Recent advances in diagnosing cutaneous melanomas

Early detection of lesions while minimising the unnecessary removal of benign lesions is the clinical aim in melanoma diagnosis. In this context, several non-invasive diagnostic modalities, such as dermoscopy, total body photography, and reflectance confocal microscopy have emerged in recent years aiming at increasing diagnostic accuracy. The main developments in this field are the integration of dermoscopy and digital photography into clinical practice

Pigmented nodular melanoma: the predictive value of dermoscopic features using multivariate analysis

BACKGROUND: Nodular melanoma (NM), representing 10-30% of all melanomas, plays a major role in global mortality related to melanoma. Nonetheless, the literature on dermoscopy of NM is scanty. OBJECTIVES: To assess odds ratios (ORs) to quantify dermoscopic features of pigmented NM vs. pigmented superficial spreading melanoma (SSM), and pigmented nodular nonmelanocytic and benign melanocytic lesions. METHODS: To assess the presence or absence of global patterns and dermoscopic criteria, digitized images of 457 pigmented skin lesions from patients with a histopathological diagnosis of NM (n = 75), SSM (n = 93), and nodular nonmelanocytic and benign melanocytic lesions (n = 289; namely, 39 basal cell carcinomas, 85 seborrhoeic keratoses, 81 blue naevi, and 84 compound/dermal naevi) were retrospectively collected and blindly evaluated by three observers. RESULTS: Multivariate analysis showed that ulceration (OR 4.07), homogeneous disorganized pattern (OR 10.76), and homogeneous blue pigmented structureless areas (OR 2.37) were significantly independent prognostic factors for NM vs. SSM. Multivariate analysis of dermoscopic features of NM vs. nonmelanocytic and benign melanocytic lesions showed that the positive correlating features leading to a significantly increased risk of NM were asymmetric pigmentation (OR 6.70), blue-black pigmented areas (OR 7.15), homogeneous disorganized pattern (OR 9.62), a combination of polymorphous vessels and milky-red globules/areas (OR 23.65), and polymorphous vessels combined with homogeneous red areas (OR 33.88). CONCLUSIONS: Dermoscopy may be helpful in improving the recognition of pigmented NM by revealing asymmetric pigmentation, blue-black pigmented areas, homogeneous disorganized pattern and abnormal vascular structures, including polymorphous vessels, milky-red globules/areas and homogeneous red areas

A method for dynamic subtraction MR imaging of the liver

BACKGROUND: Subtraction of Dynamic Contrast-Enhanced 3D Magnetic Resonance (DCE-MR) volumes can result in images that depict and accurately characterize a variety of liver lesions. However, the diagnostic utility of subtraction images depends on the extent of co-registration between non-enhanced and enhanced volumes. Movement of liver structures during acquisition must be corrected prior to subtraction. Currently available methods are computer intensive. We report a new method for the dynamic subtraction of MR liver images that does not require excessive computer time. METHODS: Nineteen consecutive patients (median age 45 years; range 37–67) were evaluated by VIBE T1-weighted sequences (TR 5.2 ms, TE 2.6 ms, flip angle 20°, slice thickness 1.5 mm) acquired before and 45s after contrast injection. Acquisition parameters were optimized for best portal system enhancement. Pre and post-contrast liver volumes were realigned using our 3D registration method which combines: (a) rigid 3D translation using maximization of normalized mutual information (NMI), and (b) fast 2D non-rigid registration which employs a complex discrete wavelet transform algorithm to maximize pixel phase correlation and perform multiresolution analysis. Registration performance was assessed quantitatively by NMI. RESULTS: The new registration procedure was able to realign liver structures in all 19 patients. NMI increased by about 8% after rigid registration (native vs. rigid registration 0.073 ± 0.031 vs. 0.078 ± 0.031, n.s., paired t-test) and by a further 23% (0.096 ± 0.035 vs. 0.078 ± 0.031, p < 0.001, paired t-test) after non-rigid realignment. The overall average NMI increase was 31%. CONCLUSION: This new method for realigning dynamic contrast-enhanced 3D MR volumes of liver leads to subtraction images that enhance diagnostic possibilities for liver lesions

Retained Surgical Items and Minimally Invasive Surgery

A retained surgical item is a surgical patient safety problem. Early reports have focused on the epidemiology of retained-item cases and the identification of patient risk factors for retention. We now know that retention has very little to do with patient characteristics and everything to do with operating room culture. It is a perception that minimally invasive procedures are safer with regard to the risk of retention. Minimally invasive surgery is still an operation where an incision is made and surgical tools are placed inside of patients, so these cases are not immune to the problem of inadvertent retention. Retained surgical items occur because of problems with multi-stakeholder operating room practices and problems in communication. The prevention of retained surgical items will therefore require practice change, knowledge, and shared information between all perioperative personnel

How accurate and statistically robust are catalytic site predictions based on closeness centrality?

<p>Abstract</p> <p>Background</p> <p>We examine the accuracy of enzyme catalytic residue predictions from a network representation of protein structure. In this model, amino acid α-carbons specify vertices within a graph and edges connect vertices that are proximal in structure. Closeness centrality, which has shown promise in previous investigations, is used to identify important positions within the network. Closeness centrality, a global measure of network centrality, is calculated as the reciprocal of the average distance between vertex <it>i </it>and all other vertices.</p> <p>Results</p> <p>We benchmark the approach against 283 structurally unique proteins within the Catalytic Site Atlas. Our results, which are inline with previous investigations of smaller datasets, indicate closeness centrality predictions are statistically significant. However, unlike previous approaches, we specifically focus on residues with the very best scores. Over the top five closeness centrality scores, we observe an average true to false positive rate ratio of 6.8 to 1. As demonstrated previously, adding a solvent accessibility filter significantly improves predictive power; the average ratio is increased to 15.3 to 1. We also demonstrate (for the first time) that filtering the predictions by residue identity improves the results even more than accessibility filtering. Here, we simply eliminate residues with physiochemical properties unlikely to be compatible with catalytic requirements from consideration. Residue identity filtering improves the average true to false positive rate ratio to 26.3 to 1. Combining the two filters together has little affect on the results. Calculated p-values for the three prediction schemes range from 2.7E-9 to less than 8.8E-134. Finally, the sensitivity of the predictions to structure choice and slight perturbations is examined.</p> <p>Conclusion</p> <p>Our results resolutely confirm that closeness centrality is a viable prediction scheme whose predictions are statistically significant. Simple filtering schemes substantially improve the method's predicted power. Moreover, no clear effect on performance is observed when comparing ligated and unligated structures. Similarly, the CC prediction results are robust to slight structural perturbations from molecular dynamics simulation.</p

A stable genetic polymorphism underpinning microbial syntrophy

Syntrophies are metabolic cooperations, whereby two organisms co-metabolize a substrate in an interdependent manner. Many of the observed natural syntrophic interactions are mandatory in the absence of strong electron acceptors, such that one species in the syntrophy has to assume the role of electron sink for the other. While this presents an ecological setting for syntrophy to be beneficial, the potential genetic drivers of syntrophy remain unknown to date. Here, we show that the syntrophic sulfate-reducing species Desulfovibrio vulgaris displays a stable genetic polymorphism, where only a specific genotype is able to engage in syntrophy with the hydrogenotrophic methanogen Methanococcus maripaludis. This 'syntrophic' genotype is characterized by two genetic alterations, one of which is an in-frame deletion in the gene encoding for the ion-translocating subunit cooK of the membrane-bound COO hydrogenase. We show that this genotype presents a specific physiology, in which reshaping of energy conservation in the lactate oxidation pathway enables it to produce sufficient intermediate hydrogen for sustained M. maripaludis growth and thus, syntrophy. To our knowledge, these findings provide for the first time a genetic basis for syntrophy in nature and bring us closer to the rational engineering of syntrophy in synthetic microbial communities