Positron Emission Tomography Radiochemistry: Improved Methodology and a Novel PET Imaging Agent for the Dopamine D3 Receptor

Positron Emission Tomography (PET) imaging is a powerful non-invasive imaging modality used to quantify biochemical processes in vivo. The work described in this thesis encompasses two aspects of PET radiochemistry: (1) the development of new chemical methodology applying the principles of green chemistry to late-stage 18F-fluorination, and (2) developing a PET radioligand for the dopamine D3 receptor. (1) As a way to simplify FDA mandated quality control and residual solvent analysis prior to the release of PET radiopharmaceuticals we sought to apply the principles of green chemistry to 18F-radiochemistry. Green radiochemistry in late-stage stage 18F-fluorination with [18F]KF employs ethanol and ethanol/water mixtures as the only solvents used throughout the entire radiopharmaceutical production: azeotropic drying, nucleophilic fluorination, purification and formulation. This work developed a method in which using ethanol in place of acetonitrile is a viable option for azeotroptic drying of [18F]fluoride. Furthermore, it demonstrated that aliphatic 18F-fluorination reactions can proceed in an optimized 15% water, 85% ethanol mixture. Proof of concept was demonstrated through the synthesis of clinically relevant PET radiopharmaceuticals. The new methodology described challenges the long held belief that nucleophilic fluorination reactions cannot proceed in protic solvents or aqueous media, and encourages further exploration into the utility of green fluorine chemistry. (2) Dopamine is a monoamine neurotransmitter in the Central Nervous System (CNS), and its signaling is mediated by pre-synaptic and post-synaptic dopamine receptors. These are D1-like (D1 and D5) and D2-like (D2, D3, D4) receptors, which are G protein-coupled receptors (GPCRs) and are classified based on these two subfamilies due to sequence homology and pharmacological similarities. The D3 receptor is implicated in many neurological and neurodegenerative diseases and disorders, including substance abuse, depression and schizophrenia. Significant efforts have gone into developing ligands as therapeutics, and as positron emission tomography (PET) diagnostics at this receptor. Significant challenges to this pursuit include the high sequence homology between the D2 and D3 receptors, and the physicochemical properties associated with BBB permeability and in vivo stability, while maintaining selectivity at this receptor. The synthesis and initial evaluation of a series of new carbon-11 and fluorine-18 PET radioligands for the D3 receptor is described. These radioligands are based on known ligands with good selectivity for the D3 receptor (pramipexole and BP897). Due to stability issues when using pramipexole-containing scaffolds, BP897 derivatives containing a naphthamide moiety were developed and evaluated in vitro using rad brain autoradiography, and in vivo using rodent microPET imaging. A carbon-11 D3-selective compound was synthesized and identified as a promising candidate, owing to its high affinity for D3 receptors, selectivity for D3 over D2 receptors, and good blood-brain barrier (BBB) penetration. Further evaluation and optimization of the scaffold is merited prior to clinical translation in the future.PHDMedicinal ChemistryUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttps://deepblue.lib.umich.edu/bitstream/2027.42/144039/1/mestewar_1.pd

An exploratory investigation of attitudes toward cause-related marketing

This paper reports on a study concerning consumer perceptions of cause-related marketing in Australia, and seeks to identify a direct link between consumer attitudes toward donating to charity (pro-social behaviour) and corporate philanthropy, and attitudes toward cause-related marketing. After a discussion on the related literature, there follows discussion on the researchmodel employed, and the fmdings of he study. Among other fmdings, statistically significant relationships between attitudes toward charitable giving and attitudes toward cause-related marketing are in evidence. In this study, respondents express a preference for local causes, as opposed to national and international causes, and also demonstrate a preference for cause types similar to those that already receive the highest level of charitable donations. The paper concludes with a discussion of the limitations of the study and presents suggestions for future research.<br /

Meaningful Relationships: Cruxes of University-Community Partnerships for Sustainable and Happy Engagement

The authors draw on organizational theory’s use of the metaphor as a way of understanding and explaining sustainable university/community-engaged partnerships. Working from the premise that transformative and reciprocal relationships prove essential to pedagogies of engagement, specifically service-learning, this essay argues that pursuing and maintaining meaningful partnerships between universities and communities or organizations in many ways parallels our efforts to sustain healthy romantic relationships. Through a description and analysis of 10 cruxes for sustaining long-term, healthy relationships, the authors offer a model for achieving intentional, ongoing, and systemic campus-community partnerships

Adequacy of existing residential care arrangements available for young people with severe physical, mental or intellectual disabilities in Australia

Acknowledging that the NDIS alone will not be able to solve the issues faced by young people in nursing homes, this review makes 12 recommendations including establishing a joint taskforce to ensure the recommendations are put in place. LIST OF RECOMMENDATIONS Recommendations to the Australian Government Recommendation 1 6.7 The committee recommends that the Australian Government compile a database of all young people under the age of 65 years living in residential aged care facilities using the data held by the Aged Care Assessment Team (ACAT) program. This list should be provided in a regularly updated form to the National Disability Insurance Agency (NDIA) and to state and territory governments. This data should include the following information: name; age and age of entry to aged care; diagnosis; length of time spent in the aged care system; and the factors that need to be addressed for the person to move out of the aged care facility. Recommendation 2 6.8 The committee recommends that the Australian Bureau of Statistics (ABS) conduct a Longitudinal Survey of Disability, Ageing and Carers in addition to its triennial survey of Disability, Ageing and Carers. Recommendation 3 6.10 The committee recommends that the Australian Government develop and implement a comprehensive assessment and placement tool or residential assessment instrument to assess the care and accommodation needs for all young people living in or at risk of entering residential care. Recommendation 4 6.12 The committee recommends that supplementary assessment guidelines and tools are developed for the ACAT program to ensure that all young people being considered for an aged care placement are properly assessed. As part of this process, the committee recommends that: all young people placed in aged care are intensively case managed; and all ACAT placements for those aged under 65 are reviewed on an annual basis. Recommendation 5 6.13 The committee recommends that the accreditation standards for residential aged care are amended to include standards relating to the clinical outcomes and lifestyle needs of young people. In order to assist with meeting these new accreditation standards, the committee recommends that the Australian Government: • provide a supplementary payment to residential aged care facilities to ensure that these accreditation standards can be met; and • invest in disability specific training for all staff involved in the care of young people living in aged care. This training should focus on building improved awareness of the needs of young people and those living with disability in order to provide better support. It should also lead to improved connectivity between the aged care sector and other service sectors including allied health and disability services. Recommendation 6 6.17 The committee recommends that the Department of Social Services\u27 current discussion paper on disability housing consider capital funding options for construction of specialised disability accommodation. 6.18 The committee recommends that the discussion paper is released as a matter of urgency. 6.19 The committee recommends that the Australian Government establish a supported disability accommodation fund similar to the Supported Accommodation Innovation Fund. Recommendations to the Joint Standing Committee on the National Disability Insurance Scheme Recommendation 7 6.21 The committee recommends that the Joint Standing Committee on the National Disability Insurance Scheme (NDIS) conduct an inquiry into the issue of disability housing after the release of the discussion paper on disability housing. Recommendations to the Council of Australian Governments (COAG) Recommendation 8 6.23 The committee recommends that the COAG develop and implement a national rehabilitation strategy including a framework for the delivery of slow stream rehabilitation in all jurisdictions. Recommendation 9 6.28 The committee recommends that the NDIS, in all NDIS trial sites, and the relevant state or territory government in all other areas: • assign an advocate to all young people living in residential care to provide information to a young person and their families about their options. If appropriate, the advocate can act on behalf of the young person; • assign an advocate to all young people at risk of entering residential care to provide information to a young person and their families about their options. If appropriate, the advocate can act on behalf of the young person. The advocate should be made available as early as possible after diagnosis of an illness or disability and be assigned before any placement commences; • extend the National Younger Onset Dementia Key Worker Program (YODKWP) to all young people identified as being at risk of placement in residential care to provide collaborative case management. The key worker should be assigned before any placement commences; and • these programs should be proactively extended to young people living in residential care facilities under the age of 65 years by June 2017. Consideration of the mental health status of young people should be prioritised with appropriate support provided where necessary. Recommendation 10 6.30 The committee recommends that the NDIS, in all NDIS trial sites, should consider how it supports those with Foetal Alcohol Spectrum Disorder (FASD). 6.31 The committee also recommends that the NDIS, in all NDIS trial sites, and the relevant state or territory government in all other areas work closely with community health services to provide the following for those with FASD agreement on a standardised diagnostic tool; and provision of early intervention services and other health services such as speech pathology, physiotherapy and occupational therapy. Recommendation 11 6.32 The committee recommends that the COAG establish a joint taskforce for young people living in residential care. This taskforce will: • facilitate the development and implementation of integrated service pathways involving a range of portfolios at a state and federal level including housing, health, aged care, disability, and transport; and • facilitate the collation and development of information packs outlining support, transition and placement options for young people. These packs should be made available to young people, their families, health practitioners and other relevant professionals in hospitals and aged care facilities. This process should collate all information and tools developed by the states during the Younger People with Disability in Residential Aged Care (YPIRAC) program and lead to the development of a standardised national information pack and make available to all state and territory governments for deployment. 6.33 The joint taskforce will also be responsible for oversight of the following for young people living in a Residential Aged Care Facility (RACF): &nbsp;access to appropriate prescribed specialist services including speech pathology, physiotherapy, occupational therapy and other allied health services; the national rehabilitation strategy; the provision of advocates; the expanded key worker program; access to fully funded equipment as part of all state and territory Aids and Equipment schemes; • a cross sector approach is adopted to explore options for the provision of short term respite services; and • that all young people who indicate that they do not wish to live in residential care are transitioned into appropriate alternate accommodation by June 2018. Recommendation 12 6.34 The committee recommends that the joint taskforce issues a half yearly report on the progress of Recommendation 11 to the COAG

US history shows that progress towards racial equity has been met with violent backlash from whites trying to keep power

The US Capitol insurrection on January 6th was an attempt to maintain white supremacy, motivated by a fear of status loss. Megan Stewart and Karin Kitchens write that such violent reactions to maintain white supremacy are not new in the US. Examining data from the post-Civil War Reconstruction period of the 1860s and 1870s, they find that measures like the deployment of Union troops can be linked to increased literacy for Black persons, but also to an increase in the number of Black persons murdered by white lynch mobs threatened by fear of status loss

Violence Prevention In High Schools: Choices for Effectiveness

Every two days, guns kill the equivalent of a classroom of youngsters and injure 60 more

The Cost of Cost-Sharing: The Impact of Medicaid Benefit Design on Influenza Vaccination Uptake

ncome persons. State Medicaid policy may affect the uptake of recommended adult vaccinations. We examined the impact of three aspects of Medicaid benefit design (coverage for vaccines, prohibiting cost-sharing, and copayment amounts) on vaccine uptake in the fee-for-service Medicaid population 19–64 years old. We combined previously published reports to obtain state Medicaid policy information from 2003 and 2012. Data on influenza vaccination uptake were taken from the Behavioral Risk Factor Surveillance System. We used a differences-in-differences framework, controlling for national trends and state differences, to estimate the effect of each benefit design factor on vaccination uptake in different Medicaid-eligible populations. Each additional dollar of copayment for vaccination decreased influenza vaccination coverage 1–6 percentage points. The effects of covering vaccines or prohibiting cost-sharing were mixed. Imposing copayments for vaccination is associated with lower vaccination coverage. These findings have implications for the implementation of Medicaid expansion in states that currently impose copayments

Factors Affecting Involvement of Urban School District Parents in their Child\u27s Education

Parental involvement in children\u27s education has been found to have a positive impact on academic achievement. Because the state has mandated that academic achievement in the study district needs to increase, identifying means of increasing parental involvement is important. Guided by the work of Epstein, this quantitative study was conducted to explore demographic factors related to parents\u27 involvement in the education of their children. Specifically, research questions examined differences in parental involvement by socioeconomic status (SES), barriers to involvement for parents, and school strategies to improve parental involvement. Parents of all 5th grade students (n = 935) from a large East Coast urban district were surveyed using the Scale of Parental Involvement to address the research questions. The data were analyzed using descriptive statistics as well as an independent-samples t test to determine the differences in involvement by SES. A significant difference in parental involvement between low- and high-SES parents was not obtained. Parents reported that barriers such as work hours, lack of feeling appreciated, culture, transportation, and child care prevented full participation in the education of their children. The findings also suggested that districts might increase parental involvement through engaging in more frequent communication with parents; providing more activities to do at home; and providing more time for training, teaching, and meeting. Implications for positive social change include providing research findings to the local district on how to increase the involvement of parents in their children\u27s education

Understanding values associated with stormwater remediation options in marine coastal ecosystems: A case study from Auckland, New Zealand

This paper describes the design and implementation of a choice experiment to understand Aucklanders’ preferences for environmental qualities associated with the effects of urban run-off on marine coastal environments. Auckland’s coastal environments are affected by a range of ecological and human factors. While much research has been undertaken in the area of ecology, little is understood of human preferences for coastal environments and their management. An unlabelled choice experiment was developed with three environmental quality attributes specified at three broad coastal categories. The environmental qualities are ecological health, water clarity, and underfoot conditions. Willingness to pay estimates for these attributes indicates that respondents show a strong preference for improved environmental quality at outer coastal beach locations over middle and upper harbour locations. Water quality leads ecological health, then underfoot conditions in importance at beach locations. An application is discussed in which a hypothetical project consisting of policy and engineering components delivers changes in water quality and underfoot conditions in the Auckland upper harbour areas. A 95% confidence estimate of the money value of that change ranges from $783 m. to$ 1,122 b. The key outcome is demonstration of the choice experiment as a statistically robust and flexible approach to making sense of Aucklanders’ complex preferences for coastal ecosystem management.Environmental Economics and Policy, Research Methods/ Statistical Methods,

Sequential Order of Swing Phase Initiation in Baseball

In order to successfully hit a baseball, hitters must utilize a series of preparatory movements (swing phases) which include shifting their body weight, stepping, landing, and swinging. The purpose of this study was to examine the differences between start times for swing phases (shifting, stepping, landing, and swinging)for currently active baseball players. Participants (n = 12) were all current collegiate baseball athletes. Retroreflective markers, surface electromyography (EMG) and two force platforms were utilized to complete a swing analysis. Each participant completed five swinging trials off a tee. All dependent variables were compared using a repeated measures 1×4 ANOVA with LSD post hoc comparison (p \u3c  0.05) if necessary. The results demonstrated that the participants started the swing phases in a statistically significant sequence of shifting, stepping, landing, and swinging. The ability of the athletes to start the swing phases in this sequential order may be advantageous to regulate spatial parameters of their swing and provide more time to generate power. These results allow for coaches to better understand how to instruct their athletes to be successful at the plate