Recurrent Clostridium difficile infection associates with distinct bile acid and microbiome profiles

Background: The healthy microbiome protects against the development of Clostridium difficile infection (CDI), which typically develops following antibiotics. The microbiome metabolises primary to secondary bile acids, a process if disrupted by antibiotics, may be critical for the initiation of CDI. Aim: To assess the levels of primary and secondary bile acids associated with CDI and associated microbial changes. Methods: Stool and serum were collected from patients with (i) first CDI (fCDI), (ii) recurrent CDI (rCDI) and (iii) healthy controls. 16S rRNA sequencing and bile salt metabolomics were performed. Random forest regression models were constructed to predict disease status. PICRUSt analyses were used to test for associations between predicted bacterial bile salt hydrolase (BSH) gene abundances and bile acid levels. Results: Sixty patients (20 fCDI, 19 rCDI and 21 controls) were enrolled. Secondary bile acids in stool were significantly elevated in controls compared to rCDI and fCDI (P < 0.0001 and P = 0.0007 respectively). Primary bile acids in stool were significantly elevated in rCDI compared to controls (P < 0.0001) and in rCDI compared to fCDI (P = 0.02). Using random forest regression, we distinguished rCDI and fCDI patients 84.2% of the time using bile acid ratios. Stool deoxycholate to glycoursodeoxycholate ratio was the single best predictor. PICRUSt analyses found significant differences in predicted abundances of bacterial BSH genes in stool samples across the groups. Conclusions: Primary and secondary bile acid composition in stool was different in those with rCDI, fCDI and controls. The ratio of stool deoxycholate to glycoursodeoxycholate was the single best predictor of disease state and may be a potential biomarker for recurrence.American College of Gastroenterology (Clinical Research Award ACGJR-017-2015

Loss of Prestin Does Not Alter the Development of Auditory Cortical Dendritic Spines

Disturbance of sensory input during development can have disastrous effects on the development of sensory cortical areas. To examine how moderate perturbations of hearing can impact the development of primary auditory cortex, we examined markers of excitatory synapses in mice who lacked prestin, a protein responsible for somatic electromotility of cochlear outer hair cells. While auditory brain stem responses of these mice show an approximately 40 dB increase in threshold, we found that loss of prestin produced no changes in spine density or morphological characteristics on apical dendrites of cortical layer 5 pyramidal neurons. PSD-95 immunostaining also showed no changes in overall excitatory synapse density. Surprisingly, behavioral assessments of auditory function using the acoustic startle response showed only modest changes in prestin KO animals. These results suggest that moderate developmental hearing deficits produce minor changes in the excitatory connectivity of layer 5 neurons of primary auditory cortex and surprisingly mild auditory behavioral deficits in the startle response

Two-Dimensional Helioseismic Power, Phase, and Coherence Spectra of {\it Solar Dynamics Observatory} Photospheric and Chromospheric Observables

While the {\it Helioseismic and Magnetic Imager} (HMI) onboard the {\it Solar Dynamics Observatory} (SDO) provides Doppler velocity [$V$], continuum intensity [$I_C$], and line-depth [$Ld$] observations, each of which is sensitive to the five-minute acoustic spectrum, the {\it Atmospheric Imaging Array} (AIA) also observes at wavelengths -- specifically the 1600 and 1700 Angstrom bands -- that are partly formed in the upper photosphere and have good sensitivity to acoustic modes. In this article we consider the characteristics of the spatio--temporal Fourier spectra in AIA and HMI observables for a 15-degree region around NOAA Active Region 11072. We map the spatio--temporal-power distribution for the different observables and the HMI Line Core [$I_L$], or Continuum minus Line Depth, and the phase and coherence functions for selected observable pairs, as a function of position and frequency. Five-minute oscillation power in all observables is suppressed in the sunspot and also in plage areas. Above the acoustic cut-off frequency, the behaviour is more complicated: power in HMI $I_C$ is still suppressed in the presence of surface magnetic fields, while power in HMI $I_L$ and the AIA bands is suppressed in areas of surface field but enhanced in an extended area around the active region, and power in HMI $V$ is enhanced in a narrow zone around strong-field concentrations and suppressed in a wider surrounding area. The relative phase of the observables, and their cross-coherence functions, are also altered around the active region. These effects may help us to understand the interaction of waves and magnetic fields in the different layers of the photosphere, and will need to be taken into account in multi-wavelength local helioseismic analysis of active regions.Comment: 18 pages, 15 figures, to be published in Solar Physic

Subsurface Flows in and Around Active Regions with Rotating and Non-rotating Sunspots

The temporal variation of the horizontal velocity in subsurface layers beneath three different types of active regions is studied using the technique of ring diagrams. In this study, we select active regions (ARs) 10923, 10930, 10935 from three consecutive Carrington rotations: AR 10930 contains a fast-rotating sunspot in a strong emerging active region while other two have non-rotating sunspots with emerging flux in AR 10923 and decaying flux in AR 10935. The depth range covered is from the surface to about 12 Mm. In order to minimize the influence of systematic effects, the selection of active and quiet regions is made so that these were observed at the same heliographic locations on the solar disk. We find a significant variation in both components of the horizontal velocity in active regions as compared to quiet regions. The magnitude is higher in emerging-flux regions than in the decaying-flux region, in agreement with earlier findings. Further, we clearly see a significant temporal variation in depth profiles of both zonal and meridional flow components in AR 10930, with the variation in the zonal component being more pronounced. We also notice a significant influence of the plasma motion in areas closest to the rotating sunspot in AR 10930 while areas surrounding the non-rotating sunspots in all three cases are least affected by the presence of the active region in their neighborhood.Comment: Solar Physics (in press), includes 11 figure

Helioseismology of Sunspots: A Case Study of NOAA Region 9787

Various methods of helioseismology are used to study the subsurface properties of the sunspot in NOAA Active Region 9787. This sunspot was chosen because it is axisymmetric, shows little evolution during 20-28 January 2002, and was observed continuously by the MDI/SOHO instrument. (...) Wave travel times and mode frequencies are affected by the sunspot. In most cases, wave packets that propagate through the sunspot have reduced travel times. At short travel distances, however, the sign of the travel-time shifts appears to depend sensitively on how the data are processed and, in particular, on filtering in frequency-wavenumber space. We carry out two linear inversions for wave speed: one using travel-times and phase-speed filters and the other one using mode frequencies from ring analysis. These two inversions give subsurface wave-speed profiles with opposite signs and different amplitudes. (...) From this study of AR9787, we conclude that we are currently unable to provide a unified description of the subsurface structure and dynamics of the sunspot.Comment: 28 pages, 18 figure

Local helioseismology of sunspot regions: comparison of ring-diagram and time-distance results

Local helioseismology provides unique information about the subsurface structure and dynamics of sunspots and active regions. However, because of complexity of sunspot regions local helioseismology diagnostics require careful analysis of systematic uncertainties and physical interpretation of the inversion results. We present new results of comparison of the ring-diagram analysis and time-distance helioseismology for active region NOAA 9787, for which a previous comparison showed significant differences in the subsurface sound-speed structure, and discuss systematic uncertainties of the measurements and inversions. Our results show that both the ring-diagram and time-distance techniques give qualitatively similar results, revealing a characteristic two-layer seismic sound-speed structure consistent with the results for other active regions. However, a quantitative comparison of the inversion results is not straightforward. It must take into account differences in the sensitivity, spatial resolution and the averaging kernels. In particular, because of the acoustic power suppression, the contribution of the sunspot seismic structure to the ring-diagram signal can be substantially reduced. We show that taking into account this effect reduces the difference in the depth of transition between the negative and positive sound-speed variations inferred by these methods. Further detailed analysis of the sensitivity, resolution and averaging properties of the local helioseismology methods is necessary for consolidation of the inversion results. It seems to be important that both methods indicate that the seismic structure of sunspots is rather deep and extends to at least 20 Mm below the surface, putting constraints on theoretical models of sunspots.Comment: 10 pages, 10 figures, submitted to Journal of Physics: Conference Series (JPCS) GONG 2010 - SoHO 24 "A new era of seismology of the Sun and solar-like stars", June 27 - July 2, 2010 Aix-en-Provence, Franc

Active region formation through the negative effective magnetic pressure instability

The negative effective magnetic pressure instability operates on scales encompassing many turbulent eddies and is here discussed in connection with the formation of active regions near the surface layers of the Sun. This instability is related to the negative contribution of turbulence to the mean magnetic pressure that causes the formation of large-scale magnetic structures. For an isothermal layer, direct numerical simulations and mean-field simulations of this phenomenon are shown to agree in many details in that their onset occurs at the same depth. This depth increases with increasing field strength, such that the maximum growth rate of this instability is independent of the field strength, provided the magnetic structures are fully contained within the domain. A linear stability analysis is shown to support this finding. The instability also leads to a redistribution of turbulent intensity and gas pressure that could provide direct observational signatures.Comment: 19 pages, 10 figures, submitted to Solar Physic

Structure and Rotation of the Solar Interior: Initial Results from the MDI Medium-L Program

The medium-l program of the Michelson Doppler Imager instrument on board SOHO provides continuous observations of oscillation modes of angular degree, l, from 0 to approximately 300. The data for the program are partly processed on board because only about 3% of MDI observations can be transmitted continuously to the ground. The on-board data processing, the main component of which is Gaussian-weighted binning, has been optimized to reduce the negative influence of spatial aliasing of the high-degree oscillation modes. The data processing is completed in a data analysis pipeline at the SOI Stanford Support Center to determine the mean multiplet frequencies and splitting coefficients. The initial results show that the noise in the medium-l oscillation power spectrum is substantially lower than in ground-based measurements. This enables us to detect lower amplitude modes and, thus, to extend the range of measured mode frequencies. This is important for inferring the Sun's internal structure and rotation. The MDI observations also reveal the asymmetry of oscillation spectral lines. The line asymmetries agree with the theory of mode excitation by acoustic sources localized in the upper convective boundary layer. The sound-speed profile inferred from the mean frequencies gives evidence for a sharp variation at the edge of the energy-generating core. The results also confirm the previous finding by the GONG (Gough et al., 1996) that, in a thin layer just beneath the convection zone, helium appears to be less abundant than predicted by theory. Inverting the multiplet frequency splittings from MDI, we detect significant rotational shear in this thin layer. This layer is likely to be the place where the solar dynamo operates. In order to understand how the Sun works, it is extremely important to observe the evolution of this transition layer throughout the 11-year activity cycle

Radiographers supporting radiologists in the interpretation of screening mammography: a viable strategy to meet the shortage in the number of radiologists.

BackgroundAn alternative approach to the traditional model of radiologists interpreting screening mammography is necessary due to the shortage of radiologists to interpret screening mammograms in many countries.MethodsWe evaluated the performance of 15 Mexican radiographers, also known as radiologic technologists, in the interpretation of screening mammography after a 6 months training period in a screening setting. Fifteen radiographers received 6 months standardized training with radiologists in the interpretation of screening mammography using the Breast Imaging Reporting and Data System (BI-RADS) system. A challenging test set of 110 cases developed by the Breast Cancer Surveillance Consortium was used to evaluate their performance. We estimated sensitivity, specificity, false positive rates, likelihood ratio of a positive test (LR+) and the area under the subject-specific Receiver Operating Characteristic (ROC) curve (AUC) for diagnostic accuracy. A mathematical model simulating the consequences in costs and performance of two hypothetical scenarios compared to the status quo in which a radiologist reads all screening mammograms was also performed.ResultsRadiographer's sensitivity was comparable to the sensitivity scores achieved by U.S. radiologists who took the test but their false-positive rate was higher. Median sensitivity was 73.3 % (Interquartile range, IQR: 46.7-86.7 %) and the median false positive rate was 49.5 % (IQR: 34.7-57.9 %). The median LR+ was 1.4 (IQR: 1.3-1.7 %) and the median AUC was 0.6 (IQR: 0.6-0.7). A scenario in which a radiographer reads all mammograms first, and a radiologist reads only those that were difficult for the radiographer, was more cost-effective than a scenario in which either the radiographer or radiologist reads all mammograms.ConclusionsGiven the comparable sensitivity achieved by Mexican radiographers and U.S. radiologists on a test set, screening mammography interpretation by radiographers appears to be a possible adjunct to radiologists in countries with shortages of radiologists. Further studies are required to assess the effectiveness of different training programs in order to obtain acceptable screening accuracy, as well as the best approaches for the use of non-physician readers to interpret screening mammography