Left with No Name: How Government Action in Intra-Church Trademark Disputes Violates the Free Exercise Clause of the First Amendment

The United States was founded in part on the principle of freedom of religion, where citizens were free to practice any religion. The founding fathers felt so strongly about this principle that it was incorporated into the First Amendment. The Free Exercise Clause states that “Congress shall make no law . . . prohibiting the free exercise thereof . . . .” The Supreme Court later adopted the neutral principles approach to avoid Free Exercise violations resulting from courts deciding real property disputes. Without the application of the same neutral principles to intellectual property disputes between churches, however, there is real danger of violating the Free Exercise Clause. This Note seeks to answer the question: Does the government’s role in approving and enforcing trademark rights in intra-church disputes violate the Establishment and Free Exercise Clauses of the First Amendment? Part II of this Note provides an overview of Supreme Court church property jurisprudence and describes the evolution of the neutral principles approach. This Note primarily focuses on property disputes between hierarchical churches, as their governing structure leaves them most vulnerable to Free Exercise implications. Part III outlines how an entity, secular or religious, registers a trademark with the U.S. Patent and Trademark Office (USPTO). The section details infringement actions and provides examples of registered church trademarks. Part IV concerns the constitutional implications of church trademark adjudication, specifically through the lens of the Establishment Clause and the Free Exercise Clause. Part IV.A concludes that the USPTO’s registering of church trademarks does not violate the Establishment Clause. Part IV.B analyzes Free Exercise implications concerning the adjudication of trademark infringement suits. Because of the neutral principles approach and the inherently ecclesiastical nature of church trademarks, Part IV.B concludes that current court action violates the Free Exercise Clause. Part V suggests that courts should uniformly apply the neutral principles approach to real and intellectual property disputes alike. This section theorizes that such an approach would prevent future Free Exercise violations

Synthesis and biological evaluation of CXCR4 chemokine receptor antagonists

The CXCR4 chemokine receptor is known to be overexpressed in many types of cancer as well as being involved in several stages of metastasis, which is responsible for the majority of deaths in cancer patients. Molecular imaging techniques, such as positron emission tomography (PET), are being used in the design of early stage CXCR4 expressing cancer diagnosis agents which can be followed by the administration of CXCR4 specific drugs targeting to an individual’s specific cancer treatment requirements to prevent the spread of cancer. Incorporation of positron emitting radioisotopes such as ¹⁸F and ⁶⁴Cu into a CXCR4 specific compound allows visualisation of the locations that the drug has accumulated. This can facilitate the diagnosis of a CXCR4 expressing cancer as large volumes of emission signals will be detected in tumours. Following diagnosis, high CXCR4-affinity targeted compounds can be administrated which prevent CXCR4’s binding partner, CXCL12, activating the receptor and enabling metastasis. This work focuses on the development of high affinity CXCR4 antagonists which can be used in therapeutic and diagnostic applications.A series of configurationally restricted complexes of copper(II), zinc(II) and nickel(II), where the metal ion is coordinated to tris-macrocycles, were synthesised. Tris-macrocycles have the potential to show improved affinity for the CXCR4 receptor because the third macrocyclic ring can facilitate more interactions with the CXCR4 receptor than reported bis-macrocycles, due to the extra interactions possible with the aspartate rich receptor surface. Biological studies revealed the tris-macrocyclic series has high affinity for CXCR4. [Zn₃18] ⁶⁺ showed nanomolar activity with an IC₅₀ value of 0.84 nM, 14 times more potent than the FDA approved drug AMD3100. Another high affinity tris-macrocycle, [Zn₃19] ⁶⁺ showed an IC₅₀ value of 1.86 nM also significantly lower than ADM3100. The high affinity compounds, [Zn₃18] ⁶⁺ and [Zn₃19] ⁶⁺, were radiolabelled with ⁶⁴Cu via transmetalation. Crude-radiochemical yields (crude-RCY) of 79% and 62% were achieved for ⁶⁴CuZn₂[18] and ⁶⁴CuZn₂[19] respectively. The complexes were identified as strongly hydrophilic with calculated LogP values of -3.69 and -2.20 for ⁶⁴CuZn₂[18] and ⁶⁴CuZn₂[19] respectively.A series of rigidified bis-macrocycle copper(II) and zinc(II) complexes were synthesised and explored as imaging agents. Routes to incorporate ¹⁸F and ⁶⁸Ga into the bis-macrocycles for applications in PET imaging were explored. Mono-macrocycles were synthesised and used in a series of test reactions to evaluate a range of pendant arm functionalisations including nitro, amine, azide and alkyne. Subsequently, azide functionalised rigidified bis-macrocycle copper(II) and zinc(II) complexes for use in copper-free click reactions were synthesised which provided an effective route to incorporate ¹⁸F into macrocycles. Biological studies identified that the functionalised bis-macrocycle complexes showed high affinity towards the CXCR4 receptor. The key compound was [Zn₂32] ⁴⁺ which showed IC₅₀ values of 3.22 nM, more than 3 times lower than AMD3100.A series of surface plasmon resonance (SPR) experiments were conducted to develop a method to determine the residence time of macrocycles on the CXCR4 receptor. A range of approaches, such as intact cell immobilisation, intact cell capture and receptor capture, were studied but all methods had drawbacks therefore association and dissociation rates of macrocycles and the CXCR4 receptor were not ascertained.This work highlights important steps towards the diagnosis of CXCR4 expressing cancers with the use of highly stable tris-macroycles. Furthermore, initial steps to incorporate the most readily available radioisotope, ¹⁸F, into macrocycles have been identified. Progress towards the development of high affinity, anti-metastatic therapeutic agents, in CXCR4 expressing cancers, has been made with the synthesis and in vitro evaluation of configurationally restricted tris-macrocycle metal complexes. Key compounds in this series were [Zn₃18] ⁶⁺ and [Zn₃19] ⁶⁺ which showed significantly better affinity for the CXCR4 receptor than AMD3100 and low toxicity

The Magnitude and Nature of Risk Selection in Employer-Sponsored Health Plans

Most existing studies of risk selection in the employer-sponsored health insurance market are case studies of a single employer or of an employer coalition in a single market. We examine risk selection in the employer-sponsored market by applying a switcher' methodology to a national, panel data set of enrollees in employer-sponsored health plans. We find that people who switched from a non-HMO to an HMO plan used 11 percent fewer medical services in the period prior to switching than people who remained in the non-HMO plan, and that this relatively low use persists once they enroll in an HMO. Furthermore, people who switch from an HMO to a non-HMO plan used 18 percent more medical services in the period prior to switching than those who remained in an HMO plan. HMOs would most likely continue to experience favorable risk selection if employers adjusted health plan payments based on enrollees' gender and age because the selection appears to occur based on enrollee characteristics that are difficult to observe such as preferences for medical care and health status.

Rationing and Disability: The Civil Rights and Wrongs of State Triage Protocols

The COVID-19 pandemic and the unprecedented natural disasters of 2020 remind us of the importance of emergency preparedness. This Article contributes to our legal and ethical readiness by examining state “Crisis Standards of Care,” which are the standards that determine how medical resources are allocated in times of scarcity. The Article identifies a flaw in the policy choice at the heart of the standards: the standards focus on saving as many lives as possible but, in so doing, will predictably disadvantage the ability of people with disabilities and racial minorities to access life-saving care. To date, scholarly attention has focused on explicit exclusions of people with particular medical conditions or the standards’ failure to be sufficiently individualized. Amending the protocols to address these concerns, while important, will simply tinker at the margins. The more consequential and harder question is how states should balance the demand to save as many lives as possible while also ensuring that people with disabilities and other vulnerable groups are treated fairly. To answer that question, this Article distills and analyzes four rationing principles that animate the state standards and contends that none ultimately balances these two important aims in a manner consistent with the Americans with Disabilities Act (ADA) and the moral commitments on which it rests. It thus provides a moral and legal framework to guide the ongoing revision of the standards. The Article concludes by proposing a novel, alternative rationing system that reserves resources to accommodate both efficiency and equity, thereby better instantiating the balance that undergirds the ADA

Nonclassical crystallization of dipicolinic acid in microemulsions

Dipicolinic acid (DPA) was crystallised in microemulsions to investigate the effect of 3D nanoconfinement on the crystallisation process. The microemulsions were acidified with 2M HCl to prevent the formation of DPA metal salts, which occurs due to a pH shift towards neutrality arising from the nanoconfinement. TEM analysis showed that 30-100 nm square-plate nanoaggregates crystallised from these acidified microemulsions. Higher resolution TEM images revealed that the nanoaggregates consisted of smaller 3-10 nm nanocrystals. The FFT’s obtained from images of these nanocrystals were similar to the diffraction pattern arising from the whole nanoaggregate confirming that the nanocrystals exhibited ordered packing and resembled mesocrystals. The crystallisation of the nanoaggregates is aided by the suppression of Ostwald ripening of the nanocrystals in the nm-sized microemulsion droplets and surfactant adsorption onto the nanocrystals

Three & One

Faculty recital at USU.https://digitalcommons.usu.edu/music_programs/1260/thumbnail.jp

Pembrolizumab monotherapy for non-small cell lung cancer (NSCLC):can patient stratification be improved in the UK Tayside population? A retrospective cohort study

OBJECTIVE: Pembrolizumab is a programmed cell death protein-1 (PD-1) inhibitor used to treat advanced patients with non-small cell lung cancer (NSCLC) with a programmed cell death ligand-1 (PD-L1) tumour proportion score (TPS) ≥50. Further sub-division of TPS-based stratification has not been evaluated in the UK, although smoking-induced tumour mutational burden and the immunogenic effects of prior radiotherapy are suggested to improve response.AIMS: To investigate if PD-L1 TPS ≥80%, smoking status or radiotherapy before or within 2 months of treatment influenced progression-free survival (PFS) in patients with NSCLC treated with pembrolizumab monotherapy.METHODS: PD-L1 TPS, smoking status and radiotherapy exposure were compared in patients with NSCLC in National Health Service (NHS) Tayside (n=100) treated with pembrolizumab monotherapy between 1 November 2017 and 18 February 2022. Survival estimates were compared using log-rank analysis, and Cox proportional hazards analysis was used to investigate the influence of potential confounding factors, including tumour stage and performance status.RESULTS: PFS was not significantly different (log-rank HR=0.330, p=0.566) comparing patients with PD-L1 TPS 50-79% and PD-L1 TPS ≥80%. Smokers had significantly improved PFS (log-rank HR=4.867, p=0.027), while patients receiving radiotherapy had significantly decreased PFS (log-rank HR=6.649, p=0.012). A Cox regression model confirmed that both radiotherapy (p=0.022) and performance status (p=0.009) were independent negative predictors of PFS.CONCLUSIONS: More rigorous PD-L1 TPS stratification did not influence survival outcomes. Smoking history improved PFS, although it was not an independent response predictor, while radiotherapy and performance status independently influenced clinical response. We suggest that further stratification of PD-L1 TPS is not warranted, while performance status and radiotherapy treatment may be additional clinically useful biomarkers of response to pembrolizumab in patients with NSCLC.</p

Applied aerial spectroscopy: A case study on remote sensing of an ancient and semi-natural woodland

An area of ancient and semi-natural woodland (ASNW) has been investigated by applied aerial spectroscopy using an unmanned aerial vehicle (UAV) with multispectral image (MSI) camera. A novel normalised difference spectral index (NDSI) algorithm was developed using principal component analysis (PCA). This novel NDSI was then combined with a simple segmentation method of thresholding and applied for the identification of native tree species as well as the overall health of the woodland. Using this new approach allowed the identification of trees at canopy level, across 7.4 hectares (73,934 m2) of ASNW, as oak (53%), silver birch (37%), empty space (9%) and dead trees (1%). This UAV derived data was corroborated, for its accuracy, by a statistically valid ground-level field study that identified oak (47%), silver birch (46%) and dead trees (7.4%). This simple innovative approach, using a low-cost multirotor UAV with MSI camera, is both rapid to deploy, was flown around 100 m above ground level, provides useable high resolution (5.3 cm / pixel) data within 22 mins that can be interrogated using readily available PC-based software to identify tree species. In addition, it provides an overall oversight of woodland health and has the potential to inform a future woodland regeneration strategy

A Phase I Trial of Allogeneic γδ T Lymphocytes From Haploidentical Donors in Patients With Refractory or Relapsed Acute Myeloid Leukemia

Introduction: We report the results of a phase I clinical trial NCT03790072 of an adoptive transfer of γδ T lymphocytes from haploidentical donors in patients with refractory/relapsed acute myeloid leukemia after lymphodepletion regimen./ Patients and methods: Healthy donor mononuclear cells collected by leukapheresis were consistently expanded to generate products of 109 to 1010 γδ T cells. Seven patients received donor-derived T cell product at doses of 106/kg (n = 3), 107/kg (n = 3), and 108/kg (n = 1)./ Results: Four patients had bone marrow evaluation at day 28. One patient had a complete remission, one was classified as morphologic leukemia-free state, one had stable disease and one had no evidence of response. In one patient, there was evidence of disease control with repeat infusions up to 100 days after first dosing. There were no treatment-related serious adverse events or treatment-related Common Terminology Criteria for Adverse Events grade 3 or greater toxicities at any dose level. Allogeneic Vγ9Vδ2 T cell infusion was shown to be safe and feasible up to a cell dose of 108/kg./ Discussion: In agreement with previously published studies, the infusion of allogeneic Vγ9Vδ2 cells was safe. The contribution of lymphodepleting chemotherapy to responses seen cannot be ruled out. Main limitation of the study is the low number of patients and interruption due to COVID-19 pandemic./ Conclusion: These positive Phase 1 results support progression to phase II clinical trials

Relational counselling as a psychosocial intervention for dementia : qualitative evidence from people living with dementia and family members

Counselling and other psychotherapeutic interventions can be offered to people with dementia and their caregivers, to treat specific conditions or symptoms (e.g. affective disorders such as depression). Psychotherapeutic interventions also offer the opportunity for individuals with dementia and their families/caregivers to engage in psychological support for a wide range of presentations. However, little is known about how those within this demographic who receive these interventions perceive the experience. This study aimed to understand the experiences of individuals with dementia or caring for someone with dementia, before and after a 12-week relational counselling intervention delivered through a third sector organisation within England. Semi-structured interviews were completed with participants (29 pre-intervention and 25 post-intervention). Framework analysis was conducted, with four main themes identified; expectations and outcomes of counselling, emotional impact of life with dementia, appraisals of identity and importance of therapeutic relationship. Participants reported that counselling interventions addressed a range of needs and concerns that they had, enabling them to reassess and reconsider these. Specific training is needed before therapists deliver therapeutic interventions with people with dementia, to ensure that appropriate support is provided for those with more severe cognitive impairment or who may have fluctuating capacity. Future research should explore the experiences of people with dementia and their caregivers, across different counselling modalities, to establish the appropriateness and effectiveness of relational counselling