31064 The Detroit Keloid Scale: A validated tool for rating keloids

Background: No keloid-specific outcome measures exist. Objective: To develop and validate the Detroit Keloid Scale (DKS), a standardized method of keloid assessment to better compare treatments. Methods: Forty-seven physicians were polled to develop the DKS. The scale was validated in 52 patients with keloids against the Vancouver Scar Scale (VSS), Patient and Observer Scar Assessment Scale (POSAS), and Dermatology Life Quality Index (DLQI) by 3 physicians. Results: The interrater reliability was “substantial” for observer component of the DKS and only “moderate” for the VSS and observer POSAS (ICC were 0.80, 0.60, and 0.47, respectively). Pearson’s correlation indicated a “moderate” association between the observer component of DKS with observer component of POSAS (ρ = 0.56, P \u3c.001) and a “substantial” relationship between the observer component of DKS and VSS (ρ = 0.63, P \u3c.001). Pearson’s correlation indicated a “moderate” association between the patient portion of DKS and patient portion of POSAS and the patient portion of the DKS and DLQI (0.61 and 0.60, respectively, P \u3c.05). The DKS total score consistently showed “substantial” relationship with POSAS total score (ρ = 0.65, P \u3c.001). Limitations: Single center study, no intrarater reliability analysis. Conclusions: The substantial interrater reliability of the DKS will allow for improved standardization in future keloid research

Reversal by RARα agonist Am580 of c-Myc-induced imbalance in RARα/RARγ expression during MMTV-Myc tumorigenesis

Introduction Retinoic acid signaling plays key roles in embryonic development and in maintaining the differentiated status of adult tissues. Recently, the nuclear retinoic acid receptor (RAR) isotypes α, β and γ were found to play specific functions in the expansion and differentiation of the stem compartments of various tissues. For instance, RARγ appears to be involved in stem cell compartment expansion, while RARα and RARβ are implicated in the subsequent cell differentiation. We found that over-expressing c-Myc in normal mouse mammary epithelium and in a c-Myc-driven transgenic model of mammary cancer, disrupts the balance between RARγ and RARα/β in favor of RARγ. Methods The effects of c-Myc on RAR isotype expression were evaluated in normal mouse mammary epithelium, mammary tumor cells obtained from the MMTV-Myc transgenic mouse model as well as human normal immortalized breast epithelial and breast cancer cell lines. The in vivo effect of the RARα-selective agonist 4-[(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)carboxamido]benzoic acid (Am580) was examined in the MMTV-Myc mouse model of mammary tumorigenesis. Results Modulation of the RARα/β to RARγ expression in mammary glands of normal mice, oncomice, and human mammary cell lines through the alteration of RAR-target gene expression affected cell proliferation, survival and tumor growth. Treatment of MMTV-Myc mice with the RARα-selective agonist Am580 led to significant inhibition of mammary tumor growth (~90%, P\u3c0.001), lung metastasis (P\u3c0.01) and extended tumor latency in 63% of mice. Immunocytochemical analysis showed that in these mice, RARα responsive genes such as Cyp26A1, E-cadherin, cellular retinol-binding protein 1 (CRBP1) and p27, were up-regulated. In contrast, the mammary gland tumors of mice that responded poorly to Am580 treatment (37%) expressed significantly higher levels of RARγ. In vitro experiments indicated that the rise in RARγ was functionally linked to promotion of tumor growth and inhibition of differentiation. Thus, activation of the RARα pathway is linked to tumor growth inhibition, differentiation and cell death. Conclusions The functional consequence of the interplay between c-Myc oncogene expression and the RARγ to RARα/β balance suggests that prevalence of RARγ over-RARα/β expression levels in breast cancer accompanied by c-Myc amplification or over-expression in breast cancer should be predictive of response to treatment with RARα-isotype-specific agonists and warrant monitoring during clinical trials. See related editorial by Garattini et al http://breast-cancer-research.com/content/14/5/11

Computing and visualising intra-voxel orientation-specific relaxation-diffusion features in the human brain

Diffusion MRI techniques are used widely to study the characteristics of the human brain connectome in vivo. However, to resolve and characterise white matter (WM) fibres in heterogeneous MRI voxels remains a challenging problem typically approached with signal models that rely on prior information and constraints. We have recently introduced a 5D relaxation–diffusion correlation framework wherein multidimensional diffusion encoding strategies are used to acquire data at multiple echo‐times to increase the amount of information encoded into the signal and ease the constraints needed for signal inversion. Nonparametric Monte Carlo inversion of the resulting datasets yields 5D relaxation–diffusion distributions where contributions from different sub‐voxel tissue environments are separated with minimal assumptions on their microscopic properties. Here, we build on the 5D correlation approach to derive fibre‐specific metrics that can be mapped throughout the imaged brain volume. Distribution components ascribed to fibrous tissues are resolved, and subsequently mapped to a dense mesh of overlapping orientation bins to define a smooth orientation distribution function (ODF). Moreover, relaxation and diffusion measures are correlated to each independent ODF coordinate, thereby allowing the estimation of orientation‐specific relaxation rates and diffusivities. The proposed method is tested on a healthy volunteer, where the estimated ODFs were observed to capture major WM tracts, resolve fibre crossings, and, more importantly, inform on the relaxation and diffusion features along with distinct fibre bundles. If combined with fibre‐tracking algorithms, the methodology presented in this work has potential for increasing the depth of characterisation of microstructural properties along individual WM pathways

Optical application and measurement of torque on microparticles of isotropic nonabsorbing material

We show how it is possible to controllably rotate or align microscopic particles of isotropic nonabsorbing material in a TEM00 Gaussian beam trap, with simultaneous measurement of the applied torque using purely optical means. This is a simple and general method of rotation, requiring only that the particle is elongated along one direction. Thus, this method can be used to rotate or align a wide range of naturally occurring particles. The ability to measure the applied torque enables the use of this method as a quantitative tool--the rotational equivalent of optical tweezers based force measurement. As well as being of particular value for the rotation of biological specimens, this method is also suitable for the development of optically-driven micromachines.Comment: 8 pages, 6 figure

Microsatellites reveal that genetic mixing commonly occurs between invasive fall armyworm populations in Africa

Abstract: Understanding the population structure and movements of the invasive fall armyworm (FAW, Spodoptera frugiperda) is important as it can help mitigate crop damage, and highlight areas at risk of outbreaks or evolving insecticide resistance. Determining population structure in invasive FAW has been a challenge due to genetic mutations affecting the markers traditionally used for strain and haplotype identification; mitochondrial cytochrome oxidase I (COIB) and the Z-chromosome-linked Triosephosphate isomerase (Tpi). Here, we compare the results from COIB and Tpi markers with highly variable repeat regions (microsatellites) to improve our understanding of FAW population structure in Africa. There was very limited genetic diversity using the COIB marker, whereas using the TpiI4 marker there was greater diversity that showed very little evidence of genetic structuring between FAW populations across Africa. There was greater genetic diversity identified using microsatellites, and this revealed a largely panmictic population of FAW alongside some evidence of genetic structuring between countries. It is hypothesised here that FAW are using long-distance flight and prevailing winds to frequently move throughout Africa leading to population mixing. These approaches combined provide important evidence that genetic mixing between invasive FAW populations may be more common than previously reported

The Two-dimensional XMM-Newton Group Survey: z<0.012 groups

We present the results of the 2-dimensional XMM-Newton Group Survey (2dXGS), an archival study of nearby galaxy groups. In this paper we consider eleven nearby systems (z<0.012) in Mulchaey et al. (2003), which span a broad range in X-ray luminosity from 10^40 to 10^43 ergs/s. We measure the iron abundance and temperature distribution in these systems and derive pressure and entropy maps. We find statistically significant evidence for structure in the entropy and pressure of the gas component of seven groups on the 10-20% level. The XMM-Newton data for the three groups with best statistics also suggest patchy metalicity distributions within the central 20--50 kpc of the brightest group galaxy, probed with 2-10 kpc resolution. This provides insights into the processes associated with thermalization of the stellar mass loss. Analysis of the global properties of the groups reveals a subclass of X-ray faint groups, which are characterized by both higher entropy and lower pressure. We suggest that the merger history of the central elliptical is responsible for both the source and the observed thermodynamical properties of the hot gas of the X-ray faint groups.Comment: 18 pages, ApJ, 646, 143, 200

Making Space for Failure in Geographic Research

The idea that field research is an inherently “messy” process has become widely accepted by geographers in recent years. There has thus far been little acknowledgment, however, of the role that failure plays in doing human geography. In this article we push back against this, arguing that failure should be recognized as a central component of what it means to do qualitative geographical field research. This article seeks to use failure proactively and provocatively as a powerful resource to improve research practice and outcomes, reconsidering and giving voice to it as everyday, productive, and necessary to our continual development as researchers and academics. This article argues that there is much value to be found in failure if it is critically examined and shared, and—crucially—if there is a supportive space in which to exchange our experiences of failing in the field

Ack1 Mediated AKT/PKB Tyrosine 176 Phosphorylation Regulates Its Activation

The AKT/PKB kinase is a key signaling component of one of the most frequently activated pathways in cancer and is a major target of cancer drug development. Most studies have focused on its activation by Receptor Tyrosine Kinase (RTK) mediated Phosphatidylinositol-3-OH kinase (PI3K) activation or loss of Phosphatase and Tensin homolog (PTEN). We have uncovered that growth factors binding to RTKs lead to activation of a non-receptor tyrosine kinase, Ack1 (also known as ACK or TNK2), which directly phosphorylates AKT at an evolutionarily conserved tyrosine 176 in the kinase domain. Tyr176-phosphorylated AKT localizes to the plasma membrane and promotes Thr308/Ser473-phosphorylation leading to AKT activation. Mice expressing activated Ack1 specifically in the prostate exhibit AKT Tyr176-phosphorylation and develop murine prostatic intraepithelial neoplasia (mPINs). Further, expression levels of Tyr176-phosphorylated-AKT and Tyr284-phosphorylated-Ack1 were positively correlated with the severity of disease progression, and inversely correlated with the survival of breast cancer patients. Thus, RTK/Ack1/AKT pathway provides a novel target for drug discovery

Pointing control for the SPIDER balloon-borne telescope

We present the technology and control methods developed for the pointing system of the SPIDER experiment. SPIDER is a balloon-borne polarimeter designed to detect the imprint of primordial gravitational waves in the polarization of the Cosmic Microwave Background radiation. We describe the two main components of the telescope's azimuth drive: the reaction wheel and the motorized pivot. A 13 kHz PI control loop runs on a digital signal processor, with feedback from fibre optic rate gyroscopes. This system can control azimuthal speed with < 0.02 deg/s RMS error. To control elevation, SPIDER uses stepper-motor-driven linear actuators to rotate the cryostat, which houses the optical instruments, relative to the outer frame. With the velocity in each axis controlled in this way, higher-level control loops on the onboard flight computers can implement the pointing and scanning observation modes required for the experiment. We have accomplished the non-trivial task of scanning a 5000 lb payload sinusoidally in azimuth at a peak acceleration of 0.8 deg/s$^2$, and a peak speed of 6 deg/s. We can do so while reliably achieving sub-arcminute pointing control accuracy.Comment: 20 pages, 12 figures, Presented at SPIE Ground-based and Airborne Telescopes V, June 23, 2014. To be published in Proceedings of SPIE Volume 914