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Purpose To describe a pharmacist-led transitional care clinic (TCC) for high-risk patients who were recently hospitalized or seen in the emergency department (ED). Summary The Memphis Veterans Affairs Medical Center (VAMC) established a pharmacist-led face-to-face and telephone follow-up TCC to improve posthospitalization follow-up care through medication optimization and disease state management, particularly for veterans with high-risk disease states such as chronic obstructive pulmonary disease (COPD) and heart failure (HF). The clinic’s clinical pharmacy specialists (CPSs) ordered diagnostic and laboratory tests, performed physical assessments, and consulted other providers and specialty services in addition to performing medication reconciliation, compliance assessment, and evaluation of adverse drug events. TCC patients were typically seen within 2 weeks of discharge and subsequently referred back to their primary care provider or a specialty care provider for continued management. A retrospective review of 2016 TCC data found that 7.8% of patients seen in the TCC were readmitted within 30 days of discharge; readmission rates for COPD and HF were reduced to 13% and 10%, respectively, compared to hospital-wide readmission rates of 17% and 24%. A separate observational analysis found that 30-day readmissions for COPD and HF were reduced in TCC patients, with pharmacists documenting an average of 6.2 interventions and 3.3 medication-related problems per patient. To reduce clinic appointment no-shows, the CPSs worked with inpatient providers and schedulers to emphasize to patients the importance of clinic attendance; also, TCC services were expanded to include telehealth appointments to increase access for rural and/or homebound patients. Conclusion A pharmacist-led TCC effectively reduced readmissions and prevented medication-related problems for high-risk patients who were hospitalized or seen in the ED.

Background: α-1 adrenergic antagonists are commonly prescribed, but there is question regarding their safety in patients at increased fall risk. Objective: The purpose of the FRAGILE study was to determine the risk for developing adverse drug events (ADEs) in veterans prescribed α-1 blockers. Methods: A single-center, retrospective, observational cohort analysis was conducted of veterans newly initiated on α-1 antagonists. Veterans were categorized into at-risk (patients who met at least 1 of 2 criteria: age 65 or older or high initial dose of α blockade) or control (veterans without either risk factor) groups. The primary outcome was the composite all-cause ADEs, including hospitalizations or emergency department (ED) visits. Secondary outcomes included number of fall-related ADEs and medication discontinuation rates with follow-up for 12 months. Results: A total of 300 veterans were evaluated. There was no significant difference in the composite outcome of all-cause ED visits between at-risk (n = 169) versus control (n = 131) groups (0.81 vs 1.17, P = 0.09) or all-cause hospitalizations (0.28 vs 0.39, P = 0.25). Seventy-three veterans in the at-risk group experienced an all-cause ADE versus 64 in the control group ( P = 0.36). No significant differences in secondary outcomes were found. Fall-related side effects occurred in 8% of the total cohort. Conclusion and Relevance: Rates of all-cause or fall-related ADEs were not significantly different. An 8% discontinuation rate resulting from fall-related ADEs and high rates of coadministered medications that could increase fall risk. Pharmacists can play a key role in optimizing α-1 blocker administration.

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Reduction of copper(II) chloride using sodium ascorbate in the presence of pure sodium 5-nitro-tetrazolate (NaNT) forms copper(I) 5-nitrotetrazolate – a known initiatory explosive (DBX-1) – and the novel mixed-ligand copper(I) chloride 5-nitrotetrazolate coordination polymer Cu3Cl(N4C-NO2)2, as well as mixtures of both. The reaction is controlled by the presence of seed crystals and transition metal compounds other than CuCl2. Cu3Cl(N4C-NO2)2 is obtained as a wine-red, air stable, water-insoluble, crystalline and highly sensitive explosive material with a greater crystal density, lower thermal stability and a higher sensitivity toward hydrolysis and shock than DBX-1. Efforts to obtain the stable and pure starting material are improved by crystallisation of NaNT as a tetrahydrate. Cu3Cl(N4C-NO2)2 and Na(H2O)4(NT) were characterised by single crystal and powder XRD, IR spectroscopy, magnetic and thermal measaurements, elemental analysis, particle size measurements, mass spectrometry, and by drop weight testing.

Research Findings: Naturalistic instruction is the intentional use of strategies embedded within typical activities of the environment to create learning opportunities for children. We used multilevel modeling to analyze data from this single-case design study that focused on improving teachers’ use of naturalistic language strategies and children’s communication through professional development with bug-in-ear coaching. Our results showed that professional development was positively associated with children’s communication during and after professional development. During generalization sessions in different types of activities, teachers’ use of the naturalistic language strategies was positively associated with children’s functional communication. We also found that children were more likely to communicate during child-led activities. Practice or Policy: Associations among professional development, teachers’ use of evidence-based strategies, and children’s outcomes have yet to be fully understoo...

Trypanosomatid parasites are causative agents of important human and animal diseases such as sleeping sickness and leishmaniasis. Most trypanosomatids are transmitted to their mammalian hosts by insects, often belonging to Diptera (or true flies). With resistance to both vector-targeted pesticides and trypanocidal drugs being reported, there is a need for novel transmission blocking strategies to be developed. Studies using the blood-feeding vectors themselves are not broadly accessible, as such, new model systems are being developed to unpick insect-trypanosmatids interactions. In this thesis the interactions between model dipteran Drosophila melanogaster and its own natural trypanosomatid Herpetomonas muscarum are investigated from the perspective of the parasite. This work describes the sequencing and annotation of the H. muscarum genome, which was shown to be highly syntenic to disease-causing trypanosomatids, especially with those of the Leishmania genus. Infections of D. melanogaster were shown to be confined to adults, where H. muscarum persisted in the crop and midgut of the flies for 3-4 days. RNA-sequencing analysis of infected flies showed that rapid, large-scale transcriptomic changes, associated with autophagy, nutrient acquisition and cell surface remodelling, are triggered in H. muscarum after ingestion by the fly. Much of the transcriptomic changes observed reflect what is known for disease-causing trypanosomatids. As such, several of the identified surface proteins are of interest as putative transmission blocking targets. Further characterisation of these genes will be greatly aided by genetic manipulation methods developed for H. muscarum as part of this work. This thesis has described multiple, evolutionarily conserved, trypanosomatid responses to ingestion by dipterans by using a Drosophila-Herpetomonas model. Future studies of these conserved responses will inform development of novel, broad-spectrum transmission blocking strategies.

The 2009 novel H1N1 influenza A virus (H1N1) became a global pandemic. Data on antiviral prescriptions by location from 2008 to 2010 have not been reported. The purpose of this study was to assess antiviral geographic trends and correlation with influenza-like illness (ILI) over 3 years. Percent of outpatient ILI visits and antiviral prescriptions from 1 January 2008 to 31 December 2010 were included. Linear regression was used to assess correlation. In total, 14 million antivirals were dispensed during this period. A 115% increase was observed in 2009 compared with prescriptions dispensed in 2008, and an 84% decrease was observed in 2010 compared with 2009. The rate of antivirals was 1.32 prescriptions/100 persons in 2008, 2.85/100 persons in 2009 and 0.435/100 persons in 2010. 2009 regional growth was observed in most states and was highest in the West (293%) and the Northeast (272%). A positive correlation was observed between antivirals and ILI visits (R(2)=0.7853; P0.0001). With the 2009 H1N1 pandemic, antivirals increased compared with 2008 or 2010. Without the concern of H1N1, antivirals decreased in 2010 to levels lower than 2008. Geographic trends were also observed, which may be a result of the different intensity of influenza transmission and difference practice patterns. ILI diagnoses correlate with influenza antiviral prescription use in the USA.

Mutations in the leucine-rich repeat kinase II (LRRK2) gene cause autosomal-dominant Parkinson’s disease (PD) which is indistinguishable from sporadic forms of the disease. However, the mechanism by which LRRK2 mutation promotes PD pathology and the functions of the LRRK2 protein itself are currently unknown. Transgenic animal models, expressing PD-linked genes, have been crucial in developing a clearer picture of the mechanisms behind PD progression. Bacterial artificial chromosome (BAC) transgenics, in particular, allow for physiologically relevant disease models to be generated, encompassing entire gene sequences and using endogenous promoters, which result in an accurate recapitulation of spatiotemporal gene expression. We have, therefore, developed BAC transgenic rats expressing human LRRK2. These lines express either human wild-type, G2019S mutant (the most common LRRK2 mutation) or R1441C mutant (the LRRK2 mutation leading to a more aggressive pathology) LRRK2. These rats display LRRK2 transgene expression patterns in the brain which highly resemble human LRRK2 expression. We subsequently aged these lines for the purposes of behavioural and molecular analysis. Additionally, we have performed a number of in vitro studies in neurons cultured from these rats to further investigate the effects of pathological forms of LRRK2. Mutant LRRK2 transgenic rats displayed progressively impaired striatal dopaminergic release along with corresponding behavioural deficits, both motor and cognitive. These motor deficits could be rescued by treatment with levodopa, implying a similar underlying pathological process to PD. These phenotypes occurred in the absence of any overt degeneration of the dopaminergic neurons of the substantia nigra pars compacta or other PD-associated neuropathological markers. We also detected a number of molecular alterations associated with mutant LRRK2 expression including altered LRRK2 phosphorylation and in vitro evidence of altered autophagic processes. In conclusion, these rats recapitulate a number of the key features of Parkinson’s disease and provide clues as to the progression of pathology in PD.

2-Methylbenzoic acid phenylhydrazide was polylithiated with excess lithium diisopropylamide, and the resulting polylithiated intermediate was condensed with methyl 4-dimethylaminobenzoate or methyl 4-methoxybenzoate to afford C-acylated intermediates that were immediately acid cyclized to afford 3-(4-(dimethylamino)-phenyl)-2-(phenylamino)isoquinolin-1(2H)-one C23H21N3O or 3-(4-methoxyphenyl)-2-(phenylamino)isoquinolin-1(2H)-one C22H18N2O2. The polylithiated intermediate underwent N-acylation when it was condensed with methyl 4-methylbenzoate to give 2-methyl-N′-(4-methylbenzoyl)-N′-phenylbenzohydrazide C22H20N2O2. Crystals of C23H21N3O 4a are triclinic, P $$ \overline{1} $$ , a = 9.138(2) A, b = 10.519(2) A, c = 11.082(2) A, α = 91.55(3)°, β = 108.92(3)°, γ = 111.16(3)°, Z = 2, V = 927.1(3) A3, R 1 = 0.0711 and wR 2 = 0.1828 for reflections with I > 2σ(I); crystals of C22H18N2O2 4b are monoclinic, P21/c, a = 8.821(1) A, b = 13.276(2) A, c = 15.482(3) A, β = 105.271(4)°, Z = 4, V = 1748.9(5) A3, R 1 = 0.0416 and wR 2 = 0.1030 for reflections with I > 2σ(I); crystals of C22H20N2O2 3 are orthorhombic, Pbca, a = 13.505(3) A, b = 9.733(2) A, c = 28.601(6) A, Z = 8, V = 3759.4(13) A3, R 1 = 0.1683 and wR 2 = 0.3526 for reflections with I > 2σ(I). X-ray crystal analysis was important for the confirmation of the structure of 3-(4-(dimethylamino)phenyl)-2-(phenylamino)isoquinolin-1(2H)-one C23H21N3O 4a, 3-(4-methoxyphenyl)-2-(phenylamino)isoquinolin-1(2H)-one C22H18N2O2 4b, and 2-methyl-N′-(4-methylbenzoyl)-N′-phenylbenzohydrazide C22H20N2O2 3 prepared from polylithiated 2-methylbenzoicacid phenylhydrazide and methyl 4-dimethylaminobenzoate, methyl 4-methoxybenzoate, or methyl 4-methylbenzoate. Crystals of C23H21N3O 4a are triclinic, P $$ \overline{1} $$ , a = 9.138(2) A, b = 10.519(2) A, c = 11.082(2) A, α = 91.55(3)°, β = 108.92(3)°, γ = 111.16(3)°, Z = 2, V = 927.1(3) A3, R 1 = 0.0711 and wR 2 = 0.1828 for reflections with I > 2σ(I); crystals of C22H18N2O2 4b are monoclinic, P21/c, a = 8.821(1) A, b = 13.276(2) A, c = 15.482(3) A, β = 105.271(4)°, Z = 4, V = 1748.9(5) A3, R 1 = 0.0416 and wR 2 = 0.1030 for reflections with I > 2σ(I); crystals of C22H20N2O2 3 are orthorhombic, Pbca, a = 13.505(3) A, b = 9.733(2) A, c = 28.601(6) A, Z = 8, V = 3759.4(13) A3, R 1 = 0.1683 and wR 2 = 0.3526 for reflections with I > 2σ(I).

Mutations in leucine-rich repeat kinase 2 (LRRK2) lead to late-onset, autosomal dominant Parkinson's disease, characterized by the degeneration of dopamine neurons of the substantia nigra pars compacta, a deficit in dopamine neurotransmission and the development of motor and non-motor symptoms. The most prevalent Parkinson's disease LRRK2 mutations are located in the kinase (G2019S) and GTPase (R1441C) encoding domains of LRRK2. To better understand the sequence of events that lead to progressive neurophysiological deficits in vulnerable neurons and circuits in Parkinson's disease, we have generated LRRK2 bacterial artificial chromosome transgenic rats expressing either G2019S or R1441C mutant, or wild-type LRRK2, from the complete human LRRK2 genomic locus, including endogenous promoter and regulatory regions. Aged (18-21 months) G2019S and R1441C mutant transgenic rats exhibit L-DOPA-responsive motor dysfunction, impaired striatal dopamine release as determined by fast-scan cyclic voltammetry, and cognitive deficits. In addition, in vivo recordings of identified substantia nigra pars compacta dopamine neurons in R1441C LRRK2 transgenic rats reveal an age-dependent reduction in burst firing, which likely results in further reductions to striatal dopamine release. These alterations to dopamine circuit function occur in the absence of neurodegeneration or abnormal protein accumulation within the substantia nigra pars compacta, suggesting that nigrostriatal dopamine dysfunction precedes detectable protein aggregation and cell death in the development of Parkinson's disease. In conclusion, our longitudinal deep-phenotyping provides novel insights into how the genetic burden arising from human mutant LRRK2 manifests as early pathophysiological changes to dopamine circuit function and highlights a potential model for testing Parkinson's therapeutics.

The Purdue Technical Assistance Program (TAP) offers a model of university engagement and service that is achieving technology adoption and performance improvement impacts in health care, manufacturing, government, and other sectors. The TAP model focuses on understanding and meeting the changing and challenging needs of those served, always seeking to engage a mix of faculty, staff, students, and others that best meet these needs. Although the TAP mission is focused on the needs of those served, participating faculty and students have experienced significant benefits, and faculty rarely decline an opportunity to participate. This essay presents the evolution of Purdue University’s engagement and service missions, and their alignment with the current thinking of engagement scholars and practitioners. The operational model for TAP is described as an important part of Purdue’s engagement mission, along with the elements necessary for its success, examples of successful engagement, and future challenges and opportunities.