Mechanoimmunology in the solid tumor microenvironment.

The tumor microenvironment (TME) is a complex and dynamic ecosystem that adjoins the cancer cells within solid tumors and comprises distinct components such as extracellular matrix, stromal and immune cells, blood vessels, and an abundance of signaling molecules. In recent years, the mechanical properties of the TME have emerged as critical determinants of tumor progression and therapeutic response. Aberrant mechanical cues, including altered tissue architecture and stiffness, contribute to tumor progression, metastasis, and resistance to treatment. Moreover, burgeoning immunotherapies hold great promise for harnessing the immune system to target and eliminate solid malignancies; however, their success is hindered by the hostile mechanical landscape of the TME, which can impede immune cell infiltration, function, and persistence. Consequently, understanding TME mechanoimmunology - the interplay between mechanical forces and immune cell behavior - is essential for developing effective solid cancer therapies. Here, we review the role of TME mechanics in tumor immunology, focusing on recent therapeutic interventions aimed at modulating the mechanical properties of the TME to potentiate T cell immunotherapies, and innovative assays tailored to evaluate their clinical efficacy.

Effectiveness of an eHealth intervention for reducing psychological distress and increasing COVID-19 knowledge and protective behaviors among racialized sexual and gender minority adults: A quasi-experimental study (#SafeHandsSafeHearts).

PURPOSE: Sexual and gender minority and racialized populations experienced heightened vulnerability during the Covid-19 pandemic. Marginalization due to structural homophobia, transphobia and racism, and resulting adverse social determinants of health that contribute to health disparities among these populations, were exacerbated by the Covid-19 pandemic and public health measures to control it. We developed and tested a tailored online intervention (#SafeHandsSafeHearts) to support racialized lesbian, gay, bisexual, transgender, queer, and other persons outside of heteronormative and cisgender identities (LGBTQ+) in Toronto, Canada during the pandemic. METHODS: We used a quasi-experimental pre-test post-test design to evaluate the effectiveness of a 3-session, peer-delivered eHealth intervention in reducing psychological distress and increasing Covid-19 knowledge and protective behaviors. Individuals ≥18-years-old, resident in Toronto, and self-identified as sexual or gender minority were recruited online. Depressive and anxiety symptoms, and Covid-19 knowledge and protective behaviors were assessed at baseline, 2-weeks postintervention, and 2-months follow-up. We used generalized estimating equations and zero-truncated Poisson models to evaluate the effectiveness of the intervention on the four primary outcomes. RESULTS: From March to November 2021, 202 participants (median age, 27 years [Interquartile range: 23-32]) were enrolled in #SafeHandsSafeHearts. Over half (54.5%, n = 110) identified as cisgender lesbian or bisexual women or women who have sex with women, 26.2% (n = 53) cisgender gay or bisexual men or men who have sex with men, and 19.3% (n = 39) transgender or nonbinary individuals. The majority (75.7%, n = 143) were Black and other racialized individuals. The intervention led to statistically significant reductions in the prevalence of clinically significant depressive (25.4% reduction, p < .01) and anxiety symptoms (16.6% reduction, p < .05), and increases in Covid-19 protective behaviors (4.9% increase, p < .05), from baseline to postintervention. CONCLUSION: We demonstrated the effectiveness of a brief, peer-delivered eHealth intervention for racialized LGBTQ+ communities in reducing psychological distress and increasing protective behaviors amid the Covid-19 pandemic. Implementation through community-based organizations by trained peer counselors supports feasibility, acceptability, and the importance of engaging racialized LGBTQ+ communities in pandemic response preparedness. This trial is registered with ClinicalTrials.gov, number NCT04870723.

The LAT Rheostat as a Regulator of Megakaryocyte Activation.

BACKGROUND: Specifically positioned negatively charged residues within the cytoplasmic domain of the adaptor protein, linker for the activation of T cells (LAT), have been shown to be important for efficient phosphorylation of tyrosine residues that function to recruit cytosolic proteins downstream of immunoreceptor tyrosine-based activation motif (ITAM) receptor signaling. LAT tyrosine 132-the binding site for PLC-γ2-is a notable exception, preceded instead by a glycine, making it a relatively poor substrate for phosphorylation. Mutating Gly131 to an acidic residue has been shown in T cells to enhance ITAM-linked receptor-mediated signaling. Whether this is generally true in other cell types is not known. METHODS: To examine whether LAT Gly131 restricts ITAM signaling in cells of the megakaryocyte lineage, we introduced an aspartic acid at this position in human induced pluripotent stem cells (iPSCs), differentiated them into megakaryocytes, and examined its functional consequences. RESULTS: iPSCs expressing G131D LAT differentiated and matured into megakaryocytes normally, but exhibited markedly enhanced reactivity to glycoprotein VI (GPVI)-agonist stimulation. The rate and extent of LAT Tyr132 and PLC-γ2 phosphorylation, and proplatelet formation on GPVI-reactive substrates, were also enhanced. CONCLUSION: These data demonstrate that a glycine residue at the -1 position of LAT Tyr132 functions as a kinetic bottleneck to restrain Tyr132 phosphorylation and signaling downstream of ITAM receptor engagement in the megakaryocyte lineage. These findings may have translational applications in the burgeoning field of in vitro platelet bioengineering.

Associations between water insecurity and mental health outcomes among lesbian, gay, bisexual, transgender and queer persons in Bangkok, Thailand and Mumbai, India: Cross-sectional survey findings.

Background: Water insecurity disproportionally affects socially marginalized populations and may harm mental health. Lesbian, gay, bisexual, transgender and queer (LGBTQ) persons are at the nexus of social marginalization and mental health disparities; however, they are understudied in water insecurity research. Yet LGBTQ persons likely have distinct water needs. We explored associations between water insecurity and mental health outcomes among LGBTQ adults in Mumbai, India and Bangkok, Thailand. Methods: This cross-sectional survey with a sample of LGBTQ adults in Mumbai and Bangkok assessed associations between water insecurity and mental health outcomes, including anxiety symptoms, depression symptoms, loneliness, alcohol misuse, COVID-19 stress and resilience. We conducted multivariable logistic and linear regression analyses to examine associations between water insecurity and mental health outcomes. Results: Water insecurity prevalence was 28.9% in Mumbai and 18.6% in Bangkok samples. In adjusted analyses, in both sites, water insecurity was associated with higher likelihood of depression symptoms, anxiety symptoms, COVID-19 stress, alcohol misuse and loneliness. In Mumbai, water insecurity was also associated with reduced resilience. Conclusion: Water insecurity was common among LGBTQ participants in Bangkok and Mumbai and associated with poorer well-being. Findings signal the importance of assessing water security as a stressor harmful to LGBTQ mental health.

Enhancing the palatability of cultivated meat.

Cultivated meat (CM) has transitioned from a futuristic concept to a present reality, with select products approved for consumption and sale in Singapore, Israel, and the USA. This evolution has emphasized scalable, cost-effective, and sustainable production, as well as navigation of regulatory pathways. As CM develops, a crucial challenge lies in delivering products that are highly appealing to consumers. Central to this will be refining CM palatability, a term encompassing food's taste, aroma, texture, tenderness, juiciness, and color. We explore the scientific and engineering approaches to producing palatable CM, including cell-line selection, cell differentiation, and post-processing techniques. This includes a discussion of the structural and compositional properties of meat that are intrinsically coupled to palatability.

"Going vaccine hunting": Multilevel influences on COVID-19 vaccination among racialized sexual and gender minority adults-a qualitative study.

High levels of COVID-19 vaccine hesitancy have been reported among Black and Latinx populations, with lower vaccination coverage among racialized versus White sexual and gender minorities. We examined multilevel contexts that influence COVID-19 vaccine uptake, barriers to vaccination, and vaccine hesitancy among predominantly racialized sexual and gender minority individuals. Semi-structured online interviews explored perspectives and experiences around COVID-19 vaccination. Interviews were recorded, transcribed, uploaded into ATLAS.ti, and reviewed using thematic analysis. Among 40 participants (mean age, 29.0 years [SD, 9.6]), all identified as sexual and/or gender minority, 82.5% of whom were racialized. COVID-19 vaccination experiences were dominated by structural barriers: systemic racism, transphobia and homophobia in healthcare and government/public health institutions; limited availability of vaccination/appointments in vulnerable neighborhoods; absence of culturally-tailored and multi-language information; lack of digital/internet access; and prohibitive indirect costs of vaccination. Vaccine hesitancy reflected in uncertainties about a novel vaccine amid conflicting information and institutional mistrust was integrally linked to structural factors. Findings suggest that the uncritical application of "vaccine hesitancy" to unilaterally explain undervaccination among marginalized populations risks conflating structural and institutional barriers with individual-level psychological factors, in effect placing the onus on those most disenfranchised to overcome societal and institutional processes of marginalization. Rather, disaggregating structural determinants of vaccination availability, access, and institutional stigma and mistrust from individual attitudes and decision-making that reflect vaccine hesitancy, may support 1) evidence-informed interventions to mitigate structural barriers in access to vaccination, and 2) culturally-informed approaches to address decisional ambivalence in the context of structural homophobia, transphobia, and racism.

Understanding park visitors' soundscape perception using subjective and objective measurement.

Environmental noise knows no boundaries, affecting even protected areas. Noise pollution, originating from both external and internal sources, imposes costs on these areas. It is associated with adverse health effects, while natural sounds contribute to cognitive and emotional improvements as ecosystem services. When it comes to parks, individual visitors hold unique perceptions of soundscapes, which can be shaped by various factors such as their motivations for visiting, personal norms, attitudes towards specific sounds, and expectations. In this study, we utilized linear models and geospatial data to evaluate how visitors' personal norms and attitudes, the park's acoustic environment, visitor counts, and the acoustic environment of visitors' neighborhoods influenced their perception of soundscapes at Muir Woods National Monument. Our findings indicate that visitors' subjective experiences had a greater impact on their perception of the park's soundscape compared to purely acoustic factors like sound level of the park itself. Specifically, we found that motivations to hear natural sounds, interference caused by noise, sensitivity to noise, and the sound levels of visitors' home neighborhoods influenced visitors' perception of the park's soundscape. Understanding how personal factors shape visitors' soundscape perception can assist urban and non-urban park planners in effectively managing visitor experiences and expectations.

Covid-19 Vaccine Hesitancy and Under-Vaccination among Marginalized Populations in the United States and Canada: A Scoping Review.

BACKGROUND: Amid persistent disparities in Covid-19 vaccination and burgeoning research on vaccine hesitancy (VH), we conducted a scoping review to identify multilevel determinants of Covid-19 VH and under-vaccination among marginalized populations in the U.S. and Canada. METHODS: Using the scoping review methodology developed by the Joanna Briggs Institute, we designed a search string and explored 7 databases to identify peer-reviewed articles published from January 1, 2020-October 25, 2022. We combine frequency analysis and narrative synthesis to describe factors influencing Covid-19 VH and under-vaccination among marginalized populations. RESULTS: The search captured 11,374 non-duplicated records, scoped to 103 peer-reviewed articles. Among 14 marginalized populations identified, African American/Black, Latinx, LGBTQ+, American Indian/Indigenous, people with disabilities, and justice-involved people were the predominant focus. Thirty-two factors emerged as influencing Covid-19 VH, with structural racism/stigma and institutional mistrust (structural)(n = 71) most prevalent, followed by vaccine safety (vaccine-specific)(n = 62), side effects (vaccine-specific)(n = 50), trust in individual healthcare provider (social/community)(n = 38), and perceived risk of infection (individual)(n = 33). Structural factors predominated across populations, including structural racism/stigma and institutional mistrust, barriers to Covid-19 vaccine access due to limited supply/availability, distance/lack of transportation, no/low paid sick days, low internet/digital technology access, and lack of culturally- and linguistically-appropriate information. DISCUSSION: We identified multilevel and complex drivers of Covid-19 under-vaccination among marginalized populations. Distinguishing vaccine-specific, individual, and social/community factors that may fuel decisional ambivalence, more appropriately defined as VH, from structural racism/structural stigma and systemic/institutional barriers to vaccination access may better support evidence-informed interventions to promote equity in access to vaccines and informed decision-making among marginalized populations.

O-linked sialic acid residues on platelet membrane glycoprotein IIb mask the human HPA-9b alloepitope.

Sialic acids occupy the terminal position of glycan chains and have the potential to influence the antigenicity of glycoproteins (GP). The polymorphisms of human platelet alloantigens (HPA)-3 and HPA-9, located near the C-terminus of the extracellular domain of platelet membrane GPIIb, are adjacent to sialyl-core 1 O-glycans emanating from serines 845 and 847. Whether the nearby O-glycans affect the antigenicity of HPA-9b or influence the binding of anti-HPA-9b alloantibodies in clinically significant cases of neonatal alloimmune thrombocytopenia is unknown. To address this issue, we generated a series of O-glycan mutant HPA-9 allele-specific induced pluripotent stem cell lines, differentiated them to megakaryocytes (MKs), and examined their ability to bind HPA-9b-specific alloantibodies. We found that both wild-type MKs treated with neuraminidase and those genetically modified to lack the sialidases ST3GAL1 and ST3GAL2 dramatically increased anti-HPA-9b alloantibody binding, indicating that the HPA-9b epitope is partially masked by terminal sialic acids on nearby O-glycans of GPIIb. Interestingly, mutating the serine residues that carry these glycan chains to alanine actually reduced the binding of anti-HPA-9b alloantibodies, indicating that these 2 O-glycan chains contribute to the presentation of the HPA-9b epitope-perhaps by stabilizing the conformation of the GP in this region. Collectively, our data suggest that detection of anti-HPA-9b alloantibodies may be enhanced through the use of HPA-9b-specific MKs that have been genetically altered to lack nearby terminal sialic acid residues but retain the glycan chains to which they are attached.

Multilevel Factors Impacting PrEP Engagement Among Young Gay Men and Young Transgender Women in Thailand: A Qualitative Analysis.

Half of new HIV infections in Thailand are among young people, the majority of whom are young gay and other men who have sex with men (YMSM) and young transgender women (YTGW). Amid low pre-exposure prophylaxis (PrEP) coverage, we explored practice-based factors that impact PrEP engagement among YMSM and YTGW. In 2018, we conducted 4 focus group discussions with 20 YMSM and 5 YTGW, and 22 in-depth interviews (5 in 2022) with healthcare providers (HCPs), community-based organization (CBO)/nongovernmental organization (NGO) staff, and peer educators. The inclusion of PrEP in universal healthcare coverage, including YMSM and YTGW, is a substantial facilitator of PrEP use; however, systemic barriers at microsocial (lack of communication about PrEP from HCPs, teachers, parents), mesosocial (healthcare-service fragmentation, lack of PrEP-competent HCPs), and macrosocial levels (annual quotas on free HIV-testing, HIV- and sexual-stigma) constrain and disincentivize adolescents' engagement with PrEP. National scale-up of youth-friendly and LGBT-affirmative CBO/NGO clinics, HCP training, and tailored programs to support adolescents' adherence may promote PrEP engagement among YMSM and YTGW in Thailand.

A scoping review of lesbian, gay, bisexual, transgender, queer, and intersex (LGBTQI+) people's health in India.

Amid incremental progress in establishing an enabling legal and policy environment for lesbian, gay, bisexual, transgender and queer-identified people, and people with intersex variations (LGBTQI+) in India, evidence gaps on LGBTQI+ health are of increasing concern. To that end, we conducted a scoping review to map and synthesize the current evidence base, identify research gaps, and provide recommendations for future research. We conducted a scoping review using the Joanna Briggs Institute methodology. We systematically searched 14 databases to identify peer-reviewed journal articles published in English language between January 1, 2010 and November 20, 2021, that reported empirical qualitative, quantitative or mixed methods data on LGBTQI+ people's health in India. Out of 3,003 results in total, we identified 177 eligible articles; 62% used quantitative, 31% qualitative, and 7% mixed methods. The majority (55%) focused on gay and other men who have sex with men (MSM), 16% transgender women, and 14% both of these populations; 4% focused on lesbian and bisexual women, and 2% on transmasculine people. Overall, studies reported high prevalence of HIV and sexually transmitted infections; multilevel risk factors for HIV; high levels of mental health burden linked to stigma, discrimination, and violence victimization; and non-availability of gender-affirmative medical care in government hospitals. Few longitudinal studies and intervention studies were identified. Findings suggest that LGBTQI+ health research in India needs to move beyond the predominant focus on HIV, and gay men/MSM and transgender women, to include mental health and non-communicable diseases, and individuals across the LGBTQI+ spectrum. Future research should build on largely descriptive studies to include explanatory and intervention studies, beyond urban to rural sites, and examine healthcare and service needs among LGBTQI+ people across the life course. Increased Indian government funding for LGBTQI+ health research, including dedicated support and training for early career researchers, is crucial to building a comprehensive and sustainable evidence base to inform targeted health policies and programs moving forward.

Programming of Multicellular Patterning with Mechano-Chemically Microstructured Cell Niches.

Multicellular patterning of stem-cell-derived tissue models is commonly achieved via self-organizing activities triggered by exogenous morphogenetic stimuli. However, such tissue models are prone to stochastic behavior, limiting the reproducibility of cellular composition and forming non-physiological architectures. To enhance multicellular patterning in stem cell-derived tissues, a method for creating complex tissue microenvironments endowed with programmable multimodal mechano-chemical cues, including conjugated peptides, proteins, morphogens, and Young's moduli defined over a range of stiffnesses is developed. The ability of these cues to spatially guide tissue patterning processes, including mechanosensing and the biochemically driven differentiation of selected cell types, is demonstrated. By rationally designing niches, the authors engineered a bone-fat assembly from stromal mesenchyme cells and regionalized germ layer tissues from pluripotent stem cells. Through defined niche-material interactions, mechano-chemically microstructured niches enable the spatial programming of tissue patterning processes. Mechano-chemically microstructured cell niches thereby offer an entry point for enhancing the organization and composition of engineered tissues, potentiating structures that better recapitulate their native counterparts.

Enabling urban systems transformations: co-developing national and local strategies.

Transformative urban development is urgent to achieve future sustainable development and wellbeing. Transformation can benefit from shared and cumulative learning on strategies to guide urban development across local to national scales, while also reflecting the complex emergent nature of urban systems, and the need for context-specific and place-based solutions. The article addresses this challenge, drawing on extensive transdisciplinary engagement and National Strategy co-development processes for Australia. This includes generation of two frameworks as boundary objects to assist such transdisciplinary strategy development. An 'enabling urban systems transformation' framework comprises four generic overarching transformation enablers and a set of necessary underpinning urban capacities. This also built cumulatively on other sustainability and urban transformation studies. A complementary 'knowledge for urban systems transformation' framework comprises key knowledge themes that can support an integrated systems approach to mission-focused urban transformations, such as decarbonising cities. The article provides insights on the transdisciplinary processes, urban systems frameworks, and scoping of key strategies that may help those developing transformation strategies from local to national scales. Science highlights • Transdisciplinary national urban strategy development is used to distil generic frameworks and strategy scopes with potential international application. • The frameworks also build on other published framings to support convergent, cumulative and transdisciplinary urban science. • The 'enabling transformations' and 'urban knowledge' frameworks include the perspective of those developing sustainable urban systems strategies. • The enabling framework also informs 'National Urban Policy' and 'Knowledge and Innovation Hub' strategies, and prevailing power imbalances. • The knowledge framework can help frame urban challenges, missions and knowledge programs. Policy and practice recommendations • An urban 'transformation imperative' and 'strategic response' can be co-developed from local to national scales. • Local initiative is crucial to drive urban strategies, but sustained national leadership with coherent policy across sectors and scales is also key. • Diversity in engagement participation and processes generates whole-of-urban-systems and local-to-national perspectives. • Urban solutions are context-specific but generic frameworks can help collaborative issue framing and responses. • Collaborative issue framing informed by generic frameworks can bring broader perspectives to context-specific and contested policy and practice issues. Supplementary Information: The online version contains supplementary material available at 10.1186/s42854-023-00049-9.

Mental health, economic well-being and health care access amid the COVID-19 pandemic: a mixed methods study among urban men who have sex with men in India.

Scant empirical research from Asia has addressed the impact of COVID-19 on sexual minority health. We aimed to explore and understand the impact of COVID-19 on income security, mental health, HIV risk and access to health services among men who have sex with men (MSM) in India. We conducted a concurrent mixed methods study from April to June 2020, including a cross-sectional survey and in-depth semi-structured interviews with MSM recruited from three non-governmental organisations providing HIV prevention services in Chandigarh, India. We examined the associations of sexual minority stressors (sexual stigma, internalised homonegativity), economic stressors, and stress due to social distancing, with depression and anxiety, HIV risk, and access to health services. Survey findings (n = 132) indicated that internalised homonegativity and stress related to social distancing were significantly associated with depressive and anxiety symptoms. Results also showed reduced access to condoms, HIV testing and counselling services. Qualitative findings (n = 10) highlighted adverse economic impacts of COVID-19, including loss of employment/wages and engaging in survival sex work, which contributed to psychological distress and HIV risk. The COVID-19 pandemic has resulted in considerable psychological and financial distress among low socioeconomic status MSM in India, including those involved in sex work - communities already marginalised in economic, family and healthcare sectors. Structural interventions to improve access to mental health and HIV services and decrease financial burden are critical to mitigate the impact of COVID-19.

The Impact of COVID-19 on Economic Well-being and Health Outcomes among Transgender Women in India.

Coronavirus disease 2019 (COVID-19)-related lockdowns in India have disrupted the meager sources of income of many transgender women, including those in the hijra subculture who largely rely on money from providing blessings, begging, and sex work. Many have expended savings and taken high-interest loans, contributing to psychological distress. For hijras engaged in sex work, challenges to negotiating condom use and adhering to COVID-19 protective measures increase risks for contracting HIV and COVID-19 amid decreased access to HIV services. Many transgender women face challenges accessing COVID-19-related government welfare programs as they lack legal gender identity documents. Multisectoral and transgender-competent approaches are needed to mitigate the impact of the pandemic.

Peer education interventions for HIV prevention and sexual health with young people in Mekong Region countries: a scoping review and conceptual framework.

WHO-recommended rights-based approaches to sexual health emphasise participatory and youth-centred processes. Among these, peer education (PE) interventions are commonly used to promote HIV prevention and sexual health for young people, particularly in low-resource, high HIV prevalence contexts. We conducted a scoping review to identify key characteristics, implementation challenges, and knowledge gaps in the literature regarding PE interventions in Mekong Region countries. Out of 6521 publications identified through database searches, 17 peer-reviewed articles were included in the review (n = 21,469 participants). Studies from Thailand (n = 7), Vietnam (n = 5), Myanmar (n = 3), Cambodia (n = 1), and Lao PDR (n = 1) included adolescent and young key populations (n = 11) and general population youth (n = 6). Findings from quantitative (descriptive) and qualitative (thematic) analysis illustrate benefits and challenges of various elements of multicomponent PE interventions in reaching vulnerable young people and improving HIV prevention and sexual health outcomes. Focal knowledge gaps emerged in regard to peer educator outcomes (increased knowledge, skill-building, empowerment); interpersonal processes between peer educators and young people (role modelling, social dynamics); and social-structural contexts (sociocultural influences, gendered power relations), which may affect PE programme implementation and effectiveness. Future research should evaluate the potential benefits of complementing evidence-based intervention approaches - focused predominantly on assessing individual-level behavioural outcomes conceptualised as external to PE programmes - with evidence-making intervention approaches that support rights-based PE programmes: incorporating a focus on dialectical and relational processes between peer educators and young people; assessing salutary outcomes among peer educators themselves; and evaluating the situated implementation of youth-engaged PE interventions in complex sociocultural systems.

Public and manager perceptions about prescribed fire in the Mid-Atlantic, United States.

Firescapes of the Mid-Atlantic are understudied compared to other ecosystems in the United States, and little is known about the acceptance of prescribed fire as a forest management tool. Yet, this region harbors high levels of wildland-urban interface (WUI), has a close intermingling of land ownerships, and reflects substantial regional heterogeneity in burning histories and fire hazards. As prescribed fire is increasingly applied in the Mid-Atlantic as a critical tool to meet various land management objectives, research is needed to help managers understand community perceptions of prescribed fire implementation. Through intercept surveys of forest recreationists and online surveys of fire managers, this study investigates perceptions about prescribed fire use in the Mid-Atlantic, in addition to the critical contributing factors of public support toward prescribed fires. Two states, Pennsylvania and New Jersey, were selected as case studies to explore regional differences in social perception due to their contrasts in fire history, policy, management objectives, and social exposure. Our results show moderate social awareness of local prescribed fires, moderate to high familiarity with prescribed burning, high agency trust, and strong community support toward prescribed fires. However, the perceived concerns and benefits differed between managers and forest recreationists and between recreationists from Pennsylvania and New Jersey. The factors influencing the support of prescribed burning practices included forest management beliefs, concern about prescribed fire effects, familiarity with prescribed fires as a forest management tool, and awareness of local prescribed fires. Collectively, these results highlighted needs in public outreach to strengthen education, build broader community awareness, engage critical stakeholder groups such as forest recreationists, and re-align public outreach messages based on community-level concerns and perceived benefits. Additionally, it will be vital for the scientific community to help monitor critical shifts in forest value orientations and fill in significant research gaps regarding prescribed fire benefits.

Prophylactic administration of HPA-1a-specific antibodies prevents fetal/neonatal alloimmune thrombocytopenia in mice.

Fetal/neonatal alloimmune thrombocytopenia (FNAIT) is a life-threatening bleeding disorder caused by maternal alloantibodies directed against paternally inherited human platelet alloantigens (HPAs) present on the surface of fetal and neonatal platelets. There are currently no approved therapies for the prevention of FNAIT. We report herein the ability of 2 human HPA-1a-specific therapeutic candidates, one a polyclonal, and the other a monoclonal antibody, to prevent alloimmunization in a novel preclinical mouse model of FNAIT. Both antibody preparations effected the rapid and complete elimination of HPA-1a+ platelets from circulation and prevented the development of HPA-1a alloantibodies. HPA-1a- female mice treated prophylactically with anti-HPA-1a antibody prior to exposure to HPA-1a+ platelets gave birth to HPA-1a+/- pups with significantly improved platelet counts and no bleeding symptoms. These preclinical data establish both the potential and threshold exposure targets for prophylactic treatment with HPA-1a-specific antibodies for the prevention of FNAIT in humans.

A stochastic simulation model for assessing the masking effects of road noise for wildlife, outdoor recreation, and bioacoustic monitoring.

Traffic noise is one of the leading causes of reductions in animal abundances near roads. Acoustic masking of conspecific signals and adventitious cues is one mechanism that likely causes animals to abandon loud areas. However, masking effects can be difficult to document in situ and the effects of infrequent noise events may be impractical to study. Here, we present the Soundscapes model, a stochastic individual-based model that dynamically models the listening areas of animals searching for acoustic resources ("searchers"). The model also studies the masking effects of noise for human detections of the searchers. The model is set in a landscape adjacent to a road. Noise produced by vehicles traveling on that road is represented by calibrated spectra that vary with speed. Noise propagation is implemented using ISO-9613 procedures. We present demonstration simulations that quantify declines in searcher efficiency and human detection of searchers at relatively low traffic volumes, fewer than 50 vehicles per hour. Traffic noise is pervasive, and the Soundscapes model offers an extensible tool to study the effects of noise on bioacoustics monitoring, point-count surveys, the restorative value of natural soundscapes, and auditory performance in an ecological context.