Actinic keratoses show variable histological basal growth patterns - a proposed classification adjustment

Background: Common histological classification schemes of actinic keratoses (AK) do not evaluate growth patterns at basal epidermal aspects of AK. Until now, the importance of basal epidermal growth patterns of AK has not been studied. Objective: To investigate the extent of atypical keratinocytes throughout the epidermis and variation in basal growth patterns of AK. Methods: AK lesions occurring on the head/face from patients seen in routine practice were assessed histologically. We determined histological grade (AK I-III), basal growth patterns of atypical keratinocytes (crowding, budding, papillary sprouting) and accompanying parameters. Results: Of the 246 lesions included, 28.0% were histologically classified as AK I, 46.7% as AK II, and 25.2% as AK III. 26.4% of the basal growth patterns were classified as crowding (pro I), 49.6% as budding (pro II), 17.9% as papillary sprouting (pro III) and 6.1% without basal directed growth. No significant correlation of the histological AK I-III grading and underlying growth patterns was observed (P= 0.4666). However, adnexal structure involvement (OR= 2.37; 95%CI 1.21-4.65), infiltration (OR= 2.53; 95%CI 1.31-4.90) and increased number of vessels (OR= 2.56; 95%CI 1.42-4.65) were independent positive predictive markers for pro II and pro III basal growth patterns. Conclusions: Basal growth patterns (pro I-III) in AK do not correlate with the established AK I-III histological grading system. Besides the degree of upward extension, varying degrees of downward extension exist. Histological classification should consider both, upwards and downward growth patterns when assessing AK

Merged infrared catalogue

A compilation of equatorial coordinates, spectral types, magnitudes, and fluxes from five catalogues of infrared observations is presented. This first edition of the Merged Infrared Catalogue contains 11,201 oservations from the Two-Micron Sky Survey, Observations of Infrared Radiation from Cool Stars, the Air Force Geophysics Laboratory four Color Infrared Sky Survey and its Supplemental Catalog, and from Catalog of 10 micron Celestial Objects (HALL). This compilation is a by-product of a computerized infrared data base under development at Goddard Space Flight Center; the objective is to maintain a complete and current record of all infrared observations from 1 micron m to 1000 micron m of nonsolar system objects. These observations are being placed into a standardized system

Actinic keratosis area and severity index (AKASI) is associated with the incidence of squamous cell carcinoma

Background: Actinic keratoses (AKs) are commonly diagnosed clinically. Actinic keratosis area and severity index (AKASI) is a new easy-to-use tool to assess the severity of AK on the head. Objective: To determine the association between chronically UV-induced tumours such as basal cell carcinomas (BCC) or squamous cell carcinomas (SCC) and AKASI. Methods: We performed a retrospective analysis of patients who had undergone oncological surgery due to UV-induced tumours and who were assessed for AKASI and Physician's Global Assessment (PGA) prior to surgery. Statistical analysis was performed to evaluate correlation between AKASI, PGA and invasive carcinomas. Results: Of the 210 patients included, 26 patients had histologically diagnosed SCCs and presented with a median (range) AKASI of 6.9 (0 – 13.0) and PGA of 2 (0 - 4). In contrast, the 82 patients with BCCs showed a median (range) AKASI of 3.3 (0 -15.2) and PGA of 1 (0 - 4). The Mann-Whitney U test showed significant differences (p= 0.0018) between AKASI of patients with SCC and BCC. In addition, we found a significantly higher AKASI in patients with SCC compared to patients with non-invasive lesions like AK and Bowen disease (BD) (p= 0.0275). Spearman's coefficient of rank correlation between AKASI and PGA indicates that these measures of AK severity were strongly correlated (p< 0.0001; r = 0.90; 95%CI 0,865 to 0,920). Conclusions: Patients with SCC show significantly higher AKASI than patients with BCC or patients without invasive tumours. Hence, AKASI may be used to stratify risk for developing invasive SCC

Turbulent particle transport as a function of toroidal rotation in DIII-D H-mode plasmas

In this paper we show how changes in toroidal rotation, by controlling the injected torque, affect particle transport and confinement. The toroidal rotation is altered using the co- and counter neutral beam injection (NBI) in low collisionality H-mode plasmas on DIII-D (Luxon 2002 Nucl. Fusion 42 614) with dominant electron cyclotron heating (ECH). We find that there is no correlation between the toroidal rotation shear and the inverse density gradient, which is observed on AUG when T-e/T-i is varied using ECH (Angioni et al 2011 Phys. Rev. Lett. 107 215003). In DIII-D, we find that in a discharge with balanced torque injection, the E x B shear is smaller than the linear gyrokinetic growth rate for small k(theta)rho(s) for rho = 0.6-0.85. This results in lower particle confinement. In the co- and counter-injected discharges the E x B shear is larger or close to the linear growth rate at the plasma edge and both configurations have higher particle confinement. In order to measure particle transport, we use a small periodic perturbative gas puff. This gas puff perturbs the density profiles and allows us to extract the perturbed diffusion and inward pinch coefficients. We observe a strong increase in the inward particle pinch in the counter-torque injected plasma. Finally, the calculated quasi-linear particle flux, nor the linear growth rates using TGLF (Staebler et al 2005 Phys. Plasmas 12 102508) agree with experimental observations

Constraints to the sustainability of a ‘systematised’ approach to livestock marketing amongst smallholder cattle producers in South Africa

Commercialization of smallholder agriculture in South Africa is underpinned by reforms to improve livestock off-take in communal areas and engage smallholder farmers with formal markets. To achieve this, Custom Feeding Programmes (CFPs) were established to improve the condition of communal cattle prior to their sale into formal markets and to ‘systematise’ the informal marketing of cattle in communal areas by enabling participants to achieve higher informal market prices. We evaluate the sustainability of eight CFPs located in Eastern Cape Province in terms of their ability to add value to smallholder cattle production and encourage market participation. Communities with CFPs achieved a 16.6% mean cattle off-take rate, substantially higher than in most communal systems. Furthermore, cattle sold through CFPs attained a 17% higher mean selling price than those sold through other marketing channels. However, these benefits were mainly realized by better-off farmers with larger cattle herds and greater ability to transport animals to and from CFPs. More marginalized farmers, particularly women, had low participation. CFPs also face challenges to their sustainability, including inconsistent feed and water supplies, poor infrastructure and high staff turnover. Key to enhancing participation in CFPs, will be improving the way they are supported and embedded within communities

Numerical electrokinetics

A new lattice method is presented in order to efficiently solve the electrokinetic equations, which describe the structure and dynamics of the charge cloud and the flow field surrounding a single charged colloidal sphere, or a fixed array of such objects. We focus on calculating the electrophoretic mobility in the limit of small driving field, and systematically linearise the equations with respect to the latter. This gives rise to several subproblems, each of which is solved by a specialised numerical algorithm. For the total problem we combine these solvers in an iterative procedure. Applying this method, we study the effect of the screening mechanism (salt screening vs. counterion screening) on the electrophoretic mobility, and find a weak non-trivial dependence, as expected from scaling theory. Furthermore, we find that the orientation of the charge cloud (i. e. its dipole moment) depends on the value of the colloid charge, as a result of a competition between electrostatic and hydrodynamic effects.Comment: accepted for publication in Journal of Physics Condensed Matter (proceedings of the 2012 CODEF conference

Particle transport in low-collisionality H-mode plasmas on DIII-D

In this paper we show that changing from an ion temperature gradient (ITG) to a trapped electron mode (TEM) dominant turbulence regime (based on linear gyrokinetic simulations) results experimentally in a strong density pump-out (defined as a reduction in line-averaged density) in low collisionality, low power H-mode plasmas. We vary the turbulence drive by changing the heating from predominantly ion heated using neutral beam injection to electron heated using electron cyclotron heating, which changes the T-e/T-i ratio and the temperature gradients. Perturbed gas puff experiments show an increase in transport outside rho = 0.6, through a strong increase in the perturbed diffusion coefficient and a decrease in the inward pinch. Linear gyrokinetic simulations with TGLF show an increase in the particle flux outside the mid-radius. In conjunction an increase in intermediate-scale length density fluctuations is observed, which indicates an increase in turbulence intensity at typical TEM wavelengths. However, although the experimental changes in particle transport agree with a change from ITG to TEM turbulence regimes, we do not observe a reduction in the core rotation at mid-radius, nor a rotation reversal

A diffusive system driven by a battery or by a smoothly varying field

We consider the steady state of a one dimensional diffusive system, such as the symmetric simple exclusion process (SSEP) on a ring, driven by a battery at the origin or by a smoothly varying field along the ring. The battery appears as the limiting case of a smoothly varying field, when the field becomes a delta function at the origin. We find that in the scaling limit, the long range pair correlation functions of the system driven by a battery turn out to be very different from the ones known in the steady state of the SSEP maintained out of equilibrium by contact with two reservoirs, even when the steady state density profiles are identical in both models

Cutaneous squamous cell carcinomas are associated with basal proliferating actinic keratoses

Background: In addition to the extent of atypical keratinocytes throughout the epidermis, actinic keratoses (AKs) are histologically characterized by downward directed basal layer expansion. It is not known if this growth pattern correlates with the risk of developing invasive squamous cell carcinoma (iSCC). Objective: To characterize the prevalence of downward directed basal layer expansion of AKs adjacent to iSCC. Methods: The epidermis overlying and adjacent to iSCCs was assessed histologically. We determined the histological grade (AKI‐III), basal growth pattern (PROI‐III) and accompanying parameters such as adnexal involvement. Results: Of 307 lesions, 52.4% of AKs were histologically classified as AKI, 38.1% as AKII, and 6.8% as AKIII (chi‐squared; P<0.0001). 2.6% of adjacent epidermis did not show any atypical keratinocytes. The epidermis adjacent to iSCCs was classified as having a PROI basal growth pattern in 25.7%, PROII in 31.9%, and PROIII in 39.4% cases. 2.9% of AKs showed no basal growth (chi‐squared; P<0.0001).118 (48.8%) AKs showed extension into adnexal structures. These AKs were graded as PROI in 18.6%, PROII in 30.5%, and PROIII in 50.8%. The epidermis above iSCCs could only be assessed for upwards directed growth and showed no significant differences in the three AK grades (P=0.4211). Conclusions: Basal proliferative AKs as well as atypical keratinocytes restricted to the lower third of the epidermis are most commonly seen adjacent to iSCC with less evidence for full thickness epidermal dysplasia. Our study supports the important role of dysplastic keratinocytes in the epidermal basal layer and their potential association with iSCC

Antibacterial Activity of and Resistance to Small Molecule Inhibitors of the ClpP Peptidase

There is rapidly mounting evidence that intracellular proteases in bacteria are compelling targets for antibacterial drugs. Multiple reports suggest that the human pathogen Mycobacterium tuberculosis and other actinobacteria may be particularly sensitive to small molecules that perturb the activities of self-compartmentalized peptidases, which catalyze intracellular protein turnover as components of ATP-dependent proteolytic machines. Here, we report chemical syntheses and evaluations of structurally diverse β-lactones, which have a privileged structure for selective, suicide inhibition of the self-compartmentalized ClpP peptidase. β-Lactones with certain substituents on the α- and β-carbons were found to be toxic to M. tuberculosis. Using an affinity-labeled analogue of a bioactive β-lactone in a series of chemical proteomic experiments, we selectively captured the ClpP1P2 peptidase from live cultures of two different actinobacteria that are related to M. tuberculosis. Importantly, we found that the growth inhibitory β-lactones also inactivate the M. tuberculosis ClpP1P2 peptidase in vitro via formation of a covalent adduct at the ClpP2 catalytic serine. Given the potent antibacterial activity of these compounds and their medicinal potential, we sought to identify innate mechanisms of resistance. Using a genome mining strategy, we identified a genetic determinant of β-lactone resistance in Streptomyces coelicolor, a non-pathogenic relative of M. tuberculosis. Collectively, these findings validate the potential of ClpP inhibition as a strategy in antibacterial drug development and define a mechanism by which bacteria could resist the toxic effects of ClpP inhibitors.National Institutes of Health (U.S.) (Grant GM-101988