Feeding Difficulties and Gastrostomy in Dravet Syndrome: A UK-Wide Survey and 2-Center Experience.

Background and Objectives: Dravet syndrome (DS) is one of the most common monogenic epilepsies. Alongside the core seizure and developmental phenotypes, problems with appetite, swallowing, and weight loss are frequently reported, necessitating gastrostomy in some. We explored the burden of feeding difficulties and need for gastrostomy across 3 DS populations in the United Kingdom. We document caregiver opinion and postgastrostomy outcomes, and provide guidance regarding feeding issues and gastrostomy in DS. Methods: A retrospective, observational study was conducted; data were collected from medical records of 124 individuals with DS attending clinics at the National Hospital for Neurology and Neurosurgery, and Great Ormond Street Hospital, and from 65 DS caregiver responses to a UK-wide survey. Results: In total, 64 of 124 (52%) had at least 1 feeding difficulty; 21 of 124 (17%) had a gastrostomy, and gastrostomy was being considered in 5%; the most common reasons for gastrostomy were poor appetite (81%) and weight loss/failure to gain weight (71%). Median age at gastrostomy was 17 years (range 2.5-59). Multivariate analyses identified several factors that in combination contributed to risk of feeding difficulties and gastrostomy, including treatment with several antiseizure medications (ASMs), of which stiripentol made a unique contribution to risk of gastrostomy (p = 0.048, odds ratio 3.20, 95% CI 1.01-10.16). Preinsertion, 88% of caregivers were worried about the gastrostomy, with concerns across a range of issues. Postgastrostomy, 88% of caregivers were happy that their child had the gastrostomy, and >90% agreed that the gastrostomy ensured medication compliance, that their child's overall health was better, and that quality of life improved. Discussion: Feeding difficulties are common in DS, and 17% require a gastrostomy to address these. Risk factors for feeding difficulties in DS are unknown, but ASMs may play a role. There is a high level of caregiver concern regarding gastrostomy preprocedure; however, postgastrostomy caregiver opinion is positive. Feeding difficulties should be proactively sought during review of people with DS, and the potential need for gastrostomy should be discussed.

Impact of Electronic Health Record Use on Cognitive Load and Burnout Among Clinicians: Narrative Review.

The cognitive load theory suggests that completing a task relies on the interplay between sensory input, working memory, and long-term memory. Cognitive overload occurs when the working memory's limited capacity is exceeded due to excessive information processing. In health care, clinicians face increasing cognitive load as the complexity of patient care has risen, leading to potential burnout. Electronic health records (EHRs) have become a common feature in modern health care, offering improved access to data and the ability to provide better patient care. They have been added to the electronic ecosystem alongside emails and other resources, such as guidelines and literature searches. Concerns have arisen in recent years that despite many benefits, the use of EHRs may lead to cognitive overload, which can impact the performance and well-being of clinicians. We aimed to review the impact of EHR use on cognitive load and how it correlates with physician burnout. Additionally, we wanted to identify potential strategies recommended in the literature that could be implemented to decrease the cognitive burden associated with the use of EHRs, with the goal of reducing clinician burnout. Using a comprehensive literature review on the topic, we have explored the link between EHR use, cognitive load, and burnout among health care professionals. We have also noted key factors that can help reduce EHR-related cognitive load, which may help reduce clinician burnout. The research findings suggest that inadequate efforts to present large amounts of clinical data to users in a manner that allows the user to control the cognitive burden in the EHR and the complexity of the user interfaces, thus adding more "work" to tasks, can lead to cognitive overload and burnout; this calls for strategies to mitigate these effects. Several factors, such as the presentation of information in the EHR, the specialty, the health care setting, and the time spent completing documentation and navigating systems, can contribute to this excess cognitive load and result in burnout. Potential strategies to mitigate this might include improving user interfaces, streamlining information, and reducing documentation burden requirements for clinicians. New technologies may facilitate these strategies. The review highlights the importance of addressing cognitive overload as one of the unintended consequences of EHR adoption and potential strategies for mitigation, identifying gaps in the current literature that require further exploration.

The eukaryotic-like characteristics of small GTPase, roadblock and TRAPPC3 proteins from Asgard archaea.

Membrane-enclosed organelles are defining features of eukaryotes in distinguishing these organisms from prokaryotes. Specification of distinct membranes is critical to assemble and maintain discrete compartments. Small GTPases and their regulators are the signaling molecules that drive membrane-modifying machineries to the desired location. These signaling molecules include Rab and Rag GTPases, roadblock and longin domain proteins, and TRAPPC3-like proteins. Here, we take a structural approach to assess the relatedness of these eukaryotic-like proteins in Asgard archaea, the closest known prokaryotic relatives to eukaryotes. We find that the Asgard archaea GTPase core domains closely resemble eukaryotic Rabs and Rags. Asgard archaea roadblock, longin and TRAPPC3 domain-containing proteins form dimers similar to those found in the eukaryotic TRAPP and Ragulator complexes. We conclude that the emergence of these protein architectures predated eukaryogenesis, however further adaptations occurred in proto-eukaryotes to allow these proteins to regulate distinct internal membranes.

Leiomyosarcoma of the prostate: a novel approach to treatment-case report and review of the literature.

Leiomyosarcoma of the prostate is a rare and aggressive tumor, with a quarter of the patients harboring metastatic disease, commonly in the lung. It usually presents with urinary obstruction in a relatively younger patient group. A 29-year-old male presented with lower urinary tract symptoms to the urologist. Computed tomography scan revealed a large pelvic mass involving the prostate. Biopsy on two occasions yielded leiomyoma. Instead of conventional radical surgery, en-bloc resection of the mass was done while preserving the remaining portion of the prostate, seminal vesicles, and ejaculatory duct. Histopathology revealed a high-grade leiomyosarcoma with negative margins. The patient had excellent recovery of defecation, erectile, and ejaculatory functions within 2 months after adjuvant radiotherapy. At the 24-month follow-up there was no evidence of disease. En-bloc resection of the tumor can be considered in select cases to improve functional outcomes and sustain a higher quality of life in patients.

Short Peptide Amyloids Are a Potential Sequence Pool for the Emergence of Proteins.

Under prebiotic conditions, peptides are capable of self-replication through a structure-based template-assisted mechanism when they form amyloids. Furthermore, peptide amyloids can spontaneously form inside fatty acid vesicles creating membrane enclosed complex structures of variable morphologies. This is possible because fatty acid vesicle membranes act as filters allowing passage of activated amino acids while some amino acids derived from the activated species become non-permeable and trapped in the vesicles. Similarly, nascent peptides derived from the condensation of the activated amino acids are also trapped in the vesicles. It is hypothesized that such preselected peptide amyloids become a sequence pool for the emergence of proteins in life and that after billions of years of cellular evolution, the sequences in the current proteome have diverged significantly from these original seed peptides. If this hypothesis is correct, it could be possible to detect the traces of these seed sequences in current proteomes. Here, we show for all possible 3, 6, 7, 8 or 9 residue sequence motifs that those motifs that are most amyloidogenic/aggregation prone are over-represented in extant proteomes compared to a sequence-randomized proteome. Furthermore, we find that there is a greater proportion of amyloidogenic sequence motifs in archaea proteomes than in the larger primate proteomes. This suggests that the evolution towards larger proteomes leads to smaller proportion of amyloidogenic sequences.

Poststroke Depression: An Update.

The presence of neuropsychiatric disorders after stroke has been recognized for more than 100 years, but controlled systematic studies did not begin until the 1970s. The most clinically important advances, however, have been in the treatment and prevention of poststroke depression (PSD). Recent meta-analyses of randomized controlled trials (RCTs) for the treatment of PSD have demonstrated the efficacy of antidepressants. Similarly, RCTs for the prevention of PSD have shown that antidepressants significantly decrease the incidence of PSD compared with placebo. Early treatment of PSD with antidepressants also appears to enhance both physical and cognitive recovery from stroke and may increase survival up to 10 years. Genetic and epigenetic variations, white matter disease, cerebrovascular deregulation, altered neuroplasticity, and changes in glutamate neurotransmission may be relevant etiological factors.

Structural displacement model of chitooligosaccharide transport through chitoporin.

VhChiP is a chitooligosaccharide-specific porin identified in the outer membrane of Vibrio campbellii type strain American Type Culture Collection BAA 1116. VhChiP contains three identical subunits, and in each subunit, the 19-amino acid N-terminal segment serves as a molecular plug (the "N-plug") that controls the closed/open dynamics of the neighboring pores. In this study, the crystal structures of VhChiP lacking the N-plug were determined in the absence and presence of chitohexaose. Binding studies of sugar-ligand interactions by single-channel recordings and isothermal microcalorimetry experiments suggested that the deletion of the N-plug peptide significantly weakened the sugar-binding affinity due to the loss of hydrogen bonds around the central affinity sites. Steered molecular dynamic simulations revealed that the movement of the sugar chain along the sugar passage triggered the ejection of the N-plug, while the H-bonds transiently formed between the reducing end GlcNAc units of the sugar chain with the N-plug peptide may help to facilitate sugar translocation. The findings enable us to propose the structural displacement model, which enables us to understand the molecular basis of chitooligosaccharide uptake by marine Vibrio bacteria.

Structural and binding studies of a new chitin-active AA10 lytic polysaccharide monooxygenase from the marine bacterium Vibrio campbellii.

Vibrio spp. play a crucial role in the global recycling of the highly abundant recalcitrant biopolymer chitin in marine ecosystems through their ability to secrete chitin-degrading enzymes to efficiently hydrolyse chitinous materials and use them as their major carbon source. In this study, the first crystal structures of a complete four-domain chitin-active AA10 lytic polysaccharide monooxygenase from the chitinolytic bacterium Vibrio campbellii type strain ATCC BAA-1116 are reported. The crystal structures of apo and copper-bound VhLPMO10A were resolved as homodimers with four distinct domains: an N-terminal AA10 catalytic (CatD) domain connected to a GlcNAc-binding (GbpA_2) domain, followed by a module X domain and a C-terminal carbohydrate-binding module (CBM73). Size-exclusion chromatography and small-angle X-ray scattering analysis confirmed that VhLPMO10A exists as a monomer in solution. The active site of VhLPMO10A is located on the surface of the CatD domain, with three conserved residues (His1, His98 and Phe170) forming the copper(II)-binding site. Metal-binding studies using synchrotron X-ray absorption spectroscopy and X-ray fluorescence, together with electron paramagnetic resonance spectroscopy, gave consistently strong copper(II) signals in the protein samples, confirming that VhLPMO10A is a copper-dependent enzyme. ITC binding data showed that VhLPMO10A could bind various divalent cations but bound most strongly to copper(II) ions, with a Kd of 0.1 ± 0.01 µM. In contrast, a Kd of 1.9 nM was estimated for copper(I) ions from redox-potential measurements. The presence of ascorbic acid is essential for H2O2 production in the reaction catalysed by VhLPMO10A. MALDI-TOF MS identified VhLPMO10A as a C1-specific LPMO, generating oxidized chitooligosaccharide products with different degrees of polymerization (DP2ox-DP8ox). This new member of the chitin-active AA10 LPMOs could serve as a powerful biocatalyst in biofuel production from chitin biomass.

Temporal avoidance as a means of reducing competition between sympatric species.

Human activity has modified the availability of natural resources and the abundance of species that rely on them, potentially changing interspecific competition dynamics. Here, we use large-scale automated data collection to quantify spatio-temporal competition among species with contrasting population trends. We focus on the spatial and temporal foraging behaviour of subordinate marsh tits Poecile palustris among groups of socially and numerically dominant blue tits Cyanistes caeruleus and great tits Parus major. The three species exploit similar food resources in mixed groups during autumn-winter. Using 421 077 winter recordings of individually marked birds at 65 automated feeding stations in Wytham Woods (Oxfordshire, UK), we found that marsh tits were less likely to join larger groups of heterospecifics, and they accessed food less frequently in larger groups than in smaller ones. Marsh tit numbers within groups declined throughout the diurnal and winter periods, while the number of blue and great tits increased. However, sites that attracted larger groups of these heterospecifics also attracted more marsh tits. The results suggest that subordinate species exhibit temporal avoidance of socially and numerically dominant heterospecifics, but have limited ability for spatial avoidance, indicating that behavioural plasticity enables only a partial reduction of interspecific competition.

Effect of insulin-like growth factor system on luteinising angiogenesis.

Preovulatory follicle growth and the luteal transition requires intense angiogenesis. This enables progesterone production to increase sufficiently to support a pregnancy. Inadequate follicular or luteal vascularisation can lead to reduced ovarian function and thus compromise fertility. Insulin-like growth factor 1 (IGF1) and IGF2 regulate multiple ovarian processes and are key links between an animal's reproductive and metabolic status. This study investigated the role that the IGF system plays in regulating luteinising follicular endothelial cell (EC) networks and progesterone production in vitro. Bovine luteinising follicular angiogenesis cultures were treated with 1) LR3-IGF1 (10 or 100ng/ml) under basal and angiogenic-stimulated conditions or 2) IGF1 receptor inhibitor (picropodophyllin (PPP); 1µM) in the presence or absence of LR3-IGF1, IGF2, or combined LR3-IGF1+IGF2 (10ng/ml). EC networks were quantified by von Willebrand factor immunohistochemistry. Progesterone production was analysed by ELISA and cell proliferation was determined by MTT assay. LR3-IGF1 had limited effects on EC growth parameters, whilst PPP (p<0.001) markedly reduced EC growth parameters (by 60-70%). Cell proliferation was slightly increased (by 3-5%) by LR3-IGF1 (p<0.001). LR3-IGF1 had variable effects on progesterone production, whilst PPP reduced progesterone concentration (p<0.001) with or without LR3-IGF1 or IGF2 alone or in combination. IGF1 was detected in cell conditioned media and was increased by LH (50ng/ml) (p<0.001). In conclusion, exogenous IGF1 and IGF2 had minimal effects on luteinising follicular angiogenesis and progesterone production, but the inhibitory effect of the IGFR1 inhibitor (PPP) suggests that IGF1 receptor signalling is critical for the development of EC networks and progesterone production in luteinising follicular cells.

Collation of a century of soil invertebrate abundance data suggests long-term declines in earthworms but not tipulids.

Large-scale declines in terrestrial insects have been reported over much of Europe and across the world, however, population change assessments of other key invertebrate groups, such as soil invertebrates, have been largely neglected through a lack of available monitoring data. This study collates historic data from previously published studies to assess whether it is possible to infer previously undocumented long-term changes in soil invertebrate abundance. Earthworm and tipulid data were collated from over 100 studies across the UK, spanning almost 100 years. Analyses suggested long-term declines in earthworm abundance of between 1.6 to 2.1% per annum, equivalent to a 33% to 41% decline over 25 years. These appeared greatest in broadleaved woodlands and farmland habitats, and were greater in pasture than arable farmland. Significant differences in earthworm abundance between habitats varied between models but appeared to be highest in urban greenspaces and agricultural pasture. More limited data were available on tipulid abundance, which showed no significant change over time or variation between enclosed farmland and unenclosed habitats. Declines in earthworm populations could be contributing to overall declines in ecosystem function and biodiversity as they are vital for a range of ecosystem services and are keystone prey for many vertebrate species. If robust, our results identify a previously undetected biodiversity decline that would be a significant conservation and economic issue in the UK, and if replicated elsewhere, internationally. We highlight the need for long-term and large-scale soil invertebrate monitoring, which potentially could be carried out by citizen/community scientists.

Mechanisms underpinning community stability along a latitudinal gradient: Insights from a niche-based approach.

At large scales, the mechanisms underpinning stability in natural communities may vary in importance due to changes in species composition, mean abundance, and species richness. Here we link species characteristics (niche positions) and community characteristics (richness and abundance) to evaluate the importance of stability mechanisms in 156 butterfly communities monitored across three European countries and spanning five bioclimatic regions. We construct niche-based hierarchical structural Bayesian models to explain first differences in abundance, population stability, and species richness between the countries, and then explore how these factors impact community stability both directly and indirectly (via synchrony and population stability). Species richness was partially explained by the position of a site relative to the niches of the species pool, and species near the centre of their niche had higher average population stability. The differences in mean abundance, population stability, and species richness then influenced how much variation in community stability they explained across the countries. We found, using variance partitioning, that community stability in Finnish communities was most influenced by community abundance, whereas this aspect was unimportant in Spain with species synchrony explaining most variation; the UK was somewhat intermediate with both factors explaining variation. Across all countries, the diversity-stability relationship was indirect with species richness reducing synchrony which increased community stability, with no direct effects of species richness. Our results suggest that in natural communities, biogeographical variation observed in key drivers of stability, such as population abundance and species richness, leads to community stability being limited by different factors and that this can partially be explained due to the niche characteristics of the European butterfly assemblage.

AlphaFold2: A versatile tool to predict the appearance of functional adaptations in evolution: Profilin interactions in uncultured Asgard archaea: Profilin interactions in uncultured Asgard archaea.

The release of AlphaFold2 (AF2), a deep-learning-aided, open-source protein structure prediction program, from DeepMind, opened a new era of molecular biology. The astonishing improvement in the accuracy of the structure predictions provides the opportunity to characterize protein systems from uncultured Asgard archaea, key organisms in evolutionary biology. Despite the accumulation in metagenomics-derived Asgard archaea eukaryotic-like protein sequences, limited structural and biochemical information have restricted the insight in their potential functions. In this review, we focus on profilin, an actin-dynamics regulating protein, which in eukaryotes, modulates actin polymerization through (1) direct actin interaction, (2) polyproline binding, and (3) phospholipid binding. We assess AF2-predicted profilin structures in their potential abilities to participate in these activities. We demonstrate that AF2 is a powerful new tool for understanding the emergence of biological functional traits in evolution.

Expanding the phenotype of children presenting with hypoventilation with biallelic TBCK pathogenic variants and literature review.

Individuals with biallelic TBCK pathogenic variants present in infancy with distinctive facial features, profound hypotonia, severe intellectual impairment and epilepsy. Although rare, it may mimic other neurogenetic disorders leading to extensive investigations. Improved understanding of the clinical phenotype can support early monitoring of complications due to respiratory insufficiency. We present six individuals who were found to have pathogenic biallelic TBCK variants. The clinico-radiological and diagnostic records were reviewed. Five individuals were diagnosed with hypoventilation, requiring respiratory support, highlighting the need for early respiratory surveillance. Characteristic brain imaging in our cohort included periventricular leukomalacia-like changes. We recommend screening for TBCK in hypotonic children with periventricular leukomalacia-like changes, particularly in the absence of prematurity.

Standardised empirical dispersal kernels emphasise the pervasiveness of long-distance dispersal in European birds.

Dispersal is a key life-history trait for most species and is essential to ensure connectivity and gene flow between populations and facilitate population viability in variable environments. Despite the increasing importance of range shifts due to global change, dispersal has proved difficult to quantify, limiting empirical understanding of this phenotypic trait and wider synthesis. Here, we introduce a statistical framework to estimate standardised dispersal kernels from biased data. Based on this, we compare empirical dispersal kernels for European breeding birds considering age (average dispersal; natal, before first breeding; and breeding dispersal, between subsequent breeding attempts) and sex (females and males) and test whether different dispersal properties are phylogenetically conserved. We standardised and analysed data from an extensive volunteer-based bird ring-recoveries database in Europe (EURING) by accounting for biases related to different censoring thresholds in reporting between countries and to migratory movements. Then, we fitted four widely used probability density functions in a Bayesian framework to compare and provide the best statistical descriptions of the different age and sex-specific dispersal kernels for each bird species. The dispersal movements of the 234 European bird species analysed were statistically best explained by heavy-tailed kernels, meaning that while most individuals disperse over short distances, long-distance dispersal is a prevalent phenomenon in almost all bird species. The phylogenetic signal in both median and long dispersal distances estimated from the best-fitted kernel was low (Pagel's λ < 0.25), while it reached high values (Pagel's λ >0.7) when comparing dispersal distance estimates for fat-tailed dispersal kernels. As expected in birds, natal dispersal was on average 5 km greater than breeding dispersal, but sex-biased dispersal was not detected. Our robust analytical framework allows sound use of widely available mark-recapture data in standardised dispersal estimates. We found strong evidence that long-distance dispersal is common among European breeding bird species and across life stages. The dispersal estimates offer a first guide to selecting appropriate dispersal kernels in range expansion studies and provide new avenues to improve our understanding of the mechanisms and rules underlying dispersal events.

La dispersión es un rasgo clave del ciclo vital de la mayoría de las especies y es esencial para garantizar la conectividad y el flujo genético entre poblaciones y contribuir a la viabilidad de la población en contextos de ambiente variable. A pesar de que la dispersión es clave para estudiar los cambios en el área de distribución de las especies debido al cambio global, la dispersión es difícil de cuantificar, lo que limita la comprensión empírica de este rasgo fenotípico y su síntesis más amplia. Aquí introducimos un marco de trabajo estadístico para estimar de manera estandarizada los kernels de dispersión a partir de datos sesgados. Basándonos en este marco, comparamos los kernels de dispersión empíricos para las aves reproductoras europeas considerando la edad (dispersión media vital; natal, antes de la primera reproducción; y dispersión reproductora, entre los intentos de reproducción posteriores) y el sexo (hembras y machos), además de explorar si las diferentes propiedades de dispersión se conservan filogenéticamente. Estandarizamos y analizamos los datos de una extensa base de datos de anillamiento de aves en Europa (EURING), basada en voluntarios, teniendo en cuenta los sesgos relacionados con los diferentes umbrales de comunicación de las anillas entre países y con los movimientos migratorios. A continuación, ajustamos, en un marco bayesiano, cuatro funciones de probabilidad ampliamente utilizadas para comparar y proporcionar las mejores descripciones estadísticas de los diferentes kernels de dispersión por edad y sexo para cada especie de ave. Los movimientos de dispersión de las 234 especies de aves europeas analizadas se explicaron estadísticamente mejor mediante kernels de cola pesada, lo que significa que, aunque la mayoría de los individuos se dispersan en distancias cortas, la dispersión a larga distancia es un fenómeno prevalente en casi todas las especies de aves. La señal filogenética tanto en las distancias de dispersión medias como en las largas estimadas a partir del kernel mejor ajustado fue baja (λ de Pagel < 0,25), mientras que alcanzó valores altos (λ de Pagel >0,7) al comparar las estimas de distancia de dispersión para los kernels de cola pesada. Como se esperaba en las aves, la dispersión natal fue en promedio 5 km mayor que la dispersión reproductiva, pero no se detectó una dispersión sesgada por sexo. Nuestro robusto marco analítico permite un buen uso de los datos de marcaje y recaptura disponibles para la estimación estandarizada de las distancias de dispersión. Hemos encontrado pruebas sólidas de que la dispersión a larga distancia es común entre las especies de aves reproductoras europeas y en todas las etapas de la vida. Las estimas de dispersión ofrecen un primer paso para seleccionar los kernels de dispersión adecuados para los estudios de expansión del rango de distribución y proporcionar nuevas vías de investigación para mejorar nuestra comprensión de los mecanismos y procesos que subyacen a los eventos de dispersión.

Germline homozygous missense DEPDC5 variants cause severe refractory early-onset epilepsy, macrocephaly and bilateral polymicrogyria.

DEPDC5 (DEP Domain-Containing Protein 5) encodes an inhibitory component of the mammalian target of rapamycin (mTOR) pathway and is commonly implicated in sporadic and familial focal epilepsies, both non-lesional and in association with focal cortical dysplasia. Germline pathogenic variants are typically heterozygous and inactivating. We describe a novel phenotype caused by germline biallelic missense variants in DEPDC5. Cases were identified clinically. Available records, including magnetic resonance imaging and electroencephalography, were reviewed. Genetic testing was performed by whole exome and whole-genome sequencing and cascade screening. In addition, immunohistochemistry was performed on skin biopsy. The phenotype was identified in nine children, eight of which are described in detail herein. Six of the children were of Irish Traveller, two of Tunisian and one of Lebanese origin. The Irish Traveller children shared the same DEPDC5 germline homozygous missense variant (p.Thr337Arg), whereas the Lebanese and Tunisian children shared a different germline homozygous variant (p.Arg806Cys). Consistent phenotypic features included extensive bilateral polymicrogyria, congenital macrocephaly and early-onset refractory epilepsy, in keeping with other mTOR-opathies. Eye and cardiac involvement and severe neutropenia were also observed in one or more patients. Five of the children died in infancy or childhood; the other four are currently aged between 5 months and 6 years. Skin biopsy immunohistochemistry was supportive of hyperactivation of the mTOR pathway. The clinical, histopathological and genetic evidence supports a causal role for the homozygous DEPDC5 variants, expanding our understanding of the biology of this gene.

Spatial consistency in drivers of population dynamics of a declining migratory bird.

Many migratory species are in decline across their geographical ranges. Single-population studies can provide important insights into drivers at a local scale, but effective conservation requires multi-population perspectives. This is challenging because relevant data are often hard to consolidate, and state-of-the-art analytical tools are typically tailored to specific datasets. We capitalized on a recent data harmonization initiative (SPI-Birds) and linked it to a generalized modelling framework to identify the demographic and environmental drivers of large-scale population decline in migratory pied flycatchers (Ficedula hypoleuca) breeding across Britain. We implemented a generalized integrated population model (IPM) to estimate age-specific vital rates, including their dependency on environmental conditions, and total and breeding population size of pied flycatchers using long-term (34-64 years) monitoring data from seven locations representative of the British breeding range. We then quantified the relative contributions of different vital rates and population structure to changes in short- and long-term population growth rate using transient life table response experiments (LTREs). Substantial covariation in population sizes across breeding locations suggested that change was the result of large-scale drivers. This was supported by LTRE analyses, which attributed past changes in short-term population growth rates and long-term population trends primarily to variation in annual survival and dispersal dynamics, which largely act during migration and/or nonbreeding season. Contributions of variation in local reproductive parameters were small in comparison, despite sensitivity to local temperature and rainfall within the breeding period. We show that both short- and long-term population changes of British breeding pied flycatchers are likely linked to factors acting during migration and in nonbreeding areas, where future research should be prioritized. We illustrate the potential of multi-population analyses for informing management at (inter)national scales and highlight the importance of data standardization, generalized and accessible analytical tools, and reproducible workflows to achieve them.

Blastomycosis Presenting as a Primary Tracheal Tumor: A Rare Presentation.

Blastomycosis is a rare fungal infection that typically presents as a pulmonary infection. Systemic involvement of blastomycosis from the lungs commonly occurs in the skin and bones. Tracheal involvement is an unusual presentation of blastomycosis, which makes it a formidable diagnostic challenge. We herein report an unusual case of an 85-year-old man presenting with tracheal blastomycosis presenting as a primary tracheal tumor. We also highlight the challenges that were faced in the diagnosis of such an uncommon presentation. To the best of our knowledge, this is only the third occurrence of blastomycosis with tracheal involvement.

Anatomic pathology quality assurance: Developing an LIS based tracking and documentation module for intradepartmental consultations.

Background: An electronic intradepartmental consultation system for anatomic pathology (AP) was conceived and developed in the laboratory information system (LIS) in 2019. Previously, all surgical pathology intradepartmental consultative activities were initiated and documented with paper forms which circulated with the pertinent microscopic slides and were eventually filed. In this study, we discuss the implementation and utilization of an electronic intradepartmental AP consultation system. Methods: Workflows and procedures were developed to organize intradepartmental surgical pathology consultations from the beginning to the end point of the consultative activities entirely using a paperless system that resided in the LIS. Results: The electronic consult system allowed electronic documentation of all steps of intradepartmental consultative activities. The system provided tracking ability for consulted cases and improved access to consult discussion for all departmental personnel, staff, and trainees. Consultation work queue was created for each pathologist and a summary of individual consultative workload was possible. Documentation of anatomic pathology quality assurance for intradepartmental consultative activity was easily assessed. Conclusions: The electronic intradepartmental consult system has allowed our department to electronically track intradepartmental consult cases, store the consultative opinion text with the case, record the pathologists involved, and document the consultation for internal quality assurance review as well as for accrediting organizations. Summarization of pathologist workload related to consultative activity was quantifiable and optimization of the consultative process was maximized for education in an academic setting.

Hinfluences severe disease-mediated population declines in two of the most common garden bird species in Great Britain.

The influence of supplementary feeding of wildlife on disease transmission and its consequent impacts on population dynamics are underappreciated. In Great Britain, supplementary feeding is hypothesised to have enabled the spread of the protozoan parasite, Trichomonas gallinae, from columbids to finches, leading to epidemic finch trichomonosis and a rapid population decline of greenfinch (Chloris chloris). More recently, chaffinch (Fringilla coelebs), has also declined markedly from the second to fifth commonest bird in Britain. Using citizen science data, we show that both declines were driven primarily by reduced adult survival, with the greatest reductions occurring in peri-domestic habitats, where supplementary food provision is common. Post-mortem examinations showed a proportional increase in chaffinch trichomonosis cases, near-contemporaneous with its population decline. Like greenfinches, chaffinches often use supplementary food, but are less associated with human habitation. Our results support the hypothesis that supplementary feeding can increase parasite transmission frequency within and between common species. However, the dynamics behind resultant population change can vary markedly, highlighting the need for integrating disease surveillance with demographic monitoring. Other species susceptible to T. gallinae infection may also be at risk. Supplementary feeding guidelines for wildlife should include disease mitigation strategies to ensure that benefits to target species outweigh risks.