Low-dose methotrexate: not the hepatotoxic medication we once thought

Methotrexate is a highly efficacious and frequently utilised disease-modifying medication. Concern regarding methotrexate-related hepatotoxicity has impeded the widespread application of the drug, despite a lack of high-quality evidence demonstrating a causal relationship.Methotrexate monitoring guidelines differ across various specialities. A single centre audit (n=150) demonstrated monitoring guidelines are not adhered to in over 2/3rds of patients evaluated, and hepatological concern was a significant cause of methotrexate cessation. Risk factors for alternative causes of liver disease such as Non-alcoholic fatty liver disease were commonplace, and alcohol intake was poorly documented.A large cross-sectional study of 600 individuals attending outpatient rheumatology and dermatology secondary care demonstrated a prevalence of liver fibrosis of 17.5%. There was no significant difference in prevalence between those taking methotrexate, and those who had never been exposed to it. Markers of adiposity; body mass index, waist circumference and fat mass were associated with an elevated FibroScan score. Multiple linear regression demonstrated neither methotrexate prescription nor cumulative dose of methotrexate were significant predictors of liver fibrosis.To our knowledge, this is the largest cohort study evaluating methotrexate use with liver fibrosis. There was no demonstrable relationship between the two. Although at odds with historically published reports, our findings are in keeping with the contemporaneous evidence. It seems likely that hepatotoxicity related to non-alcoholic fatty liver disease was incorrectly attributed to methotrexate.A survey of 300 patients taking methotrexate reinforced the positive effect it had had on individuals’ lives; 41% of respondents citing it’s advantageous consequences. Four in ten participants reported concerns regarding potential side-effects of methotrexate, demonstrating an apprehension about potential consequences, including hepatotoxicity. This survey suggests that the out-dated concerns relating to methotrexate-related hepatotoxicity are still negatively impacting patients to this day

Behaviour of axially loaded structural bolting assemblies in fire

Bolt assemblies used in structural connections may fail in tension via two modes: Necking, which is a ductile failure, and thread stripping, which is a brittle failure mechanism. During a fire, a ductile failure mode is preferable as it provides continued load transfer from beams to columns for the longest amount of time, allowing for building evacuation. Bolt assemblies have been tested under tension at a range of strain rates and temperatures to observe both failure modes. Tests showed that those bolts with a non-martensitic microstructure failed in a beneficial ductile manner, contrary to the current standards

Pronounced genetic structure and low genetic diversity in European red-billed chough (Pyrrhocorax pyrrhocorax) populations

Conservation Genetics August 2015, Volume 16, Issue 4, pp 1011–1012 Erratum to: Pronounced genetic structure and low genetic diversity in European red-billed chough (Pyrrhocorax pyrrhocorax) populations Erratum to: Conserv Genet (2012) 13:1213–1230 DOI 10.1007/s10592-012-0366-6 In the original publication, Tables 3 and 6 were published with incorrect estimates of population heterozygosities. All other diversity statistics were correct as originally presented. Updated versions of Tables 3 and 6 with corrected heterozygosity estimates confirmed using Arlequin 3.5 (Excoffier and Lischer 2010) as in Dávila et al. (2014) are provided in this erratum. Discrepancies were minor for populations on the British Isles. The correct estimates for Spain are slightly larger than those reported for La Palma by Dávila et al. (2014), but this does not necessarily affect their interpretation that choughs on La Palma may have originated from multiple migration events. The original conclusion that chough populations on the British Isles have low genetic diversity compared to continental European populations remains and is now, in fact, strengthened.Peer reviewedPostprin

High-tech and tactile: Cognitive enrichment for zoo-housed gorillas

The field of environmental enrichment for zoo animals, particularly great apes, has been revived by technological advancements such as touchscreen interfaces and motion sensors. However, direct animal-computer interaction (ACI) is impractical or undesirable for many zoos. We developed a modular cuboid puzzle maze for the troop of six Western lowland gorillas (Gorilla gorilla gorilla) at Bristol Zoo Gardens, United Kingdom. The gorillas could use their fingers or tools to interact with interconnected modules and remove food rewards. Twelve modules could be interchanged within the frame to create novel iterations with every trial. We took a screen-free approach to enrichment: substituting ACI for tactile, physically complex device components, in addition to hidden automatic sensors, and cameras to log device use. The current study evaluated the gorillas’ behavioral responses to the device, and evaluated it as a form of “cognitive enrichment.” Five out of six gorillas used the device, during monthly trials of 1 h duration, over a 6 month period. All users were female including two infants, and there were significant individual differences in duration of device use. The successful extraction of food rewards was only performed by the three tool-using gorillas. Device use did not diminish over time, and gorillas took turns to use the device alone or as one mother-infant dyad. Our results suggest that the device was a form of cognitive enrichment for the study troop because it allowed gorillas to solve novel challenges, and device use was not associated with behavioral indicators of stress or frustration. However, device exposure had no significant effects on gorilla activity budgets. The device has the potential to be a sustainable enrichment method in the long-term, tailored to individual gorilla skill levels and motivations. Our study represents a technological advancement for gorilla enrichment, an area which had been particularly overlooked until now. We wholly encourage the continued development of this physical maze system for other great apes under human care, with or without computer logging technology

The miR-430 locus with extreme promoter density forms a transcription body during the minor wave of zygotic genome activation

In anamniote embryos, the major wave of zygotic genome activation starts during the mid-blastula transition. However, some genes escape global genome repression, are activated substantially earlier, and contribute to the minor wave of genome activation. The mechanisms underlying the minor wave of genome activation are little understood. We explored the genomic organization and cis -regulatory mechanisms of a transcrip-tion body, in which the minor wave of genome activation is first detected in zebrafish. We identified the miR-430 cluster as having excessive copy number and the highest density of Pol-II-transcribed promoters in the genome, and this is required for forming the transcription body. However, this transcription body is not essential for, nor does it encompasse, minor wave transcription globally. Instead, distinct minor-wave -specific promoter architecture suggests that promoter-autonomous mechanisms regulate the minor wave of genome activation. The minor-wave-specific features also suggest distinct transcription initiation mecha-nisms between the minor and major waves of genome activation

Exposing the Science in Citizen Science:Fitness to Purpose and Intentional Design

Citizen science is a growing phenomenon. With millions of people involved and billions of in-kind dollars contributed annually, this broad extent, fine grain approach to data collection should be garnering enthusiastic support in the mainstream science and higher education communities. However, many academic researchers demonstrate distinct biases against the use of citizen science as a source of rigorous information. To engage the public in scientific research, and the research community in the practice of citizen science, a mutual understanding is needed of accepted quality standards in science, and the corresponding specifics of project design and implementation when working with a broad public base. We define a science-based typology focused on the degree to which projects deliver the type(s) and quality of data/work needed to produce valid scientific outcomes directly useful in science and natural resource management. Where project intent includes direct contribution to science and the public is actively involved either virtually or hands-on, we examine the measures of quality assurance (methods to increase data quality during the design and implementation phases of a project) and quality control (post hoc methods to increase the quality of scientific outcomes). We suggest that high quality science can be produced with massive, largely one–off, participation if data collection is simple and quality control includes algorithm voting, statistical pruning, and/or computational modeling. Small to mid-scale projects engaging participants in repeated, often complex, sampling can advance quality through expert-led training and well-designed materials, and through independent verification. Both approaches—simplification at scale and complexity with care—generate more robust science outcomes