Pink verrucous plaque in a man with systemic mastocytosis

Porokeratosis ptychotropica is a rare and commonly misdiagnosed subtype of porokeratosis involving the body folds. We present a 53-year-old man with systemic mastocytosis who presented with a pruritic, verrucous plaque in the gluteal fold that showed multiple cornoid lamellae on histopathologic evaluation, diagnostic of porokeratosis ptychotropica. Various treatments have been reported, including topical corticosteroids, retinoids, vitamin D analogs, calcineurin inhibitors, imiquimod, phototherapy, cryotherapy, or ablative laser therapy, but recurrences are common

Confirmatory structural validation and refinement of the Recurrent Urinary Tract Infection Symptom Scale

AbstractObjectivesTo confirm the structural validity of the Recurrent Urinary Tract Infection Symptom Scale (RUTISS), determining whether a bifactor model appropriately fits the questionnaire's structure and identifying areas for refinement. Used in conjunction with established clinical testing methods, this patient‐reported outcome measure addresses the urgent need to validate the patient perspective.Patients and methodsA clinically and demographically diverse sample of 389 people experiencing recurrent UTI across 37 countries (96.9% female biological sex, aged 18–87 years) completed the RUTISS online. A bifactor graded response model was fitted to the data, identifying potential items for deletion if they indicated significant differential item functioning (DIF) based on sociodemographic characteristics, contributed to local item dependence or demonstrated poor fit or discrimination capability.ResultsThe final RUTISS comprised a 3‐item symptom frequency section, a 1‐item global rating of change scale and an 11‐item general ‘rUTI symptom and pain severity’ subscale with four sub‐factor domains measuring ‘urinary symptoms’, ‘urinary presentation’, ‘UTI pain and discomfort’ and ‘bodily sensations’. The bifactor model fit indices were excellent (root mean square error of approximation [RMSEA] = 0.041, comparative fit index [CFI] = 0.995, standardised root mean square residual [SRMSR] = 0.047), and the mean‐square fit statistics indicated that all items were productive for measurement (mean square fit indices [MNSQ] = 0.64 – 1.29). Eighty‐one per cent of the common model variance was accounted for by the general factor and sub‐factors collectively, and all factor loadings were greater than 0.30 and communalities greater than 0.60. Items indicated high discrimination capability (slope parameters > 1.35).ConclusionThe 15‐item RUTISS is a patient‐generated, psychometrically robust questionnaire that dynamically assesses the patient experience of recurrent UTI symptoms and pain. This brief tool offers the unique opportunity to enhance patient‐centred care by supporting shared decision‐making and patient monitoring

Performance Evaluation of Cetacean Species Distribution Models Developed Using Generalized Additive Models and Boosted Regression Trees

Species distribution models (SDMs) are important management tools for highly mobile marine species because they provide spatially and temporally explicit information on animal distribution. Two prevalent modeling frameworks used to develop SDMs for marine species are generalized additive models (GAMs) and boosted regression trees (BRTs), but comparative studies have rarely been conducted; most rely on presence-only data; and few have explored how features such as species distribution characteristics affect model performance. Since the majority of marine species BRTs have been used to predict habitat suitability, we first compared BRTs to GAMs that used presence/absence as the response variable. We then compared results from these habitat suitability models to GAMs that predict species density (animals per km2) because density models built with a subset of the data used here have previously received extensive validation. We compared both the explanatory power (i.e., model goodness of fit) and predictive power (i.e., performance on a novel dataset) of the GAMs and BRTs for a taxonomically diverse suite of cetacean species using a robust set of systematic survey data (1991–2014) within the California Current Ecosystem. Both BRTs and GAMs were successful at describing overall distribution patterns throughout the study area for the majority of species considered, but when predicting on novel data, the density GAMs exhibited substantially greater predictive power than both the presence/absence GAMs and BRTs, likely due to both the different response variables and fitting algorithms. Our results provide an improved understanding of some of the strengths and limitations of models developed using these two methods. These results can be used by modelers developing SDMs and resource managers tasked with the spatial management of marine species to determine the best modeling technique for their question of interest

Performance evaluation of cetacean species distribution models developed using generalized additive models and boosted regression trees

Species distribution models (SDMs) are important management tools for highly mobile marine species because they provide spatially and temporally explicit information on animal distribution. Two prevalent modeling frameworks used to develop SDMs for marine species are generalized additive models (GAMs) and boosted regression trees (BRTs), but comparative studies have rarely been conducted; most rely on presence-only data; and few have explored how features such as species distribution characteristics affect model performance. Since the majority of marine species BRTs have been used to predict habitat suitability, we first compared BRTs to GAMs that used presence/absence as the response variable. We then compared results from these habitat suitability models to GAMs that predict species density (animals per km2) because density models built with a subset of the data used here have previously received extensive validation. We compared both the explanatory power (i.e., model goodness of fit) and predictive power (i.e., performance on a novel dataset) of the GAMs and BRTs for a taxonomically diverse suite of cetacean species using a robust set of systematic survey data (1991–2014) within the California Current Ecosystem. Both BRTs and GAMs were successful at describing overall distribution patterns throughout the study area for the majority of species considered, but when predicting on novel data, the density GAMs exhibited substantially greater predictive power than both the presence/absence GAMs and BRTs, likely due to both the different response variables and fitting algorithms. Our results provide an improved understanding of some of the strengths and limitations of models developed using these two methods. These results can be used by modelers developing SDMs and resource managers tasked with the spatial management of marine species to determine the best modeling technique for their question of interest

New ophthalmosaurid ichthyosaurs from the European lower cretaceous demonstrate extensive ichthyosaur survival across the Jurassic–Cretaceous boundary

Background Ichthyosauria is a diverse clade of marine amniotes that spanned most of the Mesozoic. Until recently, most authors interpreted the fossil record as showing that three major extinction events affected this group during its history: one during the latest Triassic, one at the Jurassic–Cretaceous boundary (JCB), and one (resulting in total extinction) at the Cenomanian-Turonian boundary. The JCB was believed to eradicate most of the peculiar morphotypes found in the Late Jurassic, in favor of apparently less specialized forms in the Cretaceous. However, the record of ichthyosaurs from the Berriasian–Barremian interval is extremely limited, and the effects of the end-Jurassic extinction event on ichthyosaurs remains poorly understood. Methodology/Principal Findings Based on new material from the Hauterivian of England and Germany and on abundant material from the Cambridge Greensand Formation, we name a new ophthalmosaurid, Acamptonectes densus gen. et sp. nov. This taxon shares numerous features with Ophthalmosaurus, a genus now restricted to the Callovian–Berriasian interval. Our phylogenetic analysis indicates that Ophthalmosauridae diverged early in its history into two markedly distinct clades, Ophthalmosaurinae and Platypterygiinae, both of which cross the JCB and persist to the late Albian at least. To evaluate the effect of the JCB extinction event on ichthyosaurs, we calculated cladogenesis, extinction, and survival rates for each stage of the Oxfordian–Barremian interval, under different scenarios. The extinction rate during the JCB never surpasses the background extinction rate for the Oxfordian–Barremian interval and the JCB records one of the highest survival rates of the interval. Conclusions/Significance There is currently no evidence that ichthyosaurs were affected by the JCB extinction event, in contrast to many other marine groups. Ophthalmosaurid ichthyosaurs remained diverse from their rapid radiation in the Middle Jurassic to their total extinction at the beginning of the Late Cretaceous

Engaging End-users to Inform the Development of the Global Standard for the Identification of Key Biodiversity Areas

We report results from an end-user engagement process, convened by the International Union for Conservation of Nature (IUCN), which informed the development of the Global Standard for the Identification of Key Biodiversity Areas. Key Biodiversity Areas are sites contributing significantly to the global persistence of biodiversity. We used a mixed methods approach involving interviews and an online questionnaire with end-users to determine their needs and concerns in relation to the Key Biodiversity Area approach. We found a remarkable level of convergence in end-user opinion on 12 important topics. Four topics resulted in a divergence in end-user opinion requiring further dialogue and consideration, including: (i) the value of a global standard compared to various national approaches; (ii) the prioritisation of Key Biodiversity Areas over other areas; (iii) whether Key Biodiversity Area data should be made freely available; and (iv) whether or not development activities should be permitted in Key Biodiversity Areas. Our results informed the development of the Global Standard for the Identification of Key Biodiversity Areas and a new governance structure, the Key Biodiversity Area Consultative Forum, which provides a mechanism for ongoing dialogue with end-users. We conclude by sharing five good practice recommendations for future end-user engagement processes

A qualitative study of community pharmacists’ clinical decision-making skills.

In recent years, self-care has been in the forefront of UK health policy [1], with community pharmacies being promoted as a first point of contact for patients [2], when seeking advice for the treatment of a variety of conditions and minor ailments. As more medicines have become available without prescription this has led to community pharmacists dealing with a wider range of presenting problems and spending more time on making clinical decisions. Aims / objectives The area of how community pharmacists make a clinical diagnosis is under-researched. The aim of this exploratory study was to gain an initial insight on how community pharmacists make clinical decisions in order to reach a diagnosis. Method A qualitative methodology was employed where semi-structured, face-to-face interviews were conducted with community pharmacists that had been practicing for at least six months at the time of the interviews and did not hold, or were working towards, a prescribing qualification. Pharmacists were identified through snow balling sampling and consent sheets sent to their pharmacies’ registered address. Pharmacists who returned completed consent forms were recruited to the study. All interviews were audio recorded and transcribed ad verbatim. Interviews were analysed, with a team-based approach, using a clinical reasoning based framework analysis to identify themes and subthemes. Ethical approval was granted by the ethics committee at the University of Wolverhampton. Results Eight interviews were conducted across England, with five male and three female pharmacists, who had been practicing for periods ranging from one to forty years. The major theme that emerged from the analysis was the poor diagnostic knowledge and ability of the pharmacists and a non-evidence based approach to decision-making. Pharmacists constantly used and overly relied on mnemonic methods both for diagnostic purposes and product selection. Their motives within consultations appeared to be establishing an appropriate product to recommend, rather than the need to establish a diagnosis, and the inability to differentiate between the two processes. However, they did have a sense of the limitations of the methods they used and an awareness for the need to ‘delve deeper’ during consultations but could not articulate how or why this was the case. Themes and sub-themes are explained using confirmatory quotes from the data. Discussion or Conclusion The findings of this study suggest that even though community pharmacists are tasked with advising symptom-presenting patients, their poor clinical reasoning skills are preventing them from reaching appropriate diagnoses. In order for community pharmacists to better perform this role, greater emphasis should be given in teaching and practicing clinical reasoning skills during their studies and through continuous professional development. The study is limited by its small sample size. 1. Department of Health. The NHS Plan. A Plan for Investment, A Plan for Reform [Internet]. London: National Health Service; 2000 [cited 6 October 2012]. Available from: http://webarchive.nationalarchives.gov.uk/+/www.dh.gov.uk/en/publicationsandstatistics/publications/publicationspolicyandguidance/dh_4002960 2. Royal Pharmaceutical Society. Improving Urgent and Emergency care through better use of pharmacists [Internet]; 2014 [cited 5 October 2016]. Available from: http://www.rpharms.com/policy-pdfs/urgent-and-emergency-care.pd

Appropriate use criteria in dermatopathology: Initial recommendations from the American Society of Dermatopathology

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/145218/1/cup13142.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/145218/2/cup13142_am.pd

Neoamphimedine Circumvents Metnase-Enhanced DNA Topoisomerase IIα Activity Through ATP-Competitive Inhibition

Type IIα DNA topoisomerase (TopoIIα) is among the most important clinical drug targets for the treatment of cancer. Recently, the DNA repair protein Metnase was shown to enhance TopoIIα activity and increase resistance to TopoIIα poisons. Using in vitro DNA decatenation assays we show that neoamphimedine potently inhibits TopoIIα-dependent DNA decatenation in the presence of Metnase. Cell proliferation assays demonstrate that neoamphimedine can inhibit Metnase-enhanced cell growth with an IC50 of 0.5 μM. Additionally, we find that the apparent Km of TopoIIα for ATP increases linearly with higher concentrations of neoamphimedine, indicating ATP-competitive inhibition, which is substantiated by molecular modeling. These findings support the continued development of neoamphimedine as an anticancer agent, particularly in solid tumors that over-express Metnase

Reimagining the potential of Earth observations for ecosystem service assessments

The benefits nature provides to people, called ecosystem services, are increasingly recognized and accounted for in assessments of infrastructure development, agricultural management, conservation prioritization, and sustainable sourcing. These assessments are often limited by data, however, a gap with tremendous potential to be filled through Earth observations (EO), which produce a variety of data across spatial and temporal extents and resolutions. Despite widespread recognition of this potential, in practice few ecosystem service studies use EO. Here, we identify challenges and opportunities to using EO in ecosystem service modeling and assessment. Some challenges are technical, related to data awareness, processing, and access. These challenges require systematic investment in model platforms and data management. Other challenges are more conceptual but still systemic; they are byproducts of the structure of existing ecosystem service models and addressing them requires scientific investment in solutions and tools applicable to a wide range of models and approaches. We also highlight new ways in which EO can be leveraged for ecosystem service assessments, identifying promising new areas of research. More widespread use of EO for ecosystem service assessment will only be achieved if all of these types of challenges are addressed. This will require non-traditional funding and partnering opportunities from private and public agencies to promote data exploration, sharing, and archiving. Investing in this integration will be reflected in better and more accurate ecosystem service assessments worldwide