Malignant melanoma of the rectum: a case report

<p>Abstract</p> <p>Introduction</p> <p>Anorectal melanoma represents an unusual but important presentation of rectal malignancy. There have only been a few cases reported and the optimum management for this condition is still undecided, however, prompt diagnosis is essential. We have outlined current treatment options.</p> <p>Case presentation</p> <p>We report a case of malignant melanoma of the rectum in a 55-year-old Caucasian man presenting as an emergency with rectal bleeding. Biopsies were taken of the fleshy mass found on digital examination, which confirmed malignant melanoma. No distant metastases were found. He underwent an abdominoperineal resection. We report the surgical management of this rare and aggressive malignancy.</p> <p>Conclusion</p> <p>Treatment options for this condition are divergent. Surgical management varies from wide local excision to abdominoperineal resection. Clinical awareness in both medical and surgical clinics is required for prompt diagnosis and treatment.</p

Pelizaeus-Merzbacher-Like disease presentation of MCT8 mutated male subjects.

Pelizaeus-Merzbacher Disease is an X-linked hypomyelinatiing leukodystrophy. We report mutations in the thyroid hormone transporter gene MCT8 in 11% of 53 families affected by hypomyelinating leukodystrophies of unknown aetiology. The 12 MCT8 mutated patients express initially a Pelizaeus-Merzbacher-Like disease phenotype with a latter unusual improvement of magnetic resonance imaging white matter signal despite absence of clinical progression. This observation underlines the interest of determining both free T3 and free T4 serum concentrations to screen for MCT8 mutations in young patients (<3 y) with a severe Pelizaeus-Merzbacher-Like disease presentation or older severe mentally retarded male patients with "hypomyelinated" regions

Hyperdoctrines and the Ontology of Stratified Semantics

I present a version of Kit Fine's stratified semantics for the logic RWQ and define a natural family of related structures called RW hyperdoctrines. After proving that RWQ is sound with respect to RW hyperdoctrines, we show how to construct, for each stratified model, a hyperdoctrine that verifies precisely the same sentences. Completeness of RWQ for hyperdoctrinal semantics then follows from completeness for stratified semantics, which is proved in an appendix. By examining the base category of RW hyperdoctrines, we find reason to be worried about the ontology of stratified models

The United States, PMSCs and the state monopoly on violence: Leading the way towards norm change

This is the author's accepted manuscript. The final published article is available from the link below. Copyright @ 2013 Sage.The proliferation of private military and security companies (PMSCs) in Iraq and Afghanistan has raised many questions regarding the use of armed force by private contractors. This article addresses the question of whether the increased acceptance of PMSCs indicates a transformation of the international norm regarding the state monopoly on the legitimate use of armed force. Drawing on theoretical approaches to the analysis of norm change, the article employs four measures to investigate possible changes in the strength and meaning of this norm: modifications in state behaviour, state responses to norm violation, the promulgation of varying interpretations of the norm in national and international laws and regulations, and changes in norm discourse. Based on an analysis of empirical evidence from the United States of America and its allies, the article concludes that these measures suggest that the USA is leading the way towards a transformation of the international norm of the state monopoly on violence, involving a revised meaning. Although this understanding has not yet been formally implemented in international law, it has allowed a growing number of countries to tolerate, accept or legalize the use of armed force by PMSCs in the international arena.The Alexander von Humboldt Foundation and the Peace Research Institute Frankfurt

A de Sitter Hoedown

Rotating black holes in de Sitter space are known to have interesting limits where the temperatures of the black hole and cosmological horizon are equal. We give a complete description of the thermal phase structure of all allowed rotating black hole configurations. Only one configuration, the rotating Nariai limit, has the black hole and cosmological horizons both in thermal and rotational equilibrium, in that both the temperatures and angular velocities of the two horizons coincide. The thermal evolution of the spacetime is shown to lead to the pure de Sitter spacetime, which is the most entropic configuration. We then provide a comprehensive study of the wave equation for a massless scalar in the rotating Nariai geometry. The absorption cross section at the black hole horizon is computed and a condition is found for when the scattering becomes superradiant. The boundary-to-boundary correlators at finite temperature are computed at future infinity. The quasinormal modes are obtained in explicit form. Finally, we obtain an expression for the expectation value of the number of particles produced at future infinity starting from a vacuum state with no incoming particles at past infinity. Some of our results are used to provide further evidence for a recent holographic proposal between the rotating Nariai geometry and a two-dimensional conformal field theory.Comment: 35 + 1 pages, 9 figures; v3: typos correcte

A pragmatic cluster randomised trial evaluating three implementation interventions

Background Implementation research is concerned with bridging the gap between evidence and practice through the study of methods to promote the uptake of research into routine practice. Good quality evidence has been summarised into guideline recommendations to show that peri-operative fasting times could be considerably shorter than patients currently experience. The objective of this trial was to evaluate the effectiveness of three strategies for the implementation of recommendations about peri-operative fasting. Methods A pragmatic cluster randomised trial underpinned by the PARIHS framework was conducted during 2006 to 2009 with a national sample of UK hospitals using time series with mixed methods process evaluation and cost analysis. Hospitals were randomised to one of three interventions: standard dissemination (SD) of a guideline package, SD plus a web-based resource championed by an opinion leader, and SD plus plan-do-study-act (PDSA). The primary outcome was duration of fluid fast prior to induction of anaesthesia. Secondary outcomes included duration of food fast, patients' experiences, and stakeholders' experiences of implementation, including influences. ANOVA was used to test differences over time and interventions. Results Nineteen acute NHS hospitals participated. Across timepoints, 3,505 duration of fasting observations were recorded. No significant effect of the interventions was observed for either fluid or food fasting times. The effect size was 0.33 for the web-based intervention compared to SD alone for the change in fluid fasting and was 0.12 for PDSA compared to SD alone. The process evaluation showed different types of impact, including changes to practices, policies, and attitudes. A rich picture of the implementation challenges emerged, including inter-professional tensions and a lack of clarity for decision-making authority and responsibility. Conclusions This was a large, complex study and one of the first national randomised controlled trials conducted within acute care in implementation research. The evidence base for fasting practice was accepted by those participating in this study and the messages from it simple; however, implementation and practical challenges influenced the interventions' impact. A set of conditions for implementation emerges from the findings of this study, which are presented as theoretically transferable propositions that have international relevance. Trial registration ISRCTN18046709 - Peri-operative Implementation Study Evaluation (POISE

Composition, Development, and Function of Uterine Innate Lymphoid Cells.

Innate lymphoid cells (ILCs), including NK cells, contribute to barrier immunity and tissue homeostasis. In addition to the role of uterine NK cells in placentation and fetal growth, other uterine ILCs (uILCs) are likely to play roles in uterine physiology and pathology. In this article, we report on the composition of uILCs in the endometrium during the luteal phase and in the decidua during early pregnancy. Whereas nonkiller uILC1s and uILC2s are barely detectable in mouse and not detected in humans, a sizeable population of uILC3s is found in human endometrium and decidua, which are mostly NCR(+) and partially overlap with previously described IL-22-producing uterine NK cells. Development of mouse uILC3 is Nfil3 independent, suggesting unique features of uILCs. Indeed, although the cytokine production profile of mouse uILCs recapitulates that described in other tissues, IL-5, IL-17, and IL-22 are constitutively produced by uILC2s and uILC3s. This study lays the foundation to understand how ILCs function in the specialized uterine mucosa, both in tissue homeostasis and barrier immunity and during pregnancy.Work supported by grants from the Wellcome Trust, the Medical Research Council, the British Heart Foundation and the Leukaemia & Lymphoma Research to FC. EB is the recipient of a Centre for Trophoblast Research Graduate Studentship. SB is the recipient of a Marie Curie FP7 Fellowship.This is the final version of the article. It first appeared from the American Association of Immunologists via http://dx.doi.org/10.4049/​jimmunol.150068

HUWE1 E3 ligase promotes PINK1/PARKINindependent mitophagy by regulating AMBRA1 activation via IKKa

The selective removal of undesired or damaged mitochondria by autophagy, known as mitophagy, is crucial for cellular homoeostasis, and prevents tumour diffusion, neurodegeneration and ageing. The pro-autophagic molecule AMBRA1 (autophagy/beclin-1 regulator-1) has been defined as a novel regulator of mitophagy in both PINK1/PARKIN-dependent and -independent systems. Here, we identified the E3 ubiquitin ligase HUWE1 as a key inducing factor in AMBRA1-mediated mitophagy, a process that takes place independently of the main mitophagy receptors. Furthermore, we show that mitophagy function of AMBRA1 is post-translationally controlled, upon HUWE1 activity, by a positive phosphorylation on its serine 1014. This modification is mediated by the IKKα kinase and induces structural changes in AMBRA1, thus promoting its interaction with LC3/GABARAP (mATG8) proteins and its mitophagic activity. Altogether, these results demonstrate that AMBRA1 regulates mitophagy through a novel pathway, in which HUWE1 and IKKα are key factors, shedding new lights on the regulation of mitochondrial quality control and homoeostasis in mammalian cells

Design and characterization of a direct ELISA for the detection and quantification of leucomalachite green

Malachite green (MG), a member of the N-methylated triphenylmethane class of dyes, has long been used to control fungal and protozoan infections in fish. MG is easily absorbed by fish during waterborne exposure and is rapidly metabolized into leucomalachite green (LMG), which is known for its long residence time in edible fish tissue. This paper describes the development of an enzyme-linked immunosorbent assay (ELISA) for the detection and quantification of LMG in fish tissue. This development includes a simple and versatile method for the conversion of LMG to monodesmethyl-LMG, which is then conjugated to bovine serum albumin (BSA) to produce an immunogenic material. Rabbit polyclonal antibodies are generated against this immunogen, purified and used to develop a direct competitive enzyme-linked immunosorbent assay (ELISA) for the screening and quantification of LMG in fish tissue. The assay performed well, with a limit of detection (LOD) and limit of quantification (LOQ) of 0.1 and 0.3 ng g−1 of fish tissue, respectively. The average extraction efficiency from a matrix of tilapia fillets was approximately 73% and the day-to-day reproducibility for these extractions in the assay was between 5 and 10%

The global distribution and burden of dengue.

Dengue is a systemic viral infection transmitted between humans by Aedes mosquitoes. For some patients, dengue is a life-threatening illness. There are currently no licensed vaccines or specific therapeutics, and substantial vector control efforts have not stopped its rapid emergence and global spread. The contemporary worldwide distribution of the risk of dengue virus infection and its public health burden are poorly known. Here we undertake an exhaustive assembly of known records of dengue occurrence worldwide, and use a formal modelling framework to map the global distribution of dengue risk. We then pair the resulting risk map with detailed longitudinal information from dengue cohort studies and population surfaces to infer the public health burden of dengue in 2010. We predict dengue to be ubiquitous throughout the tropics, with local spatial variations in risk influenced strongly by rainfall, temperature and the degree of urbanization. Using cartographic approaches, we estimate there to be 390 million (95% credible interval 284-528) dengue infections per year, of which 96 million (67-136) manifest apparently (any level of disease severity). This infection total is more than three times the dengue burden estimate of the World Health Organization. Stratification of our estimates by country allows comparison with national dengue reporting, after taking into account the probability of an apparent infection being formally reported. The most notable differences are discussed. These new risk maps and infection estimates provide novel insights into the global, regional and national public health burden imposed by dengue. We anticipate that they will provide a starting point for a wider discussion about the global impact of this disease and will help to guide improvements in disease control strategies using vaccine, drug and vector control methods, and in their economic evaluation