Objectives/Goals: Primary sclerosing cholangitis (PSC) manifests with an inflammatory milieu that leads to fibrotic scarring of the liver. Human PSC liver bile ducts are enriched with neutrophils; however, their infiltration and functional role is unexplored. Our goal is to investigate the mechanism and impact of peribiliary neutrophil infiltration observed in PSC. Methods/Study Population: Primary cholangiocytes (bile duct cells) isolated from WT and mouse models of PSC (3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC)-fed mice and Mdr2-/- mice) were analyzed by RNA-sequencing. Immunofluorescence (IF) was performed on liver tissues from PSC patients and mouse models of PSC for markers of bile ducts and neutrophils (KRT19 and MPO). Intrahepatic leukocytes (IHL) isolated from mice livers were evaluated for neutrophil abundance and activation state. Anti-Ly6G antibody-mediated neutrophil depletion in Mdr2-/- mice was analyzed by IF, histology, and cytometry by time-of-flight (CyTOF). Cholangiocytes stimulated with TNFα (to induce an inflammatory phenotype) were analyzed for neutrophil chemoattractants with genetic and pharmacological interventions. Results/Anticipated Results: RNA-seq analysis of primary cholangiocytes from PSC mouse models revealed enrichment in inflammatory and neutrophil degranulation pathways. Flow cytometry and RT-PCR analysis revealed an increase in the neutrophil population in PSC mice with activated phenotype. Peripheral depletion of neutrophils in Mdr2-/- mice alleviated liver injury and inflammation, along with a reduction in peribiliary neutrophil infiltration and attenuated bridging fibrosis. CyTOF analysis showed a significant reduction in CD8+ T cells upon neutrophil depletion, implying neutrophils sustain CD8+ T cells in PSC liver. Mechanistically in cholangiocytes, TNFα mediates expression of neutrophil chemoattractants, CXCL1 and CXCL8, through the cyclic GMP-AMP synthase stimulator of interferon genes (cGAS-STING) pathway. Discussion/Significance of Impact: Our findings suggest that activation of the STING pathway in cholangiocytes in cholestatic liver disease triggers an immune response resulting in peri-portal neutrophil infiltration via CXC chemokines. The sustained presence of these activated neutrophils engages the adaptive immune system to perpetuate the inflammation and fibrosis seen in PSC.

Objectives/Goals: Aspiration causes or aggravates lung diseases. While bedside swallow evaluations are not sensitive/specific, gold standard tests for aspiration are invasive, uncomfortable, expose patients to radiation, and are resource intensive. We propose the development and validation of an AI model that analyzes voice to noninvasively predict aspiration. Methods/Study Population: Retrospectively recorded [i] phonations from 163 unique ENT patients were analyzed for acoustic features including jitter, shimmer, harmonic to noise ratio (HNR), etc. Patients were classified into three groups: aspirators (Penetration-Aspiration Scale, PAS 6–8), probable (PAS 3–5), and non-aspirators (PAS 1–2) based on video fluoroscopic swallow (VFSS) findings. Multivariate analysis evaluated patient demographics, history of head and neck surgery, radiation, neurological illness, obstructive sleep apnea, esophageal disease, body mass index, and vocal cord dysfunction. Supervised machine learning using five folds cross-validated neural additive network modelling (NAM) was performed on the phonations of aspirator versus non-aspirators. The model was then validated using an independent, external database. Results/Anticipated Results: Aspirators were found to have quantifiably worse quality of sound with higher jitter and shimmer but lower harmonics noise ratio. NAM modeling classified aspirators and non-aspirators as distinct groups (aspirator NAM risk score 0.528+0.2478 (mean + std) vs. non-aspirator (control) risk score of 0.252+0.241 (mean + std); p Discussion/Significance of Impact: We report the use of voice as a novel, noninvasive biomarker to detect aspiration risk using machine learning techniques. This tool has the potential to be used for the safe and early detection of aspiration in a variety of clinical settings including intensive care units, wards, outpatient clinics, and remote monitoring.

The conditional expectation $m_{X}(s)=\mathrm{E}[X|S=s]$, where X and Y are two independent random variables with $S=X+Y$, plays a key role in various actuarial applications. For instance, considering the conditional mean risk-sharing rule, $m_X(s)$ determines the contribution of the agent holding the risk X to a risk-sharing pool. It is also a relevant function in the context of risk management, for example, when considering natural capital allocation principles. The monotonicity of $m_X(\!\cdot\!)$ is particularly significant under these frameworks, and it has been linked to log-concave densities since Efron (1965). However, the log-concavity assumption may not be realistic in some applications because it excludes heavy-tailed distributions. We consider random variables with regularly varying densities to illustrate how heavy tails can lead to a nonmonotonic behavior for $m_X(\!\cdot\!)$. This paper first aims to identify situations where $m_X(\!\cdot\!)$ could fail to be increasing according to the tail heaviness of X and Y. Second, the paper aims to study the asymptotic behavior of $m_X(s)$ as the value s of the sum gets large. The analysis is then extended to zero-augmented probability distributions, commonly encountered in applications to insurance, and to sums of more than two random variables and to two random variables with a Farlie–Gumbel–Morgenstern copula. Consequences for risk sharing and capital allocation are discussed. Many numerical examples illustrate the results.

Particle image velocimetry is used to study the control of swirl momentum, delivered through an orifice formed by a physically rotating tube of finite length, relevant to the evolution of vortex rings produced at a Reynolds number ${Re}\approx 1000$ based on the average discharge velocity, for swirl numbers ${S} \in [0, 1]$. Experiments without discharge, reinforced with complimentary numerical predictions, reveal the presence of an intriguing secondary flow pattern in the rotating tube, preventing attainment of a solid-body-like swirl distribution. Nevertheless, it is found that fully established rings produced in this way, following discharge once conditions in the tube have reached a steady state, exhibit similar characteristics to rings formed by an otherwise solid-body rotating initial condition as explored computationally by Ortega-Chavez et al. (2023, J. Fluid Mech. 967, A16). Namely, opposite-signed vorticity forms due to vortex tilting, which subsequently interacts with the ring, promoting vorticity cancellation and vortex ring breakdown. A key feature of the experimental work is that partially established vortex rings, produced before a steady-state rotating tube condition is reached, show unique characteristics. Their creation, a short time after the onset of tube rotation: (i) facilitates more efficient delivery of swirl momentum to the vortex core area; (ii) maintains a low level of swirl in the ring bubble’s central region which would otherwise promote the formation of opposite-signed vorticity and vortex breakdown.

Illiberal actors in Western democracies increasingly exploit the superficial defence of liberal values like gender equality and LGBTQ+ rights to demonize ethnic out-groups, portraying Muslims as inherently opposed to Western values. This paper investigates whether this stereotype reflects widespread public beliefs and asks: is the stereotypical view of the Muslim community as an illiberal ‘bogeyman’ endorsed by citizens? Leveraging an original double-list experiment design that minimizes sensitivity bias, we identify population-level estimates of this stereotype in Britain, Germany, the Netherlands, and the USA. Our cross-national results reveal a pervasive and ubiquitous stereotype of Muslims as a threat to LGBTQ+ communities across Western democracies. The implications of these findings are concerning as they signal that societal tolerance of ethnic out-groups across liberal democracies remains tainted by prejudicial stereotypes. The results also underscore the alarming electoral potential of far-right parties that exploit homonationalist and femonationalist stereotype-based threat perceptions to their political advantage.

In the rural villages of the Sierra Madre region of Chiapas, women experiencing hardship show signs of emotional distress that are diagnosed as depression and anxiety by health professionals. In this study, we critically analyze the impact of a pilot mental health group intervention (Women’s Circles) facilitated by community mental health workers. The intervention consisted of eight structured sessions that included psychoeducation from a gender perspective, mindfulness exercises, interactive activities, arts and crafts, and sharing personal experiences. We carried out participant observation and 27 semi-structured interviews with the participants. The main outcomes were, first, that participants’ moods improved, and second, that the improvement was mainly due to gathering with others and having someone to talk to. In addition, we observed that lessons during the Circles were often prescriptive, which, rather than creating a space for reflection on personal experiences, imposed globalized views of mental health and gender. In sum, we describe both the positive impact this program had on mental well-being and the problematic spreading of psychoeducation.

Members of the genus Oncicola Travassos, 1916 are generalist parasites able to infect a broad spectrum of carnivorous hosts, such as marsupials, procyonids, felids, and canids, and are distributed globally. Adult specimens were collected from the intestines of three white-nosed coatis (N. narica), whereas cystacanths (larval form) were found in the body cavities of two amphibian species (paratenic hosts) in localities from northern and southeastern Mexico. Morphologically, both stages were identified as O. luehei (Travassos, 1917) on the basis of the following features: trunk cylindrical, narrow anteriorly, enlarging midbody, tapering gradually to narrow posteriorly; proboscis globular with six circular rows of hooks with six hooks each, decreasing in size posteriorly; neck short with sensory papilla; tubular lemnisci long, extending to the posterior region; protonephridia dendritic type; and eight cement glands, compact with a single giant nuclei. Sequences from cytochrome c oxidase subunit 1 from mtDNA were aligned and compared with sequences available in GenBank. Phylogenetic analyses revealed that adults and cystacanths formed a clade with two other isolates identified as Oncicola sp. and O. luehei from Mexico. The intraspecific genetic divergence among the isolates was low, ranging from 0.0% to 3.0%, indicating that the two stages of the life cycle belong to the same species. The haplotype network was inferred with 11 sequences and revealed a lack of shared haplotypes between populations, suggesting a reduced recombination rate and a high pattern of genetic variation among individuals. Finally, these new records of O. luehei increase the distribution range of O. luehei on both coasts of Mexico.

How does social science insulate police from social movements’ demand for abolition? We explore this through a content analysis of policing social science research funded by Arnold Ventures, the MacArthur Foundation, and the National Institute of Justice published from 2011 to 2022 (N = 143 studies). Our mixed method content analysis revealed what we call “Academic Copaganda,” or studies contesting social movement claims by authors (1) masking their conflicts of interest, or (2) espousing police epistemology. Although Academic Copaganda comprised 20% of studies in the sample, they received most media mentions after the 2020 police killing of George Floyd. We conclude by discussing our contributions to legal scholarship on police legitimacy and empirical critical race theory.

Besides being unjustly incarcerated, Sabrina Butler, Kristine Bunch, Ru-el Sailor and Larry DeLisle endured various forms of police mistreatment, as detailed in a collection of transcripts from the Wrongful Conviction Podcast (WCP). Understandably enough, their criminalization had a profound impact on their perception of external and internal realities. Given their unique socio-demographic backgrounds, variations in the discursive patterns of their communicative interactions are anticipated. As extensively analyzed in sociolinguistics, both gender and ethnicity influence how individuals construct discourse; particularly, these traits appear to account for how the subjects under study express their emotions and opinions. This is because they are silenced and unable to directly confront their trauma; often, they are incapable of discussing their feelings or identifying those responsible for these traumatic events. Drawing on Appraisal Theory, this paper investigates the language of evaluation used in these texts taken from the WCP. To this end, our analysis of the data is performed using UAM CorpusTool.

A limitation in fine-tuned tree-ring radiocarbon (14C) data is normally associated with overall data uncertainty. Tree-ring 14C data variance as a result of sample heterogeneity can be reduced by adopting best practices at the time of sample collection and subsequent preparation and analysis. Variance-reduction of 14C data was achieved by meticulous sample handling during increment core or cross-sectional cuttings, in-laboratory wood reductions, and cellulose fiber homogenization of whole rings. To demonstrate the performance of those procedures to final 14C results, we took advantage of the replicated data from assigned calendar years of two Pantropical post-1950 AD tree-ring 14C reconstructions. Two Cedrela fissilis Vell. trees spaced 22.5 km apart, and two trees of this species together with one Peltogyne paniculata Benth tree spaced 0.2 to 5 km apart were sampled in a tropical dry and moist forest, respectively. Replicate 14C data were then obtained from grouped tree-ring samples from each site. A total of 88% of the replicated 14C results fell into a remarkably consistent precision/accuracy range of 0.3% or less, even though multiple tree species were used as pairs/sets. This finding illustrates how adopting a few simple strategies, in tandem with already established chemical extraction procedures and high-precision 14C analysis, can improve 14C data results of tropical trees.

Introduction: Motor impairment remains underexplored in Alzheimer’s disease. We previously described the functional impairment of gait and exploratory activity of male 3xTg-AD mice at different stages of Alzheimer’s disease progression. We describe movement limitations and muscle weakness as indicators of severity.

Methods: In the present report, a cross-sectional study was carried out that analyzed the muscular structure of the quadriceps and triceps surae muscles of transgenic (3xTg-AD) and non-transgenic males in the early (6 months), intermediate (12 months), and advanced (16 months) stages of Alzheimer’s disease. Longitudinal sections of the quadriceps and triceps surae stained with hematoxylin and eosin (H&E) were evaluated. Using conventional histological techniques, they were then rinsed with PBS, pH 7.4. For the F-actine immunohistochemistry, the sections were blocked by incubating them in IgG-free 2% bovine serum albumin (BSA, Sigma) for 60 min. Then specimens were incubated for 10 minutes with 0.2% Triton X-100 in PBS at room temperature. The slides were incubated overnight at 4 °C with F-actin (Santa Cruz Biotechnology Inc., CA, USA). Slides were counterstained with VectaShield using 4, 60-diamino-2-phenylindole dihydrochloride (DAPI) (Vector Labs., CA, USA) for nuclei staining and visualized in the blue channel.

Results: Lower fluorescence labeling was detected in 3xTg-AD mice at all ages, with a greater decline at older ages. Signs of sarcopenia are also present in an advanced stage of AD, with differences in fiber distribution, the number of cell nuclei, and the presence of adipose tissue.

Conclusions: The previously reported gait alterations in Alzheimer’s disease could be the result of structural deficiencies due to sarcopenia and poor muscle contraction, which leads to the limitations of movement in locomotion reported in 3xTg-AD mice.

Adults of the genus Posthodiplostomum, Dubois, 1936 are parasites of fish-eating birds, mainly of the family Ardeidae, and are globally distributed. The genus currently comprises 35 species, although recent molecular evidence has shown that the diversity of the genus is underestimated since several candidate species have been recognized. In the Neotropical region of Mexico, at least 6 Posthodiplostomum lineages have been detected with metacercaria stages recovered from unrelated fish hosts. Here, we obtained adult specimens of Posthodiplostomum from 6 fish-eating birds representing 2 families (Butorides virescens, Ardea herodias, Nycticorax nycticorax, Tigrisoma mexicanum – Ardeidae, and Rynchops niger and Leucophaeus atricilla – Lariidae) from 4 localities in southern Mexico. Specimens were sequenced for 2 nuclear (28S and ITS1–5.8S–ITS2) and 1 mitochondrial (cox1) molecular marker. Phylogenetic analyses allowed us to link metacercariae and adult specimens and recognized a lineage, which was described morphologically. The new species can be distinguished from its congeners by its prosoma morphology and body size; this is the first described species in the Neotropical region of Mexico. Additionally, new host and locality records for P. macrocotyle and P. pricei are presented, expanding their geographical distribution range in the Americas.

According to International Union for the Conservation of Nature (IUCN) guidelines, all species must be assessed against all criteria during the Red Listing process. For organismal groups that are diverse and understudied, assessors face considerable challenges in assembling evidence due to difficulty in applying definitions of key terms used in the guidelines. Challenges also arise because of uncertainty in population sizes (Criteria A, C, D) and distributions (Criteria A2/3/4c, B). Lichens, which are often small, difficult to identify, or overlooked during biodiversity inventories, are one such group for which specific difficulties arise in applying Red List criteria. Here, we offer approaches and examples that address challenges in completing Red List assessments for lichens in a rapidly changing arena of data availability and analysis strategies. While assessors still contend with far from perfect information about individual species, we propose practical solutions for completing robust assessments given the currently available knowledge of individual lichen life-histories.