BRAF mutational status as a prognostic marker for survival in malignant melanoma: a systematic review and meta-analysis.

Background: The analysis of the BRAF mutational status has been established as a standard procedure during diagnosis of advanced malignant melanoma due to the fact that BRAF inhibitors constitute a cornerstone in the treatment of metastatic disease. However, the general impact of BRAF mutational status on survival remains unclear. Our study aimed to assess the underlying prognostic significance of BRAF mutant versus wild type (WT) malignant melanoma on overall survival (OS), disease-free survival (DFS) and progression-free survival (PFS).Material and methods: A systematic literature search in EMBASE, Medline and Cochrane CENTRAL was performed. Studies were included if they reported survival outcomes for BRAF mutant versus WT patients as hazard ratios (HR) or in Kaplan-Meier (KM) curves. Random-effects meta-analysis models were used to pool HRs across the studies.Results: Data from 52 studies, representing 7519 patients, were pooled for analysis of OS. The presence of a BRAF mutation was statistically significantly associated with a reduced OS (HR [95% confidence interval (CI)]: 1.23 [1.09-1.38]), however, with substantial heterogeneity between the studies (I2: 58.0%). Meta-regression and sensitivity analyses showed that age, sex and BRAF mutation testing method did not have a significant effect on the OS HR. BRAF mutant melanoma showed comparable effect on DFS to non-BRAF mutant melanoma in stage I-III melanoma (combined HR: 1.16, 95% CI: 0.92-1.46), and on PFS in stage III-IV (HR: 0.98 (95% CI: 0.68-1.40)).Conclusion: Although there was substantial heterogeneity between the studies, the overall results demonstrated a poorer prognosis and OS in patients harbouring BRAF mutations. Future studies should take this into account when evaluating epidemiological data and treatment effects of new interventions in patients with malignant melanoma.

Non-harmonic potential of a single beam optical trap.

Since the invention of optical traps based on a single laser beam, the potential experienced by a trapped specimen has been assumed harmonic, in the central part of the trap. It has remained unknown to what extent the harmonic region persists and what occurs beyond. By employing a new method, we have forced the trapped object to extreme positions, significantly further than previously achieved in a single laser beam, and thus experimentally explore an extended trapping potential. The potential stiffens considerably as the bead moves to extreme positions and therein is not well described by simple Uhlenbeck theories.

Optical tweezers cause physiological damage to Escherichia coli and Listeria bacteria.

We investigated the degree of physiological damage to bacterial cells caused by optical trapping using a 1,064-nm laser. The physiological condition of the cells was determined by their ability to maintain a pH gradient across the cell wall; healthy cells are able to maintain a pH gradient over the cell wall, whereas compromised cells are less efficient, thus giving rise to a diminished pH gradient. The pH gradient was measured by fluorescence ratio imaging microscopy by incorporating a pH-sensitive fluorescent probe, green fluorescent protein or 5(6)-carboxyfluorescein diacetate succinimidyl ester, inside the bacterial cells. We used the gram-negative species Escherichia coli and three gram-positive species, Listeria monocytogenes, Listeria innocua, and Bacillus subtilis. All cells exhibited some degree of physiological damage, but optically trapped E. coli and L. innocua cells and a subpopulation of L. monocytogenes cells, all grown with shaking, showed only a small decrease in pH gradient across the cell wall when trapped by 6 mW of laser power for 60 min. However, another subpopulation of Listeria monocytogenes cells exhibited signs of physiological damage even while trapped at 6 mW, as did B. subtilis cells. Increasing the laser power to 18 mW caused the pH gradient of both Listeria and E. coli cells to decrease within minutes. Moreover, both species of Listeria exhibited more-pronounced physiological damage when grown without shaking than was seen in cells grown with shaking, and the degree of damage is therefore also dependent on the growth conditions.

Singularity during the onset of an electrohydrodynamic spout

When one applies a sufficiently large electrical field normal to the surface of a conducting liquid the fluid rises in a spout to form a jet leaving the surface. Using high-speed photography, we have studied the development of this electrohydrodynamical spout and found that its curvature and height can be scaled with respect to a critical time indicating the presence of a critical point in the dynamics underlying the instability.