Culturally Centered Implementation of Video Telehealth for Rural Native Veterans.

Introduction: Native American Veterans are the most rural and experience heightened risk for mental health (MH) challenges while facing significant health care inequities and access barriers. Rural Native Veterans (RNVs) have experienced historical loss and racial discrimination, contributing to mistrust of Veterans Health Administration (VHA) and other Federal systems. Telemedicine, including video telehealth (VTH), can improve access to MH care for RNVs by addressing barriers. Understanding the cultural context and existing community resources can improve engagement and implementation efforts with RNVs. Objective: This article describes a model of culturally centered MH care and a flexible implementation approach, Personalized Implementation of Virtual Treatments for Rural Native Veterans (PIVOT-RNV), used to disseminate the model. Methods: Participants included four VHA sites serving large RNV populations where PIVOT-RNV was applied to expand the availability of virtual solutions, including VTH, for RNVs. A mixed methods formative evaluation tracked VTH utilization and used provider and RNV feedback to inform iterative process improvements. Results: Where PIVOT-RNV was used, number of providers using VTH with RNVs, number of unique RNVs receiving MH care through VTH, and number of VTH encounters with RNVs grew annually. Provider and RNV feedback highlighted the importance of addressing the unique barriers and cultural context of RNVs. Conclusions: PIVOT-RNV demonstrates promise for improving implementation of virtual treatments and access to MH care for RNVs. The integration of implementation science within a cultural safety framework helps address specific barriers to adoption of virtual treatments for RNVs. Next steps include expanding PIVOT-RNV efforts at additional sites.

Getting Connected: a Retrospective Cohort Investigation of Video-to-Home Telehealth for Mental Health Care Utilization Among Women Veterans.

BACKGROUND: Increasingly, women are serving in the military and seeking care at the Veterans Health Administration (VHA). Women veterans face unique challenges and barriers in seeking mental health (MH) care within VHA. VA Video Connect (VVC), which facilitates video-based teleconferencing between patients and providers, can reduce barriers while maintaining clinical effectiveness. OBJECTIVE: Primary aims were to examine gender differences in VVC use, describe changes in VVC use over time (including pre-COVID and 6 months following the beginning of COVID), and determine whether changes over time differed by gender. DESIGN: A retrospective cohort investigation of video-to-home telehealth for MH care utilization among veterans having at least 1 MH visit from October 2019 to September 2020. PARTICIPANTS: Veterans (236,268 women; 1,318,024 men). INTERVENTIONS (IF APPLICABLE): VVC involves face-to-face, synchronous, video-based teleconferencing between patients and providers, enabling care at home or another private location. MAIN MEASURES: Percentage of MH encounters delivered via VA Video Connect. KEY RESULTS: Women veterans were more likely than men to have at least 1 VVC encounter and had a greater percentage of MH care delivered via VVC in FY20. There was an increase in the percentage of MH encounters that were VVC over FY20, and this increase was greater for women than men. Women veterans who were younger than 55 (compared to those 55 and older), lived in urban areas (compared to those in rural areas), or were Asian (compared to other races) had a greater percentage of MH encounters that were VVC since the start of the pandemic, controlling for the mean percentage of VVC MH encounters in the 6 months pre-pandemic. CONCLUSIONS: VVC use for MH care is greater in women veterans compared to male veterans and may reduce gender-specific access barriers. Future research and VVC implementation efforts should emphasize maximizing patient choice and satisfaction.

Bringing Assessment-to-Instruction (A2i) Technology to Scale: Exploring the Process from Development to Implementation.

Bringing effective, research-based literacy interventions into the classroom is challenging, especially given the cultural and linguistic diversity of today's classrooms. We examined the promise of Assessment-to-Instruction (A2i) technology redesigned to be used at scale to support teachers' implementation of the individualized student instruction (ISI) intervention from kindergarten through third grade. In seven randomized controlled trials, A2i and ISI have demonstrated efficacy. However, the research version of A2i was not scalable. In order to bring A2i to scale in schools serving linguistically diverse students, we carried out the current study across two phases. This study represents both an exploration of what it takes to bring an educational intervention to scale (Phase 1) and a quasi-experiment on the literacy outcomes of learners whose teachers used the technology (Phase 2). We integrated assessments of vocabulary, word decoding, and reading comprehension; revised the A2i algorithms to account for the constellation of skills English learners (ELs) bring to the classroom; updated the user interfaces and added new graphic features; and improved bandwidth and stability of the technology. Findings were mixed, including several non-significant results, a marginally significant intent-to-treat effect on word reading in kindergarten and first grade for English monolingual students and ELs, and one significant interaction effect, which suggested ELs and students with less developed reading skills in second and third grade benefitted most from the intervention. With some caution, we conclude that A2i demonstrates potential to be used at scale and promise of effectiveness for improving code-focused skills for diverse learners.

Exploring Adolescents' (Non-)Use of Modern Contraceptives in Ghana Through the Lens of the Theory of Gender and Power.

Despite the benefits of modern contraceptives, its usage is low among adolescents in sub-Saharan Africa. Based on the theory of gender and power, this study explored adolescents' (non-)use of contraceptives in the context of their sexual and reproductive health. Data were collected from adolescents (15-19 years) through focus group discussions as well as through interviews with five key informants. The collected data were investigated through thematic analysis. The study revealed that gender and power influenced adolescents sexual behavior. Both young men and young women engaged in risky sexual behavior, which exposed them to unintended pregnancy. Whereas some young women engaged in risky sexual behaviors due to financial reasons, young men engaged in such behaviors for pleasure. Lack of knowledge about the correct use of modern contraceptives, type of sexual relationship, and cultural norms of adolescent girls' appropriate sexual behavior influenced the use of contraceptives by adolescent girls. Avoiding pregnancy could be easier for adolescent girls if only they could have easy access to more long-term and reliable contraceptive methods. Education on the need to use condoms during sexual intercourse should be intensified to create awareness about using condoms to avoid sexually transmitted infections in addition to unwanted pregnancy.

Simulation of fluvial sediment dynamics through strategic assessment of stream gaging data: A targeted watershed sediment loading analysis.

Near-channel sediment loading (NCSL) is localized and episodic, making it difficult to accurately quantify its cumulative contribution to watershed sediment loading, let alone predict the effects from changes in river discharge due to climate change or land management practices. We developed a methodological framework, using commonly available stream gaging data, for estimating watershed-scale NCSL, a feature generally absent in most watershed models. The method utilizes a network of paired gages that bracket the incised river corridors of 15 tributaries to the Minnesota River, in which near-channel sources are often the dominant contributors of sediment loading. For each set of paired gages, we calculate NCSL as the difference between the upstream and downstream sediment loading minus the field contribution between the gages. NCSL generally increases with river discharge when it exceeds the observed threshold benchmark in the tributaries of Minnesota River Basin; accordingly, we developed a predictive model for quantifying NCSL using river discharge as the independent variable. This approach provides a predictive basis for evaluating the impacts on near-channel sediment supply from increases in runoff and river discharge. Application of this approach includes evaluation of watershed-scale conservation trade-offs, where benefits of landscape management practices, such as wetlands and reservoirs are measured in terms of reduction in downstream near-channel sediment loading in the incised river corridors.

Building Word Knowledge, Learning Strategies, and Metacognition with the Word-Knowledge E-Book.

Many children fail to comprehend what they read because they do not monitor their understanding, which requires making accurate judgements of what they know and then employing repair strategies when comprehension fails. Relying on research from learning science and cognitive and developmental psychology, we developed the Word Knowledge e-Book (WKe-Book) to improve children's calibration of their word knowledge, strategy use, and word knowledge overall; skills which are associated with reading comprehension. The WKe-Book, which is read on a tablet computer, is a choose-your-own adventure book where choices require choosing between two rare words (e.g., cogitate vs. procrastinate). Depending on the word chosen, the story follows a different plot. There are also embedded comprehension questions where students receive immediate feedback with consequences for incorrect answers, such as being sent back to reread a few pages. In a randomized controlled trial, we tested whether students (N = 603 in 25 third through fifth grade classrooms in Arizona in the US) reading the WKe-Book would demonstrate improved word knowledge, strategy use, and word knowledge calibration. Classrooms were randomly assigned to read the WKe-Book immediately (treatment) or later (delayed-treatment control), and within classrooms, students were randomly assigned to either participate in a 15-minute weekly book club (book club treatment) or to read the WKe-Book independently with no book club (no book club control). Results revealed a significant treatment effect of the WKe-Book on students' word knowledge, word knowledge calibration, and strategy use, which predicted student performance on standardized reading comprehension and vocabulary measures. The effects were greater for students who participated in weekly book clubs compared to students in the no book club control. These findings suggest that the affordances offered by technology, which are unavailable in paper-based books, can support students' development of metacognition, including word knowledge calibration, strategy use, and word learning skills.

Profiles of Foundational Learning Components among First Graders.

School readiness includes a constellation of skills and behaviors, such as social and emotional development, language and literacy, and self-regulation that provide a basis critical for classroom participation and learning. Whereas it has been well-established that students who enter kindergarten with weaknesses in language and literacy are more likely to struggle academically, less research has focused on the variability and educational impact of other foundational learning components, including internalizing and externalizing behaviors, particularly in first grade. This study used latent profile analysis to identify the following four subgroups (profiles) of students, using foundational learning components, in a sample of first graders (n = 324): Emergent Hyperactive, Externalizing, Generally Good Students, and Internalizing. Latent class growth analysis illustrated significant differences in the average rate of growth in literacy skills from the beginning to the end of first grade across the four profiles, after controlling for gender and socioeconomic status. Findings indicated the greatest growth in literacy skills for students in the Externalizing profile and the least amount of vocabulary growth for students in the Emergent Hyperactive profile followed by the Internalizing profile. Educational implications of how researchers and educators might consider students' individual differences across profiles of foundational learning components to inform ways to support development and learning in the classroom are discussed.

Recent Advances in Delivering Mental Health Treatment via Video to Home.

PURPOSE OF REVIEW: Telemental health has rapidly evolved as technology and policy advances have allowed new and innovative approaches, including the remote delivery of services directly to patients' homes. This review examined the literature on video to home (VTH) delivery of mental health services to synthesize information regarding (1) the comparative clinical effectiveness of VTH to in-person mental health treatment, (2) impact of VTH on treatment adherence, (3) patient and provider satisfaction with VTH, (4) cost effectiveness of VTH, and (5) clinical considerations for VTH use. RECENT FINDINGS: Clinical effectiveness, treatment adherence, and patient satisfaction outcomes are comparable for VTH and in-person delivery of psychotherapy and psychiatric consultation services. Clinical applications for VTH have expanded in an effort to provide mental health care to difficult to reach, underserved populations. VTH is less costly than in-person care when assuming that patients could employ existing personal technologies. VTH delivery offers a safe and effective option for increasing access to mental health care for patients who face logistical and stigma-related barriers to receiving in-person treatment. VTH should be routinely offered to patients as an option for receiving care, maximizing patient choice, and coordination of care.

The evolutionary origination of a novel expression pattern through an extreme heterochronic shift.

The evolutionary origins of morphological structures are thought to often depend upon the redeployment of old genes into new developmental settings. Although many examples of cis-regulatory divergence have shown how pre-existing patterns of gene expression have been altered, only a small number of case studies have traced the origins of cis-regulatory elements that drive new expression domains. Here, we elucidate the evolutionary history of a novel expression pattern of the yellow gene within the Zaprionus genus of fruit flies. We observed a unique pattern of yellow transcript accumulation in the wing disc during the third larval instar, a stage that precedes its typical expression pattern associated with cuticular melanization by about a week. The region of the Zaprionus wing disc that expresses yellow subsequently develops into a portion of the thorax, a tissue for which yellow expression has been reported for several fruit fly species. Tests of GFP reporter transgenes containing the Zaprionus yellow regulatory region revealed that the wing disc pattern arose by changes in the cis-regulatory region of yellow. Moreover, the wing disc enhancer activity of yellow depends upon a short conserved sequence with ancestral thoracic functions, suggesting that the pupal thorax regulatory sequence was genetically reprogrammed to drive expression that commences much earlier during development. These results highlight how novel domains of gene expression may arise by extreme shifts in timing during the origins of novel traits.

Cyclic citrullinated MBP87-99 peptide stimulates T cell responses: Implications in triggering disease.

Amino acid mutations to agonist peptide epitopes of myelin proteins have been used to modulate immune responses and experimental autoimmune encephalomyelitis (EAE, animal model of multiple sclerosis). Such amino acid alteration are termed, altered peptide ligands (APL). We have shown that the agonist myelin basic protein (MBP) 87-99 epitope (MBP87-99) with crucial T cell receptor (TCR) substitutions at positions 91 and 96 (K91,P96 (TCR contact residues) to R91,A96; [R91,A96]MBP87-99) results in altered T cell responses and inhibits EAE symptoms. In this study, the role of citrullination of arginines in [R91,A96]MBP87-99 peptide analog was determined using in vivo experiments in combination with computational studies. The immunogenicity of linear [Cit91,A96,Cit97]MBP87-99 and its cyclic analog - cyclo(87-99)[Cit91,A96,Cit97]MBP87-99 when conjugated to the carrier mannan (polysaccharide) were studied in SJL/J mice. It was found that mannosylated cyclo(87-99)[Cit91,A96,Cit97]MBP87-99 peptide induced strong T cell proliferative responses and IFN-gamma cytokine secretion compared with the linear one. Moreover, the interaction of linear and cyclic peptide analogs with the major histocompatibility complex (MHC II, H2-IAs) and TCR was analyzed using molecular dynamics simulations at the receptor level, in order to gain a better understanding of the molecular recognition mechanisms that underly the different immunological profiles of citrullinated peptides compared to its agonist native counterpart MBP87-99 epitope. The results demonstrate that the citrullination of arginine in combination with the backbone conformation of mutated linear and cyclic analogs are significant elements for the immune response triggering the induction of pro-inflammatory cytokines.

Reciprocal Effects of Self-Regulation, Semantic Knowledge, and Reading Comprehension in Early Elementary School.

Many assume that cognitive and linguistic processes, such as semantic knowledge (SK) and self-regulation (SR), subserve learned skills like reading. However, complex models of interacting and bootstrapping effects of SK, SR, instruction, and reading hypothesize reciprocal effects. Testing this "lattice" model with children (n = 852) followed from first to second grade (5.9-10.4 years of age) revealed reciprocal effects for reading and SR, and reading and SK, but not SR and SK. More effective literacy instruction reduced reading stability over time. Findings elucidate the synergistic and reciprocal effects of learning to read on other important linguistic, self-regulatory, and cognitive processes; the value of using complex models of development to inform intervention design; and how learned skills may influence development during middle childhood.

Individual differences in fifth graders' reading and language predict their comprehension monitoring development: An eye-movement study.

In this study, we investigated fifth-graders' (n=52) fall literacy, academic language, and motivation, and how these skills predicted fall and spring comprehension monitoring on an eye movement task. Comprehension monitoring was defined as the identification and repair of misunderstandings when reading text. In the eye movement task, children read two sentences; the second included either a plausible or implausible word in the context of the first sentence. Stronger readers had shorter reading times overall suggesting faster processing of text. Generally fifth-graders reacted to the implausible word (i.e., longer gaze duration on the implausible v. the plausible word, which reflects lexical access). Students with stronger academic language, compared to those with weaker academic language, generally spent more time re-reading the implausible target compared to the plausible target. This difference increased from fall to spring. Results support the centrality of academic language for meaning integration, setting standards of coherence, and utilizing comprehension repair strategies.

Methods of effective conjugation of antigens to nanoparticles as non-inflammatory vaccine carriers.

It has recently become clear that nanoparticle size is a major determinant for how antigen presenting cells (APCs), and specifically dendritic cells (DC) recognize and handle particles, and hence a critical parameter for the formulation of particulate vaccines that aim to induce immunity by targeting DC. Our previous studies in mice and sheep have shown polystyrene nanoparticles of 40-50 nm (PSNPs) with covalently bound antigen offer a new class of vaccines, which contain only 2 elements, antigen and particle, and no added inflammatory stimuli, but evoke very potent combined CD8 T cell and antibody responses. Herein we have optimized the methods for antigen conjugation to PSNPs to controllably promote a single antigen (protein or peptide) layer coating on the nanoparticle. Surprisingly, these nanovaccines not only continued to induce high levels of CD8 T cells in vivo, but were further more potent antibody inducers than nanoparticles containing multiple antigen layers. Addressing the issue of antigen loading on PSNPs, we found an optimal range, above or below which immunogenicity is changed either for antibodies or CD8 T cells. The mechanism behind the induction of high levels of CD8 T cells was further explored by assessing the DC subset that takes up the PSNPs in vivo, and these were found to be preferentially CD8(+) CD11c(+) DC in the lymph node draining the injection site. Since the levels of induced antibodies were highly elevated, and CD8(+) DC do not traditionally induce antibodies, we further sought to find if, despite no detectable inflammation at the injection site, the PSNPs may perhaps induce inflammatory cytokines locally in the lymph node after injection, or systemically in sera, resulting in an adjuvant effect. The initial findings presented herein show no detectable induction of the key inflammatory cytokines such as TNF-α, IL-1 or IL-6, suggesting a novel "non-inflammatory" adjuvant mechanism.

Capturing the complexity: Content, type, and amount of instruction and quality of the classroom learning environment synergistically predict third graders' vocabulary and reading comprehension outcomes.

We examined classrooms as complex systems that affect students' literacy learning through interacting effects of content and amount of time individual students spent in literacy instruction along with the global quality of the classroom-learning environment. We observed 27 third grade classrooms serving 315 target students using two different observation systems. The first assessed instruction at a more micro-level; specifically, the amount of time individual students spent in literacy instruction defined by the type of instruction, role of the teacher, and content. The second assessed the quality of the classroom-learning environment at a more macro level focusing on classroom organization, teacher responsiveness, and support for vocabulary and language. Results revealed that both global quality of the classroom learning environment and time individual students spent in specific types of literacy instruction covering specific content interacted to predict students' comprehension and vocabulary gains whereas neither system alone did. These findings support a dynamic systems model of how individual children learn in the context of classroom literacy instruction and the classroom-learning environment, which can help to improve observations systems, advance research, elevate teacher evaluation and professional development, and enhance student achievement.

High variation across E. coli hybrid isolates identified in metabolism-related biological pathways co-expressed with virulent genes.

Virulent genes present in Escherichia coli (E. coli) can cause significant human diseases. These enteropathogenic E. coli (EPEC) and enterotoxigenic E. coli (ETEC) isolates with virulent genes show different expression levels when grown under diverse laboratory conditions. In this research, we have performed differential gene expression analysis using publicly available RNA-seq data on three pathogenic E. coli hybrid isolates in an attempt to characterize the variation in gene interactions that are altered by the presence or absence of virulent factors within the genome. Almost 26.7% of the common genes across these strains were found to be differentially expressed. Out of the 88 differentially expressed genes with virulent factors identified from PATRIC, nine were common in all these strains. A combination of Weighted Gene Co-Expression Network Analysis and Gene Ontology Enrichment Analysis reveals significant differences in gene co-expression involving virulent genes common among the three investigated strains. The co-expression pattern is observed to be especially variable among biological pathways involving metabolism-related genes. This suggests a potential difference in resource allocation or energy generation across the three isolates based on genomic variation.

Rural-Urban Disparities in Video Telehealth Use During Rapid Mental Health Care Virtualization Among American Indian/Alaska Native Veterans.

Importance: American Indian/Alaska Native veterans experience a high risk for health inequities, including mental health (MH) care access. Rapid virtualization of MH care in response to the COVID-19 pandemic facilitated care continuity across the Veterans Health Administration (VHA), but the association between virtualization of care and health inequities among American Indian/Alaska Native veterans is unknown. Objective: To examine differences in video telehealth (VTH) use for MH care between American Indian/Alaska Native and non-American Indian/Alaska Native veterans by rurality and urbanicity. Design, Setting, and Participants: In this cohort study, VHA administrative data on VTH use among a veteran cohort that received MH care from October 1, 2019, to February 29, 2020 (prepandemic), and April 1 to December 31, 2020 (early pandemic), were examined. Exposures: At least 1 outpatient MH encounter during the study period. Main Outcomes and Measures: The main outcome was use of VTH among all study groups (ie, American Indian/Alaska Native, non-American Indian/Alaska Native, rural, or urban) before and during the early pandemic. American Indian/Alaska Native veteran status and rurality were examined as factors associated with VTH utilization through mixed models. Results: Of 1 754 311 veterans (mean [SD] age, 54.89 [16.23] years; 85.21% male), 0.48% were rural American Indian/Alaska Native; 29.04%, rural non-American Indian/Alaska Native; 0.77%, urban American Indian/Alaska Native; and 69.71%, urban non-American Indian/Alaska Native. Before the pandemic, a lower percentage of urban (b = -0.91; SE, 0.02; 95% CI, -0.95 to -0.87; P < .001) and non-American Indian/Alaska Native (b = -0.29; SE, 0.09; 95% CI, -0.47 to -0.11; P < .001) veterans used VTH. During the early pandemic period, a greater percentage of urban (b = 1.37; SE, 0.05; 95% CI, 1.27-1.47; P < .001) and non-American Indian/Alaska Native (b = 0.55; SE, 0.19; 95% CI, 0.18-0.92; P = .003) veterans used VTH. There was a significant interaction between rurality and American Indian/Alaska Native status during the early pandemic (b = -1.49; SE, 0.39; 95% CI, -2.25 to -0.73; P < .001). Urban veterans used VTH more than rural veterans, especially American Indian/Alaska Native veterans (non-American Indian/Alaska Native: rurality b = 1.35 [SE, 0.05; 95% CI, 1.25-1.45; P < .001]; American Indian/Alaska Native: rurality b = 2.91 [SE, 0.38; 95% CI, 2.17-3.65; P < .001]). The mean (SE) increase in VTH was 20.34 (0.38) and 15.35 (0.49) percentage points for American Indian/Alaska Native urban and rural veterans, respectively (difference in differences [DID], 4.99 percentage points; SE, 0.62; 95% CI, 3.77-6.21; t = -7.999; df, 11 000; P < .001), and 12.97 (0.24) and 11.31 (0.44) percentage points for non-American Indian/Alaska Native urban and rural veterans, respectively (DID, 1.66; SE, 0.50; 95% CI, 0.68-2.64; t = -3.32; df, 15 000; P < .001). Conclusions and Relevance: In this cohort study, although rapid virtualization of MH care was associated with greater VTH use in all veteran groups studied, a significant difference in VTH use was seen between rural and urban populations, especially among American Indian/Alaska Native veterans. The findings suggest that American Indian/Alaska Native veterans in rural areas may be at risk for VTH access disparities.

Feasibility of Group-Based Implementation Facilitation for Video Telemental Health.

Video telehealth experienced rapid growth throughout the COVID-19 pandemic in many healthcare sectors, including mental health. The Veterans Health Administration's video telehealth platform, VA Video Connect, has been widely used to reach veterans who may have experienced difficulty accessing care, such as those living in rural areas or other barriers (e.g., transportation). Implementing VVC requires a multifaceted approach, including training providers on technical skills, increasing access to equipment for providers and veterans, and integrating VVC within the culture and processes of the clinic unit. Prior successful VVC implementation efforts in rural areas have focused on simultaneous one-on-one provider and leadership engagement using implementation facilitation (IF). However, given the rapid need for VVC expansion in light of limits and dangers associated with in-person care during the pandemic, our team developed group facilitation to increase the reach of VVC implementation through IF. Group facilitation combined training in technical and policy elements of VVC with IF with groups of providers from clinic units. This approach was designed to rapidly disseminate the necessary knowledge to conduct VVC combined with collaborative problem solving as a team to improve the ability of the clinical team to sustain VVC. Attendees were asked for feedback on the session through multiple choice and open-ended questions. Participants (N = 26) reported being highly satisfied with the training and reported a high degree of confidence in their ability to use VVC. Based on evaluation data and interview feedback, providers and clinic leaders were satisfied with group facilitation. Group facilitation may be a helpful tool in rapidly training clinical teams to implement and sustain video telemental health.

Synthesis and immunological evaluation of self-assembling and self-adjuvanting tricomponent glycopeptide cancer-vaccine candidates.

Self-adjuvanting tricomponent vaccines were prepared and assessed for their self-assembly and immunological activity in mouse models. The vaccines each consisted of a peptide or glycopeptide antigen that corresponds to a complete copy of the variable-number tandem repeat (VNTR) of the tumor-associated mucin 1 (MUC1) glycoprotein, the universal T-cell helper peptide epitope PADRE, and the immunoadjuvant Pam(3)CysSer. The vaccines were shown to spontaneously self-assemble in water to form isotropic particles varying in size from 17 to 25 nm and elicited robust humoral responses in murine models without the addition of an external adjuvant. The serum antibodies could recognize tumor-associated MUC1 epitopes on the surface of MCF7 breast-cancer cells and B16 melanoma cells, which overexpress this tumor-associated glycoprotein.

Evaluating vaccinia virus cytokine co-expression in TLR GKO mice.

Using Toll-like receptor (TLR) and MyD88 gene knock-out (GKO) mice the effect of TLRs and MyD88 on virus replication, interferon (IFN)-ß production, natural killer (NK) cell and CD8T cell responses were assessed following ectromelia virus (ECTV) and recombinant vaccinia virus (rVV) infection. The capacity for rVVs encoding cytokines to restore immune function in MyD88(-/-) mice was clearly demonstrated. Results showed that TLR2(-/-), TLR4(-/-)and TLR7(-/-) mice survived ECTV infection whereas MyD88(-/-) and TLR9(-/-)mice, in contrast, were highly susceptible. Next, following infection with rVV, MyD88(-/-) mice elicited reduced serum IFN-ß, NK cell and CD8T cell responses compared with wild-type mice, whereas TLR9(-/-) mice showed elevated CD8T cell responses. When MyD88(-/-)mice were infected with rVV co-expressing IFN-ß these mice were able to restore IFN-ß levels and CD8T cell responses but not NK cell activation. Interestingly, even though rVV co-expressing interleukin (IL)-2 enhanced NK cell activation in MyD88(-/-) mice, this was not associated with an antiviral effect, as observed in normal mice. Surprisingly, co-infection with rVV IL-2/rVV IL-12, but not rVV IL-2/rVV IFN-ß, restored the attenuated phenotype of rVV IL-2 in MyD88(-/-) mice indicating that the IL-2/IL-12 combination promotes antiviral responses. Our results clearly show that the CD8T cell defect observed in MyD88(-/-) mice to vaccinia virus infection can be restored by rVV-encoding IFN-ß demonstrating the critical role of this cytokine in T cell mediated immunity and illustrates that the model can provide an effective platform for the elucidation of cytokine immunobiology.

Large shift in source of fine sediment in the upper Mississippi river.

Although sediment is a natural constituent of rivers, excess loading to rivers and streams is a leading cause of impairment and biodiversity loss. Remedial actions require identification of the sources and mechanisms of sediment supply. This task is complicated by the scale and complexity of large watersheds as well as changes in climate and land use that alter the drivers of sediment supply. Previous studies in Lake Pepin, a natural lake on the Mississippi River, indicate that sediment supply to the lake has increased 10-fold over the past 150 years. Herein we combine geochemical fingerprinting and a suite of geomorphic change detection techniques with a sediment mass balance for a tributary watershed to demonstrate that, although the sediment loading remains very large, the dominant source of sediment has shifted from agricultural soil erosion to accelerated erosion of stream banks and bluffs, driven by increased river discharge. Such hydrologic amplification of natural erosion processes calls for a new approach to watershed sediment modeling that explicitly accounts for channel and floodplain dynamics that amplify or dampen landscape processes. Further, this finding illustrates a new challenge in remediating nonpoint sediment pollution and indicates that management efforts must expand from soil erosion to factors contributing to increased water runoff.