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Recent material advancements in organic plastic scintillators enable marked increases in material detection efficiency, light yield, and pulse shape discrimination properties. These advances may resolve significant capability gaps for low-cost, portable, and durable dual-particle imaging (DPI) systems for nuclear safety, security, and safeguard purposes. One such material, a 21% bismuth-loaded polyvinyl toluene (BiPVT), is computationally evaluated as a small, pixelated radiographic array using Monte Carlo N-Particle (MCNP) and Zemax OpticStudio, and it is compared to identical evaluations of EJ-200 and EJ-256 arrays. MCNP software enables estimates of particle interaction and energy deposition, while OpticStudio computes optical light transport within each material. Computational estimates of spatial resolution and relative light collection at 370 kVp are found to agree with experimental results for both EJ-200 and EJ-256 arrays, thereby validating predictions of the same for the BiPVT array. As such, for equivalent exposures at 370 kVp, a BiPVT array may provide $\sim 20\times $ the light collection expected from EJ-200 and $\sim 10\times $ that expected from EJ-256. Similar comparisons of estimated light collection are also computed at 150 and 270 kVp, and these results suggest that BiPVT will provide significantly improved performance over EJ-200 and EJ-256 across all energies practical for portable X-ray radiography.

A three-dimensional, prognostic Atmospheric Boundary Layer Environment–Lattice Boltzmann Model (ABLE-LBM) using the multiple-relaxation-time lattice Boltzmann method was developed for large-eddy simulation of urban boundary layer atmospheric flows. In this article we describe the details of the ABLE-LBM for urban flow, its implementation of complex boundaries, and the subgrid turbulence parameterizations. As a first validation of this newly developed model, the simulation results were evaluated with two wind-tunnel datasets that were collected using particle image velocimetry and Irwin probes, respectively. The ABLE-LBM simulations use the same building layout and Reynolds numbers used in the laboratory wind tunnels. The ABLE-LBM simulations compare favorably to both laboratory studies in terms of the mean wind fields. The turbulent fluxes simulated by the model in the observational planes also agreed reasonably well with the laboratory results. The model produced urban canyon flows and vortices on the lee side and over the building tops that are similar to those of the laboratory studies in strength and location. This validation study using laboratory data indicates that our new ABLE-LBM is a viable approach for modeling atmospheric turbulent flows in urban environments. A numerical implementation using a graphics processing unit shows that real-time simulations are achieved for these two validation cases.

Governments frequently use financial incentives to encourage the creation, expansion, or relocation of businesses within their borders. Previous research on financial incentives have given little clarity as to what impact these incentives may have on the government. While incentives may draw in more economic growth, they also pull resources from the government’s coffers and may commit future funding for public services that benefit the incentivized business. Using a panel of 32 states from 1990 to 2015, we seek to understand how incentives affect a state’s fiscal health. After controlling for the governmental, political, economic, and demographic characteristics of a state, we find that incentives draw resources away from the state. Ultimately, the results show that financial incentives negatively affect the overall fiscal health of a state.

Plastic scintillators utilizing iridium complex fluorophores offer substantial improvements in light yield, and their light yield is not significantly quenched in compositions with bismuth metalorganic loading, at a loading level of 21 wt% bismuth metal. This new bismuth plastic (Ir-Bi-Plastic) offers improved detection efficiency over commercial plastic scintillators. One application for Ir-Bi-Plastic is in low-cost, portable, and durable dual-particle imaging (DPI) systems supporting nuclear safety, security, and safeguards. However, new materials must undergo investigation using industry standards to quantify their capabilities. In this work, an Ir-Bi-Plastic was experimentally evaluated as a small, pixelated radiographic array in a fast neutron environment, with individual pixel dimensions of 2×2×19 mm. For comparison, identical evaluations were conducted for two similarly sized arrays made from EJ-200 and EJ-256. A separate Ir-Bi-Plastic array with 5×5×20 mm pixels was also evaluated. ASTM methods were leveraged to determine the modulation transfer function and spatial resolution for each array. Edge response measurements of a 2-in thick tungsten block were recorded by pressure coupling all four arrays to a commercial a-Si digital radiographic panel. Experimental results were then compared for all four arrays, and the results demonstrated that the Ir-Bi-Plastic outperforms similar arrays made from EJ-200 and EJ-256 (5 wt% Pb). These findings suggest that DPI systems utilizing Ir-Bi-Plastic hold promise for continued development over older, more traditional, alternatives.

Early-onset colorectal cancer has been on the rise in Western populations. Here, we compare patient characteristics between those with early- (&lt, 50 years) vs. late-onset (≥50 years) disease in a large multinational cohort of colorectal cancer patients (n = 2193). We calculated descriptive statistics and assessed associations of clinicodemographic factors with age of onset using mutually-adjusted logistic regression models. Patients were on average 60 years old, with BMI of 29 kg/m2, 52% colon cancers, 21% early-onset, and presented with stage II or III (60%) disease. Early-onset patients presented with more advanced disease (stages III–IV: 63% vs. 51%, respectively), and received more neo and adjuvant treatment compared to late-onset patients, after controlling for stage (odds ratio (OR) (95% confidence interval (CI)) = 2.30 (1.82–3.83) and 2.00 (1.43–2.81), respectively). Early-onset rectal cancer patients across all stages more commonly received neoadjuvant treatment, even when not indicated as the standard of care, e.g., during stage I disease. The odds of early-onset disease were higher among never smokers and lower among overweight patients (1.55 (1.21–1.98) and 0.56 (0.41–0.76), respectively). Patients with early-onset colorectal cancer were more likely to be diagnosed with advanced stage disease, to have received systemic treatments regardless of stage at diagnosis, and were less likely to be ever smokers or overweight.

We investigated if obesity/steatosis promotes mitochondrial remodeling in the liver of ob/ob mice (an obesity model). Liver mitochondria from ob/ob mice (21 weeks with significant steatosis) had ~ 2-fold increases in state III respiration compared with control (C57BL/6J, C57BL/6NJ) for all respiratory substrates examined (glutamate/malate, succinate, octanoate, and glycerol 3-phosphate). A corresponding 2-fold increase in the expression of respiratory complexes (I, IV, and V) and other respiratory proteins (glycerol phosphate dehydrogenase-2 and medium-chain acyl-coenzyme A dehydrogenase) occur in liver mitochondria of mature ob/ob mice. Conversely, respiration in liver mitochondria from young ob/ob mice (6 weeks) does not differ from control with any respiratory substrates examined. Overall, mitochondrial remodeling that enhances respiration increases with obesity/steatosis in the liver of ob/ob mice.

A prototype of a three-dimensional (3-D) radiation model is developed using the lattice Boltzmann method (LBM) and implemented on a graphical processing unit (GPU) to accelerate the model’s computational speed. This radiative transfer-lattice Boltzmann model (RT-LBM) results from a discretization of the radiative transfer equation in time, space, and solid angle. The collision and streaming computation algorithm, widely used in LBM for fluid flow modeling, is applied to speed up the RT-LBM computation on the GPU platform. The isotropic scattering is assumed in this study. The accuracy is evaluated using Monte Carlo method (MCM) simulations, showing RT-LBM is quite accurate when typical atmospheric coefficients of scattering and absorption are used. RT-LBM runs about 10 times faster than the MCM in a same CPU. When implemented on a NVidia Tesla V100 GPU in simulation with a large number of computation grid points, for example, RT-LBM runs ~120 times faster than running on a single CPU. The test results indicate RT-LBM is an accurate and fast model and is viable for simulating radiative transfer in the atmosphere with ranges for the isotropic atmosphere radiative parameters of albedo scattering (0.1~0.9) and optical depth (0.1~12).

Radiation protection factor (RPF) values are relevant to various US defense and civil support organizations. An equation was developed to quantify the angular-dependent protection of a shielding configuration in the presence of a mono-energetic radiation field. Values of ambient dose equivalent, H*(10), were computed with version 6.1 of the Monte Carlo N-Particle Code (MCNP6.1) for more than 70 distinct, mono-energetic, planar photon and neutron fields using both the kerma approximation and energy deposition from primary and secondary radiations. The two computational approaches were compared, and the MCNP6.1 models were then modified to simulate the same radiation fields and compute values of directional dose equivalent, H′(10,α), in a tissue sphere centered inside a surrogate vehicle for 13 angles of incidence. Values of H*(10) and H′(10,α) were recast as energy- and angular-dependent RPF values for the incident field–shielding geometries and tabulated. Examples of implementation are provided, and limitations are discussed.

The feeding of alcohol orally (Lieber-DeCarli diet) to rats has been shown to cause declines in mitochondrial respiration (state III), decreased expression of respiratory complexes, and decreased respiratory control ratios (RCR) in liver mitochondria. These declines and other mitochondrial alterations have led to the hypothesis that alcohol feeding causes "mitochondrial dysfunction" in the liver. If oral alcohol feeding leads to mitochondrial dysfunction, one would predict that increasing alcohol delivery by intragastric (IG) alcohol feeding to rats would cause greater declines in mitochondrial bioenergetics in the liver. In this study, we examined the mitochondrial alterations that occur in rats fed alcohol both orally and intragastrically. Oral alcohol feeding decreased glutamate/malate-, acetaldehyde- and succinate-driven state III respiration, RCR, and expression of respiratory complexes (I, III, IV, V) in liver mitochondria, in agreement with previous results. IG alcohol feeding, on the other hand, caused a slight increase in glutamate/malate-driven respiration, and significantly increased acetaldehyde-driven respiration in liver mitochondria. IG feeding also caused liver mitochondria to experience a decline in succinate-driven respiration, but these decreases were smaller than those observed with oral alcohol feeding. Surprisingly, oral and IG alcohol feeding to rats increased mitochondrial respiration using other substrates, including glycerol-3-phosphate (which delivers electrons from cytoplasmic NADH to mitochondria) and octanoate (a substrate for beta-oxidation). The enhancement of glycerol-3-phosphate- and octanoate-driven respiration suggests that liver mitochondria remodeled in response to alcohol feeding. In support of this notion, we observed that IG alcohol feeding also increased expression of mitochondrial glycerol phosphate dehydrogenase-2 (GPD2), transcription factor A (TFAM), and increased mitochondrial NAD+-NADH and NADP+-NADPH levels in the liver. Our findings suggest that mitochondrial dysfunction represents an incomplete picture of mitochondrial dynamics that occur in the liver following alcohol feeding. While alcohol feeding causes some mitochondrial dysfunction (i.e. succinate-driven respiration), our work suggests that the major consequence of alcohol feeding is mitochondrial remodeling in the liver as an adaptation. This mitochondrial remodeling may play an important role in the enhanced alcohol metabolism and other adaptations in the liver that develop with alcohol intake.

Most embedded components manufactured today are made either by photolithography to pattern inner board layer materials or by placing discrete components on an inner board layer followed by planarization with a potting compound. These traditional methods produce devices with poor tolerance due to inherent variances in the photolithography and etch process, and parasitic capacitance of long traces. Discrete embedded components increase thickness and weight and suffer from reduced reliability caused by the planarization process. This paper introduces an alternative patterning method to integrate in-line embedded passive and active components without photolithography processing. This additive printing process uses high precision, high feature density shadow masks with micrometer-level registration. Devices are built layer by layer using off-the-shelf bulk materials instead of inks to produce tight tolerance passive and active components that can be integrated into traditional PCB and wafer-level processing. Examples of such additively manufactured devices for both DC and RF applications and preliminary test data are presented in this paper.

PURPOSE: The ColoCare Study is an international cohort of men and women (>18 years age) newly diagnosed with stage I-IV colorectal cancer from seven centers in the United States and Germany. Study enrollment is currently ongoing. Here, we describe the clinical and demographic characteristics of this large cohort of prospectively followed colorectal cancer patients and describe differences in demographic, lifestyle, and clinical characteristics by age of onset and tumor site. METHODS: Data on demographics (sex, age, race, ethnicity) and lifestyle factors (smoking, body mass index) collected at baseline are included in this analysis, in addition to information on tumor characteristics (tumor stage and site), treatment (neoadjuvant and adjuvant therapy), and clinical outcomes (vital status, recurrence). Patients were categorized into early- ( RESULTS: Data on 1,933 stage I-IV colorectal cancer cases were included in this study, 19% of which were deceased at the time of this analysis. On average, patients were 60 years old, had a BMI of 29 kg/m2, and were predominantly diagnosed with stage II (25%) and stage III (33%) colorectal cancer. Fifty three percent of cases were diagnosed with colon cancer, while 47% were rectal cancer cases. Twenty percent (n=364) of patients were diagnosed before age 50 (i.e. early-onset cases). The early-onset group presented with a higher percentage of rectal cancer (52%) and more advanced disease (64% stage III-IV cancer) compared to late-onset cases (46% and 48%, respectively). Percentages of ever smokers were higher among late-onset compared to early-onset patients (51% vs. 38%), independent of tumor site. Early-onset cancers were more likely to originate in the rectum compared to colon, particularly among women (61% vs. 51%). Early-onset rectal cancer cases were more likely to be female as compared to late-onset rectal cancer cases (61% vs. 36%). Corresponding with national trends, early-onset cases received more aggressive adjuvant therapy after surgical resection compared to late-onset patients (54% vs. 40%). DISCUSSION: Within this large international multi-center cohort, patients with early-onset colorectal cancer were more likely to be diagnosed with rectal cancer and advanced stage disease. The majority of early-onset cases in the ColoCare Study were non-smokers. As expected, more aggressive treatment modalities were used in patients with early-onset disease. Citation Format: Caroline Himbert, Jane Figueiredo, Lyen Huang, Biljana Gigic, Courtney L. Scaife, Bartley Pickron, Laura Lambert, Jessica Cohan, Mary Bronner, Jolanta Jedrzkiewicz, Esther Herpel, Matthias Kloor, Johanna Nattenmueller, Hans-Ulrich Kauczor, Alexis Ulrich, Seth Felder, Julian Sanchez, Sophie Dessureault, Nathan Hinkle, Justin Monroe, Matthew Mutch, Cory Bernadt, Deyali Chatterjee, Mika Sinanan, Stacey Cohen, Ulrik Wallin, Deepti Reddi, Mukta Krane, Afshin E. Gabayan, David M. Hoffman, Yosef Y. Nasseri, Robert W. Decker, Karen Zaghiyan, Zuri A. Murrell, Andrew E. Hendifar, Jun Gong, Eiman Firoozmand, Alexandra Gangi, Beth A. Moore, Kyle G. Cologne, Maryliza El-Masry, William Grady, Martin Schneider, Stephanie L. Schmit, Erin Siegel, David Shibata, Adetunji Toriola, Christopher Li, Cornelia Ulrich, Sheetal Hardikar. Clinical characteristics and outcomes of colorectal cancer in the ColoCare Study: Differences by age of onset [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2364.

SUMMARYAlzheimer’s disease (AD) is a complex and heterogenous brain disease that affects multiple inter-related biological processes. This complexity contributes, in part, to existing difficulties in the identification of successful disease-modifying therapeutic strategies. To address this, systems approaches are being used to characterize AD-related disruption in molecular state. To evaluate the consistency across these molecular models, a consensus atlas of the human brain transcriptome was developed through coexpression meta-analysis across the AMP-AD consortium. Consensus analysis was performed across five coexpression methods used to analyze RNA-seq data collected from 2114 samples across 7 brain regions and 3 research studies. From this analysis, five consensus clusters were identified that described the major sources of AD-related alterations in transcriptional state that were consistent across studies, methods, and samples. AD genetic associations, previously studied AD-related biological processes, and AD targets under active investigation were enriched in only three of these five clusters. The remaining two clusters demonstrated strong heterogeneity between males and females in AD-related expression that was consistently observed across studies. AD transcriptional modules identified by systems analysis of individual AMP-AD teams were all represented in one of these five consensus clusters except ROS/MAP-identified Module 109, which was specific for genes that showed the strongest association with changes in AD-related gene expression across consensus clusters. The other two AMP-AD transcriptional analyses reported modules that were enriched in one of the two sex-specific Consensus Clusters. The fifth cluster has not been previously identified and was enriched for genes related to proteostasis. This study provides an atlas to map across biological inquiries of AD with the goal of supporting an expansion in AD target discovery efforts.

Computational and experimental estimates of radiation protection factor (RPF) values are of significant interest to various defense-related organizations. Values of the operational quantity of ambient dose equivalent were computed, using version 6.1 of the Monte Carlo N-Particle® code (MCNP6.1), for 25 photon energies and 53 neutrons energies. Energy-dependent values for absorbed dose at a 10-mm depth in the 30-cm-diameter ICRU tissue-equivalent sphere, D * ( 10 ) , were estimated using the kerma approximation for photon (MCNP F6:p tally) and neutron (MCNP F6:n tally) radiation fields, and then transformed to fluence-to-ambient dose equivalent conversion coefficients, H * ( 10 ) / ϕ , using appropriate quality factors, Q, and radiation fluences. MCNP6.1-computed values of H * ( 10 ) / ϕ were compared with tabulated values from ICRP Publication 74. The published conversion coefficients for photon radiation fields were within the error bounds of all MCNP6.1-calculated values. For neutron fields, the computed and published conversion coefficients agreed within calculated error bounds for neutron energies of 100 keV and above, while responses to neutron fields below 100 keV exhibited the same shape and were consistent with the kerma approximation applied in the computational model. The MCNP6.1 models were then modified to simulate the same radiation fields, but H * ( 10 ) / ϕ conversion coefficients were calculated in the shielded environment of a surrogate vehicle (steel cube)—in keeping with historical and recent studies—and the ratios of shielded and unshielded vehicle response functions were expressed as energy-dependent RPF values. The MCNP6.1-computed neutron RPF values were compared with two prior experimental studies involving a mono-energetic neutron source and a high-yield, short-duration fission neutron spectrum and found to agree within the uncertainty of the experimentally-measured values. Limitations of the computed RPF values are discussed.

Background ABT-126 is a novel, safe, and well-tolerated α7 nicotinic receptor agonist in a Phase 2 Alzheimer's disease study. We tested the antidyskinetic effect of ABT-126 in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine–treated squirrel monkeys with moderate and more severe nigrostriatal damage. Methods Monkeys (n = 21, set 1) were lesioned with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine 1-2×. When parkinsonian, they were gavaged with levodopa (10 mg/kg)/carbidopa (2.5 mg/kg) twice daily and dyskinesias rated. They were then given nicotine in drinking water (n = 5), or treated with vehicle (n = 6) or ABT-126 (n = 10) twice daily orally 30 min before levodopa. Set 1 was then re-lesioned 1 to 2 times for a total of 3 to 4 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine injections. The antidyskinetic effect of ABT-126, nicotine, and the β2* nicotinic receptor agonist ABT-894 was re-assessed. Another group of monkeys (n = 23, set 2) were lesioned with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine only 1× to 2×. They were treated with levodopa/carbidopa, administered the α7 agonist ABT-107 (n = 6), ABT-894 (n = 6), nicotine (n = 5), or vehicle (n = 6) and dyskinesias evaluated. All monkeys were euthanized and the dopamine transporter measured. Results With moderate nigrostriatal damage (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine 1×-2×), ABT-126 dose-dependently decreased dyskinesias (∼60%), with similar results seen with ABT-894 (∼60%) or nicotine (∼60%). With more severe damage (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine 3-4×), ABT-126 and nicotine reduced dyskinesias, but ABT-894 did not. The dopamine transporter was 41% and 8.9% of control, with moderate and severe nigrostriatal damage, respectively. No drug modified parkinsonism. Conclusion The novel α7 nicotinic receptor drug ABT-126 reduced dyskinesias in monkeys with both moderate and severe nigrostriatal damage. ABT-126 may be useful to reduce dyskinesias in both early- and later-stage Parkinson's disease. © 2015 International Parkinson and Movement Disorder Society

This clinical policy focuses on critical issues in the evaluation and management of patients with acute myocardial infarction or unstable angina. A MEDLINE search for articles published between January 1993 and December 1998 was performed using combinations of the key words chest pain, acute myocardial infarction, unstable angina, thrombolytics, primary angioplasty, 12-lead ECG, ST-segment monitoring, cardiac serum markers, and chest pain centers. Subcommittee members and expert peer reviewers also supplied articles with direct bearing on the policy. This policy focuses on 5 areas of current interest and/or controversy: (1) ECG eligibility criteria for fibrinolytic therapy, (2) role of primary angioplasty in patients with acute myocardial infarction, (3) use of serum markers to diagnose acute myocardial infarction, (4) serial 12-lead ECGs during the initial evaluation, and (5) chest pain evaluation units. Recommendations for patient management are provided for each of these 5 topics based on strength of evidence (Standards, Guidelines, Options). Standards represent patient management principles that reflect a high degree of clinical certainty; Guidelines represent patient management principles that reflect moderate clinical certainty; and Options represent other patient management strategies based on preliminary, inconclusive, or conflicting evidence, or based on panel consensus. This guideline is intended for physicians working in hospital-based emergency departments or chest pain evaluation units. [American College of Emergency Physicians. Clinical policy: critical issues in the evaluation and management of adult patients presenting with suspected acute myocardial infarction or unstable angina. Ann Emerg Med. May 2000;35:521-544.].

Background Anaphylaxis is a potentially life-threatening allergic reaction that may require emergency medical system (EMS) transport. Fatal anaphylaxis is associated with delayed epinephrine administration. Patient outcome data to assess appropriateness of EMS epinephrine administration are sparse. Objectives The objectives of this study are to (1) determine the frequency of epinephrine administration in EMS-transported patients with allergic complaints, (2) identify predictors of epinephrine administration, and (3) determine frequency of emergency department (ED) epinephrine administration after EMS transport. Methods A cohort study was conducted from over 5 years. A total of 59187 EMS transports of an Advanced Life Support (ALS) ambulance service were studied. Results One hundred and three patient transports for allergic complaints were analyzed. Fifteen patients received EMS epinephrine, and epinephrine was recommended for 2 additional patients who refused, for a total of 17 (17%) patients for whom epinephrine was administered or recommended. Emergency medical system epinephrine administration or recommendation was associated with venom as a trigger (29% vs 8%; odds ratio [OR], 4.70; 95% confidence interval [CI], 1.28-17.22; P = .013), respiratory symptoms (88% vs 52%; OR, 6.83; 95% CI, 1.47-31.71; P = .006), and fulfillment of anaphylaxis diagnostic criteria (82% vs 49%; OR, 3.50; 95% CI, 0.94-13.2; P = .0498). Four (4%) patients received epinephrine after ED arrival. Conclusion Low rates of epinephrine administration were observed. The association of EMS administration of epinephrine with respiratory symptoms, fulfillment of anaphylaxis diagnostic criteria, and low rate of additional epinephrine administration in the ED suggest that ALS EMS administered epinephrine based on symptom severity. Additional studies of EMS anaphylaxis management including ED management and outcomes are needed.

L-dopa is the gold standard treatment for Parkinson’s disease motor symptoms 1, 2. However, although L-dopa improves the tremor, rigidity and bradykinesia, particularly in the early stages, there is a loss of efficacy with disease progression. Moreover, side effects arise including abnormal involuntary movements or dyskinesias that limit its usefulness 3, 4. New treatment strategies to reduce L-dopa-induced dyskinesias (LIDs) are therefore a key research focus. Extensive studies show that drugs targeting the serotonergic, glutamatergic adrenergic, noradrenergic, cannabinoid and histaminergic systems attenuate LIDs to varying extents in animal models of Parkinson’s disease 4-9. Furthermore, L-dopa treatment modulates expression of numerous molecular and cellular markers linked to these neurotransmitters. Thus drugs targeting these CNS systems have potential as antidyskinetic agents. However, useful clinical candidates have proved elusive because they cause parkinsonism or lead to other adverse side effects 4. Recent pre-clinical studies show that drugs directed to the nicotinic cholinergic system improve LIDs in parkinsonian mice, rats and monkeys 10-14. Nicotine reduced LIDs using several methods of administration including oral application, injection and slow-release minipump with no decline in its effectiveness with time 10-14. Nicotine acts at nAChRs, of which there are multiple subtypes. This includes receptors in both the peripheral and central nervous system, such as α1β1*, α3β4*, α4β2*, α6β2* and α7 as well as other minor receptor subtypes 15, 16. The asterisk denotes the possible presence of other nAChR subunits in the receptor. Notably, the α4β2* and α6β2* nAChR subtypes are expressed only in the brain 15, 17. These subtypes are of relevance to LIDs, as studies in α4, α6, and β2 nAChR null mutant mice show that they regulate LIDs 14. Thus, drugs targeting α4β2* and α6β2* nAChRs may yield a selective therapy to reduce LIDs. Studies have been done to evaluate whether such drugs reduce LIDs in parkinsonian animals. The general nAChR agonist varenicline, as well as several β2* selective agonists including A-85380, sazetidine, TC-2696, TI-10165, TC-8831 and TC-10600 reduced LIDs to varying extents in rats with a unilateral 6-hydroxydopamine lesion 18, 19. Additionally, varenicline and TC-8831 decreased LIDs ~50% in nonhuman primates with no development of tolerance 20, 21. These combined results suggest that nAChR drugs may be useful for the management of LIDs, although a limitation of the drugs tested to date in nonhuman primates was the development of emesis 22. The objective of the present experiments was to investigate the potential of two β2* selective nAChR agonists that had previously been evaluated in phase 2 clinical trials for other indications with minimal side effects. This included ABT-089, a partial nAChR agonist 23-27, as well as the full agonist ABT-894 28-30. The results show that ABT-089 and ABT-894 reduced LIDs in nonhuman primates with no adverse responses, suggesting they may be a useful treatment for LIDs in Parkinson’s disease.