Publications by authors named "Andrew Maynard"

67 Publications

The Ethical and Responsible Development and Application of Advanced Brain Machine Interfaces.

J Med Internet Res 2019 10 31;21(10):e16321. Epub 2019 Oct 31.

School for the Future of Innovation in Society, Arizona State University, Tempe, AZ, United States.

Advanced brain machine interfaces provide potentially transformative approaches to treating neurological conditions and enhancing the performance of users. Yet, as technological capabilities continue to progress in leaps and bounds, there is a possibility that these capabilities outstrip our collective understanding of how to ensure brain machine interfaces are developed and used ethically and responsibly. In this case, there is an overt danger of rapid technological developments leading to unanticipated harm through a lack of foresight including threats to privacy, autonomy, self-identity, and other areas of personal and social value which, while hard to quantify, represent substantial risks. There is also a very real likelihood of such risks undermining value creation around the technologies and the associated enterprises, as key stakeholders push back against perceived and actual threats to what they, in turn, hold to be of value. In order to successfully traverse the resulting risk landscape, researchers and developers will need to become increasingly adept at integrating a sophisticated understanding of ethical and socially responsible innovation into their enterprises. Here, we illustrate how a "risk innovation" approach may provide novel insights into mapping out this landscape and revealing potentially blindsiding risks. We show how this approach can be used to illuminate challenges and opportunities to the successful, ethical, and responsible development of advanced brain machine interfaces. In addition, we emphasize how success will ultimately depend on the willingness of innovators and others to take ethical and responsible innovation seriously and to draw on the interdisciplinary and transdisciplinary expertise that is necessary to translate good intentions into positive outcomes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2196/16321DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7351257PMC
October 2019

Are assumptions of consumer views impeding nano-based water treatment technologies?

Nat Nanotechnol 2018 08;13(8):673-674

Fulton Schools of Engineering, Arizona State University, Tempe, AZ, USA.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41565-018-0230-zDOI Listing
August 2018

Small molecule inhibition of RAS/MAPK signaling ameliorates developmental pathologies of Kabuki Syndrome.

Sci Rep 2018 Jul 17;8(1):10779. Epub 2018 Jul 17.

Center for Human Disease Modeling, Duke University School of Medicine, Durham, NC, 27701, USA.

Kabuki Syndrome (KS) is a rare disorder characterized by distinctive facial features, short stature, skeletal abnormalities, and neurodevelopmental deficits. Previously, we showed that loss of function of RAP1A, a RAF1 regulator, can activate the RAS/MAPK pathway and cause KS, an observation recapitulated in other genetic models of the disorder. These data suggested that suppression of this signaling cascade might be of therapeutic benefit for some features of KS. To pursue this possibility, we performed a focused small molecule screen of a series of RAS/MAPK pathway inhibitors, where we tested their ability to rescue disease-relevant phenotypes in a zebrafish model of the most common KS locus, kmt2d. Consistent with a pathway-driven screening paradigm, two of 27 compounds showed reproducible rescue of early developmental pathologies. Further analyses showed that one compound, desmethyl-Dabrafenib (dmDf), induced no overt pathologies in zebrafish embryos but could rescue MEK hyperactivation in vivo and, concomitantly, structural KS-relevant phenotypes in all KS zebrafish models (kmt2d, kmd6a and rap1). Mass spectrometry quantitation suggested that a 100 nM dose resulted in sub-nanomolar exposure of this inhibitor and was sufficient to rescue both mandibular and neurodevelopmental defects. Crucially, germline kmt2d mutants recapitulated the gastrulation movement defects, micrognathia and neurogenesis phenotypes of transient models; treatment with dmDf ameliorated all of them significantly. Taken together, our data reinforce a causal link between MEK hyperactivation and KS and suggest that chemical suppression of BRAF might be of potential clinical utility for some features of this disorder.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-018-28709-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6050262PMC
July 2018

Thinking Differently about Risk.

Authors:
Andrew D Maynard

Astrobiology 2018 02 30;18(2):244-245. Epub 2018 Jan 30.

Arizona State University School for the Future of Innovation in Society; Director of the ASU Risk Innovation Lab, Tempe, Arizona.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1089/ast.2017.1774DOI Listing
February 2018

Mitigating Risks to Pregnant Teens from Zika Virus.

J Law Med Ethics 2016 12;44(4):657-659

Andrew D. Maynard, Ph.D., is Director, Risk Innovation Lab; Chair, Master of Science and Technology Policy and Professor, School for the Future of Innovation in Society, Arizona State University (ASU). Diana M. Bowman, L.L.B, Ph.D., is Associate Professor, Sandra Day O'Connor College of Law and School for the Future of Innovation in Society, ASU. James G. Hodge, Jr., J.D., LL.M., is Professor of Public Health Law and Ethics and Director, Public Health Law and Policy Program, Sandra Day O'Connor College of Law, ASU.

Zika infection in pregnant women is associated with an elevated probability of giving birth to a child with microcephaly and multiple other disabilities. Public health messaging on Zika prevention has predominantly targeted women who know they are pregnant or intend to become pregnant, but not teenage females for whom unintended pregnancy is more likely. Vulnerabilities among this population to reproductive risks associated with Zika are further amplified by restrictive abortion laws in several Zika-impacted states. Key to prevention is enhanced, targeted public health messaging centered on teens nationally and particularly in certain high-risk regions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/1073110516684814DOI Listing
December 2016

Angioedema: Perioperative management.

SAGE Open Med Case Rep 2017 8;5:2050313X17713912. Epub 2017 Jun 8.

Department of Anesthesiology and Critical Care Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.

Objective: To describe the perioperative management of a patient with acquired angioedema (AAE).

Methods: A 66-year-old Caucasian male presented from an outside hospital with a history of acquired angioedema and gastrointestinal stromal tumor-related intractable urticaria and mastocytosis. He was admitted for urgent laparoscopic partial gastrectomy, secondary to gastric outlet obstruction symptomatology. Previous combined attacks were characterized by a widespread rash, abdominal pain and respiratory distress resulting in hospitalization. Following preoperative consultation with the patient's allergist and a hospital pharmacist, he was treated preoperatively with fresh frozen plasma and his home prednisone dose. C1-inhibitor (Berinert®) was on standby along with epinephrine, given that the underlying etiology (C1- inhibitor deficiency vs histaminergic) was not known.

Results: There were no intraoperative complications, and the patient was discharged home 3 days after the procedure.

Conclusions: Optimization of perioperative outcomes in patients, especially during urgent or emergent surgery, with a history of angioedema requires the development of a patient-specific perioperative plan, including prophylaxis, rescue therapies and opioid-sparing strategies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/2050313X17713912DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5467965PMC
June 2017

Tiger on the prowl: Invasion history and spatio-temporal genetic structure of the Asian tiger mosquito Aedes albopictus (Skuse 1894) in the Indo-Pacific.

PLoS Negl Trop Dis 2017 04 14;11(4):e0005546. Epub 2017 Apr 14.

University of Queensland, Brisbane, Australia.

Background: Within the last century, increases in human movement and globalization of trade have facilitated the establishment of several highly invasive mosquito species in new geographic locations with concurrent major environmental, economic and health consequences. The Asian tiger mosquito, Aedes albopictus, is an extremely invasive and aggressive daytime-biting mosquito that is a major public health threat throughout its expanding range.

Methodology/principal Findings: We used 13 nuclear microsatellite loci (on 911 individuals) and mitochondrial COI sequences to gain a better understanding of the historical and contemporary movements of Ae. albopictus in the Indo-Pacific region and to characterize its population structure. Approximate Bayesian computation (ABC) was employed to test competing historical routes of invasion of Ae. albopictus within the Southeast (SE) Asian/Australasian region. Our ABC results show that Ae. albopictus was most likely introduced to New Guinea via mainland Southeast Asia, before colonizing the Solomon Islands via either Papua New Guinea or SE Asia. The analysis also supported that the recent incursion into northern Australia's Torres Strait Islands was seeded chiefly from Indonesia. For the first time documented in this invasive species, we provide evidence of a recently colonized population (the Torres Strait Islands) that has undergone rapid temporal changes in its genetic makeup, which could be the result of genetic drift or represent a secondary invasion from an unknown source.

Conclusions/significance: There appears to be high spatial genetic structure and high gene flow between some geographically distant populations. The species' genetic structure in the region tends to favour a dispersal pattern driven mostly by human movements. Importantly, this study provides a more widespread sampling distribution of the species' native range, revealing more spatial population structure than previously shown. Additionally, we present the most probable invasion history of this species in the Australasian region using ABC analysis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1371/journal.pntd.0005546DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5406021PMC
April 2017

Protein Corona-Induced Modification of Silver Nanoparticle Aggregation in Simulated Gastric Fluid.

Environ Sci Nano 2016 Dec 9;3(6):1510-1520. Epub 2016 Nov 9.

Department of Environmental Health Sciences, University of Michigan, Ann Arbor, MI.

Due to their widespread incorporation into a range of biomedical and consumer products, the ingestion of silver nanoparticles (AgNPs) is of considerable concern to human health. However, the extent to which AgNPs will be modified within the gastric compartment of the gastrointestinal tract is still poorly understood. Studies have yet to fully evaluate the extent of physicochemical changes to AgNPs in the presence of biological macromolecules, such as pepsin, the most abundant protein in the stomach, or the influence of AgNPs on protein structure and activity. Herein, AgNPs of two different sizes and surface coatings (20 and 110 nm, citrate or polyvinylpyrrolidone) were added to simulated gastric fluid (SGF) with or without porcine pepsin at three pHs (2.0, 3.5, and 5.0), representing a range of values between preprandial (fasted) and postprandial (fed) conditions. Rapid increases in diameter were observed for all AgNPs, with a greater increase in diameter in the presence of pepsin, indicating that pepsin facilitated AgNPs aggregation. AgNPs interaction with pepsin only minimally reduced the protein's proteolytic functioning capability, with the greatest inhibitory effect caused by smaller (20 nm) particles of both coatings. No changes in pepsin secondary structural elements were observed for the different AgNPs, even at high particle concentrations. This research highlights the size-dependent kinetics of nanoparticle aggregation or dissolution from interaction with biological elements such as proteins in the gastrointestinal tract. Further, these results demonstrate that, in addition to mass, knowing the chemical form and aggregation state of nanoparticles is critical when evaluating toxicological effects from nanoparticle exposure in the body.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/C6EN00278ADOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5366255PMC
December 2016

Family Functioning Predicts Body Mass Index and Biochemical Levels of Youths with Nonalcoholic Fatty Liver Disease.

J Dev Behav Pediatr 2017 Feb/Mar;38(2):155-160

*Department of Psychiatry and Behavioral Sciences and Department of Preventive Medicine, Center for Prevention Implementation Methodology, Feinberg School of Medicine, Northwestern University, Chicago, IL; †Department of Psychiatry, Boston Children's Hospital, Harvard Medical School, Boston, MA; ‡Department of Anesthesiology, Vanderbilt University School of Medicine, Nashville, TN; §Department of Gastroenterology, Baylor College of Medicine, Houston, TX.

: Family functioning is associated with obesity-related chronic illnesses and impedes effective treatment of weight-related conditions, such as nonalcoholic fatty liver disease (NAFLD).

Objectives: Evaluate the utility of a brief screening measure of family functioning among youth aged 8 to 18 years being treated in a specialty care clinic for NAFLD.

Methods: Thirty-nine youths and their caregivers participated. Relations between family functioning and anthropometric and biochemical variables assessed 3 to 6 months later were evaluated using regression analyses, controlling for child age, gender, and ethnicity.

Results: Family functioning was related to significantly higher body mass index (BMI) and levels of cholesterol, HbA1c, and glucose, but not serum alanine aminotransferase (ALT)-a marker of NAFLD-controlling for baseline levels. The magnitudes of effects were medium for models of BMI (Cohen's f = 0.29), cholesterol (0.32), and blood glucose (0.30) and small to medium for HbA1c (0.23) and ALT (0.10).

Conclusion: This is the first study to examine the role of family functioning in youth with NALFD. Treatment programs might consider screening for family functioning to identify families that could benefit from a family-centered behavioral intervention.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/DBP.0000000000000379DOI Listing
December 2017

'Safe handling of nanotechnology' ten years on.

Nat Nanotechnol 2016 Dec;11(12):998-1000

SAFENANO at the Institute of Occupational Medicine (IOM), Riccarton, Edinburgh, EH14 4AP, UK.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/nnano.2016.270DOI Listing
December 2016

Is nanotech failing casual learners?

Authors:
Andrew D Maynard

Nat Nanotechnol 2016 09;11(9):734-5

Risk Innovation Lab at Arizona State University, PO Box 875603, ASU, Tempe, Arizona 85387-5603, USA.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/nnano.2016.167DOI Listing
September 2016

Are we ready for spray-on carbon nanotubes?

Authors:
Andrew D Maynard

Nat Nanotechnol 2016 06;11(6):490-491

Risk Innovation Lab at Arizona State University, PO Box 875603, ASU, Tempe, Arizona 85387-5603, USA.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/nnano.2016.99DOI Listing
June 2016

Exposure to Power-Frequency Magnetic Fields and the Risk of Infertility and Adverse Pregnancy Outcomes: Update on the Human Evidence and Recommendations for Future Study Designs.

J Toxicol Environ Health B Crit Rev 2016 ;19(1):29-45

a Department of Environmental Health Sciences , University of Michigan School of Public Health , Ann Arbor , Michigan , USA.

Infertility and adverse pregnancy outcomes are significant public health concerns with global prevalence. Over the past 35 years, research has addressed whether exposure to power-frequency magnetic fields is one of the etiologic factors attributed to these conditions. However, no apparent authoritative reviews on this topic have been published in the peer-reviewed literature for nearly 15 years. This review provides an overview and critical analysis of human studies that were published in the peer-reviewed literature between 2002 and July 2015. Using PubMed, 13 epidemiology studies published during this time frame that concern exposure to magnetic fields and adverse prenatal (e.g., miscarriage), neonatal (e.g., preterm birth or birth defects), and male fertility (e.g., poor semen quality) outcomes were identified. Some of these studies reported associations whereas others did not, and study design limitations may explain these inconsistencies. Future investigations need to be designed with these limitations in mind to address existing research gaps. In particular, the following issues are discussed: (1) importance of selecting the appropriate study population, (2) need for addressing confounding due to unmeasured physical activity, (3) importance of minimizing information bias from exposure measurement error, (4) consideration of alternative magnetic field exposure metrics, and (5) implications and applications of personal exposure data that are correlated within female-male couples. Further epidemiologic research is needed, given the near ubiquitous exposures to power-frequency magnetic fields in the general population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/10937404.2015.1134370DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4848457PMC
August 2016

Navigating the risk landscape.

Authors:
Andrew D Maynard

Nat Nanotechnol 2016 Mar;11(3):211-2

Risk Innovation Lab at Arizona State University, PO Box 875603, ASU, Tempe, Arizona 85387-5603, USA.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/nnano.2016.28DOI Listing
March 2016

PERSONAL MEASURES OF POWER-FREQUENCY MAGNETIC FIELD EXPOSURE AMONG MEN FROM AN INFERTILITY CLINIC: DISTRIBUTION, TEMPORAL VARIABILITY AND CORRELATION WITH THEIR FEMALE PARTNERS' EXPOSURE.

Radiat Prot Dosimetry 2016 Dec 24;172(4):401-408. Epub 2015 Dec 24.

Department of Environmental Health Sciences, University of Michigan School of Public Health, 1415 Washington Heights, Ann Arbor, MI 48109, USA

Power-frequency magnetic field exposure science as it relates to men and couples have not been explored despite the advantage of this information in the design and interpretation of reproductive health epidemiology studies. This analysis examined the distribution and temporal variability of exposures in men, and the correlation of exposures within couples using data from a longitudinal study of 25 men and their female partners recruited from an infertility clinic. The average and 90th percentile demonstrated fair to good reproducibility, whereas the maximum showed poor reproducibility over repeated sampling days, each separated by a median of 4.6 weeks. Average magnetic field exposures were also strongly correlated within couples, suggesting that one partner's data could be used as a surrogate in the absence of data from the other for this metric. Environment was also an important effect modifier in these explored matters. These issues should be considered in future relevant epidemiology studies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/rpd/ncv515DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5204365PMC
December 2016

Navigating the fourth industrial revolution.

Authors:
Andrew D Maynard

Nat Nanotechnol 2015 Dec;10(12):1005-6

Risk Innovation Lab at Arizona State University, PO Box 875603, ASU, Tempe, Arizona 85387-5603, USA.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/nnano.2015.286DOI Listing
December 2015

Repeated dose (28-day) administration of silver nanoparticles of varied size and coating does not significantly alter the indigenous murine gut microbiome.

Nanotoxicology 2016 2;10(5):513-20. Epub 2015 Nov 2.

a Unit for Laboratory Animal Medicine, University of Michigan , Ann Arbor , MI , USA .

Silver nanoparticles (AgNPs) have been used as antimicrobials in a number of applications, including topical wound dressings and coatings for consumer products and biomedical devices. Ingestion is a relevant route of exposure for AgNPs, whether occurring unintentionally via Ag dissolution from consumer products, or intentionally from dietary supplements. AgNP have also been proposed as substitutes for antibiotics in animal feeds. While oral antibiotics are known to have significant effects on gut bacteria, the antimicrobial effects of ingested AgNPs on the indigenous microbiome or on gut pathogens are unknown. In addition, AgNP size and coating have been postulated as significantly influential towards their biochemical properties and the influence of these properties on antimicrobial efficacy is unknown. We evaluated murine gut microbial communities using culture-independent sequencing of 16S rRNA gene fragments following 28 days of repeated oral dosing of well-characterized AgNPs of two different sizes (20 and 110 nm) and coatings (PVP and Citrate). Irrespective of size or coating, oral administration of AgNPs at 10 mg/kg body weight/day did not alter the membership, structure or diversity of the murine gut microbiome. Thus, in contrast to effects of broad-spectrum antibiotics, repeat dosing of AgNP, at doses equivalent to 2000 times the oral reference dose and 100-400 times the effective in vitro anti-microbial concentration, does not affect the indigenous murine gut microbiome.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3109/17435390.2015.1078854DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5023147PMC
November 2016

Why we need risk innovation.

Authors:
Andrew D Maynard

Nat Nanotechnol 2015 Sep;10(9):730-1

Risk Innovation Lab at Arizona State University, PO Box 875603, ASU, Tempe, Arizona 85387-5603, USA.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/nnano.2015.196DOI Listing
September 2015

Rapid Kinetics of Size and pH-Dependent Dissolution and Aggregation of Silver Nanoparticles in Simulated Gastric Fluid.

J Phys Chem C Nanomater Interfaces 2015 Sep 28;119(35):20632-20641. Epub 2015 Jul 28.

Department of Environmental Health Sciences, School of Public Health, University of Michigan, Ann Arbor, Michigan 48109, United States; Department of Chemistry, University of Michigan, Ann Arbor, Michigan 48109, United States.

As silver nanoparticles (AgNPs) are used in a wide array of commercial products and can enter the human body through oral exposure, it is important to understand the fundamental physical and chemical processes leading to changes in nanoparticle size under the conditions of the gastrointestinal (GI) tract. Rapid AgNP growth was observed using nanoparticle tracking analysis with 30 s resolution over a period of 17 min in simulated gastric fluid (SGF) to explore rapid kinetics as a function of pH (SGF at pH 2, 3.5, 4.5 and 5), size (20 and 110 nm AgNPs), and nanoparticle coating (citrate and PVP). Growth was observed for 20 nm AgNP at each pH, decreasing in rate with increasing pH, with the kinetics shifting from second-order to first-order. The 110 nm AgNP showed growth at ≤3.5 pH, with no growth observed at higher pH. This behavior can be explained by the generation of Ag in acidic environments, which precipitates with Cl, leading to particle growth and facilitating particle aggregation by decreasing their electrostatic repulsion in solution. These results highlight the need to further understand the importance of initial size, physicochemical properties, and kinetics of AgNPs after ingestion to assess potential toxicity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.jpcc.5b03634DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5376073PMC
September 2015

Effects of particle size and coating on toxicologic parameters, fecal elimination kinetics and tissue distribution of acutely ingested silver nanoparticles in a mouse model.

Nanotoxicology 2016 24;10(3):352-60. Epub 2015 Aug 24.

b Toxicology Program, Department of Environmental Health Sciences, University of Michigan , Ann Arbor , MI , USA .

Consumer exposure to silver nanoparticles (AgNP) via ingestion can occur due to incorporation of AgNP into products such as food containers and dietary supplements. AgNP variations in size and coating may affect toxicity, elimination kinetics or tissue distribution. Here, we directly compared acute administration of AgNP of two differing coatings and sizes to mice, using doses of 0.1, 1 and 10 mg/kg body weight/day administered by oral gavage for 3 days. The maximal dose is equivalent to 2000× the EPA oral reference dose. Silver acetate at the same doses was used as ionic silver control. We found no toxicity and no significant tissue accumulation. Additionally, no toxicity was seen when AgNP were dosed concurrently with a broad-spectrum antibiotic. Between 70.5% and 98.6% of the administered silver dose was recovered in feces and particle size and coating differences did not significantly influence fecal silver. Peak fecal silver was detected between 6- and 9-h post-administration and <0.5% of the administered dose was cumulatively detected in liver, spleen, intestines or urine at 48 h. Although particle size and coating did not affect tissue accumulation, silver was detected in liver, spleen and kidney of mice administered ionic silver at marginally higher levels than those administered AgNP, suggesting that silver ion may be more bioavailable. Our results suggest that, irrespective of particle size and coating, acute oral exposure to AgNP at doses relevant to potential human exposure is associated with predominantly fecal elimination and is not associated with accumulation in tissue or toxicity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3109/17435390.2015.1072588DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4767695PMC
December 2016

Quantifying, Visualizing, and Monitoring Lead Optimization.

J Med Chem 2016 05 21;59(9):4189-201. Epub 2015 Aug 21.

GlaxoSmithKline, 5 Moore Drive, Research Triangle Park, North Carolina 27709-3398, United States.

Although lead optimization (LO) is by definition a process, process-centric analysis and visualization of this important phase of pharmaceutical R&D has been lacking. Here we describe a simple statistical framework to quantify and visualize the progression of LO projects so that the vital signs of LO convergence can be monitored. We refer to the resulting visualizations generated by our methodology as the "LO telemetry" of a project. These visualizations can be automated to provide objective, holistic, and instantaneous analysis and communication of LO progression. This enhances the ability of project teams to more effectively drive LO process, while enabling management to better coordinate and prioritize LO projects. We present the telemetry of five LO projects comprising different biological targets and different project outcomes, including clinical compound selection, termination due to preclinical safety/tox, and termination due to lack of tractability. We demonstrate that LO progression is accurately captured by the telemetry. We also present metrics to quantify LO efficiency and tractability.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.jmedchem.5b00948DOI Listing
May 2016

Learning from the past.

Authors:
Andrew D Maynard

Nat Nanotechnol 2015 Jun;10(6):482-3

Risk Science Center, University of Michigan School of Public Health, 1415 Washington Heights, Ann Arbor, Michigan 48109, USA.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/nnano.2015.120DOI Listing
June 2015

The (nano) entrepreneur's dilemma.

Authors:
Andrew D Maynard

Nat Nanotechnol 2015 Mar;10(3):199-200

Risk Science Center, University of Michigan School of Public Health, 1415 Washington Heights, Ann Arbor, Michigan 48109, USA.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/nnano.2015.35DOI Listing
March 2015

Could we 3D print an artificial mind?

Authors:
Andrew D Maynard

Nat Nanotechnol 2014 Dec;9(12):955-6

Risk Science Center, University of Michigan School of Public Health, 1415 Washington Heights, Ann Arbor, Michigan 48109, USA.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/nnano.2014.294DOI Listing
December 2014

Old materials, new challenges?

Authors:
Andrew D Maynard

Nat Nanotechnol 2014 Sep;9(9):658-9

Risk Science Center, University of Michigan School of Public Health, 1415 Washington Heights, Ann Arbor, Michigan 48109, USA.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/nnano.2014.196DOI Listing
September 2014

Is novelty overrated?

Authors:
Andrew D Maynard

Nat Nanotechnol 2014 Jun;9(6):409-10

Risk Science Center, University of Michigan School of Public Health, 1415 Washington Heights, Ann Arbor, Michigan 48109, USA.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/nnano.2014.116DOI Listing
June 2014

Design and synthesis of spirocyclic compounds as HCV replication inhibitors by targeting viral NS4B protein.

Bioorg Med Chem Lett 2014 May 3;24(10):2288-94. Epub 2014 Apr 3.

GlaxoSmithKline, Antiviral Discovery Performance Unit, 5 Moore Drive, Research Triangle Park, NC 27709, USA.

Two novel series of spirocyclic piperidine analogs appended to a pyrazolo[1,5-a]pyridine core were designed, synthesized and evaluated for their anti-HCV activity. A series of piperidine ketals afforded dispiro 6p which showed excellent in vitro anti-HCV activities (EC50 of 1.5nM and 1.2nM against genotype 1a and 1b replicons, respectively). A series of piperidine oxazolidinones afforded 27c which showed EC50's of 10.9nM and 6.1nM against 1a and 1b replicons, respectively. Both compounds 6p and 27c bound directly to non-structural NS4B protein in vitro (IC50's=10.2 and 30.4nM, respectively) and exhibited reduced potency in replicons containing resistance mutations encoding changes in the NS4B protein.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bmcl.2014.03.080DOI Listing
May 2014

A decade of uncertainty.

Authors:
Andrew D Maynard

Nat Nanotechnol 2014 Mar;9(3):159-60

Risk Science Center, University of Michigan School of Public Health, 1415 Washington Heights, Ann Arbor, Michigan 48109, USA.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/nnano.2014.43DOI Listing
March 2014

Novel spiroketal pyrrolidine GSK2336805 potently inhibits key hepatitis C virus genotype 1b mutants: from lead to clinical compound.

J Med Chem 2014 Mar 26;57(5):2058-73. Epub 2014 Feb 26.

GlaxoSmithKline , 5 Moore Drive, Research Triangle Park, North Carolina 27709-3398, United States.

Rapid clinical progress of hepatitis C virus (HCV) replication inhibitors, including these selecting for resistance in the NS5A region (NS5A inhibitors), promises to revolutionize HCV treatment. Herein, we describe our explorations of diverse spiropyrrolidine motifs in novel NS5A inhibitors and a proposed interaction model. We discovered that the 1,4-dioxa-7-azaspiro[4.4]nonane motif in inhibitor 41H (GSK2236805) supported high potency against genotypes 1a and 1b as well as in genotype 1b L31V and Y93H mutants. Consistent with this, 41H potently suppressed HCV RNA in the 20-day RNA reduction assay. Pharmacokinetic and safety data supported further progression of 41H to the clinic.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/jm4013104DOI Listing
March 2014

The psychology of 'regrettable substitutions': Examining consumer judgements of Bisphenol A and its alternatives.

Health Risk Soc 2014 7;16(7-8):649-666. Epub 2014 Nov 7.

Risk Science Center, School of Public Health, University of Michigan, Columbia, USA.

Bisphenol A is a chemical used to make certain types of plastics and is found in numerous consumer products. Because scientific studies have raised concerns about Bisphenol A's potential impact on human health, it has been removed from some (but not all) products. What many consumers do not know, however, is that Bisphenol A is often replaced with other, less-studied chemicals whose health implications are virtually unknown. This type of situation is known as a potential 'regrettable substitution', because the substitute material might actually be worse than the material that it replaces. Regrettable substitutions are a common concern among policymakers, and they are a real-world manifestation of the tension that can exist between the desire to avoid risk (known possible consequences that might or might not occur) and ambiguity (second-order uncertainty), which is itself aversive. In this article we examine how people make such trade-offs using the example of Bisphenol A. Using data from Study 1, we show that people have inconsistent preferences toward these alternatives and that choice is largely determined by irrelevant contextual factors such as the order in which the alternatives are evaluated. Using data from Study 2 we further demonstrate that when people are informed of the presence of substitute chemicals, labeling the alternative product as 'free' of Bisphenol A causes them to be significantly more likely to choose the alternative despite its ambiguity. We discuss the relevance of these findings for extant psychological theories as well as their implications for risk, policy and health communication.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/13698575.2014.969687DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5788195PMC
November 2014
-->