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Abstract The present study investigated children's understanding that an object's history may increase its significance, an appreciation that underpins the concept of "historical authenticity" (i.e., the idea that an item's history determines its true identity, beyond its functional or material qualities, leading people to value real items over copies or fakes). We examined the development of historical significance through the lens of parent-child conversations, and children's performance on an authenticity assessment. The final sample was American, 79.2% monoracial White, and mid-high socio-economic status (SES) and included 48 parent-child pairs: 24 with younger children (R = 3.5 to 4.5 years) and 24 with older children (R = 5.5 to 6.5 years). Parent-child pairs discussed three books we created, with three storylines: a museum (culturally authentic) storyline, a clean-up (personally authentic) storyline, and a control storyline. Across measures, conversations suggested that authenticity may begin as a "placeholder concept" that is initially rooted in a broad appreciation for the significance of old objects and only later filled in with specifics. This placeholder initially directs children's learning about authenticity by linking, in an unspecified way, the value and significance of objects to their past. For example, we found that young children appropriately appealed to history (vs. perceptual or functional features of objects) in contexts regarding authentic objects but struggled in determining which objects were more significant on the post-test assessment, suggesting that they attend to object history but are not yet sure how histories matter for making authenticity judgments. We also found some evidence that directing children's attention toward conceptual information related to object history may in turn direct them away from material or perceptual considerations, as seen in trade-offs in parents' and children's conversations. Together, this exploratory report offers many new avenues for work on the development of authenticity concepts in childhood.

Despite increases in visibility, gender-nonconforming young people continue to be at risk for bullying and discrimination. Prior work has established that gender essentialism in children correlates with prejudice against people who do not conform to gender norms, but to date no causal link has been established. The present study investigated this link more directly by testing whether children's gender essentialism and prejudice against gender nonconformity can be reduced by exposure to anti-essentialist messaging. Children ages 6--10 years of age (N = 102) in the experimental condition viewed a short video describing similarities between boys and girls and variation within each gender; children in the control condition (N = 102) viewed a corresponding video describing similarities between two types of climate and variation within each. Children then received measures of gender essentialism and prejudice against gender nonconformity. Finally, to ask whether manipulating children's gender essentialism extends to another domain, we included assessments of racial essentialism and prejudice. We found positive correlations between gender essentialism and prejudice against gender nonconformity; both also correlated negatively with participant age. However, we observed no differences between children in the experimental versus control conditions in overall essentialism or prejudice, indicating that our video was largely ineffective in manipulating essentialism. Accordingly, we were unable to provide evidence of a causal relationship between essentialism and prejudice. We did, however, see a difference between conditions on the discreteness measure, which is most closely linked to the wording in the video. This finding suggests that specific aspects of essentialism in young children may be modifiable.

The COVID-19 pandemic in the United States has had a disproportionate impact on Black, low-income, and elderly individuals. We recruited 175 predominantly white children ages 5-12 and their parents (N = 112) and asked which of two individuals (differing in age, gender, race, social class, or personality) was more likely to get sick with either COVID-19 or the common cold and why. Children and parents reported that older adults were more likely to get sick than younger adults, but reported few differences based on gender, race, social class, or personality. Children predominantly used behavioral explanations, but older children used more biological and structural explanations. Thus, children have some understanding of health disparities, and their understanding increases with age.

Peyronies disease (PD) is a debilitating pathology which is associated with penile curvature and erectile dysfunction due to the formation of fibrotic plaques in the penile tunica albuginea. In the present study, we developed a novel rabbit model of PD via subtunical injection of recombinant transforming growth factor (TGF)-β1 protein and characterized erectile function and histopathological endpoints following plaque formation. Ten adult male, New Zealand white rabbits were randomized into 3 experimental groups including nonsurgical controls (NSC, N = 3) and those receiving subtunical injections of vehicle (N = 3) or TGF-β1 protein (0.5 µg/50 µl; N = 4). Following 1 month post-op, focal fibrous plaques composed of disorganized collagen type I and III bundles as well as fragmented elastin fibers at TGF-β1 injection sites were observed in contrast to control groups. Cavernosometric and cavernosographic evaluations revealed no significant differences in maximum intracorporal pressures or substantial curvature during papaverine-induced erection in either the vehicle or TGF-β1 cohorts. Immunohistochemical and histomorphometric analyses demonstrated significant increases in elastase 2B expression in TGF-β1-induced plaques as well as significant declines in matrix metalloproteinase (MMP)-2 and -9 expression relative to control levels. Our results demonstrate that PD-like fibrotic plaques can be created in the rabbit penile tunica albuginea following TGF-β1 injection.

Macrophages (MΦ) infected with human immunodeficiency virus (HIV)-1 or activated by its envelope protein gp120 exert neurotoxicity. We found previously that signaling via p38 mitogen-activated protein kinase (p38 MAPK) is essential to the neurotoxicity of HIVgp120-stimulated MΦ. However, the associated downstream pathways remained elusive. Here we show that cysteinyl-leukotrienes (CysLT) released by HIV-infected or HIVgp120 stimulated MΦ downstream of p38 MAPK critically contribute to neurotoxicity. SiRNA-mediated or pharmacological inhibition of p38 MAPK deprives MΦ of CysLT synthase (LTC4S) and, pharmacological inhibition of the cysteinyl-leukotriene receptor 1 (CYSLTR1) protects cerebrocortical neurons against toxicity of both gp120-stimulated and HIV-infected MΦ. Components of the CysLT pathway are differentially regulated in brains of HIV-infected individuals and a transgenic mouse model of NeuroHIV (HIVgp120tg). Moreover, genetic ablation of LTC4S or CysLTR1 prevents neuronal damage and impairment of spatial memory in HIVgp120tg mice. Altogether, our findings suggest a novel critical role for cysteinyl-leukotrienes in HIV-associated brain injury.

Left ventricular assist devices (LVAD) are increasingly used for management of heart failure; infection remains a frequent complication. Phage therapy has been successful in a variety of antibiotic refractory infections and is of interest in treating LVAD infections. We performed a retrospective review of four patients that underwent five separate courses of intravenous (IV) phage therapy with concomitant antibiotic for treatment of endovascular Pseudomonas aeruginosa LVAD infection. We assessed phage susceptibility, bacterial strain sequencing, serum neutralization, biofilm activity, and shelf-life of phage preparations. Five treatments of one to four wild-type virulent phage(s) were administered for 14-51 days after informed consent and regulatory approval. There was no successful outcome. Breakthrough bacteremia occurred in four of five treatments. Two patients died from the underlying infection. We noted a variable decline in phage susceptibility following three of five treatments, four of four tested developed serum neutralization, and prophage presence was confirmed in isolates of two tested patients. Two phage preparations showed an initial titer drop. Phage biofilm activity was confirmed in two. Phage susceptibility alone was not predictive of clinical efficacy in P. aeruginosa endovascular LVAD infection. IV phage was associated with serum neutralization in most cases though lack of clinical effect may be multifactorial including presence of multiple bacterial isolates with varying phage susceptibility, presence of prophages, decline in phage titers, and possible lack of biofilm activity. Breakthrough bacteremia occurred frequently (while the organism remained susceptible to administered phage) and is an important safety consideration.

Interindividual variation of human immunodeficiency virus (HIV) RNA setpoint in cerebrospinal fluid (CSF) and its determinants are poorly understood, but relevant for HIV neuropathology, brain reservoirs, viral escape, and reseeding after antiretroviral interruptions. Longitudinal multicentric study on demographic, clinical, and laboratory correlates of CSF HIV RNA in 2000 follow-up visits from 597 people with HIV (PWH) off antiretroviral therapy (ART) and with plasma HIV RNA > the lower limit of quantification (LLQ). Factors associated with CSF control (CSFC; CSF HIV RNA  LLQ) and with CSF/plasma discordance (CSF > plasma HIV RNA > LLQ) were also assessed through mixed-effects models. Posthoc and sensitivity analyses were performed for persistent CSFC and ART-naïve participants, respectively. Over a median follow-up of 2.1 years, CSF HIV RNA was associated with CD4+ and CD8+ T cells, CSF leukocytes, blood-brain barrier (BBB) integrity, biomarkers of iron and lipid metabolism, serum globulins, past exposure to lamivudine, and plasma HIV RNA (model p

Abstract Persuasion plays a crucial role in human communication. Yet, convincing someone to change their mind is often challenging. Here, we demonstrate that a subtle linguistic device, generic-you (i.e., “you” that refers to people in general, e.g., “You win some, you lose some”), is associated with successfully shifting people’s pre-existing views in a naturalistic context. Leveraging Large Language Models, we conducted a preregistered study using a large ( $$N_{trials}$$ = 204,120) online debate dataset. Every use of generic-you in an argument was associated with an up to 14% percent increase in the odds of successful persuasion. These findings underscore the need to distinguish between the specific and generic uses of “you” in large-scale linguistic analyses, an aspect that has been overlooked in the literature. The robust association between generic-you and persuasion persisted with the inclusion of various covariates, and above and beyond other pronouns (i.e., specific-you, I or we). However, these findings do not imply causality. In Supplementary Experiment 2, arguments with generic-you (vs. first-person singular pronouns, e.g., I) were rated as more persuasive by open-minded individuals. In Supplementary Experiment 3, generic-you (vs. specific-you) arguments did not differentially predict attitude change. We discuss explanations for these results, including differential mechanisms, boundary conditions, and the possibility that people intuitively draw on generic-you when expressing more persuasive ideas. Together, these findings add to a growing literature on the interpersonal implications of broadening one’s perspective via a subtle shift in language, while motivating future research on contextual and individual differences that may moderate these effects.

In today's data-sharing paradigm, personal data has become a valuable resource that intensifies the risk of unauthorized access and data breach. Increased data mining techniques used to analyze big data have posed significant risks to data security and privacy. Consequently, data breaches are a significant threat to individual privacy. Privacy is a multifaceted concept covering many areas, including the right to access, erasure, and rectify personal data. This paper explores the legal aspects of privacy harm and how they transform into legal action. Privacy harm is the negative impact to an individual as a result of the unauthorized release, gathering, distillation, or expropriation of personal information. Privacy Enhancing Technologies (PETs) emerged as a solution to address data privacy issues and minimize the risk of privacy harm. It is essential to implement privacy enhancement mechanisms to protect Personally Identifiable Information (PII) from unlawful use or access. FIPPs (Fair Information Practice Principles), based on the 1973 Code of Fair Information Practice (CFIP), and the Organization for Economic Cooperation and Development (OECD), are a collection of widely accepted, influential US codes that agencies use when evaluating information systems, processes, programs, and activities affecting individual privacy. Regulatory compliance places a responsibility on organizations to follow best practices to ensure the protection of individual data privacy rights. This paper will focus on FIPPs, relevance to US state privacy laws, their influence on OECD, and reference to the EU General Data Processing Regulation. (GDPR).

For few taxonomic groups do conservation efforts have such a disproportionate impact on biodiversity and human well-being as they do with bats. Bats face significant conservation challenges that affect their long-term viability, inhibit their ecosystem functions and services, and increase zoonotic spillover risks. Protecting bat populations and their habitats ultimately reduces these conservation threats, helps prevent pandemics, and supports essential ecosystem services. MENTOR-Bat is a fellowship program focused on strengthening technical research, and leadership capacity in the Global South to promote healthy environments where bats and humans can coexist with reduced risks of pathogen transmission. Co-designed by the United States Fish and Wildlife Service (USFWS) and Bat Conservation International (BCI), MENTOR-Bat mirrors the One Health framework by featuring a transdisciplinary team of three mentors and nine fellows from Cameroon, Colombia, and Indonesia. Fellows and mentors receive academic and field-based training on bat ecology and conservation, One Health, human dimensions of conservation, behavior change, strategic communications, international policy, adaptive management, project planning, conservation leadership, and public health. Fellows will then design and implement team pilot projects to advance One Health and bat conservation in their respective countries. Program evaluation of MENTOR-Bat is based on Kirkpatrick’s Hierarchy and focuses on measuring the development of established One Health core competences. By incorporating One Health and conservation within its activities, MENTOR-Bat can become a valuable programmatic template for transdisciplinary programming advancing evidence-based strategies for improving the well-being of bats, humans, and the environment.

BACKGROUND: Preclinical animal models which mimic the dimensions of long urethral strictures (>2 cm in length) encountered in the clinic are necessary to evaluate prospective graft designs for urethroplasty. The purpose of this study was to develop both male and female porcine models of long urethral strictures (∼4 cm in length) and characterize histological and functional outcomes of iatrogenic stricture formation between genders. METHODS: Focal, partial thickness urethral injuries were created over 5-6 cm long segments in male and female swine (N = 4 per gender) via electrocoagulation and the degree of stricture formation was monitored for up to 6 weeks by urethroscopy and retrograde urethrography. Animals were sacrificed following stricture confirmation and histological, immunohistochemical, and histomorphometric analyses were performed on strictured and uninjured control urethral segments to profile wound healing responses. RESULTS: Urethral stricture formation was detected in all female swine by 2 weeks and 100 % of male swine at 3.2 ± 1.8 weeks, post-operatively. The mean length of urethral strictures in both male and female swine was ∼4 cm. Substantial variations in the degree of stricture severity between sexes were observed with males exhibiting significant urethral stenosis and loss of α-smooth muscle actin+ smooth muscle bundles in comparison to controls, while females primarily displayed defects in pan-cytokeratin+ epithelia as well as functional urethral obstruction. CONCLUSIONS: Electrocoagulation injury is sufficient to produce long urethral strictures in male and female swine and the degree of stricture severity and nature of urethral obstruction was observed to be dependent on gender. Animal Protocol: AUP-19-150. KEY MESSAGE: Novel male and female models of long urethral strictures in swine were created to characterize histological and functional outcomes of iatrogenic stricture formation between genders.

Data literacy for students in nonquantitative fields is important as statistics become the grammar of research and how the world’s decisions are made. Statistics courses are typically offered by mathematics or statistics departments or by social and natural sciences such as economics, political science, psychology, and biology. Here we discuss how to construct a statistics course for students in nonquantitative fields, with a goal of integrating statistical material with students’ substantive interests, using student-focused teaching methods and technology to increase student involvement. We demonstrate this kind of hybrid course with the example of an introductory applied statistics class, taught at both the University of Toronto’s Anne Tanenbaum Center for Jewish Studies and the United States Naval Academy.

Abstract Skeletal muscle atrophy and dysfunction commonly accompany cardiovascular diseases such as peripheral arterial disease and may be partially attributable to systemic inflammation. We sought to determine whether acute systemic inflammation in a model of hindlimb ischaemia (HLI) could affect skeletal muscle macrophage infiltration, fibre size, or capillarization, independent of the ischaemia. Eight‐week‐old C57BL/6 male mice underwent either Sham or HLI surgery, and were killed 1, 3, or 7 days post‐surgery. Circulating inflammatory cytokine concentrations were measured, as well as immune cell infiltration and morphology of skeletal muscle from both limbs of HLI and Sham mice. In HLI compared with Sham mice at day 1, plasma interleukin‐1β levels were 216% higher (0.48 ± 0.10 vs. 0.15 ± 0.01 pg/μL, P = 0.005) and decreased by day 3. This was followed by increased macrophage presence in muscle from both ischaemic and non‐ischaemic limbs of HLI mice by day 7 (7.3‐ and 2.3‐fold greater than Sham, respectively, P

As in other subfields of psychology, developmental science faces a long-standing problem of limited diversity in research participants. This issue especially raises concerns when researchers make unwarranted broad claims about their results, such as using generic language that implies that a finding is unvarying and applies across participants and contexts. Variation in editorial practices may contribute to the extent to which generic language is used or how much information is provided about participant demographics. The present study expands on an existing corpus of articles published in developmental psychology journals and examines the extent to which generic language differed by journal and sample characteristics (such as racial/ethnic diversity or sample size). We observed widespread use of generic language: 73% of articles included at least one generic statement in article components that were coded (i.e. titles, highlights, and abstracts). However, differences across journals were observed: Articles published in "Developmental Science" and "JECP" (which require authors to include short research highlights) tended to have higher rates of generic language than articles published in "Child Development" and "Developmental Psychology" (which did not require highlights). Articles that fully reported sample race and ethnicity also included fewer generic statements to describe their results than articles with more incomplete reporting. We conclude by highlighting the importance of editorial policies in shaping scholarship, as well as challenges and opportunities for researchers to consider when reporting demographic information in a global field and clearly and accurately communicating the importance of research findings.

COVID-19 has revealed and intensified economic and health disparities, prompting a profound national and global examination of racist systems perpetuating such disadvantage. The historic confluence of COVID-19 with movements for social justice offers a window, which COVID fatigue may already be closing, for us to enact true change in the process and content of a graduate social work education. This moment calls for re-envisioned process and content that addresses issues of oppression, social justice, trauma, mental illness, and health. As social work educators with a specialization in trauma, we are thinking deeply about how to harness this juncture to shape a more rigorous and responsive social work educational process. We believe trauma-informed principles must be applied across the social work curriculum, beyond trauma-focused or clinical courses, and to our social work educational institutions. We offer examples of how we have revisioned social work training for ourselves and our students, from our multiple standpoints as faculty, administrator, and field advisor, for the complex challenges and opportunities of chronic syndemic times. We conclude with an invitation to shift away from the social work education status quo and truly practice what we teach.

When working with multimodal Bayesian posterior distributions, Markov chain Monte Carlo (MCMC) algorithms have difficulty moving between modes, and default variational or mode-based approximate inferences will understate posterior uncertainty. And, even if the most important modes can be found, it is difficult to evaluate their relative weights in the posterior. Here we propose an approach using parallel runs of MCMC, variational, or mode-based inference to hit as many modes or separated regions as possible and then combine these using Bayesian stacking, a scalable method for constructing a weighted average of distributions. The result from stacking efficiently samples from multimodal posterior distribution, minimizes cross validation prediction error, and represents the posterior uncertainty better than variational inference, but it is not necessarily equivalent, even asymptotically, to fully Bayesian inference. We present theoretical consistency with an example where the stacked inference approximates the true data generating process from the misspecified model and a non-mixing sampler, from which the predictive performance is better than full Bayesian inference, hence the multimodality can be considered a blessing rather than a curse under model misspecification. We demonstrate practical implementation in several model families: latent Dirichlet allocation, Gaussian process regression, hierarchical regression, horseshoe variable selection, and neural networks.

The paper deals with glazed ceramics and porcelain from the sites of the Eastern Xia (Dong Xia) (1215–1234), found in Primorye. The artifacts under study are part of a group of prestigious items of the Jurchen population. The historical conditions for the formation of a changed regional settling model in the new state formation are characterized. The origin of glazed pottery and porcelain wares are analyzed, and the place they occupied in domestic and foreign trade among the Jurchens is explained. Items made in the Jin (1115–1234) and Southern Song (960–1279) kilns are considered separately. It has been established that after the conquest of Northern China, the Jurchens retained the production of kilns of Ding wares, Cizhou wares, Chün wares, Northern celadons, and items with colored lead glazes. Products made in kilns for producing Jian (temmoku) wares, Longquan celadon, and Ch'in-pai wares came to Jin from the Southern Song. The Song imperial style proved popular among the Jurchens. In general, the considered glazed ceramics and porcelain not only characterize trade relations in Jin on the eve of the formation of the Eastern Xia in 1215, but also the preferences of the Jurchen elite. The value of glazed ware increased as a result of the new political and economic situation.

Abstract The study of HIV infection and pathogenicity in physical reservoirs requires a biologically relevant model. The human immune system (HIS) mouse is an established model of HIV infection, but defects in immune tissue reconstitution remain a challenge for examining pathology in tissues. We utilized exogenous injection of the human recombinant FMS-like tyrosine kinase 3 ligand (rFLT-3 L) into the hematopoietic stem cell (HSC) cord blood HIS mouse model to significantly expand the total area of lymph node (LN) and the number of circulating human T cells. The results enabled visualization and quantification of HIV infectivity, CD4 T cell depletion and other measures of pathogenesis in the secondary lymphoid tissues of the spleen and LN. Treatment with the Caspase-1/4 inhibitor VX-765 limited CD4+ T cell loss in the spleen and reduced viral load in both the spleen and axillary LN. In situ hybridization further demonstrated a decrease in viral RNA in both the spleen and LN. Transcriptomic analysis revealed that in vivo inhibition of caspase-1/4 led to an upregulation in host HIV restriction factors including SAMHD1 and APOBEC3A. These findings highlight the use of rFLT-3 L to augment human immune system characteristics in HIS mice to support investigations of HIV pathogenesis and test host directed therapies, though further refinements are needed to further augment LN architecture and cellular populations. The results further provide in vivo evidence of the potential to target inflammasome pathways as an avenue of host-directed therapy to limit immune dysfunction and virus replication in tissue compartments of HIV+ persons.