Transcriptional landscape of trans-kingdom communication between Candida albicans and Streptococcus gordonii.

Recent studies have shown that the transcriptional landscape of the pleiomorphic fungus Candida albicans is highly dependent upon growth conditions. Here using a dual RNA-seq approach we identified 299 C. albicans and 72 Streptococcus gordonii genes that were either upregulated or downregulated specifically as a result of co-culturing these human oral cavity microorganisms. Seventy-five C. albicans genes involved in responses to chemical stimuli, regulation, homeostasis, protein modification and cell cycle were significantly (P ≤ 0.05) upregulated, whereas 36 genes mainly involved in transport and translation were downregulated. Upregulation of filamentation-associated TEC1 and FGR42 genes, and of ALS1 adhesin gene, concurred with previous evidence that the C. albicans yeast to hypha transition is promoted by S. gordonii. Increased expression of genes required for arginine biosynthesis in C. albicans was potentially indicative of a novel oxidative stress response. The transcriptional response of S. gordonii to C. albicans was less dramatic, with only eight S. gordonii genes significantly (P ≤ 0.05) upregulated at least two-fold (glpK, rplO, celB, rplN, rplB, rpsE, ciaR and gat). The expression patterns suggest that signals from S. gordonii cause a positive filamentation response in C. albicans, whereas S. gordonii appears to be transcriptionally less influenced by C. albicans.

Image features of true positive and false negative cancers in screening mammograms.

The location, tissue background and imaging characteristics of true positive and false negative screens of breast cancers have been studied. This data can aid decisions in optimizing the display of mammographic information with the objective of minimizing false negative screens. Screening mammograms for four groups of women were digitized; those with screen detected cancers, those with false negative interval cancers, and matched normals for both groups. The optical density (OD) distribution in the main breast region of each mammogram was determined. The OD in three regions of interest around the cancers was also measured. Cancer locations were mapped and warped onto a typical image to show their spatial distribution. Where a cancer was detectable by calcifications alone it had a relatively low probability of being a false negative interval cancer. The mean OD differences between the cancer and the cancer background region (excluding calcifications) were approximately a factor of two lower in dense breasts compared with other breast types. Poorly defined masses that became interval cancers had mean OD differences that were approximately a factor of 0.1 OD lower than those that were detectable by screening. 22% of false negative cancers were located near the chest wall edge of the mammograms compared with 10% of the true positives. The results indicate the importance of effectively displaying information in the lighter areas of the mammogram, corresponding to glandular tissues, with sufficient contrast for suspicious mammographic details to be detected. Where the mean OD differences between the cancer and its background region are low, as measured for some poorly defined masses, there is an increased risk of a false negative interval cancer. Particular attention should be given to the chest wall area of the film, especially in the lower retroglandular region, during routine screening.

Rhythms of differentiation and diacylglycerol in Neurospora.

Although the fungus Neurospora crassa is a relatively simple lower eukaryote, its circadian system may be more complex than previously thought. In this paper we review evidence suggesting that there may be several output pathways coupled in complex ways to a single oscillator, or that there may be more than one oscillator driving independent output pathways. We have described two new rhythms in Neurospora that are not tightly coupled to the rhythm of conidiation bands that is the standard assay for the state of the Neurospora circadian clock. The first is a rhythm in the timing of differentiation, i.e. the production of aerial hyphae and spores. Large regions of the mycelium differentiate synchronously, as if responding to a spatially widespread signal. This rhythm may be distinct from the timer that sets the determination switch controlling the spatial pattern of conidiation bands. The second new rhythm is an oscillation in the levels of the neutral lipid diacylglycerol (DAG). This rhythm is found in all regions of a colony and is not always in phase with the rhythm of conidiation bands. The DAG rhythm shares some characteristics with the differentiation rhythm and has the potential to act as the signal that induces rhythmic differentiation.

Implications of using high contrast mammography X-ray film-screen combinations.

The objective of this study was to determine the implications of using Fuji AD-M and Kodak min-R 2000, two high contrast X-ray film types developed for mammography. Evaluation of the Fuji AD-M film was divided into two parts. The first part was a contralateral comparison between mammograms using Fuji AD-M and Fuji UM-MA HC film-screen combinations. Fuji AD-M contrast was about 25% higher than that of Fuji UM-MA HC. The effect of increased contrast on image quality was investigated by visually grading the quality of information in different parts of each mammogram. Fuji AD-M film was generally judged to be better for overall diagnosis. However, 2.3% of mammograms produced using Fuji AD-M film were not acceptable and might have led to a technical recall of the patient. In the second part of this study, sets of mammograms from women attending mobile screening units were reviewed. One unit used Fuji AD-M film and the other used Kodak min-R 2000 film. Both samples of mammograms were digitized and analysed. The average film gradients between an optical density (OD) of 0.25 and 2.00 above base plus fog were 4.38 for Fuji AD-M film and 3.77 for Kodak min-R 2000 film. The main breast regions of the mammograms were judged to be satisfactorily displayed when breast tissues were above ODs of approximately 0.6 for Fuji AD-M film and 0.8 for Kodak min-R 2000 film.

sn-1,2-diacylglycerol levels in the fungus Neurospora crassa display circadian rhythmicity.

The fungus Neurospora crassa is a model organism for investigating the biochemical mechanism of circadian (daily) rhythmicity. When a choline-requiring strain (chol-1) is depleted of choline, the period of the conidiation rhythm lengthens. We have found that the levels of sn-1,2-diacylglycerol (DAG) increase in proportion to the increase in period. Other clock mutations that change the period do not affect the levels of DAG. Membrane-permeant DAGs and inhibitors of DAG kinase were found to further lengthen the period of choline-depleted cultures. The level of DAG oscillates with a period comparable to the rhythm of conidiation in wild-type strains, choline-depleted cultures, and frq mutants, including a null frq strain. The DAG rhythm is present at the growing margin and also persists in older areas that have completed development. The phase of the DAG rhythm can be set by the light-to-dark transition, but the level of DAG is not immediately affected by light. Our results indicate that rhythms in DAG levels in Neurospora are driven by a light-sensitive circadian oscillator that does not require the frq gene product. High levels of DAG may feed back on that oscillator to lengthen its period.

Analysis of optical density and contrast in mammograms.

The objective of this project is the development of tools for the UK NHSBSP to assess image quality quantitatively in clinical films, for the purposes of optimizing imaging procedures and audit. As an initial step, 120 mammograms of 46 women on a single day of screening were digitized and analysed to produce indices of optical density (OD) and contrast. Analysis was performed on three regions of interest (ROI): pectoral muscle, main breast and skin edge. Two radiologists independently graded the quality of information in the different parts of each mammogram, and categorized breast type as either "dense", "mixed density" or "fatty". Measurements of contrast and OD generally correlated well with the opinions of the radiologists. For the oblique mammograms, the mean OD in the main breast ranged between films from 1.25 to 2.24 with a mean of 1.69 +/- 0.02. In the craniocaudal mammograms, the mean OD in the main breast ROI ranged from 1.14 to 1.94 with a mean of 1.61 +/- 0.05. The OD for a quality control film of a 40 mm block of PMMA exposed on the same day with this system was 1.53. A contrast index (CI) was calculated for each mammogram as the difference between the points of maximum and minimum OD in the main breast. Mean CI was 1.02 +/- 0.09 for fatty breasts, 1.50 +/- 0.10 for mixed density breasts and 2.05 +/- 0.23 for dense breasts. A review of the radiologist assessments indicated that the main breast was satisfactorily displayed when glandular and fatty tissues were displayed within the OD range 0.8-2.9. An analysis of the dynamic range requirements showed that 17% of films had a dynamic range that lay above that calculated using the suggested OD limits.

Effect of automatic kV selection on dose and contrast for a mammographic X-ray system.

The effect of automatic tube potential (kV) selection on breast dose and contrast has been assessed using a Philips MammoDiagnost 3000 mammography X-ray set. The performance of the X-ray set using automatic kV selection has been compared with that found using a fixed kV of 28. The AUTOKV mode selected 25 kV for breasts with thickness up to about 50 mm, which increased the contrast by 5-10%, and increased the mean glandular dose (MGD) per film by, on average, 30-40%. For large breasts with a compressed thickness of 70 mm and above, kVs up to 30 were selected so that the average MGD per film was reduced by 19% from 3.62 to 2.94 mGy, with an estimated loss in contrast of about 4-8%. For all breasts the mean MGD per film was 1.85 +/- 0.05 mGy where AUTOKV was used, and 1.74 +/- 0.08 mGy per film when 28 kV was used. The overall image quality of the mammograms was found to be higher when AUTOKV was used. Overall, the AUTOKV facility on this X-ray set generally worked well and resulted in slightly higher contrast and slightly better image quality at the price of a small increase in the average dose for this patient group when compared with the usual UK procedure of using a fixed 28 kV.

Dose and image quality in mammography with an automatic beam quality system.

Radiation dose, contrast and image quality for automatic beam quality selection (OPDOSE) with the Siemens Mammomat 3000 has been investigated for different breast thicknesses and compared with those found using manually set tube potentials and a molybdenum target and filter. Automatic beam quality selection was found to have a negligible effect for breasts with a compressed breast thickness of less than 45 mm. However, for larger breasts substantial dose savings were achieved for a loss in contrast. For mammograms of compressed breast with a thickness in excess of 60 mm the mean glandular dose (MGD) per film was 2.90 mGy for manually selected tube potentials with a molybdenum/molybdenum target filter combination as compared with 1.87 mGy using 26 kVp and a tungsten target with rhodium filtration. The contrast loss in using OPDOSE was measured with a test object to be about 10% for breast thicknesses in excess of 45 mm. The standard breast model, which assumes a 50% glandular content, did not provide a good fit to the MGD for women attending for breast screening in the age range 50 to 64 years.

Mammographic film density and detection of small breast cancers.

From its inception, the UK National Breast Screening Programme (NHSBSP) has recognized that optimum image quality of the mammographic screening test is a key objective. The overall optical density of the mammography film is one of the factors expected to have a significant effect on the image quality of the mammogram with the potential to influence cancer detection. In a previous review of the performance of mammography equipment in the NHSBSP, it was observed that there was a very wide range in the mammographic film densities used at different breast screening centres. In this study a mammography test object was used to show experimentally that, for a typical mammography system, image quality increased substantially with increased film density. Summary data was therefore requested from radiologists in the NHSBSP on the rate of detection of small invasive cancers (diam. < or = 10 mm) and the typical film density used during that year. Proforma were completed for 61 annual sets of results from 31 screening centres involving over 500,000 women. Where centres reported using film densities of less than 1.2D the average small cancer detection rate was 0.12% +/- 0.01%, as compared to an average of 0.17% +/- 0.01% for centres using higher film densities. The results indicate that there is a need for national guidelines in the setting of film densities, and a range for target film densities of 1.4D to 1.8D has been suggested. Attention to optimizing image quality by increasing film density is of particular importance to any screening centre where film densities of less than 1.2D are used, as there may be the potential to increase the detection of small breast cancers by as much as 50%.

Extremity doses during interventional radiology.

The radiation doses received by the unprotected parts of a radiologist undertaking biliary and renal interventional techniques using an overcouch X-ray tube have been measured with thermoluminescent dosimeters. Mean doses to the eyes, thyroid and fingers ranged from 0.27 to 1.29 mSv per examination. The results substantiate the need for such monitoring but the study demonstrates that the doses to the radiologist can be kept to an acceptable level with careful technique.