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Assessing trans‐endothelial transport of nanoparticles for delivery to abdominal aortic aneurysms
No full textAbdominal aortic aneurysms (AAAs) are localized, rupture‐prone expansions of the abdominal aorta wall. In this condition, structural extracellular matrix (ECM) proteins of the aorta wall, elastic fibers and collagen fibers, that impart elasticity and stiffness respectively, are slowly degraded by overexpressed matrix metalloproteinases (MMPs) following an injury stimulus. We are seeking to deliver therapeutics to the AAA wall using polymer nanoparticles (NPs) that are capable of stimulating on‐site matrix regeneration and repair. This study aimed to determine how NP shape and size impacts endocytosis and transmigration past the endothelial cell (EC) layer from circulation into the medial layer of the AAA wall. First, rod‐shaped NPs were shown to be created based mechanical stretching of PLGA NPs while embedded in a PVA film with longer rod‐shaped NPs created based of the degree in which the PVA films are stretched. Live/dead assay reveals that our PLGA NPs are safe and do not cause cell death. Immunofluorescence staining reveal cytokine activation causes endothelial dysfunction in ECs by increasing expression of inflammatory marker Integrin αVβ3 and decreasing expression of adhesion protein vascular endothelial (VE)‐cadherin. We showed this disruption enable greater EC uptake and translocation of NPs. Fluorescence studies demonstrate high endothelial transmigration and endocytosis with rod‐shaped NPs in cytokine activated ECs compared to healthy control cells, arguing for the benefits of using higher aspect ratio (AR) NPs for accumulation at the aneurysm site. We also demonstrated that the mechanisms of NP transmigration across an activated EC layer depend on NP AR. These results show the potential of using shape as a modality for enhancing permeation of NPs into the aneurysm wall. These studies are also significance to understanding the mechanisms that are likely engaged by NPs for penetrating the endothelial lining of aneurysmal wall segments
The DECam Ecliptic Exploration Project (DEEP). IV. Constraints on the Shape Distribution of Bright Trans-Neptunian Objects
No full textAbstract
We present the methods and results from the discovery and photometric measurement of 26 bright VR > 24 trans-Neptunian objects (TNOs) during the first year (2019–20) of the DECam Ecliptic Exploration Project (DEEP). The DEEP survey is an observational TNO survey with wide sky coverage, high sensitivity, and a fast photometric cadence. We apply a computer vision technique known as a progressive probabilistic Hough transform to identify linearly moving transient sources within DEEP photometric catalogs. After subsequent visual vetting, we provide a photometric and astrometric catalog of our TNOs. By modeling the partial lightcurve amplitude distribution of the DEEP TNOs using Monte Carlo techniques, we find our data to be most consistent with an average TNO axis ratio b/a < 0.5, implying a population dominated by non-spherical objects. Based on ellipsoidal gravitational stability arguments, we find our data to be consistent with a TNO population containing a high fraction of contact binaries or other extremely non-spherical objects. We also discuss our data as evidence that the expected binarity fraction of TNOs may be size-dependent.</jats:p
Effectiveness of CT radiomic features combined with clinical factors in predicting prognosis in patients with limited-stage small cell lung cancer
No full textAbstract
Background
The prognosis of SCLC is poor and difficult to predict. The aim of this study was to explore whether a model based on radiomics and clinical features could predict the prognosis of patients with limited-stage small cell lung cancer (LS-SCLC).
Methods
Simulated positioning CT images and clinical features were retrospectively collected from 200 patients with histological diagnosis of LS-SCLC admitted between 2013 and 2021, which were randomly divided into the training (n = 140) and testing (n = 60) groups. Radiomics features were extracted from simulated positioning CT images, and the t-test and the least absolute shrinkage and selection operator (LASSO) were used to screen radiomics features. We then constructed radiomic score (RadScore) based on the filtered radiomics features. Clinical factors were analyzed using the Kaplan–Meier method. The Cox proportional hazards model was used for further analyses of possible prognostic features and clinical factors to build three models including a radiomic model, a clinical model, and a combined model including clinical factors and RadScore. When a model has prognostic predictive value (AUC > 0.7) in both train and test groups, a nomogram will be created. The performance of three models was evaluated using area under the receiver operating characteristic curve (AUC) and Kaplan–Meier analysis.
Results
A total of 1037 features were extracted from simulated positioning CT images which were contrast enhanced CT of the chest. The combined model showed the best prediction, with very poor AUC for the radiomic model and the clinical model. The combined model of OS included 4 clinical features and RadScore, with AUCs of 0.71 and 0.70 in the training and test groups. The combined model of PFS included 4 clinical features and RadScore, with AUCs of 0.72 and 0.71 in the training and test groups. T stages, ProGRP and smoke status were the independent variables for OS in the combined model, whereas T stages, ProGRP and prophylactic cranial irradiation (PCI) were the independent factors for PFS. There was a statistically significant difference between the low- and high-risk groups in the combined model of OS (training group, p‚Äâ<‚Äâ0.0001; testing group, p‚Äâ=‚Äâ0.0269) and PFS (training group, p‚Äâ<‚Äâ0.0001; testing group, p‚Äâ<‚Äâ0.0001).
Conclusion
Combined models involved RadScore and clinical factors can predict prognosis in LS-SCLC and show better performance than individual radiomics and clinical models.
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Electron microscopy characterization of chalcogenide based quantum dots prepared via low temperature, aqueous phase synthesis routes
No full textQuantum dots (QDs) are a class of semiconductor nanomaterials that have a tunable electronic band gap through quantum confinement. QD materials have a variety of technological applications including photocatalytic water splitting, energy generation via solar cells, light emission in display technologies and luminescent biomarkers. However, a challenge in sustainably producing these materials is to move away from the high synthesis temperatures and toxic nature of the precursors used in current preparation routes. In this work, low temperature, aqueous phase, bioinspired synthesis routes have been used to prepare a variety of chalcogenide-based QD systems. Multiple characterization techniques have been used to evaluate the structure and properties of the synthesized QD material. In particular, aberration corrected scanning transmission electron microscopy (AC-STEM) has been used to show how different synthesis conditions affect size, morphology, crystal structure and composition of the particles.The room temperature, aqueous biosynthesis of CdS QDs using the cystathionine ?-lyase enzyme (CSE) was performed utilizing L-cysteine as a capping ligand and sulfur source. The nucleation and growth mechanisms for this synthesis route were investigated and compared with syntheses involving controlled additions of sulfur via NaHS. AC-STEM characterization of the CdS QD materials produced showed them to have controllable particle size distributions (PSDs) and comprise a mixture of wurtzite/zincblende type structures. In addition, a new bio-inspired non-enzymatic aqueous preparation route with L-cysteine, pyridoxal phosphate (PLP), and FeCl3 showed that removing the enzyme expands the effective range of temperature and pH over which the wurtzite/zincblende type CdS QDs can be controllably synthesized. The quality of the CdS QDs produced by both these methods compared favorably with commercially produced \u27organic phase\u27 CdS particles that had undergone ligand exchange to stabilize them in water. Studies were performed to see if the biomineralization synthesis procedure could be adapted to grow CdS QDs directly onto a pre-existing TiO2 substrate. After confirming that the CSE enzyme retained its activity after immobilization, it was used to directly synthesize CdS QDs onto the TiO2 support particles. It was also found that even though the enzyme activity decreased after multiple QD synthesis cycles, it\u27s activity for QD formation was recoverable by addition of a PLP co-enzyme. In a separate series of experiments, attempts were made to attach pre-formed biomineralized CdS QDs to the surface of partially reduced graphene oxide (rGO) in order to improve charge separation during the water splitting reaction. This goal was partially accomplished via the addition of poly-L-lysine (PLL) as a linker molecule between the L-cysteine capping ligand and the rGO surface, which allowed for particle attachment, but unfortunately reduced the photocatalytic performance of the QDs. To reduce the length of the linkage between CdS QDs and the rGO support, a ligand exchange reaction was performed whereby cystathionine (CA) replaced L-cysteine. This modification promoted the electrostatic attachment of CdS to rGO and simultaneously provided the desired charge separation effect required for improved photocatalytic action. In order to use untethered biomineralized CdS colloids as photocatalysts for the water splitting reaction, modifications had to be made stabilize and improve their catalytic activity. A sequential biomineralization process was used to form CdS/ZnS particles. For these materials, no secondary populations of ZnS were produced, the structure of the core CdS particles was unchanged, and zinc association with the CdS particles was confirmed by XEDS. The CdS/ZnS particles exhibited a greater structural stability compared to CdS QDs alone, but unfortunately a lower activity. Hence an optimal compromise Zn loading was identified which significantly improved particle stability without blocking all the catalytically active surface sites. Another way of improving the photocatalytic performance of CdS QD systems is to introduce a co-catalyst such as NixSy or Pt. NixSy was found to form a complex with L-cysteine under normal biomineralization conditions, and so has to be produced separately under low pH conditions. When added a co-catalyst, the relatively large amorphous NixSy particles generated became atomically dispersed and incorporated into/onto the CdS QDs. The photocatalytic performance of the resultant CdS/NixSy material was shown to be much higher than that of the base CdS QDs, and comparable to that of CdS/Pt catalysts prepared via photodeposition. Copper zinc tin sulfide (CZTS) QDs were also biosynthesized and tested for application in a quantum dot sensitized solar cells device. These QDs are attractive due to the relative abundance of the constituent elements and their low toxicity compared to CdS. Firstly, CuS, ZnS and SnS were all confirmed to be compatible with the biomineralization route, and then a one-pot synthesis method was devised for preparing CZTS particles. Detailed structural and compositional analyses of a series of CZTS samples with differing Cu:Zn:Sn ratios was required in order to optimize the optoelectronic performance of the material. In addition, the fabrication process by which the QDs were incorporated in the solar cell structure heavily impacted the device\u27s performance, with drop cast CZTS layers showing inferior performance to films having CZTS particles grown in-situ within the TiO2 active layer. Finally, aqueous phase AgInS QDs with Zn additions were biosynthesized and investigated as materials for cell biomarker applications due to their inherent low toxicity and biocompatibility. This was achieved by biosynthesizing InS QDs, and then subsequently converting them to AgInS QDs, and then finally adding Zn to form AgInS/ZnS structured materials. The optoelectronic performance of these materials was correlated with AC-STEM compositional and structural studies. The optimum ratio of Ag-In was found to be 1:5, the particles exhibited a AgIn5S8 type structure. The final Zn addition did not change the base AgInS particle structure or form separate ZnS particles, but rather is believed to form a surface stabilizing ZnS species. Cell viability studies, and conjugation of the AgInS/ZnS particles to macrophage cells were successfully performed, which allowed for the targeted attachment of these fluorescent QDs to the outer membrane of THP-1 monocytes and macrophages
The Rise and Downfall of the Pennsylvania Coal and Iron Police
No full textAbstractIn 1905, Pennsylvania pioneered the establishment of the first modern state police force in the nation. While historians attribute the formation of this institution to intense confrontations between workers and the privately funded Coal and Iron Police, notably during the Anthracite Coal Strike of 1902, seldom does a single event result in such profound systemic transformation. This dissertation delves into the origins and activities of the Coal and Iron Police, examining how its sustained presence ultimately precipitated the creation of the state police. From the antebellum period, American society struggled with how to maintain order, and to do so within certain societal parameters. Citizens did not want to pay exorbitant taxes to equip a police force that might not only traduce their liberties, but also create a stronger government. Nor did they want to pay taxes for a force that would primarily service private interests. These concerns were first addressed at the local level, in particular in urban centers such as Boston, New York and Philadelphia which established the country\u27s first police departments. After the Civil War the issue of maintaining order arose at the state level as transportation innovations and industrialization engendered a more transient and decentralized workforce, in particular along the railroads and in the coal regions. Rural counties had few resources to quell labor unrest except to call out the state militia, a cumbersome and slow process. For Pennsylvania the Railroad Police and Coal and Iron Police, for a time, became the solution. These forces were paid for by private employers, but were invested with state policing authority. Starting with the origins the Coal and Iron Police, this dissertation traces pivotal episodes of this institution, culminating with the Anthracite Coal Strike of 1905. The primary questions that work aims to answer are "Why were the Pennsylvania Coal and Iron Police created? What was the function, or role, of this force once it was in place? Finally, who were the men who comprised this force, and what did they actually do?" Answering these questions offers fresh insights into matters extending beyond Pennsylvania, encompassing broader discussions on policing, state formation, labor-industry relations, and the maintenance of public order
The Alignment Between Principal Perception of Fieldwork, Pennsylvania Leadership Standards, and Acting Administrator Responsibilities
No full textAbstractAt the turn of the century, a school leadership crisis emerged with school districts facing high turnover and a lack of replacements, as well as available new hires with the requisite skills, knowledge, and experience necessary to succeed in leading a school (Gates et al., 2003). School principals play a key role in student success and principal preparation programs are developed to provide the foundational skills to be an effective school leader. Davis et al. (2012) added that an increased number of preparation programs are beginning to place more emphasis on the qualities of activities of the fieldwork experiences and the state accreditation standards. Through the triangulation and analysis of three data sources: fieldwork logs, survey/daily logs, and semi-structured interviews, this phenomenological study explored the lived experiences of acting assistant principals and principals who completed the fieldwork component of their principal preparation program. The results of the study showed that although the participants\u27 shared experiences varied, the pre-service and in-service activities were similar, but overall, the fieldwork experience did not provide the most effective leadership development
Checked In or Checked Out?: A Survey Regarding Positive Behavioral Supports
No full textSchool-Wide Positive Behavioral Interventions and Supports (SWPBIS) are an integral part of schools across the United States. When implementing SWPBIS, academic achievement, emotional regulation, prosocial behavior increases while behavioral problems, bullying, exclusionary discipline teacher stress and teacher burnout decrease. Despite the utility of SWPBIS, there is a limited amount of literature that has evaluated tiered behavioral interventions. Furthermore, there is limited research that focused on a common Tier 2 intervention, Check in/Check out (CICO). Previous literature has reported how schools used and evaluated Tier 2 behavioral interventions, identified common team configuration for Tiers 2 and 3, and evaluated how teams evaluate and intervene using behavioral intervention success. This survey study sought to expand the literature by assessing common team practices nationwide (e.g., team members, fidelity, data reviewed, how responsiveness is identified), and focused on a specific Tier 2 intervention (i.e., CICO). Precisely, this study examined how teams determine responsiveness to CICO and identified if adaptations used for CICO. The results found that teams are represented by a variety of school personnel, use data to make decisions, and are adapting CICO. Additionally, a significant outcome was that the longer schools implement SWPBIS, there is a larger number of Tier 2 interventions offered. Lastly, the results indicate no significant finding that CICO fidelity was predicted by the number of years implementing SWPBIS. Limitations, future directions, and implications are discussed
The Moderating Impact of Child Maltreatment Risk Factors on the Relation between Early Head Start Home Visitors\u27 Wellness, Family Engagement, and Child Outcomes
No full textYoung children are at increased risk for child maltreatment (United States Department of Health and Human Services, 2021), and child maltreatment poses a substantial risk and long-lasting negative impact on children\u27s development (Centers for Disease Control and Prevention, 2020). Given the recommendation that delivering services to young children in natural environments, the Early Head Start home-based option (EHSHBO) can be a promising way to support the healthy development of young children from families who face socioeconomic disadvantages and elevated risks for maltreatment. In the EHSHBO, home visitors play a critical role in providing effective services to children and their families (Love et al., 2005). Unfortunately, working with families at risk of maltreatment can present challenges to home visitors\u27 psychological and occupational wellbeing, which can negatively impact their ability to support children and their families. (Schreier et al. 2018; West et al., 2018). Yet, research on home visitors\u27 wellness is still in its infancy. Accordingly, the purposes of the current study were to examine 1) the moderating impact of child maltreatment risk factors on the relation between EHS home visitors\u27 wellness and family engagement and 2) the impact of EHS home visitors\u27 wellness on family engagement and child outcomes. The current study used a preexisting dataset from the Early Head Start Family and Child Experiences Survey (Baby FACES 2018) and adopted a latent moderated structural equations approach to investigate the moderating relationship. Results demonstrated that child maltreatment risk factors were significantly related to family engagement, but the moderating impact of child maltreatment risk factors on the relation between home visitors\u27 wellness and family engagement was not significant. Clinical and research implications are discussed
The Role of Ageism, Aging Anxiety, and Death Anxiety in Understanding Trainees\u27 Therapeutic Expectations and Interest in End-of-Life Care
No full textThe field of mental health is not yet equipped to meet the needs of the growing older adult population. More psychologists are needed in the field of geropsychology across all specialties, including end-of-life care. However, no known research has examined psychology trainees\u27 attitudes or interest in providing end-of-life care to older adults. Under the frame of Terror Management Theory (TMT; Martens et al., 2005), this study examined the relationship of ageism, aging anxiety, and death anxiety with psychology trainees\u27 therapeutic expectations and interest in engaging in end-of-life care for clients in later life. Using structural equation modeling, two models were proposed to assess 1) ageism as a partial mediator of aging anxiety and death anxiety\u27s relationship to therapeutic expectations and interest and 2) ageism, aging anxiety, and death anxiety as independent predictors of interest and therapeutic expectations in a sample of 197 psychology doctoral students enrolled in an APA-accredited program. Although the hypothesized model did not converge, the alternative model, representing ageism, aging anxiety, and ageism as independent predictors of therapeutic expectations and interest in working with older adults near end of life, showed good fit after modifications. Higher aging anxiety predicted lower interest working with this population as well as worse therapeutic expectations. Ageism was not significantly related to therapeutic expectations but was positively related to interest. Death anxiety did not significantly predict either outcome variable. These findings suggest training programs and early clinical opportunities should consider the role of existential anxiety, particularly aging anxiety, as well as ageism\u27s impact on trainees\u27 career interests and perceptions towards working with older adults living with life-limiting illness