Range-wide salamander densities reveal a key component of terrestrial vertebrate biomass in eastern North American forests.

Characterizing the population density of species is a central interest in ecology. Eastern North America is the global hotspot for biodiversity of plethodontid salamanders, an inconspicuous component of terrestrial vertebrate communities, and among the most widespread is the eastern red-backed salamander, Plethodon cinereus. Previous work suggests population densities are high with significant geographic variation, but comparisons among locations are challenged by lack of standardization of methods and failure to accommodate imperfect detection. We present results from a large-scale research network that accounts for detection uncertainty using systematic survey protocols and robust statistical models. We analysed mark-recapture data from 18 study areas across much of the species range. Estimated salamander densities ranged from 1950 to 34 300 salamanders ha-1, with a median of 9965 salamanders ha-1. We compared these results to previous estimates for P. cinereus and other abundant terrestrial vertebrates. We demonstrate that overall the biomass of P. cinereus, a secondary consumer, is of similar or greater magnitude to widespread primary consumers such as white-tailed deer (Odocoileus virginianus) and Peromyscus mice, and two to three orders of magnitude greater than common secondary consumer species. Our results add empirical evidence that P. cinereus, and amphibians in general, are an outsized component of terrestrial vertebrate communities in temperate ecosystems.

Soil moisture and water redistribution patterns in white oak (Quercus alba) saplings and trees in fragmented urban woodlands.

In the midwestern United States, models predict extended summer heatwaves and increasingly frequent and prolonged drought conditions. In the Chicago region, the potential for large-scale mortality of white oak trees (Quercus alba) coupled with the ongoing decline of white oak sapling recruitment are major concerns for researchers and practitioners. In this study, we determined the sources of water used by mature white oak trees and saplings in three qualitatively different sites within a remnant oak forest in Chicago during the 2021 drought. We investigated soil moisture dynamics (volumetric water content, VWC) and water isotope composition of leaf tissues (δD, δ18O), rainwater, and groundwater. These data were linked to sapling height (proxy for biomass) and ectomycorrhizal (ECM) functional types. We predicted that: (i) mature oak trees use deeper water sources and conducted hydraulic redistribution (HR), and (ii) mature trees shared water with saplings during dry periods via long-distance ECM functional types. Soil moisture decreased progressively from June to October (spring to fall), with August and September having the lowest moisture (<20 % VWC). Following rainfall recharge, temporal patterns of soil moisture showed gravity drainage and then ongoing stair-stepwise drawdown consistent with plant evapotranspiration. Leaf δD and δ18O values in mature trees and saplings were consistent with water uptake from rainfall and subsequent enrichment via evapotranspiration. In two sites, mature trees and saplings demonstrated distinct δD: δ18O slopes, with mature trees more enriched than saplings. In the third site, mature trees and saplings δD: δ18O slopes overlapped but here, the ECM community was dominated by contact-type ECM and sapling height increased with distance from the mature oak. Our findings indicate that HR was not a component of site ecohydrology, and future climate conditions may present increasing challenges for white oak recruitment as both mature trees and saplings compete for limited rainfall-derived soil moisture.

Large cell neuroendocrine lung carcinoma: consensus statement from The British Thoracic Oncology Group and the Association of Pulmonary Pathologists.

Over the past 10 years, lung cancer clinical and translational research has been characterised by exponential progress, exemplified by the introduction of molecularly targeted therapies, immunotherapy and chemo-immunotherapy combinations to stage III and IV non-small cell lung cancer. Along with squamous and small cell lung cancers, large cell neuroendocrine carcinoma (LCNEC) now represents an area of unmet need, particularly hampered by the lack of an encompassing pathological definition that can facilitate real-world and clinical trial progress. The steps we have proposed in this article represent an iterative and rational path forward towards clinical breakthroughs that can be modelled on success in other lung cancer pathologies.

RETROSPECTIVE REVIEW OF OPHIDIOMYCOSIS (OPHIDIOMYCES OPHIODIICOLA) AT THE SMITHSONIAN'S NATIONAL ZOOLOGICAL PARK (1983-2017).

A retrospective review of systemic or localized mycotic infections in captive snakes confirmed via biopsy or necropsy from 1983 to 2017 was performed at the Smithsonian's National Zoological Park. Quantitative polymerase chain reaction (qPCR) confirmed infection with Ophidiomyces ophiodiicola (Oo) in 36.8% (n = 14) of the 38 mycotic infections. Infections with Oo were evenly distributed over the 35-y period and lacked a sex predilection. There was a period prevalence of 4.5% of completed snake necropsy or biopsy cases that were Oo positive. Species affected included green anaconda (Eunectes murinus, n = 4), garden tree boa (Corallus hortulanus, n = 1), false water cobra (Hydrodynastes gigas, n = 5), yellow anaconda (Eunectes notaeus, n = 1), eastern milksnake (Lampropeltis triangulum, n = 1), Brazilian rainbow boa (Epicrates cenchria cenchria, n = 1), and eastern diamondback rattlesnake (Crotalus adamanteus, n = 1). Histopathology demonstrated one or more of the following: heterophilic to necrotizing epidermitis with or without granulomatous dermatitis (n = 12), granulomatous pneumonia (n = 5), granulomatous endophthalmitis (n = 1), and subcutaneous-intramuscular fungal granuloma (n = 1). This study documents the presence of ophidiomycosis in a captive collection for almost 40 years, despite current literature designating it a recently emerging pathogen.

Associations Between Engagement With an Online Health Community and Changes in Patient Activation and Health Care Utilization: Longitudinal Web-Based Survey.

BACKGROUND: Participation in online health communities (OHCs) is a popular trend in the United Kingdom. However, so far, no evidence exists to indicate an association between participation in OHCs and improved health outcomes. OBJECTIVE: This study aimed to (1) determine changes in patient activation over 3 months in new users of an OHC, (2) describe patterns of engagement with an OHC, (3) examine whether patients' characteristics at baseline were associated with subsequent patterns of engagement, and (4) determine if patterns of engagement during the 3 months were associated with changes in patient activation, health care utilization, and health status. METHODS: Active new OHC users on HealthUnlocked (HU) were surveyed to measure demographics, levels of patient activation (describing a person's confidence in managing their own health; scale 0-100 with 4 categories), health care utilization, and health status using a Web-based survey at baseline and 3 months. Patient activation at baseline and 3 months was compared (aim 1). Alongside, for a sample of HU users and survey responders, daily OHC website usage data were automatically captured. This was used to identify clusters of engagement with HU (aim 2). For survey responders, baseline characteristics, patient activation, health care utilization, and health status were compared at baseline and 3 months, overall, and between engagement clusters using t tests and chi-square tests (aims 3 and 4). RESULTS: In 329 people who completed both surveys, baseline activation was most frequently level 3, described as taking action but still lacking confidence. At follow-up, a change of 2.6 points was seen, with the greatest change seen in those at lowest baseline activation levels. In addition, 4 clusters of engagement were identified: low, medium, high, and very high, who were active on HU for a mean of 4, 12, 29, and 59 days, respectively. Survey responders were more commonly high or very high engagers. Baseline activation was highest in low and very high engagers. Overall activation increased over time in all engagement groups. Very high engagers had the greatest improvement in activation (5 points), although the average change was not above what is considered clinically meaningful for any group. Fewer accident and emergency visits were seen at follow-up in those with higher engagement, although this trend was not seen for other health care utilization measures. There was no change in health status at 3 months. CONCLUSIONS: This observational study provides some insight into how patterns of engagement with OHCs are associated with changes in patient activation, health care utilization, and health status. Over 3 months, overall, the change in activation was not clinically significant, and there were some indications that OHCs may be of benefit to particular groups. However, the study limitations prevent firm conclusions about causal relationships.

How Online Communities of People With Long-Term Conditions Function and Evolve: Network Analysis of the Structure and Dynamics of the Asthma UK and British Lung Foundation Online Communities.

BACKGROUND: Self-management support can improve health and reduce health care utilization by people with long-term conditions. Online communities for people with long-term conditions have the potential to influence health, usage of health care resources, and facilitate illness self-management. Only recently, however, has evidence been reported on how such communities function and evolve, and how they support self-management of long-term conditions in practice. OBJECTIVE: The aim of this study is to gain a better understanding of the mechanisms underlying online self-management support systems by analyzing the structure and dynamics of the networks connecting users who write posts over time. METHODS: We conducted a longitudinal network analysis of anonymized data from 2 patients' online communities from the United Kingdom: the Asthma UK and the British Lung Foundation (BLF) communities in 2006-2016 and 2012-2016, respectively. RESULTS: The number of users and activity grew steadily over time, reaching 3345 users and 32,780 posts in the Asthma UK community, and 19,837 users and 875,151 posts in the BLF community. People who wrote posts in the Asthma UK forum tended to write at an interval of 1-20 days and six months, while those in the BLF community wrote at an interval of two days. In both communities, most pairs of users could reach one another either directly or indirectly through other users. Those who wrote a disproportionally large number of posts (the superusers) represented 1% of the overall population of both Asthma UK and BLF communities and accounted for 32% and 49% of the posts, respectively. Sensitivity analysis showed that the removal of superusers would cause the communities to collapse. Thus, interactions were held together by very few superusers, who posted frequently and regularly, 65% of them at least every 1.7 days in the BLF community and 70% every 3.1 days in the Asthma UK community. Their posting activity indirectly facilitated tie formation between other users. Superusers were a constantly available resource, with a mean of 80 and 20 superusers active at any one time in the BLF and Asthma UK communities, respectively. Over time, the more active users became, the more likely they were to reply to other users' posts rather than to write new ones, shifting from a help-seeking to a help-giving role. This might suggest that superusers were more likely to provide than to seek advice. CONCLUSIONS: In this study, we uncover key structural properties related to the way users interact and sustain online health communities. Superusers' engagement plays a fundamental sustaining role and deserves research attention. Further studies are needed to explore network determinants of the effectiveness of online engagement concerning health-related outcomes. In resource-constrained health care systems, scaling up online communities may offer a potentially accessible, wide-reaching and cost-effective intervention facilitating greater levels of self-management.

Practical considerations for pathological diagnosis and molecular profiling of cholangiocarcinoma: an expert review for best practices.

INTRODUCTION: Advances in precision medicine have expanded access to targeted therapies and demand for molecular profiling of cholangiocarcinoma (CCA) patients in routine clinical practice. However, pathologists face challenges in establishing a definitive intrahepatic CCA (iCCA) diagnosis while preserving sufficient tissue for molecular profiling. Additionally, they frequently face challenges in optimal tissue handling to preserve nucleic acid integrity. AREAS COVERED: This article first identifies the challenges in establishing a definitive diagnosis of iCCA in a lesional liver biopsy while preserving sufficient tissue for molecular profiling. Then, the authors explore the clinical value of molecular profiling, the basic principles of single gene and next-generation sequencing (NGS) techniques, and the challenges in tissue sampling for genomic testing. They also propose an algorithm for best practice in tissue management for molecular profiling of CCA. EXPERT OPINION: Several practical challenges face pathologists during tissue sampling and processing for molecular profiling. Optimized tissue processing, careful tissue handling, and selection of appropriate approaches to molecular testing are essential to ensure that the highest possible quality of diagnostic information is provided in the greatest proportion of cases.

The systemic response to brain injury and disease.

The idea that the brain is immunologically privileged and displays an atypical leukocyte recruitment profile following injury has influenced our ideas about how signals might be carried between brain and the periphery. For many, this has encouraged a cerebrocentric view of immunological responses to CNS injury, with little reference to the potential contribution from other organs. However, it is clear that bidirectional pathways between the brain and the peripheral immune system are important in the pathogenesis of CNS disease. In recent years, we have begun to understand the signals that are carried to the periphery and discovered new functions for known chemokines, made by the liver in response to brain injury, as important regulators of the CNS inflammatory response.

Improving Patient Involvement in the Drug Development Process: Case Study of Potential Applications from an Online Peer Support Network.

To date, social media has been used predominantly by the pharmaceutical industry to market products and to gather feedback and comments on products from consumers, a process termed social listening. However, social media has only been used cautiously in the drug development cycle, mainly because of regulations, restrictions on engagement with patients, or a lack of guidelines for social media use from regulatory bodies. Despite this cautious approach, there is a clear drive, from both the industry and consumers, for increased patient participation in various stages of the drug development process. The authors use the example of HealthUnlocked, one of the world's largest health networks, to illustrate the potential applications of online health communities as a means of increasing patient involvement at various stages of the drug development process. Having identified the willingness of the user population to be involved in research, numerous ways to engage users on the platform have been identified and explored. This commentary describes some of these approaches and reports how online health networks that encourage people to share their experiences in managing their health can, in turn, enable rapid patient engagement for clinical research within the constraints of industry regulation.

Establishment of Requirements and Methodology for the Development and Implementation of GreyMatters, a Memory Clinic Information System.

INTRODUCTION: The aim of the paper is to establish the requirements and methodology for the development process of GreyMatters, a memory clinic system, outlining the conceptual, practical, technical and ethical challenges, and the experiences of capturing clinical and research oriented data along with the implementation of the system. METHODS: The methodology for development of the information system involved phases of requirements gathering, modeling and prototype creation, and 'bench testing' the prototype with experts. The standard Institute of Electrical and Electronics Engineers (IEEE) recommended approach for the specifications of software requirements was adopted. An electronic health record (EHR) standard, EN13606 was used, and clinical modelling was done through archetypes and the project complied with data protection and privacy legislation. RESULTS: The requirements for GreyMatters were established. Though the initial development was complex, the requirements, methodology and standards adopted made the construction, deployment, adoption and population of a memory clinic and research database feasible. The electronic patient data including the assessment scales provides a rich source of objective data for audits and research and to establish study feasibility and identify potential participants for the clinical trials. CONCLUSION: The establishment of requirements and methodology, addressing issues of data security and confidentiality, future data compatibility and interoperability and medico-legal aspects such as access controls and audit trails, led to a robust and useful system. The evaluation supports that the system is an acceptable tool for clinical, administrative, and research use and forms a useful part of the wider information architecture.

Interdisciplinary cognitive task analysis: a strategy to develop a comprehensive endoscopic retrograde cholangiopancreatography protocol for use in fellowship training.

BACKGROUND: Endoscopic retrograde cholangiopancreatography is a challenging procedure performed by surgeons and gastroenterologists. We employed cognitive task analysis to identify steps and decision points for this procedure. METHODS: Standardized interviews were conducted with expert gastroenterologists (7) and surgeons (4) from 4 institutions. A procedural step and cognitive decision point protocol was created from audio-taped transcriptions and was refined by 5 additional surgeons. RESULTS: Conceptual elements, sequential actions, and decision points were iterated for 5 tasks: patient preparation, duodenal intubation, selective cannulation, imaging interpretation with related therapeutic intervention, and complication management. A total of 180 steps were identified. Gastroenterologists identified 34 steps not identified by surgeons, and surgeons identified 20 steps not identified by gastroenterologists. CONCLUSION: The findings suggest that for complex procedures performed by diverse practitioners, more experts may help delineate distinctive emphases differentiated by training background and type of practice.

Hemodialysis treatment of monomorphic ventricular tachycardia associated with chronic lithium toxicity.

INTRODUCTION: A patient with chronic lithium toxicity developed a life-threatening ventricular arrhythmia that resolved during removal of lithium by hemodialysis. Chronic lithium toxicity commonly results from diminished elimination and can produce neurotoxicity. Cardiovascular complications have been reported and generally affect the sinoatrial node and produce bradyarrhythmias. The majority of these arrhythmias require no emergent intervention. Ventricular arrhythmias associated with lithium toxicity are occasionally mentioned in the literature, but actual cases are rarely reported. CASE REPORT: A 74-year-old man was brought into the emergency department with a 3-day history of progressive encephalopathy, tremor, and weakness. The lithium level was elevated at 2.2 mmol/L, with a normal serum potassium. Electrocardiography revealed nonsustained monomorphic ventricular tachycardia (120-130 beats/min) lasting up to 1 min, alternating with sinus bradycardia and wandering atrial pacemaker. Episodes of monomorphic ventricular tachycardia recurred >100 times. The patient required a norepinephrine infusion for hypotension. Emergent hemodialysis was initiated to remove lithium and to treat the monomorphic ventricular tachycardia, which was felt to be secondary to lithium toxicity. Episodes of monomorphic ventricular tachycardia abated as hemodialysis progressed. The episodes resolved completely within 4 h of initiating hemodialysis. The patient was discharged home in sinus rhythm on day 5. Lithium was not reinstated. CONCLUSION: Monomorphic ventricular tachycardia associated with chronic lithium toxicity is exceptionally rare. Hemodialysis is a treatment option.

Development and evaluation of a memory clinic information system.

AIM: To describe the requirements, development and evaluation of a cognitive disorders and older persons' clinical and research application, outlining the conceptual and practical challenges. METHODS: A technology development methodology was used to develop a database of people being investigated for or diagnosed with cognitive disorders as well as their carers. The methodology involved phases of requirements gathering, modeling and prototype creation, and 'bench testing' the prototype with experts. RESULTS: This case study suggests that construction and population of a memory clinic and research database is feasible, but initial development is complex. Its utility can be evaluated to some extent and was found to be acceptable to most users. DISCUSSION AND CONCLUSIONS: The development of a system needs to take in account existing data collection methods and other information systems used. The GreyMatters system can be considered a supplementary or complementary health record that sits alongside the main Trust information system. Integrating data from multiple systems enhances utility to clinical and research users.