electromagnetic signal, are robust, magnetic (allowing their piloted movement), and have the potential to be functionalized for the detection of CBRNE threats. Various chemical methods were utilized for synthesis of magnetic (iron) and luminescent rare earth (RE) components, and their mixtures. Effects of integrating an iron core into RE luminescent lattices (excited by UV, emit in the VIS) were investigated. The determination of the optimum balances between magnetic and luminescent components such that the magnetism was maximized while maintaining acceptable fluorescence integrity will be discussed. The emphasis of this work is focused on developing a distributed sensor suitable for use in the terrestrial environment. The robust properties of using a RE luminescent shell would allow the particles to be resistant to photobleaching. Additionally the chemical stability of the RE shell would allow operation in a variety of pH conditions. The magnetic core will ultimately allow the distributed particles to be recollected

Inspection time and general speed of processing

Recent research suggests that the relationship between inspection time (IT) and psychometric intelligence arises because IT is a measure of general speed of processing (Gs). However, hierarchical models of intelligence propose several distinct speed of processing factors; this study examines IT in relation to these multiple speed factors. Participants (N=102) completed tests of speed of processing yielding 18 measures. Factor analysis revealed a second order general speed factor (Gs) and four group factors: perceptual speed, visualisation speed, decision time and movement time. IT correlated with a visualisation speed factor (r=0.36) and with a perceptual speed factor (r=0.28). However, the correlation between IT and perceptual speed was near-zero when the correlation with visualisation speed was partialled out. These findings are consistent with the notion that IT is a measure of Gs but suggest that IT most directly measures speed of visualisation processes. These results are also congruent with research on the psychophysics of IT.Tess A. O’Connor and Nicholas R. Burnshttp://www.elsevier.com/wps/find/journaldescription.cws_home/603/description#descriptio

Detection of a pair density wave state in UTe2

Spin-triplet topological superconductors should exhibit many unprecedented electronic properties, including fractionalized electronic states relevant to quantum information processing. Although UTe2 may embody such bulk topological superconductivity1,2,3,4,5,6,7,8,9,10,11, its superconductive order parameter Δ(k) remains unknown12. Many diverse forms for Δ(k) are physically possible12 in such heavy fermion materials13. Moreover, intertwined14,15 density waves of spin (SDW), charge (CDW) and pair (PDW) may interpose, with the latter exhibiting spatially modulating14,15 superconductive order parameter Δ(r), electron-pair density16,17,18,19 and pairing energy gap17,20,21,22,23. Hence, the newly discovered CDW state24 in UTe2 motivates the prospect that a PDW state may exist in this material24,25. To search for it, we visualize the pairing energy gap with μeV-scale energy resolution using superconductive scanning tunnelling microscopy (STM) tips26,27,28,29,30,31. We detect three PDWs, each with peak-to-peak gap modulations of around 10 μeV and at incommensurate wavevectors Pi=1,2,3 that are indistinguishable from the wavevectors Qi=1,2,3 of the prevenient24 CDW. Concurrent visualization of the UTe2 superconductive PDWs and the non-superconductive CDWs shows that every Pi:Qi pair exhibits a relative spatial phase δϕ ≈ π. From these observations, and given UTe2 as a spin-triplet superconductor12, this PDW state should be a spin-triplet PDW24,25. Although such states do exist32 in superfluid 3He, for superconductors, they are unprecedented

Detection of a Pair Density Wave State in UTe2_2

Although UTe$_2$ is a very promising candidate material to embody bulk topological superconductivity, its superconductive order-parameter $\Delta(\mathbf{k})$ remains unknown. Many diverse forms for $\Delta(\mathbf{k})$ are physically possible because, in uranium-based heavy fermion materials, strongly hybridized flat bands of composite fermions generate highly complex interactions. Moreover, in such materials intertwined density waves of spin (SDW), charge (CDW) and pairs (PDW) may interpose, with the latter state exhibiting spatially modulating superconductive order-parameter $\Delta(\mathbf{r})$, electron pair density and pairing energy-gap. Hence, the newly discovered CDW state in UTe$_2$ motivates the exciting prospect that a PDW state may exist in this material. To search for a PDW in UTe$_2$, we visualize the pairing energy-gap with $\mu$$V$-scale energy-resolution made possible by superconductive STM tips at subkelvin temperatures. We detect three PDWs, each with peak-peak gap modulations circa 10 $\mu$$eV$ and at incommensurate wavevectors $\mathbf{P}_{i=1,2,3}$ that are indistinguishable from the wavevectors $\mathbf{Q}_{i=1,2,3}$ of the prevenient CDW. Concurrent visualization of the UTe$_2$ superconductive PDWs and the non-superconductive CDWs reveals that every $\mathbf{P}_i$ : $\mathbf{Q}_i$ pair is registered to each other spatially, but with a relative phase $\delta\phi \approx \pi$. From these observations, and given UTe$_2$ as a spin-triplet superconductor, the PDW state detected here should be a spin-triplet pair density wave. While such states do exist in superfluid $^{3}$He, for superconductors they are unprecedented.Comment: 37 pages, 13 figure

Supernova Limits on the Cosmic Equation of State

We use Type Ia supernovae studied by the High-Z Supernova Search Team to constrain the properties of an energy component which may have contributed to accelerating the cosmic expansion. We find that for a flat geometry the equation of state parameter for the unknown component, alpha_x=P_x/rho_x, must be less than -0.55 (95% confidence) for any value of Omega_m and is further limited to alpha_x<-0.60 (95%) if Omega_m is assumed to be greater than 0.1 . These values are inconsistent with the unknown component being topological defects such as domain walls, strings, or textures. The supernova data are consistent with a cosmological constant (alpha_x=-1) or a scalar field which has had, on average, an equation of state parameter similar to the cosmological constant value of -1 over the redshift range of z=1 to the present. Supernova and cosmic microwave background observations give complementary constraints on the densities of matter and the unknown component. If only matter and vacuum energy are considered, then the current combined data sets provide direct evidence for a spatially flat Universe with Omega_tot=Omega_m+Omega_Lambda = 0.94 +/- 0.26 (1-sigma).Comment: Accepted for publication in ApJ, 3 figure

Clinical translation of a click-labeled 18F-octreotate radioligand for imaging neuroendocrine tumors

© 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc. We conducted the first-in-human study of 18F-fluoroethyl triazole [Tyr3] octreotate (18F-FET-βAG-TOCA) in patients with neuroendocrine tumors (NETs) to evaluate biodistribution, dosimetry, and safety. Despite advances in clinical imaging, detection and quantification of NET activity remains a challenge, with no universally accepted imaging standard. Methods: Nine patients were enrolled. Eight patients had sporadic NETs, and 1 had multiple endocrine neoplasia type 1 syndrome. Patients received 137-163 MBq (mean ± SD, 155.7 ± 8 MBq) of 18F-FET-βAG-TOCA. Safety data were obtained during and 24 h after radioligand administration. Patients underwent detailed wholebody PET/CT multibed scanning over 4 h with sampling of venous bloods for radioactivity and radioactive metabolite quantification. Regions of interest were defined to derive individual and mean organ residence times; effective dose was calculated with OLINDA 1.1. Results: All patients tolerated 18F-FET-βAG-TOCA with no adverse events. Over 60% parent radioligand was present in plasma at 60 min. High tumor (primary and metastases)-to-background contrast images were observed. Physiologic distribution was seen in the pituitary, salivary glands, thyroid, and spleen, with low background distribution in the liver, an organ in which metastases commonly occur. The organs receiving highest absorbed dose were the gallbladder, spleen, stomach, liver, kidneys, and bladder. The calculated effective dose over all subjects (mean ± SD) was 0.029 ± 0.004 mSv/MBq. Conclusion: The favorable safety, imaging, and dosimetric profile makes 18F-FET-βAGTOCA a promising candidate radioligand for staging and management of NETs. Clinical studies in an expanded cohort are ongoing to clinically qualify this agent

Evaluation of SmartStax and SmartStax PRO Maize against Western Corn Rootworm and Northern Corn Rootworm: Efficacy and Resistance Management

Background: Cases of western corn rootworm (WCR) field-evolved resistance to Cry3Bb1 and other corn rootworm (CRW) control traits have been reported. Pyramid products expressing multiple CRW traits can delay resistance compared to single trait products. We used field studies to assess the pyramid CRW corn products, SmartStax (expressing Cry3Bb1 and Cry34Ab1/Cry35Ab1) and SmartStax PRO (expressing Cry3Bb1, Cry34Ab1/Cry35Ab1 and DvSnf7), at locations with high WCR densities and possible Cry3Bb1 resistance, and to assess the reduction in adult emergence attributable to DvSnf7 and other traits. Insect resistance models were used to assess durability of SmartStax and SmartStax PRO to WCR resistance. Results: SmartStax significantly reduced root injury compared to non-CRW-trait controls at all but one location with measurable WCR pressure, while SmartStax PRO significantly reduced root injury at all locations, despite evidence of Cry3Bb1 resistance at some locations. The advantage of SmartStax PRO over SmartStax in reducing root damage was positively correlated with root damage on non-CRW-trait controls. DvSnf7 was estimated to reduce WCR emergence by approximately 80–95%, which modeling indicated will improve durability of Cry3Bb1 and Cry34Ab1/Cry35Ab1 compared to SmartStax. Conclusion: The addition of DvSnf7 in SmartStax PRO can reduce root damage under high WCR densities and prolong Cry3Bb1 and Cry34Ab1/Cry35Ab1 durability

The Circadian Clock Protein BMAL1 Acts as a Metabolic Sensor In Macrophages to Control the Production of Pro IL-1β

The transcription factor BMAL1 is a clock protein that generates daily or circadian rhythms in physiological functions including the inflammatory response of macrophages. Intracellular metabolic pathways direct the macrophage inflammatory response, however whether the clock is impacting intracellular metabolism to direct this response is unclear. Specific metabolic reprogramming of macrophages controls the production of the potent pro-inflammatory cytokine IL-1β. We now describe that the macrophage molecular clock, through Bmal1, regulates the uptake of glucose, its flux through glycolysis and the Krebs cycle, including the production of the metabolite succinate to drive Il-1β production. We further demonstrate that BMAL1 modulates the level and localisation of the glycolytic enzyme PKM2, which in turn activates STAT3 to further drive Il-1β mRNA expression. Overall, this work demonstrates that BMAL1 is a key metabolic sensor in macrophages, and its deficiency leads to a metabolic shift of enhanced glycolysis and mitochondrial respiration, leading to a heightened pro-inflammatory state. These data provide insight into the control of macrophage driven inflammation by the molecular clock, and the potential for time-based therapeutics against a range of chronic inflammatory diseases