Refinement and validation of the IDIOM score for predicting the risk of gastrointestinal cancer in iron deficiency anaemia.

OBJECTIVE: To refine and validate a model for predicting the risk of gastrointestinal (GI) cancer in iron deficiency anaemia (IDA) and to develop an app to facilitate use in clinical practice. DESIGN: Three elements: (1) analysis of a dataset of 2390 cases of IDA to validate the predictive value of age, sex, blood haemoglobin concentration (Hb), mean cell volume (MCV) and iron studies on the probability of underlying GI cancer; (2) a pilot study of the benefit of adding faecal immunochemical testing (FIT) into the model; and (3) development of an app based on the model. RESULTS: Age, sex and Hb were all strong, independent predictors of the risk of GI cancer, with ORs (95% CI) of 1.05 per year (1.03 to 1.07, p<0.00001), 2.86 for men (2.03 to 4.06, p<0.00001) and 1.03 for each g/L reduction in Hb (1.01 to 1.04, p<0.0001) respectively. An association with MCV was also revealed, with an OR of 1.03 for each fl reduction (1.01 to 1.05, p<0.02). The model was confirmed to be robust by an internal validation exercise. In the pilot study of high-risk cases, FIT was also predictive of GI cancer (OR 6.6, 95% CI 1.6 to 51.8), but the sensitivity was low at 23.5% (95% CI 6.8% to 49.9%). An app based on the model was developed. CONCLUSION: This predictive model may help rationalise the use of investigational resources in IDA, by fast-tracking high-risk cases and, with appropriate safeguards, avoiding invasive investigation altogether in those at ultra-low predicted risk

Studies of a Lacustrine-Volcanic Mars Analog Field Site with Mars-2020-like Instruments

On the upcoming Mars‐2020 rover two remote sensing instruments, Mastcam‐Z and SuperCam, and two microscopic proximity science instruments, SHERLOC and PIXL, will collect compositional (mineralogy, chemistry, and organics) data essential for paleoenvironmental reconstruction. The synergies between and limitations of these instruments were evaluated via study of a Mars analog field site in the Mojave Desert, using instruments approximating the data that will be returned by Mars‐2020. A ground truth dataset was generated for comparison to validate the results. The site consists of a succession of clay‐rich mudstones of lacustrine origin, interbedded tuffs, a carbonate‐silica travertine deposit, and gypsiferous mudstone strata. The major geological units were mapped successfully using simulated Mars‐2020 data. Simulated Mastcam‐Z data identified unit boundaries and Fe‐bearing weathering products. Simulated SuperCam passive shortwave infrared and green Raman data were essential in identifying major mineralogical composition and changes in lacustrine facies at distance; this was possible even with spectrally downsampled passive IR data. LIBS and simulated PIXL data discriminated and mapped major element chemistry. Simulated PIXL revealed mm‐scale zones enriched in zirconium, of interest for age dating. SHERLOC‐like data mapped sulfate and carbonate at sub‐mm scale; silicates were identified with increased laser pulses/spot or by averaging of hundreds of spectra. Fluorescence scans detected and mapped varied classes of organics in all samples, characterized further with follow‐on spatially targeted deep‐UV Raman spectra. Development of dedicated organics spectral libraries is needed to aid interpretation. Given these observations, the important units in the outcrop would be sampled and cached for sample return

Antimicrobial resistance in equine faecal Escherichia coli isolates from North West England

<p>Abstract</p> <p>Background</p> <p><it>Escherichia coli </it>isolates of equine faecal origin were investigated for antibiotic resistance, resistance genes and their ability to perform horizontal transfer.</p> <p>Methods</p> <p>In total, 264 faecal samples were collected from 138 horses in hospital and community livery premises in northwest England, yielding 296 resistant <it>E. coli </it>isolates. Isolates were tested for susceptibility to antimicrobial drugs by disc diffusion and agar dilution methods in order to determine minimum inhibitory concentrations (MIC). PCR amplification was used to detect genes conferring resistance to: ampicillin (TEM and SHV beta-lactamase), chloramphenicol (<it>catI, catII, catIII </it>and <it>cml</it>), tetracycline <it>(tetA, tetB, tetC, tetD, tet E </it>and <it>tetG</it>), and trimethoprim (<it>dfrA1, dfrA9, dfrA12, dfrA13, dfr7</it>, and <it>dfr17</it>).</p> <p>Results</p> <p>The proportion of antibiotic resistant isolates, and multidrug resistant isolates (MDR) was significantly higher in hospital samples compared to livery samples (MDR: 48% of hospital isolates; 12% of livery isolates, p < 0.001). Resistance to ciprofloxacin and florfenicol were identified mostly within the MDR phenotypes. Resistance genes included <it>dfr</it>, TEM beta-lactamase, <it>tet </it>and <it>cat</it>, conferring resistance to trimethoprim, ampicillin, tetracycline and chloramphenicol, respectively. Within each antimicrobial resistance group, these genes occurred at frequencies of 93% (260/279), 91%, 86.8% and 73.5%, respectively; with 115/296 (38.8%) found to be MDR isolates. Conjugation experiments were performed on selected isolates and MDR phenotypes were readily transferred.</p> <p>Conclusions</p> <p>Our findings demonstrate that <it>E. coli </it>of equine faecal origin are commonly resistant to antibiotics used in human and veterinary medicine. Furthermore, our results suggest that most antibiotic resistance observed in equine <it>E. coli </it>is encoded by well-known and well-characterized resistant genes common to <it>E. coli </it>from man and domestic animals. These data support the ongoing concern about antimicrobial resistance, MDR, antimicrobial use in veterinary medicine and the zoonotic risk that horses could potentially pose to public health.</p

SOX9 transduction of a human chondrocytic cell line identifies novel genes regulated in primary human chondrocytes and in osteoarthritis

The transcription factor SOX9 is important in maintaining the chondrocyte phenotype. To identify novel genes regulated by SOX9 we investigated changes in gene expression by microarray analysis following retroviral transduction with SOX9 of a human chondrocytic cell line (SW1353). From the results the expression of a group of genes (SRPX, S100A1, APOD, RGC32, CRTL1, MYBPH, CRLF1 and SPINT1) was evaluated further in human articular chondrocytes (HACs). First, the same genes were investigated in primary cultures of HACs following SOX9 transduction, and four were found to be similarly regulated (SRPX, APOD, CRTL1 and S100A1). Second, during dedifferentiation of HACs by passage in monolayer cell culture, during which the expression of SOX9 progressively decreased, four of the genes (S100A1, RGC32, CRTL1 and SPINT1) also decreased in their expression. Third, in samples of osteoarthritic (OA) cartilage, which had decreased SOX9 expression compared with age-matched controls, there was decreased expression of SRPX, APOD, RGC32, CRTL1 and SPINT1. The results showed that a group of genes identified as being upregulated by SOX9 in the initial SW1353 screen were also regulated in expression in healthy and OA cartilage. Other genes initially identified were differently expressed in isolated OA chondrocytes and their expression was unrelated to changes in SOX9. The results thus identified some genes whose expression appeared to be linked to SOX9 expression in isolated chondrocytes and were also altered during cartilage degeneration in osteoarthritis

Vascular changes in diabetic retinopathy-a longitudinal study in the Nile rat.

Diabetic retinopathy is the most common microvascular complication of diabetes and is a major cause of blindness, but an understanding of the pathogenesis of the disease has been hampered by a lack of accurate animal models. Here, we explore the dynamics of retinal cellular changes in the Nile rat (Arvicanthis niloticus), a carbohydrate-sensitive model for type 2 diabetes. The early retinal changes in diabetic Nile rats included increased acellular capillaries and loss of pericytes that correlated linearly with the duration of diabetes. These vascular changes occurred in the presence of microglial infiltration but in the absence of retinal ganglion cell loss. After a prolonged duration of diabetes, the Nile rat also exhibits a spectrum of retinal lesions commonly seen in the human condition including vascular leakage, capillary non-perfusion, and neovascularization. Our longitudinal study documents a range and progression of retinal lesions in the diabetic Nile rat remarkably similar to those observed in human diabetic retinopathy, and suggests that this model will be valuable in identifying new therapeutic strategies

Discovery of Interstellar Hydrogen Fluoride

We report the first detection of interstellar hydrogen fluoride. Using the Long Wavelength Spectrometer (LWS) of the Infrared Space Observatory (ISO), we have detected the 121.6973 micron J = 2 - 1 line of HF in absorption toward the far-infrared continuum source Sagittarius B2. The detection is statistically significant at the 13 sigma level. On the basis of our model for the excitation of HF in Sgr B2, the observed line equivalent width of 1.0 nm implies a hydrogen fluoride abundance of 3E-10 relative to H2. If the elemental abundance of fluorine in Sgr B2 is the same as that in the solar system, then HF accounts for ~ 2% of the total number of fluorine nuclei. We expect hydrogen fluoride to be the dominant reservoir of gas-phase fluorine in Sgr B2, because it is formed rapidly in exothermic reactions of atomic fluorine with either water or molecular hydrogen; thus the measured HF abundance suggests a substantial depletion of fluorine onto dust grains. Similar conclusions regarding depletion have previously been reached for the case of chlorine in dense interstellar clouds. We also find evidence at a lower level of statistical significance (~ 5 sigma) for an emission feature at the expected position of the 4(3,2)-4(2,3) 121.7219 micron line of water. The emission line equivalent width of 0.5 nm for the water feature is consistent with the water abundance of 5E-6 relative to H2 that has been inferred previously from observations of the hot core of Sgr B2.Comment: 11 pages (AASTeX using aaspp4.sty) plus 2 figures; to appear in ApJ Letter

The Interfascicular Matrix of Energy Storing Tendons Houses Heterogenous Cell Populations Disproportionately Affected by Aging

Energy storing tendons such as the human Achilles and equine superficial digital flexor tendon (SDFT) are prone to injury, with incidence increasing with aging, peaking in the 5th decade of life in the human Achilles tendon. The interfascicular matrix (IFM), which binds tendon fascicles, plays a key role in energy storing tendon mechanics, and aging alterations to the IFM negatively impact tendon function. While the mechanical role of the IFM in tendon function is well-established, the biological role of IFM-resident cell populations remains to be elucidated. Therefore, the aim of this study was to identify IFM-resident cell populations and establish how these populations are affected by aging. Cells from young and old SDFTs were subjected to single cell RNA-sequencing, and immunolabelling for markers of each resulting population used to localise cell clusters. Eleven cell clusters were identified, including tenocytes, endothelial cells, mural cells, and immune cells. One tenocyte cluster localised to the fascicular matrix, whereas nine clusters localised to the IFM. Interfascicular tenocytes and mural cells were preferentially affected by aging, with differential expression of genes related to senescence, dysregulated proteostasis and inflammation. This is the first study to establish heterogeneity in IFM cell populations, and to identify age-related alterations specific to IFM-localised cells

ISO LWS Spectroscopy of M82: A Unified Evolutionary Model

We present the first complete far-infrared spectrum (43 to 197 um) of M82, the brightest infrared galaxy in the sky, taken with the Long Wavelength Spectrometer of the Infrared Space Observatory (ISO). We detected seven fine structure emission lines, [OI] 63 and 145 um, [OIII] 52 and 88 um, [NII] 122 um, [NIII] 57 um and [CII] 158 um, and fit their ratios to a combination starburst and photo-dissociation region (PDR) model. The best fit is obtained with HII regions with n = 250 cm^{-3} and an ionization parameter of 10^{-3.5} and PDRs with n = 10^{3.3} cm^{-3} and a far-ultraviolet flux of G_o = 10^{2.8}. We applied both continuous and instantaneous starburst models, with our best fit being a 3-5 Myr old instantaneous burst model with a 100 M_o cut-off. We also detected the ground state rotational line of OH in absorption at 119.4 um. No excited level OH transitions are apparent, indicating that the OH is almost entirely in its ground state with a column density ~ 4x10^{14} cm^{-2}. The spectral energy distribution over the LWS wavelength range is well fit with a 48 K dust temperature and an optical depth, tau_{Dust} proportional to lambda^{-1}.Comment: 23 pages, 4 figures, accepted by ApJ, Feb. 1, 199