Hedgehog-GLI mediated control of renal formation and malformation

CAKUT is the leading cause of end-stage kidney disease in children and comprises a broad spectrum of phenotypic abnormalities in kidney and ureter development. Molecular mechanisms underlying the pathogenesis of CAKUT have been elucidated in genetic models, predominantly in the mouse, a paradigm for human renal development. Hedgehog (Hh) signaling is critical to normal embryogenesis, including kidney development. Hh signaling mediates the physiological development of the ureter and stroma and has adverse pathophysiological effects on the metanephric mesenchyme, ureteric, and nephrogenic lineages. Further, disruption of Hh signaling is causative of numerous human developmental disorders associated with renal malformation; Pallister-Hall Syndrome (PHS) is characterized by a diverse spectrum of malformations including CAKUT and caused by truncating variants in the middle-third of the Hh signaling effector GLI3. Here, we outline the roles of Hh signaling in regulating murine kidney development, and review human variants in Hh signaling genes in patients with renal malformation

Symmetry implies independence

Given a quantum system consisting of many parts, we show that symmetry of the system's state, i.e., invariance under swappings of the subsystems, implies that almost all of its parts are virtually identical and independent of each other. This result generalises de Finetti's classical representation theorem for infinitely exchangeable sequences of random variables as well as its quantum-mechanical analogue. It has applications in various areas of physics as well as information theory and cryptography. For example, in experimental physics, one typically collects data by running a certain experiment many times, assuming that the individual runs are mutually independent. Our result can be used to justify this assumption.Comment: LaTeX, contains 4 figure

Fortnightly Fluctuations in the O-C Diagram of CS 1246

Dominated by a single, large-amplitude pulsation mode, the rapidly-pulsating hot subdwarf B star CS 1246 is a prime candidate for a long-term O-C diagram study. We collected nearly 400 hours of photometry with the PROMPT telescopes over a time span of 14 months to begin looking for secular variations in the pulse timings. Interestingly, the O-C diagram is dominated by a strong sinusoidal pattern with a period of 14.1 days and an amplitude of 10.7 light-seconds. Underneath this sine wave is a secular trend implying a decrease in the 371.7-s pulsational period of Pdot = -1.9 x 10^-11, which we attribute to the evolution of the star through the H-R diagram. The sinusoidal variation could be produced by the presence of a low-mass companion, with m sin i ~ 0.12 Msun, orbiting the subdwarf B star at a distance of 20 Rsun. An analysis of the combined light curve reveals the presence of a low-amplitude first harmonic to the main pulsation mode.Comment: Accepted for publication in MNRAS. 11 pages, 8 figures, 5 table

P193 USEFUL I: musculoskeletal ultrasound to identify patients with lupus arthritis with better response to therapy

Background In SLE, musculoskeletal manifestations have an impact on quality of life, disability and clinical trial outcomes, but are harder to assess than in RA and PsA. We previously showed that joint swelling lacks sensitivity, specificity and responsiveness compared to ultrasound. USEFUL was a multicentre longitudinal study to determine clinical features predicting ultrasound synovitis and whether patients with ultrasound synovitis respond better to therapy. Methods SLE patients were recruited if the referring physician deemed they had inflammatory pain warranting treatment. Swollen joints were not required. At baseline, physicians recorded the features that led them to diagnose inflammatory pain and features of concurrent fibromyalgia and osteoarthritis. Stable doses of prednisolone (≤5 mg/day), antimalarials or immunosuppressants were allowed. Participants received depomedrone 120 mg IM then were assessed at 0, 2 and 6 weeks for 66/68 swollen and tender joint counts, BILAG-2004, SLEDAI-2K, physician global and MSK-VAS, inflammatory markers, patient pain and disease activity-VAS, HAQ-DI, LupusQoL, ultrasound of hands and wrists (blinded to patient and clinical assessor). An internal pilot determined the primary endpoint: EMS-VAS at 2 weeks (adjusted for baseline) between patients with ultrasound-synovitis vs. normal ultrasound at baseline. Sensitivity analyses adjusted for prednisolone and immunosuppressants. Results 122/133 patients recruited completed all visits. There was significant disagreement between clinical examination and ultrasound. 78/133 had ultrasound synovitis; 68% of these had ≥1 swollen joint. Of 66/133 patients with ≥ 1 swollen joint, 20% had normal ultrasound. Ultrasound-synovitis was more likely with joint swelling, a symmetrical small joint distribution and active serology. Physician-determined EMS, other lupus features or prior response to therapy were not associated. Fibromyalgia or osteoarthritis did not reduce the probability of ultrasound synovitis. In the full analysis set (n=133) there was no difference in EMS VAS at 2 weeks according to ultrasound synovial status as baseline (difference -8 mm, 95% CI -19, 4 mm, p=0.178). 32 patients had fibromyalgia. After excluding these patients, we found a statistically and clinically significantly better clinical response to depomedrone in patients with ultrasound-synovitis at baseline (baseline-adjusted EMS VAS at 2 weeks -12 mm, 95% CI -24, 0 mm, p=0.049). This difference was greater in the treatment-adjusted sensitivity analysis (-12.8 (95% CI -22, -3 mm), p=0.007) and the per-protocol-adjusted sensitivity analysis (-14.8 mm (95% CI -20.8, -8.8 mm), p<0.001). Patient with ultrasound synovitis had higher rates of improvement in the musculoskeletal BILAG-2004 (56% vs. 26%, p=0.09) and SLEDAI-2K (37% vs. 15%, p=0.03). Conclusions In lupus arthritis distribution and serology, but not other features, help identify ultrasound-synovitis. Ultrasound-synovitis was independent of features of fibromyalgia, but fibromyalgia confounded assessment of response. Excluding fibromyalgia, response to therapy was better in patients with abnormal ultrasound compared to normal. Ultrasound should be used to select patients for therapy and clinical trials, especially when there are inflammatory symptoms without swollen joints

HST Observations of New Horizontal Branch Structures in the Globular Cluster omega Centauri

The globular cluster omega Centauri contains the largest known population of very hot horizontal branch (HB) stars. We have used the Hubble Space Telescope to obtain a far-UV/optical color-magnitude diagram of three fields in omega Cen. We find that over 30% of the HB objects are ``extreme'' HB or hot post-HB stars. The hot HB stars are not concentrated toward the cluster center, which argues against a dynamical origin for them. A wide gap in the color distribution of the hot HB stars appears to correspond to gaps found earlier in several other clusters. This suggests a common mechanism, probably related to giant branch mass loss. The diagram contains a significant population of hot sub-HB stars, which we interpret as the ``blue-hook'' objects predicted by D'Cruz et al. (1996a). These are produced by late He-flashes in stars which have undergone unusually large giant branch mass loss. omega Cen has a well-known spread of metal abundance, and our observations are consistent with a giant branch mass loss efficiency which increases with metallicity.Comment: Submitted to ApJ, 12 pages, including 3 figures, also available at http://www.physics.usyd.edu.au/~noella/research.htm

Virtual Valcamonica: collaborative exploration of prehistoric petroglyphs and their surrounding environment in multi-user virtual reality

In this paper, we present a novel, multi-user, virtual reality environment for the interactive, collaborative 3D analysis of large 3D scans and the technical advancements that were necessary to build it: a multi-view rendering system for large 3D point clouds, a suitable display infrastructure and a suite of collaborative 3D interaction techniques. The cultural heritage site of Valcamonica in Italy with its large collection of prehistoric rock-art served as an exemplary use case for evaluation. The results show that our output-sensitive level-of-detail rendering system is capable of visualizing a 3D dataset with an aggregate size of more than 14 billion points at interactive frame rates. The system design in this exemplar application results from close exchange with a small group of potential users: archaeologists with expertise in rock-art and allows them to explore the prehistoric art and its spatial context with highly realistic appearance. A set of dedicated interaction techniques was developed to facilitate collaborative visual analysis. A multi-display workspace supports the immediate comparison of geographically distributed artifacts. An expert review of the final demonstrator confirmed the potential for added value in rock-art research and the usability of our collaborative interaction techniques

Play&tune: user feedback in the development of a serious game for optimizing hearing aid orientation

Many hearing aid (HA) users are dissatisfied with HA performance in social situations. One way to improve HA outcomes is training the users to understand how HAs work. Play&Tune was designed to provide this training and to foster autonomy in hearing rehabilitation. We carried out two prototype evaluations and a prerelease evaluation of Play&Tune with 71 HA users, using an interview or online survey. Users gave detailed feedback on their experiences with the app. Most participants enjoyed learning about HAs and expressed a desire for autonomy over their HA settings. Our case study reinforces the importance of user feedback during app development

Action research and democracy

This contribution explores the relationship between research and learning democracy. Action research is seen as being compatible with the orientation of educational and social work research towards social justice and democracy. Nevertheless, the history of action research is characterized by a tension between democracy and social engineering. In the social-engineering approach, action research is conceptualized as a process of innovation aimed at a specific Bildungsideal. In a democratic approach action research is seen as research based on cooperation between research and practice. However, the notion of democratic action research as opposed to social engineering action research needs to be theorized. So called democratic action research involving the implementation by the researcher of democracy as a model and as a preset goal, reduces cooperation and participation into instruments to reach this goal, and becomes a type of social engineering in itself. We argue that the relationship between action research and democracy is in the acknowledgment of the political dimension of participation: ‘a democratic relationship in which both sides exercise power and shared control over decision-making as well as interpretation’. This implies an open research design and methodology able to understand democracy as a learning process and an ongoing experiment

Hydrogen-like nitrogen radio line from hot interstellar and warm-hot intergalactic gas

Hyperfine structure lines of highly-charged ions may open a new window in observations of hot rarefied astrophysical plasmas. In this paper we discuss spectral lines of isotopes and ions abundant at temperatures 10^5-10^7 K, characteristic for warm-hot intergalactic medium, hot interstellar medium, starburst galaxies, their superwinds and young supernova remnants. Observations of these lines will allow to study bulk and turbulent motions of the observed target and will broaden the information about the gas ionization state, chemical and isotopic composition. The most prospective is the line of the major nitrogen isotope having wavelength 5.65 mm (Sunyaev and Churazov 1084). Wavelength of this line is well-suited for observation of objects at z=0.15-0.6 when it is redshifted to 6.5-9 mm spectral band widely-used in ground-based radio observations, and, for example, for z>=1.3, when the line can be observed in 1.3 cm band and at lower frequencies. Modern and future radio telescopes and interferometers are able to observe the absorption by 14-N VII in the warm-hot intergalactic medium at redshifts above z=0.15 in spectra of brightest mm-band sources. Sub-millimeter emission lines of several most abundant isotopes having hyperfine splitting might also be detected in spectra of young supernova remnants.Comment: 12 pages, 5 figures, accepted by Astronomy Letters; v3: details added; error fixe