Metastatic breast cancer is usually diagnosed after becoming symptomatic, at which point it is rarely curable. Cell-free circulating tumor DNA (ctDNA) contains tumor-specific chromosomal rearrangements that may be interrogated in blood plasma. We evaluated serial monitoring of ctDNA for earlier detection of metastasis in a retrospective study of 20 patients diagnosed with primary breast cancer and long follow-up. Using an approach combining low-coverage whole-genome sequencing of primary tumors and quantification of tumor-specific rearrangements in plasma by droplet digital PCR, we identify for the first time that ctDNA monitoring is highly accurate for postsurgical discrimination between patients with (93%) and without (100%) eventual clinically detected recurrence. ctDNA-based detection preceded clinical detection of metastasis in 86% of patients with an average lead time of 11 months (range 0–37 months), whereas patients with long-term disease-free survival had undetectable ctDNA postoperatively. ctDNA quantity was predictive of poor survival. These findings establish the rationale for larger validation studies in early breast cancer to evaluate ctDNA as a monitoring tool for early metastasis detection, therapy modification, and to aid in avoidance of overtreatment.

Increasing levels of resistance to tetracycline and to a number of other unrelated antibiotics, including chloramphenicol, beta-lactams, puromycin, and nalidixic acid, occurred in Escherichia coli after 50 to 200 generations of growth in the presence of subinhibitory concentrations of tetracycline or chloramphenicol. In the absence of selective pressure, resistances fell to low levels within 100 generations of growth. This amplification of resistance was observed in laboratory and naturally occurring E. coli strains as well as in polA and recA strains. With the exception of previously identified cmlA and cmlB mutations, tetracycline or chloramphenicol resistances were not P1 transducible. Coincident with the emergence of resistance was the appearance of a previously cryptic energy-dependent efflux system for tetracycline. The expression of resistance phenotypes and the tetracycline efflux system were temperature sensitive at 42 degrees C.

We carried out targeted sequencing of BRCA1/2 in an unselected cohort of patients diagnosed with primary breast cancer within a population without strong founder mutations. Eleven percent of cases harbored a germline or somatic BRCA1/2 mutation, and the ratio of germline versus somatic mutation was 2 : 1. This has implications for treatment, genetic counseling, and interpretation of tumor-only testing.

Spontaneous multidrug-resistant (Mdr) mutants of Klebsiella pneumniae strain ECL8 arose at a frequency of 2.2 x to a range of unrelated antibiotics, including chloramphenicol, tetracycline, nalidixic acid, ampicillin, norfloxacin, trimethoprim and puromycin. A chromosomal fragment from one such mutant was cloned, and found to confer an Mdr phenotype on Escherichia coli K12 cells that was essentially identical to that of the K. pneumoniae mutant. Almost complete loss of the OmpF porin in the E. coli transformant, and of the corresponding porin in the K. pneumniae mutant, was observed. The presence of the Mdr mutation in K. pneumoniae or the cloned K. pneumoniae ramA (msistance antibiotic multiple) locus in Em coli also resulted in active efflux of tetracycline, and increased active efflux of chloramphenicol. After transformation of a ramA plasmid into E. coli, expression of chloramphenicol resistance occurred later than expression of resistance to tetracycline, puromycin, trimethoprim and nalidixic acid. The ramA gene was localized and sequenced. It encodes a putative positive transcriptional activator that is weakly related to the Em coli MarA and SoxS proteins. A ramA gene was also found to be present in an Enferobacter cloacae fragment that has previously been shown to confer an Mdr phenotype, and it appears that ramA, rather than the m m A gene identified in that study, is responsible for multidrug resistance. The r0mA gene from the wild-type K. pneumoniae was identical to that of the mutant strain and also conferred an Mdr phenotype on E. coli, indicating that the mutation responsible for Mdr in K. pneumoniae had not been cloned. and showed increased resistance 1

ABSTRACT. CT enterography is a new non-invasive imaging technique that offers superior small bowel visualisation compared with standard abdomino-pelvic CT, and provides complementary diagnostic information to capsule endoscopy and MRI enterography. CT enterography is well tolerated by patients and enables accurate, efficient assessment of pathology arising from the small bowel wall or surrounding organs. This article reviews the clinical role of CT enterography, and offers practical tips for optimising technique and accurate interpretation. Until recently, diagnosis of small bowel pathology had relied primarily on radiological techniques, in part due to the relative inaccessibility of the small bowel to conventional endoscopy. However, new endoscopic developments-notably the recent introduction of capsule endoscopy and double balloon enteroscopy-are challenging this position. Capsule endoscopy, for example, is now generally accepted as first-line investigation for occult gastrointestinal haemorrhage, and increasingly advocated for diagnosis of early Crohn's disease. However, the radiological community has not stood still. In parallel with the development of new endoscopic techniques, rapid progress has been made in crosssectional imaging technologies, harnessing the power of multidetector row CT (MDCT), MRI and ultrasound, facilitating rapid, accurate and minimally invasive investigation of the small bowel and adjacent tissues.CT enterography was first introduced by Raptopoulos et al [1] in 1997 as a modification to ''standard'' abdomino-pelvic CT examination to specifically examine the small bowel in detail, notably to assess the extent and severity of Crohn's disease [1,2]. They combined neutral (low-density) oral contrast with ''enteric phase'' CT to optimise contrast resolution between mucosa and lumen, thereby maximising conspicuity of abnormalities arising from the small bowel wall. Several authors have subsequently described similar techniques, which are broadly categorised into CT enterography (where patients drink oral contrast) and CT enteroclysis (luminal contrast is introduced via a nasojejunal tube placed fluoroscopically prior to CT examination). Although superior jejunal distension is attained using enteroclysis, the convenience, efficiency and superior patient experience achieved with CT enterography make it the preferred technique at the authors' institutions, and therefore the focus of this review. This paper will critically review the CT enterography technique and provide practical tips on interpretation to assist radiologists and help them avoid common interpretative pitfalls. We will also examine its role relative to other complementary non-ionising radiation radiological tests. TechniqueThe technique of CT enterography combines small bowel distension with a neutral or low-density oral contrast mixture and abdomino-pelvic CT examination during the enteric phase following administration of intravenous contrast. Patients drink approximately 1.5-2 l of oral contrast over 45-60 min. Patient comp...