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Summary Background Whole-body magnetic resonance imaging (WB-MRI) could be an alternative to multi-modality staging of non-small-cell lung cancer (NSCLC), but its diagnostic accuracy, effect on staging times, number of tests needed, cost, and effect on treatment decisions are unknown. We aimed to prospectively compare the diagnostic accuracy and efficiency of WB-MRI-based staging pathways with standard pathways in NSCLC. Methods The Streamline L trial was a prospective, multicentre trial done in 16 hospitals in England. Eligible patients were 18 years or older, with newly diagnosed NSCLC that was potentially radically treatable on diagnostic chest CT (defined as stage IIIb or less). Exclusion criteria were severe systemic disease, pregnancy, contraindications to MRI, or histologies other than NSCLC. Patients underwent WB-MRI, the result of which was withheld until standard staging investigations were complete and the first treatment decision made. The multidisciplinary team recorded its treatment decision based on standard investigations, then on the WB-MRI staging pathway (WB-MRI plus additional tests generated), and finally on all tests. The primary outcome was difference in per-patient sensitivity for metastases between standard and WB-MRI staging pathways against a consensus reference standard at 12 months, in the per-protocol population. Secondary outcomes were difference in per-patient specificity for metastatic disease detection between standard and WB-MRI staging pathways, differences in treatment decisions, staging efficiency (time taken, test number, and costs) and per-organ sensitivity and specificity for metastases and per-patient agreement for local T and N stage. This trial is registered with the International Standard Randomised Controlled Trial registry, number ISRCTN50436483, and is complete. Findings Between Feb 26, 2013, and Sept 5, 2016, 976 patients were screened for eligibility. 353 patients were recruited, 187 of whom completed the trial; 52 (28%) had metastasis at baseline. Pathway sensitivity was 50% (95% CI 37–63) for WB-MRI and 54% (41–67) for standard pathways, a difference of 4% (−7 to 15, p=0·73). No adverse events related to imaging were reported. Specificity did not differ between WB-MRI (93% [88–96]) and standard pathways (95% [91–98], p=0·45). Agreement with the multidisciplinary team's final treatment decision was 98% for WB-MRI and 99% for the standard pathway. Time to complete staging was shorter for WB-MRI (13 days [12–14]) than for the standard pathway (19 days [17–21]); a 6-day (4–8) difference. The number of tests required was similar WB-MRI (one [1–1]) and standard pathways (one [1–2]). Mean per-patient costs were £317 (273–361) for WBI-MRI and £620 (574–666) for standard pathways. Interpretation WB-MRI staging pathways have similar accuracy to standard pathways, and reduce the staging time and costs. Funding UK National Institute...

Vibrio vulnificus has been shown to be the causative agent of two types of human illnesses with distinguishing routes of infections and manifestations (5). The first entails dermal infection via open wound, which can become necrotic in some cases. The second and more severe type results in disease and often death of immunocompromised individuals following the ingestion of raw shellfish. The victim most often has a preexisting condition that results in high levels of serum iron. These high iron levels have been shown to enhance the pathogenicity of V. vulnificus. The iron mouse model was implemented to mimic the septicemic state of a patient with high serum iron levels, demonstrating the increase of virulence potential in the presence of excess iron (36).While the extent of infection in both disease states is reliant upon the expression of numerous virulence factors, the negatively charged polysaccharide capsule has been shown to protect this organism from the immune system in animal models (31). As a result, the expression of capsular polysaccharide (CPS) is believed to be a primary virulence factor of V. vulnificus that is essential for pathogenicity. Although clinical strains of V. vulnificus are encapsulated, the ability to express CPS is often lost, as witnessed in the laboratory, resulting in a nonencapsulated spontaneous mutant that is no longer virulent and appears translucent. Nomenclature commonly used in the laboratory and herein to describe colony morphology is that of opaque (O) for an encapsulated strain and translucent (T) for a nonencapsulated strain. The event leading to or resulting in the loss of capsule expression is not understood; it is seemingly a spontaneous, random happening that can be visualized on the surface of an agar plate.The capsule of V. vulnificus has been partially described, both phenotypically and genetically. Multiple capsule types exist, with the carbohydrate composition characteristically acidic, containing many amino sugars, including galactosamine, fucosamine, glucosamine, and quinovosamine (7). The repeating unit is believed to consist of four sugars, with common residues shared among encapsulated strains expressing different capsule types (24). Recently, Wright et al. (37) identified a genetic locus that encodes the transport of a group 1-like CPS in an encapsulated strain of V. vulnificus. Because of these previous studies, it is anticipated that the capsule gene complex of V. vulnificus is comprised of genes that correspond to previously defined characteristics of the CPS, such as carbohydrate composition and grouping.We proposed to locate the capsule gene complex by using transposon mutagenesis. Selection and genetic analysis of four nonencapsulated transposon mutants has led to the identification of two types of loci. Numerous genes involved in capsular synthesis and expression have been identified which do correspond to possible capsule typing and phenotypic characteristics. In addition, an integron-like region has been located, similar to that of the super integr...

Septins are important components of the cytoskeleton that are highly conserved in eukaryotes and play major roles in cytokinesis, patterning, and many developmental processes. Septins form heteropolymers which assemble into higher-order structures including rings, filaments, and gauzes. In contrast to actin filaments and microtubules, the molecular mechanism by which septins assemble is not well-understood. Here, we report that in the filamentous fungus Aspergillus nidulans, four core septins form heteropolymeric complexes. AspE, a fifth septin lacking in unicellular yeasts, interacts with only one of the core septins, and only during multicellular growth. AspE is required for proper localization of three of the core septins, and requires this same subset of core septins for its own unique cortical localization. The ΔaspE mutant lacks developmentally-specific septin higher-order structures and shows reduced spore production and slow growth with low temperatures and osmotic stress. Our results show that at least two distinct septin heteropolymer populations co-exist in A. nidulans, and that while AspE is not a subunit of either heteropolymer, it is required for assembly of septin higher-order structures found in multicellular development.

Background Whole-body MRI (WB-MRI) could be an alternative to multimodality staging of colorectal cancer, but its diagnostic accuracy, effect on staging times, number of tests needed, cost, and effect on treatment decisions are unknown. We aimed to prospectively compare the diagnostic accuracy and efficiency of WB-MRI-based staging pathways with standard pathways in colorectal cancer. Methods The Streamline C trial was a prospective, multicentre trial done in 16 hospitals in England. Eligible patients were 18 years or older, with newly diagnosed colorectal cancer. Exclusion criteria were severe systemic disease, pregnancy, contraindications to MRI, or polyp cancer. Patients underwent WB-MRI, the result of which was withheld until standard staging investigations were complete and the first treatment decision made. The multidisciplinary team recorded its treatment decision based on standard investigations, then on the WB-MRI staging pathway (WB-MRI plus additional tests generated), and finally on all tests. The primary outcome was difference in per-patient sensitivity for metastases between standard and WB-MRI staging pathways against a consensus reference standard at 12 months, in the per-protocol population. Secondary outcomes were difference in per-patient specificity for metastatic disease detection between standard and WB-MRI staging pathways, differences in treatment decisions, staging efficiency (time taken, test number, and costs), and per-organ sensitivity and specificity for metastases and per-patient agreement for local T and N stage. This trial is registered with the International Standard Randomised Controlled Trial registry, number ISRCTN43958015, and is complete.