Sunscreens - Which and what for?

It is well established that sun exposure is the main cause for the development of skin cancer. Chronic continuous UV radiation is believed to induce malignant melanoma, whereas intermittent high-dose UV exposure contributes to the occurrence of actinic keratosis as precursor lesions of squamous cell carcinoma as well as basal cell carcinoma. Not only photocarcinogenesis but also the mechanisms of photoaging have recently become apparent. In this respect the use of sunscreens seemed to prove to be more and more important and popular within the last decades. However, there is still inconsistency about the usefulness of sunscreens. Several studies show that inadequate use and incomplete UV spectrum efficacy may compromise protection more than previously expected. The sunscreen market is crowded by numerous products. Inorganic sunscreens such as zinc oxide and titanium oxide have a wide spectral range of activity compared to most of the organic sunscreen products. It is not uncommon for organic sunscreens to cause photocontact allergy, but their cosmetic acceptability is still superior to the one given by inorganic sunscreens. Recently, modern galenic approaches such as micronization and encapsulation allow the development of high-quality inorganic sunscreens. The potential systemic toxicity of organic sunscreens has lately primarily been discussed controversially in public, and several studies show contradictory results. Although a matter of debate, at present the sun protection factor (SPF) is the most reliable information for the consumer as a measure of sunscreen filter efficacy. In this context additional tests have been introduced for the evaluation of not only the protective effect against erythema but also protection against UV-induced immunological and mutational effects. Recently, combinations of UV filters with agents active in DNA repair have been introduced in order to improve photoprotection. This article reviews the efficacy of sunscreens in the prevention of epithelial and nonepithelial skin cancer, the effect on immunosuppression and the value of the SPF as well as new developments on the sunscreen market. Copyright (C) 2005 S. Karger AG, Basel

Mitochondrial and nuclear markers reveal a lack of genetic structure in the entocommensal nemertean Malacobdella arrokeana in the Patagonian gulfs

Abstract Malacobdella arrokeana is an entocommensal nemertean exclusively found in the bivalve geoduck Panopea abbreviata, and it is the only representative of the genus in the southern hemisphere. To characterize its genetic diversity, population structure and recent demographic history, we conducted the first genetic survey on this species, using sequence data for the cytochrome oxidase I gene (COI), 16S rRNA (16S) and the internal transcribed spacer (ITS2). Only four different ITS2 genotypes were found in the whole sample, and the two main haplotypes identified in the mitochondrial dataset were present among all localities with a diversity ranging from 0.583 to 0.939. Nucleotide diversity was low (p = 0.001?0.002). No significant genetic structure was detected between populations, and mismatch distribution patterns and neutrality tests results are consistent with a population in expansion or under selection. Analysis of molecular variance (AMOVA) revealed that the largest level of variance observed was due to intrapopulation variation (100, 100 and 94.39 % for 16S, COI and ITS2, respectively). Fst values were also non-significant. The observed lack of population structure is likely due to high levels of genetic connectivity in combination with the lack or permeability of biogeographic barriers and episodes of habitat modification.Fil: Fernandez Alfaya, Jose Elias. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Nacional Patagónico; ArgentinaFil: Bigatti, Gregorio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Nacional Patagónico; ArgentinaFil: Machordom, Annie. Consejo Superior de Investigaciones Cientificas. Museo Nacional de Cs. Naturales; Españ

DPRESS: Localizing estimates of predictive uncertainty

<p>Abstract</p> <p>Background</p> <p>The need to have a quantitative estimate of the uncertainty of prediction for QSAR models is steadily increasing, in part because such predictions are being widely distributed as tabulated values disconnected from the models used to generate them. Classical statistical theory assumes that the error in the population being modeled is independent and identically distributed (IID), but this is often not actually the case. Such inhomogeneous error (heteroskedasticity) can be addressed by providing an individualized estimate of predictive uncertainty for each particular new object <it>u</it>: the standard error of prediction <it>s</it>_ucan be estimated as the non-cross-validated error <it>s</it>_t*for the closest object <it>t</it>* in the training set adjusted for its separation <it>d </it>from <it>u </it>in the descriptor space relative to the size of the training set.</p> <p><display-formula><graphic file="1758-2946-1-11-i1.gif"/></display-formula></p> <p>The predictive uncertainty factor <it>γ</it>_t*is obtained by distributing the internal predictive error sum of squares across objects in the training set based on the distances between them, hence the acronym: <it>D</it>istributed <it>PR</it>edictive <it>E</it>rror <it>S</it>um of <it>S</it>quares (DPRESS). Note that <it>s</it>_t*and <it>γ</it>_t*are characteristic of each training set compound contributing to the model of interest.</p> <p>Results</p> <p>The method was applied to partial least-squares models built using 2D (molecular hologram) or 3D (molecular field) descriptors applied to mid-sized training sets (<it>N </it>= 75) drawn from a large (<it>N </it>= 304), well-characterized pool of cyclooxygenase inhibitors. The observed variation in predictive error for the external 229 compound test sets was compared with the uncertainty estimates from DPRESS. Good qualitative and quantitative agreement was seen between the distributions of predictive error observed and those predicted using DPRESS. Inclusion of the distance-dependent term was essential to getting good agreement between the estimated uncertainties and the observed distributions of predictive error. The uncertainty estimates derived by DPRESS were conservative even when the training set was biased, but not excessively so.</p> <p>Conclusion</p> <p>DPRESS is a straightforward and powerful way to reliably estimate individual predictive uncertainties for compounds outside the training set based on their distance to the training set and the internal predictive uncertainty associated with its nearest neighbor in that set. It represents a sample-based, <it>a posteriori </it>approach to defining applicability domains in terms of localized uncertainty.</p

Enumerating Pathways of Proton Abstraction Based on a Spatial and Electrostatic Analysis of Residues in the Catalytic Site

The pathways of proton abstraction (PA), a key aspect of most catalytic reactions, is often controversial and highly debated. Ultrahigh-resolution diffraction studies, molecular dynamics, quantum mechanics and molecular mechanic simulations are often adopted to gain insights in the PA mechanisms in enzymes. These methods require expertise and effort to setup and can be computationally intensive. We present a push button methodology – Proton abstraction Simulation (PRISM) – to enumerate the possible pathways of PA in a protein with known 3D structure based on the spatial and electrostatic properties of residues in the proximity of a given nucleophilic residue. Proton movements are evaluated in the vicinity of this nucleophilic residue based on distances, potential differences, spatial channels and characteristics of the individual residues (polarity, acidic, basic, etc). Modulating these parameters eliminates their empirical nature and also might reveal pathways that originate from conformational changes. We have validated our method using serine proteases and concurred with the dichotomy in PA in Class A β-lactamases, both of which are hydrolases. The PA mechanism in a transferase has also been corroborated. The source code is made available at www.sanchak.com/prism

A critical review of the research literature on Six Sigma, Lean and StuderGroup's Hardwiring Excellence in the United States: the need to demonstrate and communicate the effectiveness of transformation strategies in healthcare

<p>Abstract</p> <p>Background</p> <p>U.S. healthcare organizations are confronted with numerous and varied transformational strategies promising improvements along all dimensions of quality and performance. This article examines the peer-reviewed literature from the U.S. for evidence of effectiveness among three current popular transformational strategies: Six Sigma, Lean/Toyota Production System, and Studer's Hardwiring Excellence.</p> <p>Methods</p> <p>The English language health, healthcare management, and organizational science literature (up to December 2007) indexed in Medline, Web of Science, ABI/Inform, Cochrane Library, CINAHL, and ERIC was reviewed for studies on the aforementioned transformation strategies in healthcare settings. Articles were included if they: appeared in a peer-reviewed journal; described a specific intervention; were not classified as a pilot study; provided quantitative data; and were not review articles. Nine references on Six Sigma, nine on Lean/Toyota Production System, and one on StuderGroup meet the study's eligibility criteria.</p> <p>Results</p> <p>The reviewed studies universally concluded the implementations of these transformation strategies were successful in improving a variety of healthcare related processes and outcomes. Additionally, the existing literature reflects a wide application of these transformation strategies in terms of both settings and problems. However, despite these positive features, the vast majority had methodological limitations that might undermine the validity of the results. Common features included: weak study designs, inappropriate analyses, and failures to rule out alternative hypotheses. Furthermore, frequently absent was any attention to changes in organizational culture or substantial evidence of lasting effects from these efforts.</p> <p>Conclusion</p> <p>Despite the current popularity of these strategies, few studies meet the inclusion criteria for this review. Furthermore, each could have been improved substantially in order to ensure the validity of the conclusions, demonstrate sustainability, investigate changes in organizational culture, or even how one strategy interfaced with other concurrent and subsequent transformation efforts. While informative results can be gleaned from less rigorous studies, improved design and analysis can more effectively guide healthcare leaders who are motivated to transform their organizations and convince others of the need to employ such strategies. Demanding more exacting evaluation of projects consultants, or partnerships with health management researchers in academic settings, can support such efforts.</p

TESS hunt for young and maturing exoplanets (THYME). VI. an 11 Myr giant planet transiting a very-low-mass star in lower centaurus crux

Mature super-Earths and sub-Neptunes are predicted to be ≃ Jovian radius when younger than 10 Myr. Thus, we expect to find 5–15 R⊕ planets around young stars even if their older counterparts harbor none. We report the discovery and validation of TOI 1227b, a 0.85 ± 0.05 RJ (9.5 R⊕) planet transiting a very-low-mass star (0.170 ± 0.015 M⊙) every 27.4 days. TOI 1227's kinematics and strong lithium absorption confirm that it is a member of a previously discovered subgroup in the Lower Centaurus Crux OB association, which we designate the Musca group. We derive an age of 11 ± 2 Myr for Musca, based on lithium, rotation, and the color–magnitude diagram of Musca members. The TESS data and ground-based follow-up show a deep (2.5%) transit. We use multiwavelength transit observations and radial velocities from the IGRINS spectrograph to validate the signal as planetary in nature, and we obtain an upper limit on the planet mass of ≃0.5 MJ. Because such large planets are exceptionally rare around mature low-mass stars, we suggest that TOI 1227b is still contracting and will eventually turn into one of the more common <5 R⊕ planets