Relearning the lesson – amelanotic malignant melanoma: a case report

Although not as common as the other melanomas, amelanotic melanoma often evades diagnosis by masquerading as other pathology. A high index of suspicion is therefore required for early and appropriate intervention. We present a patient who was diagnosed and managed as having paronychia of the middle finger while in actual fact he had a subungual amelanotic melanoma. By the time of his referral to the orthopaedic team it had progressed to an advanced stage. Our case underlies the importance of early recognition and referral of this rare but malignant lesion by primary care physicians

Fitness Landscape Transformation through a Single Amino Acid Change in the Rho Terminator

Regulatory networks allow organisms to match adaptive behavior to the complex and dynamic contingencies of their native habitats. Upon a sudden transition to a novel environment, the mismatch between the native behavior and the new niche provides selective pressure for adaptive evolution through mutations in elements that control gene expression. In the case of core components of cellular regulation and metabolism, with broad control over diverse biological processes, such mutations may have substantial pleiotropic consequences. Through extensive phenotypic analyses, we have characterized the systems-level consequences of one such mutation (rho*) in the global transcriptional terminator Rho of Escherichia coli. We find that a single amino acid change in Rho results in a massive change in the fitness landscape of the cell, with widely discrepant fitness consequences of identical single locus perturbations in rho* versus rhoWT backgrounds. Our observations reveal the extent to which a single regulatory mutation can transform the entire fitness landscape of the cell, causing a massive change in the interpretation of individual mutations and altering the evolutionary trajectories which may be accessible to a bacterial population

Histopathological changes in the human larynx following expanded polytetrafluroethylene (Gore-Tex(®)) implantation

BACKGROUND: Expanded polytetrafluroethelyne (e PTFE, Gore-Tex(®)) has been advocated as an implant material for medialization of the vocal fold. Animal studies involving rabbits and a porcine model have demonstrated host tolerance of the implant. There have been no reports describing the histological changes in a human laryngectomy specimen with a Gore-Tex implant. CASE PRESENTATION: The histological findings in a laryngectomy specimen of a patient previously implanted with e PTFE for medialization of a paralyzed vocal fold following excision of a vagal neurofibroma were studied. Histopathology revealed a mild foreign-body giant cell granulomatous reaction with some associated fibrosis. The granulomatous response was limited to the periphery of the Gore-Tex and although it closely followed the profile of the material it did not encroach into or significantly break up the material. There was no significant neutrophilic or lymphocytic inflammation. CONCLUSIONS: Our findings are consistent with the animal models confirming that Gore-Tex implantation does not result in a significant granulomatous reaction in the human larynx over a 13-month period. Moreover, there is no evidence of resorption or infection. Further, the lack of lymphocytes in association with the granulomas indicates that there is no significant immunological hypersensitivity. Histologically, the slight permeation by connective tissue is similar to that seen in Gore-Tex vascular and cardiac implants. The degree of the slight giant cell response appears to be dependent on the profile of the material; a sharp edge incited more of a response than a flat surface

Evidence for Centromere Drive in the Holocentric Chromosomes of Caenorhabditis

In monocentric organisms with asymmetric meiosis, the kinetochore proteins, such as CENH3 and CENP-C, evolve adaptively to counterbalance the deleterious effects of centromere drive, which is caused by the expansion of centromeric satellite repeats. The selection regimes that act on CENH3 and CENP-C genes have not been analyzed in organisms with holocentric chromosomes, although holocentrism is speculated to have evolved to suppress centromere drive. We tested both CENH3 and CENP-C for positive selection in several species of the holocentric genus Caenorhabditis using the maximum likelihood approach and sliding-window analysis. Although CENP-C did not show any signs of positive selection, positive selection has been detected in the case of CENH3. These results support the hypothesis that centromere drive occurs in Nematoda, at least in the telokinetic meiosis of Caenorhabditis

Garden and landscape-scale correlates of moths of differing conservation status: significant effects of urbanization and habitat diversity

Moths are abundant and ubiquitous in vegetated terrestrial environments and are pollinators, important herbivores of wild plants, and food for birds, bats and rodents. In recent years, many once abundant and widespread species have shown sharp declines that have been cited by some as indicative of a widespread insect biodiversity crisis. Likely causes of these declines include agricultural intensification, light pollution, climate change, and urbanization; however, the real underlying cause(s) is still open to conjecture. We used data collected from the citizen science Garden Moth Scheme (GMS) to explore the spatial association between the abundance of 195 widespread British species of moth, and garden habitat and landscape features, to see if spatial habitat and landscape associations varied for species of differing conservation status. We found that associations with habitat and landscape composition were species-specific, but that there were consistent trends in species richness and total moth abundance. Gardens with more diverse and extensive microhabitats were associated with higher species richness and moth abundance; gardens near to the coast were associated with higher richness and moth abundance; and gardens in more urbanized locations were associated with lower species richness and moth abundance. The same trends were also found for species classified as increasing, declining and vulnerable under IUCN (World Conservation Union) criteria

Using Web Search Query Data to Monitor Dengue Epidemics: A New Model for Neglected Tropical Disease Surveillance

A variety of obstacles, including bureaucracy and lack of resources, delay detection and reporting of dengue and exist in many countries where the disease is a major public health threat. Surveillance efforts have turned to modern data sources such as Internet usage data. People often seek health-related information online and it has been found that the frequency of, for example, influenza-related web searches as a whole rises as the number of people sick with influenza rises. Tools have been developed to help track influenza epidemics by finding patterns in certain web search activity. However, few have evaluated whether this approach would also be effective for other diseases, especially those that affect many people, that have severe consequences, or for which there is no vaccine. In this study, we found that aggregated, anonymized Google search query data were also capable of tracking dengue activity in Bolivia, Brazil, India, Indonesia and Singapore. Whereas traditional dengue data from official sources are often not available until after a long delay, web search query data is available for analysis within a day. Therefore, because it could potentially provide earlier warnings, these data represent a valuable complement to traditional dengue surveillance

Searching for dark matter with plasma haloscopes

We summarize the recent progress of the Axion Longitudinal Plasma Haloscope (ALPHA) Consortium, a new experimental collaboration to build a plasma haloscope to search for axions and dark photons. The plasma haloscope is a novel method for the detection of the resonant conversion of light dark matter to photons. ALPHA will be sensitive to QCD axions over almost a decade of parameter space, potentially discovering dark matter and resolving the strong CP problem. Unlike traditional cavity haloscopes, which are generally limited in volume by the Compton wavelength of the dark matter, plasma haloscopes use a wire metamaterial to create a tuneable artificial plasma frequency, decoupling the wavelength of light from the Compton wavelength and allowing for much stronger signals. We develop the theoretical foundations of plasma haloscopes and discuss recent experimental progress. Finally, we outline a baseline design for ALPHA and show that a full-scale experiment could discover QCD axions over almost a decade of parameter space

Development and validation of a short version of the Partnership Self-Assessment Tool (PSAT) among professionals in Dutch disease-management partnerships

Background: The extent to which partnership synergy is created within quality improvement programmes in the Netherlands is unknown. In this article, we describe the psychometric testing of the Partnership Self-Assessment Tool (PSAT) among professionals in twenty-two disease-management partnerships participating in quality improvement projects focused on chronic care in the Netherlands. Our objectives are to validate the PSAT in the Netherlands and to reduce the number of items of the original PSAT while maintaining validity and reliability. Methods. The Dutch version of the PSAT was tested in twenty-two disease-management partnerships with 218 professionals. We tested the instrument by means of structural equation modelling, and examined its validity and reliability. Results: After eliminating 14 items, the confirmatory factor analyses revealed good indices of fit with the resulting 15-item PSAT-Short version (PSAT-S). Internal consistency as represented by Cronbach's alpha ranged from acceptable (0.75) for the 'efficiency' subscale to excellent for the 'leadership' subscale (0.87). Convergent validity was provided with high correlations of the partnership dimensions and partnership synergy (ranged from 0.512 to 0.609) and high correlations with chronic illness care (ranged from 0.447 to 0.329). Conclusion: The psychometric properties and convergent validity of the PSAT-S were satisfactory rendering it a valid and reliable instrument for assessing partnership syne

Genome-wide association study identifies a variant in HDAC9 associated with large vessel ischemic stroke

Genetic factors have been implicated in stroke risk but few replicated associations have been reported. We conducted a genome-wide association study (GWAS) in ischemic stroke and its subtypes in 3,548 cases and 5,972 controls, all of European ancestry. Replication of potential signals was performed in 5,859 cases and 6,281 controls. We replicated reported associations between variants close to PITX2 and ZFHX3 with cardioembolic stroke, and a 9p21 locus with large vessel stroke. We identified a novel association for a SNP within the histone deacetylase 9(HDAC9) gene on chromosome 7p21.1 which was associated with large vessel stroke including additional replication in a further 735 cases and 28583 controls (rs11984041, combined P = 1.87×10−11, OR=1.42 (95% CI) 1.28-1.57). All four loci exhibit evidence for heterogeneity of effect across the stroke subtypes, with some, and possibly all, affecting risk for only one subtype. This suggests differing genetic architectures for different stroke subtypes