ULM School of Pharmacy
Spring 2016
COURSE TITLE: PHRD 4027. Principles of Drug Action II
I.
Contact Information
Ronald A. Hill, Ph.D. (Course Coordinator)
Associate Professor of Medicinal Chemistry
Office: Bienville 310
Hours: M 12:00-1:00p, 5:00-6:00p; Tu 11:00-12:00a, 4:30-6:00p;
W 12:00-12:30p, 4:00-5:30p; Th 11:00-12:00a, 4:30-6:00p; F 12:00-1:00p
Phone: (318) 342-1706
Email: rhill@ulm.edu
Khalid A. El Sayed, Ph.D.
Professor of Medicinal Chemistry
Office: Bienville 324
Hours: Mon-Thurs 10:00a-1:00p, Fridays by appointment only.
Phone: (318) 342-1725
Email: elsayed@ulm.edu
Christopher Gissendanner, Ph.D.
Associate Professor of Pharmacology
Office: Bienville 362
Hours: (pending finalization) Mon-Thurs, 2:00-4:30p
Phone: (318) 342-3314
Email: gissendanner@ulm.edu
Amal Khalil Kaddoumi, Ph.D.
Associate Professor of Pharmaceutics
Office: Bienville 386
Hours: (pending finalization) M-T-W-Th, 2-5 pm
Phone: (318) 342-1460
Email: kaddoumi@ulm.edu
Sharon A. Meyer, Ph.D.
Professor of Toxicology
Office: Bienville 262
Hours: Mon-Th, 9:30a-12:00 noon
Phone: (318) 342-1685
Email: meyer@ulm.edu
Seetharama D. Jois, Ph.D.
Associate Professor of Medicinal Chemistry
Office: Bienville 316
Hours: (pending finalization) Monday to Thursday 10 am to 1 pm, Fridays by appointment only.
Phone: (318) 342-1993
Email: jois@ulm.edu
II. Course Prerequisites/Corequisites
Completion of PHRD 4002
PHRD 4027 Spring 2016 Course Syllabus
Page-2
III. Course Description
PRINCIPLES OF DRUG ACTION II. 3 cr. A continuation of PHRD 4002. Prerequisites: Completion of
PHRD 4002.
Expanded Course Description: This course continues, from PHRD 4002, focusing on the molecular-level
composition of living organisms in relationship to the biochemical and molecular biopharmaceutical bases
of therapeutic intervention with medicinal substances, the actions of these substances (beneficial and
harmful), and, accordingly, the associated foundational concepts of pharmacology, medicinal chemistry,
and toxicology.
IV. Curricular Objectives and Outcomes
See Appendix B.
V. Course-Specific Objectives and Outcomes
The overarching objective for the course is to introduce the student to basic principles underlying the
actions (desired and undesired) of medicinal substances in the human body. For further elaboration,
please refer to Appendix A. The content of this course varies rather widely in nature; accordingly, the
expectations and corresponding nature of the assessments (tests and other grade-generating activities) will
vary. Additional detailed information concerning study and learning objectives, beyond what is given in
Appendix A, will be provided for each section, with further clarifications given during class—typically
within the context of grappling with particular types of content—or on the Moodle site, addressing
questions such as “How should I study?”, “On what aspects should I particularly focus?”, and “What will
be expected of me on the exams and other graded exercises?”
VI. Course Topics
See Course Schedule (Section X below).
VII. Instructional Methods and Activities
Instructional methods will include traditional and technology-based lectures with class discussion.
Readings, study questions, and other exercises aimed at further development of conceptual understandings
through active learning with applications, will be assigned for completion outside of regular class
meetings.
Page-3
PHRD 4027 Spring 2016 Course Syllabus
VIII. Evaluation and Grade Assignment
o Miscellaneous graded in-class and out-of-class assignments – 20% (60 points)
o Examinations – 80%
(two hourly examinations each worth 25% of the course grade (75 pts each), and a
semi-comprehensive final examination worth 30% of the course grade (90 pts)
According to university guidelines (as given in The University of Louisiana at Monroe 2015–2016
Graduate Catalog, wherein the Pharm.D. program is currently listed as a professional degree program),
grades should reflect the following:
A - EXCELLENT
B - AVERAGE
C - BELOW AVERAGE
D & F - Failing
Grading will be straight-scale: >89.9% = A, 80.0%–89.9% = B, 70.0%–79.9% = C,
60.0%–69.9% = D, <60.0% = F
IX. Class Policies and Procedures
At minimum, general policies stated in the current ULM Student Policy Manual & Organizational
Handbook will be followed (see http://www.ulm.edu/studentpolicy/). Additional class policies include:
o Preparation for class. For each class period, you may be held responsible for prior preparation,
involving: (1) viewing any e-presentations as may be assigned in advance; (2) reading over notes or
handouts, if provided in advance; (3) completing a reading if assigned as advance material for a
particular class; (4) answering or attempting to answer pre-class study questions, if given. You should
plan for a minimum of 6-7 hours per week of outside study time in support of your learning in
this class; some students may find that they need more time than this. In general, assignments and any
materials needed for prior preparation (notes, handouts, study questions) will be posted on Moodle at
least several days in advance. You should, however, habitually check the Moodle page the evening
before class for any corrections or clarifications.
o Use of Clickers. Clickers may be used on any given day to generate graded activities (such as a quiz).
Therefore, please bring your clicker every class period; if you do not have it, you may not be afforded
an alternative means to provide responses (i.e., may earn a ‘0' on the graded activity). Also, please note
that allowing someone else to use your clicker to register responses for you is Academic Misconduct,
and any instances of such use will be prosecuted accordingly. Clickers may also be used to generate the
official attendance record on any given day (see Attendance policy on the next page).
o Exams. Three examinations will be administered during the course. The two hourly exams (Exams 1
& 2) will cover the topics from the class schedule as indicated. The final exam will include a modest
comprehensive component; more details will be forthcoming. Exams may likely be administered via
ExamSoft; a policy document for this approach to testing will be posted separately on Moodle, and
discussed during the first class after it is posted.
o Dropped test questions. When, due to faculty concerns regarding a question appearing on an
administered examination, or as the result of a student-generated appeal that is judged to be valid and of
merit by course faculty, the question will generally be omitted from the grade calculation for all
students – the total points for the course will be reduced, without altering the percentages required to
earn a particular course grade given above in section VIII. Course faculty reserve the right to deviate
from this general guideline, however, according to their professional judgement as pertains to the
specifics of the issue with the question deemed to be flawed.
PHRD 4027 Spring 2016 Course Syllabus
Page-4
Class Policies and Procedures, contd.
o The School of Pharmacy Early Intervention and Remediation Policies will be followed. In addition.
any student earning a non-passing grade of “D” or “F” on an exam will be required to meet with
the course coordinator (Dr. Hill), at earliest mutually possible opportunity, to (1) review the test, if
not already done as part of a group debriefing session; and (2)establish a mandatory academic
performance improvement plan, which may include tutoring sessions offered by course faculty
and/or other documented assistance (such as student tutoring and mentoring—Rho Chi tutoring,
e.g.), until such a time as the student secures a solid passing average in the course.
A. Textbook(s) and Materials:
Access to computer with internet; various materials will be provided online via the Moodle portal.
Required textbook (online edition available via AccessPharmacy): Goodman & Gilman’s
The Pharmacological Basis of Therapeutics, 12th Edition (2010). Laurence Brunton, Bruce Chabner,
Bjorn Knollman. McGraw-Hill Professional; ISBN-10: 0071624422; ISBN-13: 978-0071624428
Required textbook: Graham L. Patrick. An Introduction to Medicinal Chemistry, 4th edition (2009)
Oxford University Press;. ISBN: 978-0-19-923447-9 (paperback)
Other required readings or instructional resources will be linked or posted via the Moodle portal, and
will often draw from available institutional subscriptions to online textbook collections, journals, and
other types of materials.
B. Attendance:
The School of Pharmacy attendance policy will be followed. Clickers may be used on any given day
to collect the official roll (see earlier section), so please bring your clicker to every class, and ensure
that it has been properly registered. Note that attendance may be taken with clickers at the beginning
of class. Also, please note that allowing someone else to use your clicker to register attendance
constitutes academic dishonesty and, in accord with federal financial aid regulations, may
furthermore be a violation of federal law.
C. Make-up Policy:
Exams, Graded In-class Exercises, and Assignment Deadlines – As a distillation of the complete
policy: the university requires that you are given a fair opportunity to complete missed gradegenerating opportunities when circumstances warrant. For examinations (and in most other instances)
such circumstances must be compelling, including: (1) you are sick enough to require medical
attention and be confined to bed; (2) there is a death in the immediate family (including grandparents;
see definition in official ULM policy); (3) there is a personal or family emergency. If the absence is
predictable (e.g., a scheduled surgery), a prior approval must be obtained from Dr. Hill (as the Course
Coordinator and Instructor-of-Record). In most instances, physical proof will be needed or you will
not be provided the opportunity to make up the grade!!! If you miss an examination or assignment
deadline, and intend to request a makeup under the above policy, Dr. Hill MUST be informed
BY PHONE OR IN-PERSON no later than the day following the missed event unless
circumstances are prohibitive. Excuses will be validated. If a makeup is allowed under these
guidelines, it will be arranged on an individual basis.
PHRD 4027 Spring 2016 Course Syllabus
Page-5
Class Policies and Procedures, contd.
D. Academic Integrity:
Faculty and students must observe the ULM published policy on Academic Dishonesty (see the
ULM Graduate Catalog, ULM Student Policy Manual (http://www.ulm.edu/studentpolicy)).
All students will adhere to the standards set forth in the ULM School of Pharmacy’s Code of Conduct
(http://www.ulm.edu/pharmacy/documents/ospa/codeofconduct.pdf). These policies will be strictly
enforced—notably, CHEATING WILL NOT BE TOLERATED, AS ANY ACADEMIC
ADVANCEMENT THEREBY GAINED IS CONSIDERED A POTENTIAL THREAT TO THE
PUBLIC. Any instances of academic dishonesty will be dealt with vigorously and doggedly, and to
the fullest extent possible.
E. Course Evaluation Policy:
At a minimum, students are expected to complete the on-line course evaluation. Student ideas that
may have potential to improve course effectiveness are welcome at any time, and may be
communicated, in a professional manner, to specific faculty members or to Dr. Hill, directly or
through class representatives.
F. Student Services:
Information concerning student services in the School of Pharmacy can be found on the School of
Pharmacy Student Handbook or the Current Students page of the School’s website. In particular,
students should pay special attention to the School’s technical standards and policies concerning
students with special needs (http://www.ulm.edu/studentpolicy). ULM student services, such as the
Student Success Center (http://ulm.edu/cass/), Counseling Center (http://ulm.edu/counselingcenter/),
and Student Health Services, is available at the following Student Services web site:
http://ulm.edu/studentaffairs/.
If you are having problems with emotional, social, and/or behavioral issues please call any of the
mental health clinics on the ULM campus to make an appointment. All services are free to ULM
students, staff, and faculty, and are strictly confidential.
· COP Office of Student and Professional Affairs: 342-3800
· ULM Counseling Center: 342-5220
· Marriage and Family Therapy Clinic: 342-5678
· Community Counseling Center: 342-1263
· ULM HELPS (Helping Educators and Learners Prevent Suicide) Project Office: 342-1335
The University of Louisiana at Monroe strives to serve students with special needs through compliance with
Sections 504 of the Rehabilitation Act of 1973 and the Americans with Disabilities Act. These laws mandate
that postsecondary institutions provide equal access to programs and services for students with disabilities
without creating changes to the essential elements of the curriculum. While students with special needs are
expected to meet our institution's academic standards, they are given the opportunity to fulfill learner outcomes
in alternative ways. Examples of accommodations may include, but are not limited to, testing accommodations
(oral testing, extended time for exams), interpreters, relocation of inaccessible classrooms, permission to
audiotape lectures, note-taking assistance, and course substitutions.
Title IX of the Education Amendments of 1972 prohibits sex discrimination against any participant in an
educational program or activity that receives federal funds, including federal loans and grants. Furthermore,
Title IX prohibits sex discrimination to include sexual misconduct, sexual violence, sexual harassment and
retaliation. If you encounter unlawful sexual harassment or gender-based discrimination, please contact Student
Services at (318) 342-5230, or to file a complaint, visit www.ulm.edu/titleix.
PHRD 4027 Spring 2016 Course Syllabus
Page-6
Class Policies and Procedures, contd.
G. Emergency Procedures:
Please review the emergency escape plan posted in the classrooms and hallways of the Bienville building.
Procedures for evacuating the room under emergency circumstances will be discussed on the first or second day
of class. (Please ask about our procedures at any time, however!) If evacuation is necessary, then, as directed
by the instructor, move quickly and in a calm, orderly manner to the appropriate stairwell, and exit the building.
The meeting place for this class will be the far end of the north parking lot (between the building and
Broadmoor Blvd.–the end towards the traffic circle). Under no circumstances is the elevator to be used for
emergency evacuation. Any student needing assistance should notify the professor immediately.
For emergencies, call 1-911 from on-campus landlines
and 342-5350 from cell phones.
Page-7
PHRD 4027 Spring 2016 Course Syllabus
X. Course Schedule
(Note: Although unlikely, faculty reserve the right to adjust the schedule if needed.)
Bienville Room 340: Tuesdays and Thursdays, 8:00-9:15 a.m. **(see Note 1)
Topic
Class
Meetings
Faculty
Member
Receptors and associated concepts
brief recap – affinity; association, dissociation, and
other molecular-level processes
efficacy: agonists, antagonists, partial agonists,
inverse agonists, and other receptor-associated
molecular mechanisms of action
target-level dose-response relationships
biochemical efficiency
1/19, 1/21
Hill
$
$
membrane microdomains (lipid rafts)
ion channels, membrane-imbedded receptors, and
macromolecular trafficking associated with membranes
as pertains to current and potential membrane-imbedded
targets of drug action
1/26, 1/28
Hill
$
more on membrane-associated drug targets
2/04
Jois
$
Review of genetic information flow
$
$
$
$
2/02, 2/11,
2/16, 2/18
Gissendanner
Fundamental aspects of intracellular signaling:
$
$
$
$
pathway regulation
multi-protein assemblies and the interactome
regulation of gene function
targeting of gene regulation by medicinals–introduction
and overview
Basic concepts and principles of pharmacogenetics and
pharmacogenomics
2/23, 02/25,
03/03, 03/08
Kaddoumi
3/10,
3/15
Gissendanner
Basic concepts and principles of epigenetics
A pharmacology-oriented introduction to systems biology,
including transcriptomics, proteomics, metabolomics,
and enviromics
3/17,
3/22
Gissendanner
contd next page
Page-8
PHRD 4027 Spring 2016 Course Syllabus
Course Schedule, contd
Drug creation, Round 2: Introduction to structure-activity
relationships, the pharmacophore concept, and related
medicinal chemistry principles
Foundational concepts associated with toxic effects of
medicinal substances
03/24
04/07
04/12,
04/14, 04/21
Hill
Meyer
Introduction to “biologics” as medicinals: proteins, enzymes,
antibodies and antibody conjugates, RNA-based agents
04/19,
05/03
Hill
Herbal products in pharmacotherapy–an introduction
04/26,
04/28
El Sayed
TBD
05/05
**Note 1: Please preserve an additional 30 minutes (until 9:45 a.m.) on the two test dates indicated below,
in case you would like some additional time (i.e., a relaxation of time pressure) to complete the
exam. Also note that these dates remain subject to change through the first 10 days of the semester.
KEY DATES:#
M 18 January
Tu 19 January
M–W 08–10 Feb
Tu 01 March *
F 11 March
F 25 March
M–F 03/28–04/01
Tu 05 Apr *
Th 05 May
M. L. K. Day holiday—no classes
first class meeting
Mardi Gras holidays—no classes
Test 1 (material through 2/18)
Midterm grades due to be posted by 11:00a
Spring Break–no classes
Spring Break–no classes
Test 2 (material from 2/23 through 3/22)
last regular class meeting
Sat 07 May
Final Exam, 9:00 a.m. (material 03/24–end, + comprehensive component)
#
Please note that all exam dates remain as tentative until declared final by school administration,
and at that point will not be subject to further change.
PHRD 4027 Spring 2016 Course Syllabus
Page-9
APPENDIX A: Course Objectives and Outcomes, Elaborated
In service of the overarching objective for this course written in Section V., this course, as a sequel to PHRD 4002
(Principles of Drug Action and Therapeutics I), aims to guide students in deepening their foundational understandings of
molecular pharmacology and its relationships to cellular and molecular biology; that is, the chemical/biochemical logic
underlying the actions (beneficial and deleterious) of medicinal substances, and corresponding theoretical frameworks.
As compared with PHRD 4002, greater emphasis is given to systems-level roles of macromolecular structures and
biochemical pathways as pertains to pharmacological interventions, current and as anticipated for the near future. Also, as
a springboard for the integrated pharmacotherapeutics sequence of modules that begins with the P2 year, selected
foundational concepts of medicinal chemistry and toxicology are introduced, followed by introductory overviews of
biologics and herbal medicine.
Course-Specific Outcomes Objectives and Competencies: Upon completion of this course, students should have made
further substantive progress towards achieving the general curricular outcomes and competencies provided in
Appendix B. More specifically, students should be equipped with knowledge and abilities as follows.
· Define and differentiate affinity and intrinsic activity (molecular-level efficacy), describe how these concepts relate to
the associated concepts of agonism, antagonism, partial agonism, and inverse agonism, and further describe in general
how these concepts are related to the patient-level actions (observed clinical pharmacology) of drugs.
· Describe structural and functional characteristics, and systems-level roles, of important molecular targets of drug
action: (1) receptors, (2) enzymes, and (3) nucleic acids.
· Define the concept of pharmacological selectivity, describe the molecular bases for selectivity from both the drug and
target aspects, and describe the general clinical significance of selectivity.
• Outline the general manner by which information contained in genes leads to the production of functional proteins.
• (1) Describe, in simple and general terms, the best-known bases by which genetic differences between individuals result
in significant differences in responses to medicinal substances; and (2) for each of these sources of interindividual
variation, outline the clinical/pharmacotherapeutics strategies that are most likely to be adopted by prescribers to
compensate for such differences.
· Describe the connections between environmental exposures, genetic polymorphisms, and risk for acquiring diseases,
especially those having prominent public health impacts.
· List, and describe in very simple/general terms, the major mechanisms by which gene expression is regulated, including
the role of cis- and trans-acting factors and effects of chromatin structure.
· Define “signal transduction”, and elaborate by describing in general terms the major strategies by which cells relay
intracellular signals in response to extracellular endocrine, paracrine, autocrine, or juxtacrine signals; and how
therapeutic interventions can target these pathways.
· Provide a simple description of "genomics", "transcriptomics", and "proteomics" and their potential use in therapeutic
discovery.
· Discuss in general terms the cellular roles of microRNAs and RNA interference and their potential as therapeutic
targets.
· Describe in a general sense what is meant by the term “structure-activity relationships”, and define the concept of a
“pharmacophore”.
· List and describe in general terms the most common types of mechanisms by which medicinal substances produce, upon
acute exposure, toxic effects on a person, and where possible, discuss the nature of the typical dose-dependencies, and
of compensatory responses, associated with each general type of mechanism.
· List and describe in general terms the most common mechanisms by which medicinal substances produce, upon chronic
exposure, toxic effects on a person.
· Comment on how information from the Preclinical phase of testing of a potential new drug contributes to design of
Phase I clinical testing.
· Compare and contrast the nature of herbal remedies vs. traditional pharmaceutical preparations.
· Demonstrate basic knowledge of the most commonly used herbal remedies, in particular, those commonly used for
digestive system maladies, hyperlipidemia, and for helping to achieve weight control.
PHRD 4027 Spring 2016 Course Syllabus
Page-10
APPENDIX B: Curricular Objectives and Outcomes Addressed by this Course
Upon successful completion of this course, the student will gain competencies that are consistent with the
educational outcomes adopted by the ULM School of Pharmacy in August 2006, which are based on CAPE#
2004 and ACPE Standards 2006--January 2012 update. [#CAPE = Center for the Advancement of Pharmaceutical
Education Advisory Panel Outcomes, as adopted by the American Association of Colleges of Pharmacy (AACP) and the
American Council on Pharmacy Education (ACPE).] In the listing of applicable outcomes provided below, sub-objectives
as originally adopted are retained to enlighten the basis for listing each of the numbered objectives given in boldface type
(the “Big-34" adopted by the school in 2009):
PROFESSIONAL-PRACTICE-BASED OUTCOMES...
> DIRECTLY IMPACTED (*concepts and principles directly applicable);
> INDIRECTLY IMPACTED (Fcrucial foundational concepts or abilities)
Provide Comprehensive Patient Specific Pharmaceutical Care
1. Evaluate the appropriateness of a given prescription or medication order based on patient and disease-specific
factors.
i. Analyze the prescription regarding the medication, dose, delivery form, and duration of use as being appropriate
for the patient and disease state.
a. Collect patient-specific data regarding demographics, medical history, diagnosis, physical assessment, and
medication history.
2) Identify and collect pertinent information from the medical chart, database, and/or the patient/caregiver
interview.
c) *Recognize appropriate patient- and drug-specific factors that will impact the drug regimen.
4) F Collaborate with other healthcare providers.
b. Analyze and interpret information gathered to identify any drug-related problem.
1) *Assess the prescription for interaction potential, including interactions with other medications (both
prescription and non-prescription), disease states, foods, and herbals.
2) *Determine [...] appropriateness of medications and dosage form.
3. Develop and implement an evidence-based care plan.
i. *Identify goals of therapy that are individualized to the patient.
ii. F Develop a plan of care that includes interventions to resolve drug therapy problems, achieve the goals of
therapy, and prevent drug therapy problems.
iv. F Evaluate patient outcomes with respect to the achievement of goals of therapy, patient adherence, patient
safety, and the development of new drug therapy problems.
5.
F
Document all activities involved with the provision of comprehensive patient-specific pharmaceutical care.
(contd next page)
PHRD 4027 Spring 2016 Course Syllabus
Page-11
Educational Outcomes, contd
Communicate Effectively
6. Counsel and educate patients regarding medication use, disease-state management, and health maintenance.
iv. FProvide information that empowers patients to effectively manage their medication-related health care.
7. Develop population-based patient education programs.
i. FDevelop disease state educational programs.
8. Collaborate with other healthcare professionals using appropriate effective communication in both written
and oral forms.
i. *Demonstrate fluency in medical terminology.
v. FPresent and defend pharmacotherapy recommendations.
Appropriately Manage and Use Resources of the Health Care System
11. Apply patient and population specific data, quality assurance strategies, and research processes to:
i. Assure that medication use systems minimize drug misadventures and optimize patient outcomes...
d. *Distinguish between patient- and population-specific data.
e. *Collect, analyze, and interpret patient- and population-specific data.
f. F Make appropriate recommendations based on data interpretation.
ii. ... and develop drug use and health policy to manage pharmacy benefits.
i. F Develop disease-specific treatment algorithms/pathways for a health care system.
Identify, Interpret, and Evaluate Literature Needed for the Provision of Drug Information
and Pharmaceutical Care
13. *Define the question that needs to be answered.
14. *Distinguish among lay, professional, and scientific literature.
17. F Evaluate literature source validity.
19. F Evaluate the appropriateness of research methodologies and statistical methods.
20. *Draw appropriate conclusions from research results.
21. F Assess the potential impact and implication of published information on current practices.
(contd next page)
PHRD 4027 Spring 2016 Course Syllabus
Page-12
Think Critically
24. Identify, retrieve, understand, analyze, synthesize, and evaluate information needed to make informed,
rational, and ethical decisions.
i. *Systematically gather, organize, and extract relevant information using a variety of methods and research tools.
ii. Analyze information within appropriate scientific, social, and clinical contexts.
a. *Identify principles of organization and the logic of arguments.
b. *Identify and test assumptions, biases, and prejudices implicit in arguments.
d. *Assess accuracy, soundness, fairness, significance, relevance, completeness, and persuasiveness of
information, arguments, and sources.
iii. *Synthesize information in order to draw conclusions, hypothesize, conjecture alternatives, or plan a course of
action.
iv. *Evaluate conclusions and solutions according to appropriate criteria, and revise as necessary.
v. *Provide support for rationale, solutions, and results.
25. Solve complex problems that require an integration of one's ideas and values within a context of scientific,
social, cultural, legal, clinical, and ethical issues.
i. *Interpret problems within appropriate contexts.
iii. *Apply systematic problem-solving strategies.
iv. F Articulate and implement a defensible solution and apply appropriate criteria to monitor outcomes.
v. F Implement modifications based on monitoring data.
26. Display habits, attitudes, and values associated with mature critical thinking.
i. *Evaluate personal assumptions, biases, prejudices, and opinions.
ii. *Display an openness to new ideas and a tolerance for ambiguity.
iii. *Display inquisitiveness and commitment to the pursuit of truth.