The Formation and Application of Polymeric Micro- and Nanoparticles

Nano- and microparticles are used in the pharmaceutical industry for sustained release drug delivery systems. For example, polymeric particles are currently used as an FDA-approved drug delivery system for leuprolide acetate to treat prostate cancer1. Our drug of interest is CPDI-02 (formerly known as EP67)—a C5a-derived decapeptide agonist of the C5a Receptor (CD88) that activates mononuclear phagocytes to produce an immune response while potentially minimizing neutrophil-mediated toxicity2. Currently in the Vetro Lab, CPDI-02 is being tested on pigs and mice to treat methicillin-resistant Staphylococcus aureus (MRSA) infections and as the adjuvant for a vaccine for cytomegalovirus (CMV). This investigation explored formulation parameters that impact particle size and loading of CPDI-02 in a traditional oil-in-water (O/W) emulsion. We also explored adapting the formulation using microfluidic chips to generate nano- and microparticles and improve run-to-run consistency in particle size.https://digitalcommons.unmc.edu/surp2022/1004/thumbnail.jp

Thinking about growth : a cognitive mapping approach to understanding small business development

School of Managemen

Perfectionism, feelings of not mattering, and suicide ideation: an integrated test of the Perfectionism Social Disconnection Model and the Existential Model of Perfectionism

The Perfectionism Social Disconnection Model (PSDM) and the Existential Model of Perfectionism and Depressive Symptoms (EMPDS) are promising models of perfectionism and psychopathology. However, research examining suicide ideation within the PSDM is scarce, and no research has examined suicide ideation as an outcome in the EMPDS. Moreover, tests of the PSDM and EMPDS have been conducted separately and most research has examined the PSDM and EMPDS using cross-sectional or two-wave longitudinal designs, which do not provide a satisfactory test of mediation. In the current study, we addressed these limitations by testing whether perfectionism confers vulnerability to suicide ideation via feelings of mattering and anti-mattering (from the PSDM) and via difficulty accepting the past (from the EMPDS) in a three-wave longitudinal design in two independent samples of undergraduate students and community adults. Participants completed measures on three occasions over 6 weeks. Findings revealed that socially prescribed perfectionism indirectly predicted suicide ideation via difficulty accepting the past in both samples. In addition, in the undergraduate sample only, socially prescribed perfectionism indirectly predicted higher suicide ideation via anti-mattering, and self-oriented perfectionism indirectly predicted higher suicide ideation via mattering. Based on our findings, we advocate for future research to include suicide ideation in the PSDM and EMPDS, to integrate explanatory models, and to examine a mattering-specific EMPDS

Vortex imaging in unconventional superconductors

The real space imaging of vortices in unconventional superconductors not only provides important information about the effectiveness of flux pinning that can inform high current applications, but also yields crucial insights into the form of the superconducting order parameter. For example, the structure of the vortex lattice reflects effective mass and order parameter anisotropies within the material, and profiles of isolated vortices provide a local measure of the magnetic penetration depth that can be used to infer the superfluid density. We describe here the analysis of recent studies whereby state-of-the-art scanning Hall probe microscopy (SHPM) has been used to perform vortex-resolved magnetic imaging on two distinct families of unconventional superconductors. Two sets of results will be analysed in detail; (i) vortex lattice structural transitions in the p-wave superconductor Sr2RuO4 that reflect underlying anisotropies in the system and (ii) a quantitative analysis of vortex profiles in Co-doped 122 pnictide superconductors (SrFe2-xCoxAs2 &amp; BaFe2-xCoxAs2) that allows one to infer the temperature-dependent superfluid density. The latter has then been compared with predictions for different order parameter models for a multiband superconductor.</p

Implementation of the CALM intervention for anxiety disorders: a qualitative study

<p>Abstract</p> <p>Background</p> <p>Investigators recently tested the effectiveness of a collaborative-care intervention for anxiety disorders: Coordinated Anxiety Learning and Management(CALM) []) in 17 primary care clinics around the United States. Investigators also conducted a qualitative process evaluation. Key research questions were as follows: (1) What were the facilitators/barriers to implementing CALM? (2) What were the facilitators/barriers to sustaining CALM after the study was completed?</p> <p>Methods</p> <p>Key informant interviews were conducted with 47 clinic staff members (18 primary care providers, 13 nurses, 8 clinic administrators, and 8 clinic staff) and 14 study-trained anxiety clinical specialists (ACSs) who coordinated the collaborative care and provided cognitive behavioral therapy. The interviews were semistructured and conducted by phone. Data were content analyzed with line-by-line analyses leading to the development and refinement of themes.</p> <p>Results</p> <p>Similar themes emerged across stakeholders. Important facilitators to implementation included the perception of "low burden" to implement, provider satisfaction with the intervention, and frequent provider interaction with ACSs. Barriers to implementation included variable provider interest in mental health, high rates of part-time providers in clinics, and high social stressors of lower socioeconomic-status patients interfering with adherence. Key sustainability facilitators were if a clinic had already incorporated collaborative care for another disorder and presence of onsite mental health staff. The main barrier to sustainability was funding for the ACS.</p> <p>Conclusions</p> <p>The CALM intervention was relatively easy to incorporate during the effectiveness trial, and satisfaction was generally high. Numerous implementation and sustainability barriers could limit the reach and impact of widespread adoption. Findings should be interpreted with the knowledge that the ACSs in this study were provided and trained by the study. Future research should explore uptake of CALM and similar interventions without the aid of an effectiveness trial.</p

Ageing and entrepreneurial preferences

Previous research on age and entrepreneurship assumed homogeneity and downplayed age-related differences in the motives and aims underlying enterprising behaviour. We argue that the heterogeneity of entrepreneurship influences how the level of entrepreneurial activity varies with age. Using a sample of 2566 respondents from 27 European countries we show that entrepreneurial activity increases almost linearly with age for individuals who prefer to only employ themselves (self-employers), whereas it increases up to a critical threshold age (late 40s) and decreases thereafter for those who aspire to hire workers (owner-managers). Age has a considerably smaller effect on entrepreneurial behaviour for those who do not prefer self-employment but are pushed into it by lack of alternative employment opportunities (reluctant entrepreneurs). Our results question the conventional wisdom that entrepreneurial activity declines with age and suggest that effective responses to demographic changes require policy makers to pay close attention to the heterogeneity of entrepreneurial preferences

Multicentre phase II study of gemcitabine and cisplatin in malignant pleural mesothelioma

Malignant pleural mesothelioma is a notoriously chemoresistant tumour. However, a recent single institution study showed an impressive activity of gemcitabine and cisplatin. Our aim is to investigate the efficacy and toxicity of a gemcitabine and cisplatin combination in selected and chemo-naive patients with histologically proven malignant pleural mesothelioma. Method: Gemcitabine 1250 mg m−2 was administered on day 1 and day 8 and cisplatin 80 mg m−2 was administered on day 1 in a 3-week cycle with a maximum of six cycles. Response and toxicity evaluations were performed according to WHO and NCIC-CTC criteria. Pathology and radiology were centrally reviewed. Results show that in 25 evaluable patients, four PR were observed (ORR 16%, 95% CI 1–31%). Responses of seven patients were unevaluable. No unexpected toxicity occurred. Time to progression was 6 months (5–7 months) with a median survival from registration of 9.6 months (95% CI 8–12 months). In conclusion this trial excludes with 90% power a response rate of greater than 30% in patients with malignant pleural mesothelioma using a combination of gemcitabine and cisplatin at the proposed dose and schedule

Dose response of the 16p11.2 distal copy number variant on intracranial volume and basal ganglia.

Carriers of large recurrent copy number variants (CNVs) have a higher risk of developing neurodevelopmental disorders. The 16p11.2 distal CNV predisposes carriers to e.g., autism spectrum disorder and schizophrenia. We compared subcortical brain volumes of 12 16p11.2 distal deletion and 12 duplication carriers to 6882 non-carriers from the large-scale brain Magnetic Resonance Imaging collaboration, ENIGMA-CNV. After stringent CNV calling procedures, and standardized FreeSurfer image analysis, we found negative dose-response associations with copy number on intracranial volume and on regional caudate, pallidum and putamen volumes (β = -0.71 to -1.37; P &lt; 0.0005). In an independent sample, consistent results were obtained, with significant effects in the pallidum (β = -0.95, P = 0.0042). The two data sets combined showed significant negative dose-response for the accumbens, caudate, pallidum, putamen and ICV (P = 0.0032, 8.9 × 10-6, 1.7 × 10-9, 3.5 × 10-12 and 1.0 × 10-4, respectively). Full scale IQ was lower in both deletion and duplication carriers compared to non-carriers. This is the first brain MRI study of the impact of the 16p11.2 distal CNV, and we demonstrate a specific effect on subcortical brain structures, suggesting a neuropathological pattern underlying the neurodevelopmental syndromes

Phase I Randomised Clinical Trial of an HIV-1CN54, Clade C, Trimeric Envelope Vaccine Candidate Delivered Vaginally

We conducted a phase 1 double-blind randomised controlled trial (RCT) of a HIV-1 envelope protein (CN54 gp140) candidate vaccine delivered vaginally to assess immunogenicity and safety. It was hypothesised that repeated delivery of gp140 may facilitate antigen uptake and presentation at this mucosal surface. Twenty two healthy female volunteers aged 18–45 years were entered into the trial, the first receiving open-label active product. Subsequently, 16 women were randomised to receive 9 doses of 100 µg of gp140 in 3 ml of a Carbopol 974P based gel, 5 were randomised to placebo solution in the same gel, delivered vaginally via an applicator. Participants delivered the vaccine three times a week over three weeks during one menstrual cycle, and were followed up for two further months. There were no serious adverse events, and the vaccine was well tolerated. No sustained systemic or local IgG, IgA, or T cell responses to the gp140 were detected following vaginal immunisations. Repeated vaginal immunisation with a HIV-1 envelope protein alone formulated in Carbopol gel was safe, but did not induce local or systemic immune responses in healthy women