The Adoption of Zero-Emissions Vehicles by Low-Income Consumers in California: An Outcome Evaluation of the Clean Vehicle Rebate Project

Is the Clean Vehicle Rebate Project (CVRP) program achieving its planned outcomes of accelerating the adoption of Zero-Emissions Vehicles (ZEVs) by low-income consumers in California? This research will evaluate what effect additional CVRP rebates provided to low-income consumers have on their adoptions of ZEVs. The purpose of this research is to determine whether the CVRP rebates are making it feasible and compelling enough for low-income consumers to adopt ZEVs at a rate that will lead to California meeting its greenhouse gas reduction goals

HUMAN ORGANIC ANION TRANSPORTERS 1 AND 3: STRUCTURAL ELEMENTS IMPACTING TRANSPORTER-SUBSTRATE BINDING INTERACTIONS

Organic anion transporters (OATs) are known to interact with a wide variety of negatively charged drugs and can impact their clinical safety and efficacy profiles. The U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) have recognized and highlighted the importance of evaluating the potential interactions with transporters, specifically hOAT1 and hOAT3, during the development of new drug entities. Little is known about OAT-drug interactions as they are difficult to discern on a molecular level in the absence of any solved crystal structures for OATs. Therefore, in a previous study, in silico homology models of hOAT1 and hOAT3 were generated based on the solved crystal structure for Piriformospora indica phosphate transporter (PiPT). The models were docked with their respective prototypical substrates, amino acid contacts involved in substrate recognition predicted, and single point mutations generated. Following mutagenesis, singly mutated hOAT1 and hOAT3 transporters were subject to accumulation and saturation studies to determine their role in substrate binding and subsequent translocation. The findings from this previous study indicated singly mutated constructs did not result in altered binding affinity (Km). However, the question remained whether these predicted amino acid contacts would significantly alter affinity when present in various double and triple combinations. In this study, multiple combination hOAT1 (Arg15Lys/Ile19Leu, Ile19Leu/Tyr230Phe, Arg15Lys/Tyr230Phe, and Arg19Lys/Ile19Leu/Tyr230Phe) and hOAT3 mutants (Phe426Tyr/Phe430Ser and Phe426Tyr/Phe430Tyr) were generated and functional accumulation screens were conducted to determine the impact on overall transport activity. Mutants that retained transport activity were then further assessed by kinetic assays to determine any changes in Km. Functional accumulation screens showed none of the hOAT1 multiple mutants retained PAH transport activity. In contrast, the generated hOAT3 double mutants retained ES transport activity. Subsequent kinetic analysis revealed the hOAT3 double mutants exhibited no statistically significant changes in estimated Km values as compared to hOAT3 wild-type. This study provides further insight as to the importance of these predicted critical amino acid residues in substrate binding interactions. Further characterizing these molecular interactions will allow for improved manipulation of drug substrate pharmacokinetics as well as prediction of drug-drug interactions, both of which can be utilized in drug design and development

Occupying the Third Space: Vietnamese American Hybridity and the Struggle for Identity

After the Vietnam War ended in 1975, over 800,000 people emigrated from Vietnam between 1975 and 1995, with more than half resettling their uprooted lives in the United States. People move to America in hopes that it will live up to its reputation of being a melting pot, but the multitude of immigrants struggling to establish an identity and assimilate into Western culture prove that America’s melting pot still has unresolved issues. Because of this struggle, many Vietnamese immigrants lack a sense of belonging, even after moving away from Vietnam and attempting to establish a life in America for many years. Post-colonial scholar Homi K. Bhabha explains in his theory of hybridity that it is a place where neither the one nor the Other exist, but where a new, third space is created for the displaced to figure out their identity. Although Vietnamese people immigrated to the United States over forty years ago, literary work by Vietnamese American writers, Andrew Xuan Pham, le thi diem thuy [sic], and Hieu Minh Nguyen, convey through poignant language and evocative experiences that many Vietnamese Americans are still struggling in this third space with their hybrid identities

A case of new-onset vitiligo in a patient on tofacitinib and brief review of paradoxical presentations with other novel targeted therapies

With recent advancements in the understanding of vitiligo pathogenesis, Janus kinase (JAK) inhibitors have emerged as a promising new treatment modality, but their effects remain incompletely elucidated. Tofacitinib, an oral JAK 1/3 inhibitor approved for the treatment of rheumatoid arthritis, has previously been shown to induce significant re-pigmentation in vitiligo. However, as with other novel targeted therapies, cutaneous adverse effects have been observed. We report a 36-year-old woman with a history of rheumatoid arthritis, refractory to multiple pharmacotherapies, who was initiated on tofacitinib and subsequently developed progressive depigmented patches consistent with new-onset vitiligo. Although definitive causation cannot be established in this case without additional studies, it is important to note that many targeted therapies have the potential to induce paradoxical effects, that is, the occurrence or exacerbation of pathologic conditions that have been shown to respond to these medications. Paradoxical findings with other targeted therapies include the occurrence of melanoma during treatment with BRAF inhibitors, keratoacanthomas with PD-1 inhibitors, vitiligo and psoriasis with TNF-alpha inhibitors, and hidradenitis suppurativa with various biologic agents. Although JAK inhibitors hold therapeutic promise in the treatment of inflammatory skin disorders, further research is warranted to more fully comprehend their effects

A dose-ranging, parallel group, split-face, single-blind phase II study of light emitting diode-red light (LED-RL) for skin scarring prevention: study protocol for a randomized controlled trial.

BackgroundSkin fibrosis is a significant global health problem that affects over 100 million people annually and has a profoundly negative impact on quality of life. Characterized by excessive fibroblast proliferation and collagen deposition, skin fibrosis underlies a wide spectrum of dermatologic conditions ranging from pathologic scars secondary to injury (e.g., burns, surgery, trauma) to immune-mediated diseases. Effective anti-scarring therapeutics remain an unmet need, underscoring the importance of developing novel approaches to treat and prevent skin fibrosis. Our in vitro data show that light emitting diode-red light (LED-RL) can modulate key cellular and molecular processes involved in skin fibrosis. In two phase I clinical trials (STARS 1 and STARS 2), we demonstrated the safety and tolerability of LED-RL at fluences of 160 J/cm2 up to 480 J/cm2 on normal human skin.Methods/designCURES (Cutaneous Understanding of Red-light Efficacy on Scarring) is a dose-ranging, randomized, parallel group, split-face, single-blind, mock-controlled phase II study to evaluate the efficacy of LED-RL to limit post-surgical skin fibrosis in subjects undergoing elective mini-facelift surgery. Thirty subjects will be randomly allocated to three treatment groups to receive LED-RL phototherapy or temperature-matched mock irradiation (control) to either periauricular incision site at fluences of 160 J/cm2, 320 J/cm2, or 480 J/cm2. Starting one week post-surgery (postoperative days 4-8), treatments will be administered three times weekly for three consecutive weeks, followed by efficacy assessments at 30 days, 3 months, and 6 months. The primary endpoint is the difference in scar pliability between LED-RL-treated and control sites as determined by skin elasticity and induration measurements. Secondary outcomes include clinical and photographic evaluations of scars, 3D skin imaging analysis, histological and molecular analyses, and adverse events.DiscussionLED-RL is a therapeutic modality of increasing importance in dermatology, and has the potential to limit skin fibrosis clinically by decreasing dermal fibroblast activity and collagen production. The administration of LED-RL phototherapy in the early postoperative period may optimize wound healing and prevent excessive scarring. The results from this study may change the current treatment paradigm for fibrotic skin diseases and help to pioneer LED-RL as a safe, non-invasive, cost-effective, portable, at-home therapy for scars.Trial registrationClinicalTrials.gov, NCT03795116 . Registered on 20 December 2018

Youth Crisis and Transition Services (CATS): Incorporating Family Peer Support Specialists to Assist Families During Crisis

Abstract Introduction: Crisis and Transition Services (CATS) provides transitional mental health services to high-acuity youth discharging from emergency departments (EDs). A novel component of CATS is the inclusion of a family peer support specialist (FSS) on the care team, who provides direct support to the parent or guardian in developing self-advocacy, crisis management skills, and self-efficacy in navigating systems. The FSS is not a typical role in a clinically oriented crisis program; empiric evaluation of this role can help guide quality improvements in the program and in workforce recruitment, training and support. Methods: Demographic and service data were collected from CATS providers, and families were surveyed two months after completing CATS to collect feedback and clinical outcomes (n=147). Participants were sorted into two groups: did engage with FSS (n=89) and did not engage with FSS (n=58). Predictive factors for successful engagement with a FSS were analyzed using Pearson’s chi-square tests. Descriptive statistics of services provided to families and family satisfaction ratings were also evaluated. A qualitative analysis of family feedback comments identified common themes regarding family experiences of the FSS. Results: When the FSS attended the first team meeting after intake, parents were more likely to engage with peer support χ2 (1, n = 147) = 20.60, p \u3c .001. As part of the follow-up survey, parents rated their experience with the FSS on a scale of 1 (completely unsatisfied) to 10 (completely satisfied). Over 70% (n = 65) of families rated their experience with the FSS as a 7 or above. The most prominent theme in the qualitative comment analysis was that parents had positive experiences with the FSS. The most common negative comment was that the parent didn’t understand how the FSS would be helpful or did not feel the FSS role would be useful for their family. Conclusions: The program elements that predict the likelihood of a family engaging with peer support, together with parent satisfaction ratings and feedback comments, provide insight into the successful implementation of parent peer support in a crisis program for youth. These have important implications for FSS professional and workforce development

Taxonomy of usage problems for improving user-centric online health information provision

Consumer health information portals (HIP) are a popular means to provide quality health information via the Web. However complex usage problems in HIPs are still a major barrier to their success. A usage-driven approach, which places emphasis on improving online services based on learnings from the data of the interactions between users and the system, is crucial to ensuring sustainable and user-centred online health provision. Inspired by this idea, we present a taxonomy of usage problems that encompasses the dimensions of the content, the systems and users, focusing on a holistic understanding of usage problems. Our taxonomy is grounded on a literature analysis empirically validated through an analysis of usage-data captured from a consumer health information portal, operational for the past five years. By exploring how usage data highlights user problems, we also present strategies for health portal improvements based on better understandings of usage data. Benefits of usage-driven health portals in terms of smart learning capabilities to improve content and user satisfaction are discussed