A multi-centre randomised controlled trial comparing radiofrequency and mechanical occlusion chemically assisted ablation of varicose veins - final results of the Venefit versus Clarivein for varicose veins trial

BACKGROUND: Endovenous thermal ablation has revolutionised varicose vein treatment. New non-thermal techniques such as mechanical occlusion chemically assisted endovenous ablation (MOCA) allow treatment of entire trunks with single anaesthetic injections. Previous non-randomised work has shown reduced pain post-operatively with MOCA. This study presents a multi-centre randomised controlled trial assessing the difference in pain during truncal ablation using MOCA and radiofrequency endovenous ablation (RFA) with six months' follow-up. METHODS: Patients undergoing local anaesthetic endovenous ablation for primary varicose veins were randomised to either MOCA or RFA. Pain scores using Visual Analogue Scale and number scale (0-10) during truncal ablation were recorded. Adjunctive procedures were completed subsequently. Pain after phlebectomy was not assessed. Patients were reviewed at one and six months with clinical scores, quality of life scores and duplex ultrasound assessment of the treated leg. RESULTS: A total of 170 patients were recruited over a 21-month period from 240 screened. Patients in the MOCA group experienced significantly less maximum pain during the procedure by Visual Analogue Scale (MOCA median 15 mm (interquartile range 7-36 mm) versus RFA 34 mm (interquartile range 16-53 mm), p = 0.003) and number scale (MOCA median 3 (interquartile range 1-5) versus RFA 4 mm (interquartile range 3-6.5), p = 0.002). 'Average' pain scores were also significantly less in the MOCA group; 74% underwent simultaneous phlebectomy. Occlusion rates, clinical severity scores, disease specific and generic quality of life scores were similar between groups at one and six months. There were two deep vein thromboses, one in each group. CONCLUSION: Pain secondary to truncal ablation is less painful with MOCA than RFA with similar short-term technical, quality of life and safety outcomes

Evaluation of early and late presentation of patients with ocular mucous membrane pemphigoid to two major tertiary referral hospitals in the United Kingdom

PURPOSE: Ocular mucous membrane pemphigoid (OcMMP) is a sight-threatening autoimmune disease in which referral to specialists units for further management is a common practise. This study aims to describe referral patterns, disease phenotype and management strategies in patients who present with either early or established disease to two large tertiary care hospitals in the United Kingdom.\ud \ud PATIENTS AND METHODS: In all, 54 consecutive patients with a documented history of OcMMP were followed for 24 months. Two groups were defined: (i) early-onset disease (EOD:<3 years, n=26, 51 eyes) and (ii) established disease (EstD:>5 years, n=24, 48 eyes). Data were captured at first clinic visit, and at 12 and 24 months follow-up. Information regarding duration, activity and stage of disease, visual acuity (VA), therapeutic strategies and clinical outcome were analysed.\ud \ud RESULTS: Patients with EOD were younger and had more severe conjunctival inflammation (76% of inflamed eyes) than the EstD group, who had poorer VA (26.7%=VA<3/60, P<0.01) and more advanced disease. Although 40% of patients were on existing immunosuppression, 48% required initiation or switch to more potent immunotherapy. In all, 28% (14) were referred back to the originating hospitals for continued care. Although inflammation had resolved in 78% (60/77) at 12 months, persistence of inflammation and progression did not differ between the two phenotypes. Importantly, 42% demonstrated disease progression in the absence of clinically detectable inflammation.\ud \ud CONCLUSIONS: These data highlight that irrespective of OcMMP phenotype, initiation or escalation of potent immunosuppression is required at tertiary hospitals. Moreover, the conjunctival scarring progresses even when the eye remains clinically quiescent. Early referral to tertiary centres is recommended to optimise immunosuppression and limit long-term ocular damage.\ud \u

A New Class of Small Molecule Inhibitor of BMP Signaling

Growth factor signaling pathways are tightly regulated by phosphorylation and include many important kinase targets of interest for drug discovery. Small molecule inhibitors of the bone morphogenetic protein (BMP) receptor kinase ALK2 (ACVR1) are needed urgently to treat the progressively debilitating musculoskeletal disease fibrodysplasia ossificans progressiva (FOP). Dorsomorphin analogues, first identified in zebrafish, remain the only BMP inhibitor chemotype reported to date. By screening an assay panel of 250 recombinant human kinases we identified a highly selective 2-aminopyridine-based inhibitor K02288 with in vitro activity against ALK2 at low nanomolar concentrations similar to the current lead compound LDN-193189. K02288 specifically inhibited the BMP-induced Smad pathway without affecting TGF-β signaling and induced dorsalization of zebrafish embryos. Comparison of the crystal structures of ALK2 with K02288 and LDN-193189 revealed additional contacts in the K02288 complex affording improved shape complementarity and identified the exposed phenol group for further optimization of pharmacokinetics. The discovery of a new chemical series provides an independent pharmacological tool to investigate BMP signaling and offers multiple opportunities for pre-clinical development

MATERNAL PREVALENCE OF TOXOPLASMA ANTIBODY BASED ON ANONYMOUS NEONATAL SEROSURVEY - A GEOGRAPHICAL ANALYSIS

A total of 12902 neonatal samples collected on absorbent paper for routine metabolic screening were tested anonymously for antibodies to toxoplasma. Seroprevalence varied from 19.5% in inner London, to 11.6% in suburban London, and 7.6% in non-metropolitan districts. Much of this variation appeared to be associated with the proportions of livebirths in each district to women born outside the UK. However, additional geographical variation remained and seroprevalence in UK-born women was estimated to be 12.7% in inner London. 7.5% in suburban London, and 5.5% in non-metropolitan areas. These estimates are considerably lower than any previously reported in antenatal sera in the UK. The wide geographical variation highlights a need for further research to determine the relative importance of different routes of transmission

Matrix-assisted laser desorption ionization time-of-flight mass spectrometry for rapid identification of mold and yeast cultures of Penicillium marneffei

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Feeding spectra and activity of the freshwater crab Trichodactylus kensleyi (Decapoda: Brachyura: Trichodactylidae) at La Plata basin

Background: In inland water systems, it is important to characterize the trophic links in order to identify the ‘trophic species’ and, from the studies of functional diversity, understand the dynamics of matter and energy in these environments. The aim of this study is to analyze the natural diet of Trichodactylus kensleyi of subtropical rainforest streams and corroborate the temporal variation in the trophic activity during day hours. Results: A total of 15 major taxonomic groups were recognized in gut contents. The index of relative importance identified the following main prey items in decreasing order of importance: vegetal remains, oligochaetes, chironomid larvae, and algae. A significant difference was found in the amount of full stomachs during day hours showing a less trophic activity at midday and afternoon. The index of relative importance values evidenced the consumption of different prey according to day moments. Results of the gut content indicate that T. kensleyi is an omnivorous crab like other trichodactylid species. Opportunistic behavior is revealed by the ingestion of organisms abundant in streams such as oligochaetes and chironomid larvae. The consumption of allochthonous plant debris shows the importance of this crab as shredder in subtropical streams. However, the effective assimilation of plant matter is yet unknown in trichodactylid crabs. Conclusions: This research provides knowledge that complements previous studies about trophic relationships of trichodactylid crabs and supported the importance of T. kensleyi in the transference of energy and matter from benthic community and riparian sources to superior trophic levels using both macro- and microfauna.Fil: Williner, Verónica. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto Nacional de Limnología. Universidad Nacional del Litoral. Instituto Nacional de Limnología; Argentina. Universidad Nacional del Litoral. Facultad de Humanidades y Ciencias; ArgentinaFil: de Azevedo Carvalho, Debora. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto Nacional de Limnología. Universidad Nacional del Litoral. Instituto Nacional de Limnología; ArgentinaFil: Collins, Pablo Agustin. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto Nacional de Limnología. Universidad Nacional del Litoral. Instituto Nacional de Limnología; Argentina. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas; Argentin

On stability of discretizations of the Helmholtz equation (extended version)

We review the stability properties of several discretizations of the Helmholtz equation at large wavenumbers. For a model problem in a polygon, a complete $k$-explicit stability (including $k$-explicit stability of the continuous problem) and convergence theory for high order finite element methods is developed. In particular, quasi-optimality is shown for a fixed number of degrees of freedom per wavelength if the mesh size $h$ and the approximation order $p$ are selected such that $kh/p$ is sufficiently small and $p = O(\log k)$, and, additionally, appropriate mesh refinement is used near the vertices. We also review the stability properties of two classes of numerical schemes that use piecewise solutions of the homogeneous Helmholtz equation, namely, Least Squares methods and Discontinuous Galerkin (DG) methods. The latter includes the Ultra Weak Variational Formulation

Set optimization - a rather short introduction

Recent developments in set optimization are surveyed and extended including various set relations as well as fundamental constructions of a convex analysis for set- and vector-valued functions, and duality for set optimization problems. Extensive sections with bibliographical comments summarize the state of the art. Applications to vector optimization and financial risk measures are discussed along with algorithmic approaches to set optimization problems

Preserving the impossible: conservation of soft-sediment hominin footprint sites and strategies for three-dimensional digital data capture.

Human footprints provide some of the most publically emotive and tangible evidence of our ancestors. To the scientific community they provide evidence of stature, presence, behaviour and in the case of early hominins potential evidence with respect to the evolution of gait. While rare in the geological record the number of footprint sites has increased in recent years along with the analytical tools available for their study. Many of these sites are at risk from rapid erosion, including the Ileret footprints in northern Kenya which are second only in age to those at Laetoli (Tanzania). Unlithified, soft-sediment footprint sites such these pose a significant geoconservation challenge. In the first part of this paper conservation and preservation options are explored leading to the conclusion that to 'record and digitally rescue' provides the only viable approach. Key to such strategies is the increasing availability of three-dimensional data capture either via optical laser scanning and/or digital photogrammetry. Within the discipline there is a developing schism between those that favour one approach over the other and a requirement from geoconservationists and the scientific community for some form of objective appraisal of these alternatives is necessary. Consequently in the second part of this paper we evaluate these alternative approaches and the role they can play in a 'record and digitally rescue' conservation strategy. Using modern footprint data, digital models created via optical laser scanning are compared to those generated by state-of-the-art photogrammetry. Both methods give comparable although subtly different results. This data is evaluated alongside a review of field deployment issues to provide guidance to the community with respect to the factors which need to be considered in digital conservation of human/hominin footprints

Astrobiological Complexity with Probabilistic Cellular Automata

Search for extraterrestrial life and intelligence constitutes one of the major endeavors in science, but has yet been quantitatively modeled only rarely and in a cursory and superficial fashion. We argue that probabilistic cellular automata (PCA) represent the best quantitative framework for modeling astrobiological history of the Milky Way and its Galactic Habitable Zone. The relevant astrobiological parameters are to be modeled as the elements of the input probability matrix for the PCA kernel. With the underlying simplicity of the cellular automata constructs, this approach enables a quick analysis of large and ambiguous input parameters' space. We perform a simple clustering analysis of typical astrobiological histories and discuss the relevant boundary conditions of practical importance for planning and guiding actual empirical astrobiological and SETI projects. In addition to showing how the present framework is adaptable to more complex situations and updated observational databases from current and near-future space missions, we demonstrate how numerical results could offer a cautious rationale for continuation of practical SETI searches.Comment: 37 pages, 11 figures, 2 tables; added journal reference belo