Unintended Consequences In Higher Education Finance Policy: Implications For Current Income-Share Agreement Legislative Efforts And Beyond

Although the creation of a federal financial aid system in the United States has greatly expanded opportunity for students seeking postsecondary education, the higher education financing system faces a handful of problems in its current state. At the same time that the higher education financing system is facing these issues, an alternative to traditional student loans known as income-share agreements (ISAs) is gaining attention. There is currently a lack of federal legislation that provides a national framework for ISA providers and students to work within. Policymakers are considering this situation and attempting to address it in a way that properly balances the interests of both ISA student and lenders, but past policy in this arena has had a tendency to cause effects that were not intended. This study seeks to understand if there is a way that policy can be examined that allows for the identification of certain types of policy that result in unintended consequences before the effects go into place. In order to do this, I examine ten higher education financing policy cases over the past sixty years in an effort to establish a theory of policy that causes unintended consequences. I then test this theory using three interviews with higher education experts relevant to the ISA space in an attempt to see if this theory can be applied to additional cases, such as proposed ISA policy. I find that, although it is difficult to establish a theory that predicts if a policy will cause unanticipated results with certain, the findings from my case studies and interviews can serve as a set of lessons of what has worked well and failed in higher education financing policy. As applied to proposed ISA policy, I conclude that policy entrepreneurs in this space will face difficulty in adopting lessons from past policies due to the challenges to policy learning they face in the current legislative climate

Venom gland organogenesis in the common house spider

Venom is a remarkable innovation found across the animal kingdom, yet the evolutionary origins of venom systems in various groups, including spiders, remain enigmatic. Here, we investigated the organogenesis of the venom apparatus in the common house spider, Parasteatoda tepidariorum. The venom apparatus consists of a pair of secretory glands, each connected to an opening at the fang tip by a duct that runs through the chelicerae. We performed bulk RNA-seq to identify venom gland-specific markers and assayed their expression using RNA in situ hybridisation experiments on whole-mount time-series. These revealed that the gland primordium emerges during embryonic stage 13 at the chelicera tip, progresses proximally by the end of embryonic development and extends into the prosoma post-eclosion. The initiation of expression of an important toxin component in late postembryos marks the activation of venom-secreting cells. Our selected markers also exhibited distinct expression patterns in adult venom glands: sage and the toxin marker were expressed in the secretory epithelium, forkhead and sum-1 in the surrounding muscle layer, while Distal-less was predominantly expressed at the gland extremities. Our study provides the first comprehensive analysis of venom gland morphogenesis in spiders, offering key insights into their evolution and development

Convergent evolution of venom gland transcriptomes across Metazoa.

Animals have repeatedly evolved specialized organs and anatomical structures to produce and deliver a mixture of potent bioactive molecules to subdue prey or predators-venom. This makes it one of the most widespread, convergent functions in the animal kingdom. Whether animals have adopted the same genetic toolkit to evolved venom systems is a fascinating question that still eludes us. Here, we performed a comparative analysis of venom gland transcriptomes from 20 venomous species spanning the main Metazoan lineages to test whether different animals have independently adopted similar molecular mechanisms to perform the same function. We found a strong convergence in gene expression profiles, with venom glands being more similar to each other than to any other tissue from the same species, and their differences closely mirroring the species phylogeny. Although venom glands secrete some of the fastest evolving molecules (toxins), their gene expression does not evolve faster than evolutionarily older tissues. We found 15 venom gland-specific gene modules enriched in endoplasmic reticulum stress and unfolded protein response pathways, indicating that animals have independently adopted stress response mechanisms to cope with mass production of toxins. This, in turn, activates regulatory networks for epithelial development, cell turnover, and maintenance, which seem composed of both convergent and lineage-specific factors, possibly reflecting the different developmental origins of venom glands. This study represents a first step toward an understanding of the molecular mechanisms underlying the repeated evolution of one of the most successful adaptive traits in the animal kingdom

Generation of CD4+ or CD8+ regulatory T cells upon mesenchymal stem cell-lymphocyte interaction

Background and Objectives Mesenchymal stem cells (MSC) have been proposed as a way to treat graft-versus-host disease based on their immunosuppressive effect. We analyzed whether regulatory T cells can be generated in co-cultures of peripheral blood mononuclear cells (PBMC) and MSC.Design and Methods MSC were obtained from the bone marrow of four healthy donors and nine patients with acute leukemia in complete remission following chemotherapy. Short-term (4 days) co-cultures of MSC and autologous or allogeneic PBMC were set up, the lymphocytes harvested and their regulatory activity assessed.Results Lymphocytes harvested from MSC-PBMC co-cultures strongly inhibit (up to 95%) mixed lymphocyte reaction (MLR), recall to alloantigen, and CD3- or phytohemagglutinin-induced lymphocyte proliferation. These lymphocytes, termed regulatory cells (Regc), were all CD45+CD2+ with variable proportions of CD25+ cells (range 40–75% n=10) and a minor fraction expressed CTLA4 (2–4%, n=10) or glucocorticoid-induced tumor necrosis factcor receptor-related gene (0.5–4% n=10). Both CD4+ and CD8+ Regc purified from MSC-PBMC co-cultures strongly inhibited lymphocyte proliferation at a 1:100 Regc:responder cell ratio. CD4+ Regc expressed high levels of forkhead box P3 (Foxp3) mRNA while CD8+ Regc did not. The effectiveness of Regc, whether CD4+ or CD8+, was 100-fold higher than that of CD4+CD25+high regulatory T cells. Regc were also generated from highly purified CD25− PBMC or CD4+ or CD8+ T cell subsets. Soluble factors, such as interleukin-10, transforming growth factor-β and prostaglandin E2 did not appear to be involved in the generation of Regc or in the Regc-mediated immuno-suppressive effect. Furthermore, cyclosporine A did not affect Regc generation or the immunosuppression induced by Regc.Interpretation and Conclusions These findings indicate that powerful regulatory CD4+ or CD8+ lymphocytes are generated in co-cultures of PBMC with MSC. This strongly suggests that these regulatory cells may amplify the reported MSC-mediated immunosuppressive effect

Determinants of invasiveness and ability to cause invasive pneumococcal disease, pneumonia and acute otitis media of different serotypes of Streptococcus pneumoniae

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Venom systems as models for studying the origin and regulation of evolutionary novelties.

A central goal in biology is to determine the ways in which evolution repeats itself. One of the most remarkable examples in nature of convergent evolutionary novelty is animal venom. Across diverse animal phyla, various specialized organs and anatomical structures have evolved from disparate developmental tissues to perform the same function, i.e. produce and deliver a cocktail of potent molecules to subdue prey or predators. Venomous organisms therefore offer unique opportunities to investigate the evolutionary processes of convergence of key adaptive traits, and the molecular mechanisms underlying the emergence of novel genes, cells, and tissues. Indeed, some venomous species have already proven to be highly amenable as models for developmental studies, and recent work with venom gland organoids provides manipulatable systems for directly testing important evolutionary questions. Here, we provide a synthesis of the current knowledge that could serve as a starting point for the establishment of venom systems as new models for evolutionary and molecular biology. In particular, we highlight the potential of various venomous species for the study of cell differentiation and cell identity, and the regulatory dynamics of rapidly-evolving, highly expressed, tissue-specific, gene paralogs. We hope that this review will encourage researchers to look beyond traditional study organisms and consider venom systems as useful tools to explore evolutionary novelties

Serological response to 13-valent pneumococcal conjugate vaccine in children and adolescents with perinatally acquired HIV infection

BACKGROUND: Children with perinatally acquired HIV (paHIV) remain at an increased risk of pneumococcal infection despite highly active antiretroviral therapy (HAART). Beyond infancy, responses to pneumococcal conjugate vaccine (PCV) remain under-investigated. There are currently no published data on serological response to 13-valent PCV (PCV13) in the HIV-infected populations. METHODS: We measured pneumococcal serotype-specific IgG in 48 paHIV-infected child patients (CP), 27 young adult healthy controls (AHC) and 30 child healthy controls (CHC). Opsonophagocytic assay (OPA) titres for three PCV13-exclusive serotypes were measured in a subset of children. Serotype-specific IgG was repeated 1 and 6 months following PCV13 vaccination of CP and AHC groups. OPA titres for four serotypes were measured at the 1-month time-point. RESULTS: The majority of CP, CHC and AHC had serotype-specific IgG above 0.35 μg/ml at baseline, although OPA activity was undetectable for two of the three serotypes studied. Baseline IgG concentrations were significantly lower in CP than AHC for a proportion of serotypes and were strongly predictive of responses to vaccine. After adjusting for baseline, postvaccination IgG concentrations were comparable, although responses to some serotypes were impaired for CP. OPA correlated well with IgG after vaccination. Detectable HIV viral load was associated with significantly lower IgG concentration and OPA titre. CONCLUSION: Children with paHIV mount a robust serological response to PCV13 for most but not all vaccine serotypes. Viral load suppression with HAART and higher baseline IgG concentration are associated with higher postvaccination antibody levels. This has implications for HAART treatment and vaccination practices

PolliRS: A 3D Printed Pollicization Retractor System that improves access and autonomy during the surgical procedure.

We demonstrate the design, manufacture, and deployment of the first custom-made 3-dimensional (3D)-printed hand retractor for the pollicization procedure. Radiological images of the patient’s hand were taken preoperatively to measure anatomical dimensions and guide the design of the device in a patient-precise manner. The 3D-printed, sterilizable, device was autoclaved and successfully used on a patient that underwent a pollicization procedure in our unit. The radiolucency of the device and the fluency enabled by the ability to exchange between different positions demonstrated the potential of this device in increasing the overall autonomy afforded to the lead-surgeon during the operation and demonstrated the potential of rapid-prototyping techniques such as 3D printing for producing patient-precise tools on-the-fly that taken account the specific needs of the patient