Until recently, the construction of a reference genome was performed using Sanger sequencing alone. The emergence of next-generation sequencing platforms now means reference genomes may incorporate ...sequence data generated from a range of sequencing platforms, each of which have different read length, systematic biases and mate-pair characteristics. The objective of this review is to inform the mammalian genomics community about the experimental strategy being pursued by the International Sheep Genomics Consortium (ISGC) to construct the draft reference genome of sheep (Ovis aries). Component activities such as data generation, sequence assembly and annotation are described, along with information concerning the key researchers performing the work. This aims to foster future participation from across the research community through the coordinated activities of the consortium. The review also serves as a 'marker paper' by providing information concerning the pre-publication release of the reference genome. This ensures the ISGC adheres to the framework for data sharing established at the recent Toronto International Data Release Workshop and provides guidelines for data users.
Objectives
To retrospectively evaluate cases presented for percutaneous ultrasound‐guided cholecystocentesis for associated complications, identify risk factors associated with complications and to ...assess ultrasonographic findings and relate these to bacterial culture results.
Methods
Data on 300 patients presented for percutaneous ultrasound‐guided cholecystocentesis were retrospectively collected and ultrasonographic images were assessed for defined structural changes. The incidence of major complications was determined. Multi‐variable multi‐level logistic regression was used to investigate the association of ultrasonographic findings with positive bile culture.
Results
Three hundred percutaneous ultrasound‐guided cholecystocentesis procedures performed in 201 dogs and 51 cats were included; 35 patients had the procedure performed more than once. The overall incidence of major complications was 8 of 300 procedures (2·7%). Bile peritonitis occurred in 2 of 300 procedures (0·7%). An ultrasonographically abnormal gall bladder was found in 52% of cases and had a sensitivity, specificity and accuracy of 82, 55·7 and 61·5% respectively, to predict a positive bile culture.
Clinical Significance
Percutaneous ultrasound‐guided cholecystocentesis is overall a safe technique when carried out in selected patients. Abnormal ultrasonographic findings are only a fair predictor of a positive bile culture.
Idiosyncratic drug toxicity refers to toxic reactions occurring in a small subset of patients and usually cannot be predicted during preclinical or early phases of clinical trials. One hypothesis for ...the pathogenesis of hepatic idiosyncratic drug reactions is that, in certain individuals, underlying inflammation results in sensitization of the liver, such that injury occurs from an agent that typically would not cause hepatotoxicity at a therapeutic dose. We explored this possibility by cotreating rats with nonhepatotoxic doses of bacterial lipopolysaccharide (LPS) and trovafloxacin (TVX), a drug that caused idiosyncratic hepatotoxicity in humans. The combination of LPS and TVX resulted in hepatotoxicity in rats, as determined by increases in serum alanine aminotransferase activity and hepatocellular necrosis, which were not observed with either agent alone. In contrast, treatment with LPS and levofloxacin, a fluoroquinolone without human idiosyncratic liability, did not result in these changes. Liver gene expression analysis identified unique changes induced by the combination of TVX and LPS, including enhanced expression of chemokines, suggestive of liver neutrophil (PMN) accumulation and activation. Consistent with a role for PMN in the hepatotoxicity induced by LPS/TVX, prior depletion of PMN attenuated the liver injury. The results suggest that gene expression profiles predictive of idiosyncratic liability can be generated in rats cotreated with LPS and drug. Furthermore, they identify gene expression changes that could be explored as biomarkers for idiosyncratic toxicity and lead to enhanced understanding of the mechanism(s) underlying hepatotoxicity induced by TVX.
zCOSMOS is a large-redshift survey that is being undertaken in the COSMOS field using 600 hr of observation with the VIMOS spectrograph on the 8 m VLT. The survey is designed to characterize the ...environments of COSMOS galaxies from the 100 kpc scales of galaxy groups up to the 100 Mpc scale of the cosmic web and to produce diagnostic Information on galaxies and active galactic nuclei. The zCOSMOS survey consists of two parts: (1) zCOSMOS-bright, a magnitude-limited I-band ha < 22.5 sample of about 20,000 galaxies with 0.1 < z < 1.2 covering the whole 1.7 deg super(2) COSMOS ACS field, for which the survey parameters at z similar to 0.7 are designed to be directly comparable to those of the 2dFGRS at z similar to 0.1; and (2) zCOSMOS-deep, a survey of approximately 10,000 galaxies selected through color-selection criteria to have 1.4 < z < 3.0, within the central 1 deg super(2). This paper describes the survey design and the construction of the target catalogs and briefly outlines the observational program and the data pipeline. In the first observing season, spectra of 1303 zCOSMOS-bright targets and 977 zCOSMOS-deep targets have been obtained. These are briefly analyzed to demonstrate the characteristics that may be expected from zCOSMOS, and particularly zCOSMOS-bright, when it is finally completed between 2008 and 2009. The power of combining spectroscopic and photometric redshifts is demonstrated, especially in correctly identifying the emission line in single-line spectra and in determining which of the less reliable spectroscopic redshifts are correct and which are incorrect. These techniques bring the overall success rate in the zCOSMOS-bright so far to almost 90% and to above 97% in the 0.5 < z < 0.8 redshift range. Our zCOSMOS-deep spectra demonstrate the power of our selection techniques to Isolate high-redshift galaxies at 1.4 < z < 3, C and of VIMOS to measure their redshifts using ultraviolet absorption lines.
Previous bisphosphonate treatment attenuates the bone-forming effect of teriparatide. We compared the effects of 12 months of romosozumab (AMG 785), a sclerostin monoclonal antibody, versus ...teriparatide on bone mineral density (BMD) in women with postmenopausal osteoporosis transitioning from bisphosphonate therapy.
This randomised, phase 3, open-label, active-controlled study was done at 46 sites in North America, Latin America, and Europe. We enrolled women (aged ≥55 to ≤90 years) with postmenopausal osteoporosis who had taken an oral bisphosphonate for at least 3 years before screening and alendronate the year before screening; an areal BMD T score of −2·5 or lower at the total hip, femoral neck, or lumbar spine; and a history of fracture. Patients were randomly assigned (1:1) via an interactive voice response system to receive subcutaneous romosozumab (210 mg once monthly) or subcutaneous teriparatide (20 μg once daily). The primary endpoint was percentage change from baseline in areal BMD by dual-energy x-ray absorptiometry at the total hip through month 12 (mean of months 6 and 12), which used a linear mixed effects model for repeated measures and represented the mean treatment effect at months 6 and 12. All randomised patients with a baseline measurement and at least one post-baseline measurement were included in the efficacy analysis. This trial is registered with ClinicalTrials.gov, number NCT01796301.
Between Jan 31, 2013, and April 29, 2014, 436 patients were randomly assigned to romosozumab (n=218) or teriparatide (n=218). 206 patients in the romosozumab group and 209 in the teriparatide group were included in the primary efficacy analysis. Through 12 months, the mean percentage change from baseline in total hip areal BMD was 2·6% (95% CI 2·2 to 3·0) in the romosozumab group and −0·6% (−1·0 to −0·2) in the teriparatide group; difference 3·2% (95% CI 2·7 to 3·8; p<0·0001). The frequency of adverse events was generally balanced between treatment groups. The most frequently reported adverse events were nasopharyngitis (28 13% of 218 in the romosozumab group vs 22 10% of 214 in the teriparatide group), hypercalcaemia (two <1% vs 22 10%), and arthralgia (22 10% vs 13 6%). Serious adverse events were reported in 17 (8%) patients on romosozumab and in 23 (11%) on teriparatide; none were judged treatment related. There were six (3%) patients in the romosozumab group compared with 12 (6%) in the teriparatide group with adverse events leading to investigational product withdrawal.
Transition to a bone-forming agent is common practice in patients treated with bisphosphonates, such as those who fracture while on therapy. In such patients, romosozumab led to gains in hip BMD that were not observed with teriparatide. These data could inform clinical decisions for patients at high risk of fracture.
Amgen, Astellas, and UCB Pharma.
We report the first extensive ovine genetic linkage map covering 2070 cM of the sheep genome. The map was generated from the linkage analysis of 246 polymorphic markers, in nine three-generation ...full-sib pedigrees, which make up the AgResearch International Mapping Flock. We have exploited many markers from cattle so that valuable comparisons between these two ruminant linkage maps can be made. The markers, used in the segregation analyses, comprised 86 anonymous microsatellite markers derived from the sheep genome, 126 anonymous microsatellites from cattle, one from deer, and 33 polymorphic markers of various types associated with known genes. The maximum number of informative meioses within the mapping flock was 222. The average number of informative meioses per marker was 140 (range 18-209). Linkage groups have been assigned to all 26 sheep autosomes
Pneumocystis carinii pneumonia is a rare disease in dogs. It is primarily reported in cavalier King Charles spaniels and miniature dachshunds with suspected underlying immunodeficiency. This case ...series reports the findings in five dogs (four cavalier King Charles spaniels and one Bedlington terrier) with confirmed P. carinii pneumonia. Thoracic (CT) revealed ground glass opacity of the pulmonary parenchyma with a diffuse or multifocal distribution. The severity of this pattern was variable. Less consistent imaging findings included parenchymal bands, bronchial dilation and signs consistent with pulmonary hypertension. Four dogs recovered well with treatment and there was resolution of CT abnormalities in all dogs with follow‐up.
The Herschel-Astrophysical Terahertz Large Area Survey (H-ATLAS) provides an unprecedented opportunity to search for blazars at sub-mm wavelengths. We cross-matched the Faint Images of the Radio Sky ...at Twenty-cm (FIRST) radio source catalogue with the 11 655 sources brighter than 35 mJy at 500 μm in the ∼135 deg2 of the sky covered by the H-ATLAS equatorial fields at 9h and 15h, plus half of the field at 12h. We found that 379 of the H-ATLAS sources have a FIRST counterpart within 10 arcsec, including eight catalogued blazars (plus one known blazar that was found at the edge of one of the H-ATLAS maps). To search for additional blazar candidates we have devised new diagnostic diagrams and found that known blazars occupy a region of the log (S
500 μm/S
350 μm) versus log (S
500 μm/S
1.4 GHz) plane separated from that of sub-mm sources with radio emission powered by star formation, but shared with radio galaxies and steep-spectrum radio quasars. Using this diagnostic we have selected 12 further possible candidates that turn out to be scattered in the (r − z) versus (u − r) plane or in the Wide-Field Infrared Survey Explorer colour-colour diagram, where known blazars are concentrated in well defined strips. This suggests that the majority of them are not blazars. Based on an inspection of all the available photometric data, including unpublished VISTA Kilo-degree Infrared Galaxy survey photometry and new radio observations, we found that the spectral energy distributions (SEDs) of only one out of the 12 newly selected sources are compatible with being synchrotron dominated at least up to 500 μm, i.e. with being a blazar. Another object may consist of a faint blazar nucleus inside a bright star-forming galaxy. The possibility that some blazar hosts are endowed with active star formation is supported by our analysis of the SEDs of Planck Early Release Compact Source Catalogue blazars detected at both 545 and 857 GHz. The estimated rest-frame synchrotron peak frequencies of H-ATLAS blazars are in the range 11.5 ≤ log (νpeak, Hz) ≤ 13.7, implying that these objects are low synchrotron peak. Six of them also show evidence of an ultraviolet excess that can be attributed to emission from the accretion disc. Allowing for the possibility of misidentifications and of contamination of the 500 μm flux density by the dusty torus or by the host galaxy, we estimate that there are seven or eight pure synchrotron sources brighter than S
500 μm = 35 mJy over the studied area, a result that sets important constraints on blazar evolutionary models.
We present the results of a cross-correlation of the Planck Early Release Compact Source catalogue (ERCSC) with the catalogue of Herschel-ATLAS sources detected in the phase 1 fields, covering ...134.55 deg2. There are 28 ERCSC sources detected by Planck at 857 GHz in this area. As many as 16 of them are probably high Galactic latitude cirrus; 10 additional sources can be clearly identified as bright, low-z galaxies; one further source is resolved by Herschel as two relatively bright sources; and the last is resolved into an unusual condensation of low-flux, probably high-redshift point sources, around a strongly lensed Herschel-ATLAS source at z = 3.26. Our results demonstrate that the higher sensitivity and higher angular resolution H-ATLAS maps provide essential information for the interpretation of candidate sources extracted from Planck sub-mm maps.
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