Complete Clearance of Resistant Granuloma Faciale With Pulsed Dye Laser After Pre-treatment With Mometasone and Tacrolimus

Introduction: Granuloma faciale is an uncommon inflammatory dermatosis which usually affects the face and is often resistant to treatment.Case Report: A 39-year-old English lady with Fitzpatrick skin phototype II presented with typical lesions of granuloma faciale, confirmed on biopsy, on her cheeks and nose. Treatment with ScleroPlus pulsed dye laser (Candela Corporation, Wayland, Mass) produced no visible improvement. The patient re-presented 5 years later with the same lesions, now more prominent. No improvement was noted with topical mometasone, however addition of topical tacrolimus caused significant flattening. Since the erythema and telangiectases persisted, treatment with ScleroPlus pulsed dye laser was re-attempted. Treatments were performed with a wavelength of 595 nm, pulse duration of 1.5 ms and 7 mm spot at a fluence of 8.5 J/cm2 in the first session and 9.5 J/cm2 in the subsequent 2 sessions. This resulted in complete resolution without scarring or pigmentary change. There was no recurrence at follow-up one year later.Conclusion: Our observation supports the use of combination therapy in resistant cases of granuloma faciale. One such combination would be the application of a topical corticosteroid and tacrolimus followed by pulsed dye laser

Anatomy, Biology and Concepts, Pertaining to Lung Cancer Stage Classification

AbstractThe proposed lung cancer stage classification system remains grounded in anatomic characteristics, although the large patient database contributing to this revision has dramatically expanded our body of knowledge. Predictably this has led to increased complexity due to the identification of an increasing number of subpopulations of patients. Patterns of clinical presentation characterizing these subgroups may provide clues about the propensity of tumors within a subgroup toward a particular pattern of biologic behavior. This article explores concepts regarding tumor biology that can be applied to the anatomically based new staging system

The Effect of Fe-Al Substitution on the Crystal Structure of MgSiO3 Bridgmanite

The crystal chemistry of ten well-characterized bridgmanite single-crystals with Fe and Al contents ranging from 0 to 0.40 atoms per two-cation formula units were investigated by single-crystal X-ray diffraction. Structural refinements indicate that Fe3+ and Al mainly occupy the Mg and Si sites, respectively, when present in similar proportions. Molar volumes of bridgmanite endmember components were refined using data from this and previous studies and found to decrease in the order Fe3+Fe3+O3 > MgFe3+O2.5 > Fe3+AlO3 > MgAlO2.5 > AlAlO3 > Fe2+SiO3 > MgSiO3. Fe3+AlO3 charge-coupled substitution leads to an anisotropic increase of B-O bond distances, resulting in more distorted octahedral B sites and in a more significant increase of the c-axis with respect to the a- and b-axes. Valence bond calculations indicate that the A site is more compressible than the B site for all bridgmanite samples studied, implying that octahedral tilting and distortion will dominate the bridgmanite compression mechanism. Guided by these crystal chemical observations, bulk moduli of bridgmanite endmember components were estimated using results of previous studies. The volume changes of equilibria controlling the speciation of bridgmanite components were then calculated at conditions relevant to the top of Earth's lower mantle. The proportion of oxygen vacancy components is predicted to decrease with pressure. While the stability of the bridgmanite Fe3+AlO3 component will drive charge disproportionation to produce iron metal at the top of the lower mantle, this appears to be much less favorable by 50 GPa. An increase in the proportion of the Fe3+Fe3+O3 bridgmanite component, however, may favor the formation of iron metal at higher pressures

Oxygen Vacancy Ordering in Aluminous Bridgmanite in the Earth's Lower Mantle

Oxygen vacancies (OVs), that charge-balance the replacement of octahedrally coordinated Si4+ by Al3+ in the mineral bridgmanite, will influence transport properties in the lower mantle but little is known about their stability and local structure. Using 27Al nuclear magnetic resonance (NMR) spectroscopy we have characterized OVs within six aluminous bridgmanite samples. In the resulting NMR spectra sixfold, fivefold, and fourfold coordinated Al species are resolved, in addition to near eightfold coordinated Al substituting for Mg. Fivefold coordinated Al is formed by single OV sites but fourfold coordination must result from short range ordering of OVs, producing OV clusters that may form through migration into twin domain walls. Characterizing the occurrence of such OV structures is an important prerequisite for understanding how transport properties change with depth and composition in the lower mantle

Autologous humanized PDX modeling for immuno-oncology recapitulates features of the human tumor microenvironment.

BACKGROUND: Interactions between immune and tumor cells are critical to determining cancer progression and response. In addition, preclinical prediction of immune-related drug efficacy is limited by interspecies differences between human and mouse, as well as inter-person germline and somatic variation. To address these gaps, we developed an autologous system that models the tumor microenvironment (TME) from individual patients with solid tumors. METHOD: With patient-derived bone marrow hematopoietic stem and progenitor cells (HSPCs), we engrafted a patient\u27s hematopoietic system in MISTRG6 mice, followed by transfer of patient-derived xenograft (PDX) tissue, providing a fully genetically matched model to recapitulate the individual\u27s TME. We used this system to prospectively study tumor-immune interactions in patients with solid tumor. RESULTS: Autologous PDX mice generated innate and adaptive immune populations; these cells populated the TME; and tumors from autologously engrafted mice grew larger than tumors from non-engrafted littermate controls. Single-cell transcriptomics revealed a prominent vascular endothelial growth factor A (VEGFA) signature in TME myeloid cells, and inhibition of human VEGF-A abrogated enhanced growth. CONCLUSIONS: Humanization of the interleukin 6 locus in MISTRG6 mice enhances HSPC engraftment, making it feasible to model tumor-immune interactions in an autologous manner from a bedside bone marrow aspirate. The TME from these autologous tumors display hallmarks of the human TME including innate and adaptive immune activation and provide a platform for preclinical drug testing

Understanding and Integrating Local Perceptions of Trees and Forests into Incentives for Sustainable Landscape Management

We examine five forested landscapes in Africa (Cameroon, Madagascar, and Tanzania) and Asia (Indonesia and Laos) at different stages of landscape change. In all five areas, forest cover (outside of protected areas) continues to decrease despite local people’s recognition of the importance of forest products and services. After forest conversion, agroforestry systems and fallows provide multiple functions and valued products, and retain significant biodiversity. But there are indications that such land use is transitory, with gradual simplification and loss of complex agroforests and fallows as land use becomes increasingly individualistic and profit driven. In Indonesia and Tanzania, farmers favor monocultures (rubber and oil palm, and sugarcane, respectively) for their high financial returns, with these systems replacing existing complex agroforests. In the study sites in Madagascar and Laos, investments in agroforests and new crops remain rare, despite government attempts to eradicate swidden systems and their multifunctional fallows. We discuss approaches to assessing local values related to landscape cover and associated goods and services. We highlight discrepancies between individual and collective responses in characterizing land use tendencies, and discuss the effects of accessibility on land management. We conclude that a combination of social, economic, and spatially explicit assessment methods is necessary to inform land use planning. Furthermore, any efforts to modify current trends will require clear incentives, such as through carbon finance. We speculate on the nature of such incentive schemes and the possibility of rewarding the provision of ecosystem services at a landscape scale and in a socially equitable manner