The Role and Value of the Basic Sciences in Medical Education: The Perspective of Clinical Education -Students’ Progress from Understanding to Action

Louis Pangaro

F. Edward Herbert School of Medicine, Uniformed Services University of the Health Sciences
Bethesda, Maryland, USA

+1 301 295 2010
+1 301 295 75792

Introduction

It is understandable that the role of basic science in the medical school curriculum should be re-examined at a time when, on the anniversary of the “Flexner report,” decades of change in the practice of medicine, and anticipated changes in the delivery of health care over the coming decades are in the forefront of discussion.1 The national movement toward redesign of medical school curricula can only be accelerated in these circumstances. Therefore, there is an urgency to reexamine all the premises of medical education, including the role of the foundational sciences for the practice of medicine in the curricula of the 21st century. This essay will explore the essential role of basic science in students’ progress toward independence as their responsibilities move from understanding into action.

Why all the concern about basic science?

In a way, it seems counter-intuitive, or even absurd to ask whether acknowledge of basic science is of central importance to the practice of medicine. How is it, then, that present concerns arise?

One concern comes from faculty. As recently noted in a collaborative statement from IAMSE on the role of basic science in medical education “there is tension between the time needed to teach an ever-expanding knowledge base science, and the time needed for increased instruction in clinical application and it behavioral, ethical and managerial knowledge and skills needed in preparation for the clinical experiences”.1

The concern also comes from a new generation of task-oriented students: “many students still have genuine doubts about the value of basic sciences to which they had been exposed.”2 And it comes from leaders in science themselves in the recent report from the Howard Hughes Medical Institute (HHMI). “In recent years the scientific knowledge important to learning and practice of medicine has changed dramatically, while the approach to science education in the premedical and medical curricula has essentially remained unchanged”.3

Sweeney goes further and argues that the curricular problem “to basic scientists is that much of clinical medicine remains unnecessarily unscientific”, and therefore “Until clinical medicine itself changes, the utility of science in the training of a physician will remain difficult to demonstrate.”4

There are several questions: whether basic science is relevant to education in medicine, or just whether science needs to be taught in a different way? Or perhaps, given the explosion of scientific information, it is a question of what needs to be taught and when?

Finnerty et al1. posed – and answered -five questions on the 100th anniversary of the Flexner report: what are the sciences that constitute the foundation for medical practice? What is the role of science in being ready for practice at different stages of training? When and how should the foundational sciences be incorporated into the medical school curriculum? (What instructional methods and what assessment tools?) What sciences are prerequisites to enter medical school? and what are examples of best practices? The purpose of this paper is to reflect on these questions from the perspective of a clinical educator, and initially on the broader question that underlies these: how does basic science knowledge contribute to the competence of a physician? This is an opinion piece, but key supporting literature will be cited.

In what way does basic science fit into competence as a physician?

Addressing how basic science is incorporated into the practice of medicine depends upon basic assumptions about what medical practice is, or more specifically, what the “competence” of an individual physician means. One accepted definition of competence was offered by Epstein and Hundert: “the habitual and judicious use of communication, knowledge, technical skills, clinical reasoning, emotions, the values and reflection in daily practice for the benefit of the individual and community being served”.5 A similar approach is embodied in the “six general competencies” into which the Accreditation Council for Graduate Medical Education (ACGME) which divides competency: medical knowledge, interpersonal and communication skills, professionalism, patient care, system-based practice and practice-based learning.6 In both of these models competence is seen as a multidimensional construct in which knowledge is given a prominent role, and a knowledge of basic sciences (normal human structure and function, and mechanisms of disease and therapy) is explicit.

The Epstein definition situates competence in the specific, local context in which the physician provides care for a specific individual patient or community. These six aspects (or seven, Epstein) into which competence is divided are applied to a specific patient. As an alternative to this “analytic” model in which competence is refracted into six domains, there is a “synthetic” model combining knowledge, skills and attitudes in which this may be said more concisely: “competence is bringing to each patient in your practice what the patient requires, and nothing extraneous”.7,8 This emphasis on a specific situation and the role of the individual within that situation may an essential consideration, since what science is required will depend on the practice (specialty, context and scope of practice) of the individual. With the changing and increasing levels of responsibility of medical students and residents, the problem can be framed more developmentally as we ask what students are expected to bring to the required situations (courses and clerkships) at a specific levels of their training. Additionally, as the student moves toward graduation and has chosen a specialty, this formulation fosters more flexible learning the basic science (individual study and electives).

Growing competence as a movement from understanding into action

Clinicians are used to seeing the medical school curriculum (whether four years as in the United States, or six years as in other parts of the world) as “preclinical” and “clinical”. In this framework a course in the first year or two of medical school is a preparation for what happens later. Typically, there is not a strict separation, and in recent decades, early clinical training in medical interviewing, physical examination and diagnostic reasoning have been included in “introduction to clinical medicine” or “doctoring” courses. Another way of looking at this progress from the initial years of medical school to subsequent years is to characterize the students’ task. This can be done rather simply by conceptualizing the process as a movement from understanding into action; for instance, we might say that initially they are responsible for understanding and explaining what is happening with their patients (from a point of view of mechanism), and later they are responsible for moving toward diagnostic and therapeutic planning. As will be discussed below, this has implications for what basic sciences must be mastered at each stage of the process.

Does science aid understanding and action?

In the past two decades there is a growing body of literature on how basic science fits into the practice of medicine, and how the competence of students develops. Most of this literature focuses on the task of diagnostic reasoning (“making a diagnosis”) rather than the broader concept of clinical decision-making which includes diagnostic and therapeutic planning, and shared decision making with patients and families. Since initially students are given responsibility for thinking through problems, but not for unsupervised care of patients, this has been an appropriate first focus for educational research.

Is basic science knowledge required for developing diagnostic reasoning? This was assumed in the original “Flexner model” in which two years of basic science was seen as a prerequisite for learning clinical medicine. The domain of medical knowledge was seen as two separate types of knowledge, one a knowledge of mechanisms (normal structure and function and derangements of these), and the other a knowledge of clinical medicine (the manifestations of disease).9 (Please see also Patel and Woods for current reviews of learning theories as they relate to basic science in medical education.)10,11

It has become a commonplace that clinicians do not “use” basic science in their decision-making, and rely rather on pattern recognition. This general observation of medical students in their own conversations with teachers has been supported by “think-aloud protocols” in which physicians are asked to explain how they arrived at their conclusions. However, this surface observation has been clarified by structured observations that clinicians with a high level of expertise have “compiled” knowledge or “encapsulations” in which their knowledge of basic science is tacit, and below the surface of their conversation.12,13 Studies have shown that experts do, in fact, use a knowledge of basic science mechanism in solving more difficult problems.14

The general principle of management by large clinical trials for both diagnosis and therapy, so-called “evidence¬based medicine” (EBM), may be replacing, I have observed, mechanism of disease and mechanism of therapy as the preferred subject for discussion by residents on work rounds. Such an approach, in which EBM is preferable to pathophysiologic analysis, could be more cost-efficient and therefore more in tune with what health care policy leaders see as a priority in practice and education.

Where does basic science fits into practice?

In discussion of straightforward cases, clinicians do not articulate a use of basic science in clinical reasoning because their knowledge is compiled or encapsulated and because the cases are routine and simple. However, and here we come to the essential point, what separates physicians from other health care workers, such as physicians assistants and those who must follow algorithmic care, is the ability to manage more difficult problems. In this respect, medical education must train those who not only follow practice guidelines, but who can write such guidelines and who have the authority to deviate from, or “violate” practice guidelines (personal communication, Ralph Jozefowicz). As noted before by Finnerty, if physicians are to be more than technicians, then an understanding of science is essential.1

Basic Science as Curricular Method and not simply as syllabus

Scientists argue, and clinicians are inclined to agree, that in addition to the a knowledge of scientific facts, the very study of science develops effective thinking skills, a ready skepticism about observations and studies, and a habit of rigor and honesty in interpreting data. In this sense basic science is more than a list of topics to be covered (syllabus) but is part of a structured experience (curriculum) that leads toward eventual independence.15 But this distinction between begs an important difference between two disciplines that differently value understanding and action. The methods of science are designed to lead to understanding, and employ clarification studies (experimenta lucifera in the terms of Francis Bacon); whereas the practice of medicine requires a praxis, or method of action that looks for benefits through studies that are “fruitful” enough to justify one course of action over another (experimenta fructifera).16,17 These should be complimentary, of course. But they reflect a difference of intention that may make it hard for medical school teachers to work together.4

There is supporting evidence that expert physicians, in dealing with difficult cases do rely on understanding of basic mechanisms.14,18 When “solving” routine or simple cases, expert clinicians in endocrinology and cardiology relied on quickly processed, non-analytic reasoning and pattern recognition.9 When, however, out of routine, they verbalized the knowledge of mechanism that helped them solve problems. Moreover, in some studies when specifically asked about disease mechanism, expert physicians do in fact have a grasp of principles and mechanism superior to students.

At this point we can address the fundamental challenge raised by Sweeney that the practice of medicine is not scientific, that is, not completely based on a data driven recognition and manipulation of cause and effect. The implication is more than the traditional formulation that medicine is a combination of both art and science. It is that in applying principles to individual patients, it is the individuality of the situation (such as co-morbid diseases and social setting) that take precedence. These complicating factors outrun available ‘evidence-based medicine’. This brings us to an even deeper difference between the disciplines of science and clinical medicine.

Ultimately, physicians must act, even in complex circumstances for which large-scale, multi-center clinical trials can only give a rough approximation of a course of action. In this setting, where “data” are not available to dictate a course of action, the physician must use professional skills to achieve a patient-centered decision; but even within the physician him/herself, the cognitive process is one of dealing with uncertainty and managing complexity. It is in this area of complexity and uncertainty where the recent studies of Patel (cited above) and others are most useful in supporting utility of having a basic understanding of disease and pharmacology mechanism available in memory.

Another concern is that medical practice may not require a true understanding of basic science to support analytic reasoning, since the vast majority (75%) seen by practitioners in their own discipline is, for them, routine. In these simple situations diagnosis may simply require a non-analytic thought process (pattern recognition), and management only requires a practice guideline. In fact, there is a growing sentiment that clinical epidemiology applied to principles of prevalence of disease and a specific population may be as important to successful diagnosis as a grasp of basic mechanisms.

What basic sciences are the foundation of medical practice?

A specific syllabus in human biology is available in extreme detail from the Content Outlines for Steps 1 and Step 2 (Clinical Knowledge) for the US Medical Licensing Examination, and principles have been reviewed extensively by Finnerty et al; these will be reviewed here only in broad outlines and general principles.1,19 The three “Ps” are closest to the surface: physiology, pathology and pharmacology for all cases/patients, with microbiology and biochemistry dominating for diseases from the internal or external ecology, and from nutrition. Anatomy is essential for localized symptoms (for instance, pain and swelling).

Using the general definition of competence as the ability to bring to the situation (patient) what is required, the level and kind of understanding required depends on the specific problem at hand, and the competent physician must be able to move “downward” (deeper) from a consideration of organ systems within the body to more detailed levels of mechanism and granularity (cellular and genetic mechanisms, and molecules), or “upward” to a broader, bio-psycho-social framework (such as substance dependence and family dynamics), moving from person to family and from local environment to society, and even, as required by the individual patient, to a health-care delivery model system level (see Figure 1). Therefore the individual physician must have access to a wide repertory of foundational sciences available from molecular biology and genomics, too physiology and organ histology, to behavioral psychology, to epidemiology and biostatistics.

What is the role of sciences in medical education?

One role is practical, related to where the student is in his/her progress towards independence, and the other is theoretical in supporting the development of rich, knowledge encapsulated in the memory of the student, and accessible as needed for complex or unexpected problems.

During medical school students are gradually given more responsibility in the care of real patients as they acquire more “competence” for their level of training. Overall, students move from understanding to action. Action in the face of uncertainly takes more than knowledge, and is a task that cannot easily be embraced within a cognitive model in which a student’s understanding alone is required. Can basic science play a role in the formation of professional character, in which behavioral and social concepts are more fundamental?20

The progress of students from understanding to action can be extracted implicitly from the ACGME competencies in which the first three items -residua of the knowledge-skills-attitude model of Bloom -knowledge, communication skills and professionalism, are prerequisites to being given clinical responsibility.21 The single most important competency, patient care, with its two pendants (system based practice and practice-based learning and improvement) then follows.

This progression from understanding to action is even more explicit in one specific formulation, the reporter-interpreter-manager-educator” framework.7,22 In this framework basic science supports the students’ gathering and explaining clinical findings on their own patients. Knowledge of the anatomy of the abdomen, for instance, is essential for diagnosing right upper quadrant pain; knowledge of the normal physiology of water regulation is essential for understanding polyuria and polydipsia; knowledge of normal and abnormal histology supports learning to interpret patterns of liver associated enzymes. The knowledge is not there for its own sake, but to support the responsibility that the student will be given. The use of clinical vignettes in which to embed the basic science questions in USMLE, Step 1, reflect this linking of cognitive expertise to a potential role for students in patient care.

The timing of basic science content areas

Some clinical problems are of sufficient importance and prevalence that they must be understood as prerequisites for any core clinical clerkship that the student happened to be on. For instance, how the body regulates blood pressure often underlies common, life-and-death situations and should be an absolute prerequisite for starting clerkships. How the body protects itself against dehydration and hypoglycemia –when patients are unable to eat or drink –puts the regulation of osmolality, and the biochemistry of glucose homeostasis on the list of prerequisites which help earn the right to take care of patients. On the other hand, learning iodine metabolism and thyroglobulin synthesis could probably be deferred until a student saw a patient in in the clerkships with thyrotoxicosis or thyroid nodule.

How do we teach basic science?

The “how” is to be answered by two tests of success, which are of equal importance: one, can the students retrieve the essential facts from memory and apply them to the patient at hand; and two, is the student driven to answer the question “Why?” So, teaching methods are not aimed solely at students’ memory, but at their intuitive search for explanations -Is there an emotional need to explain signs and symptoms through mechanism? If not, we, the faculty, have probably failed in this essential goal.

While differential diagnosis of clinical problems, such as bloody diarrhea, can be memorized as part of illness scripts, there is evidence that support by pathophysiologic understanding of mechanism supports longer term retrieval
from memory.15,23 Whether in lectures, small-group teaching or one-on-one, the teacher probes the student’s ability to unify the surface features of (symptoms, signs and laboratory findings) with underlying mechanisms.

As students move from understanding into action, and into management of common problems, a knowledge of microbiology and pharmacology becomes more and more essential, and is essential for all training in each specialty of medical practice. But are specific learning needs the same for learners at different levels? Do students need to grasp all problems at the same level as specialists? Endocrinology fellows are more apt to be thrilled by adrenal synthetic pathways than surgeons, and the actions of tyrosine kinase inhibitors in chemotherapy more needed by oncologists. The problem may be resolved by deciding the specific expectations for the role of the learner at each level, i.e., what level of competence is expected.

Prerequisites for entering medical school

In the pre-medical school curriculum students should have demonstrated to themselves and faculty that they are familiar with the terminology, methods and content of science. It may be as important that they see “science” as a process of rigorous observation and hypothesis testing than as a fixed body of knowledge to be cherished. Among several recent discussions, Lambert and others proposed a revision of legacy pre-med requirements, including a shift from organic chemistry to biochemistry, from calculus to statistics and substituting no cell biology and physiology for physics.24 Additionally, they support a decrease in total contact hours in collegiate science, and a shift to more individualized learning of science during medical school.

Almost all authors and scientists still espouse a general education in humanities: “undergraduate years are not and should not be aimed only at preparing for professional school. Instead, the undergraduate years should be devoted to creative engagement in the elements of a broad, intellectually expansive liberal arts education”.3 Consensus also strongly supports college experiences which would allow students to express themselves clearly to teachers, peers and patients. Some basic training in logic and reasoning (less and less available with the decline of formal requirements in the philosophy department) and in written and oral communication (how to write a paragraph) are also desirable. Finally, some preparation to deal with patient-centered issues (behavioral modification, clinical psychology and family dynamics, and sociology) is probably more important than calculus.

What are some best practices for incorporating basic science education into medical school curricula?

In Pre-clerkship courses

Schmidt and Rikers offer useful principles to guide education in the pre-clerkship period.13 Basic science should be taught to support the development of encapsulating concepts; not simply left to the students themselves but supported by integrated teaching (such as in an organ system approach); students should work with patients early in the curriculum; students should have exercises to reflect and elaborate on problems of patients (with a tutor/coach or in small groups) to develop knowledge structures.

Whatever the course’s format “providing students with the appropriate theoretical knowledge gives them the means to create a coherent picture of the case when the clinical features become disorganized”.11,20 In the pursuit of realistic clinical scenarios, science course directors should avoid the tendency to provide complicated clinical scenarios (paper, simulated or real) whose clinical details might distract students from grasping the essential mechanism and pathophysiology underneath. I have proposed elsewhere that competence in my own discipline of internal medicine is the ability to embrace complexity, but act with simplicity”; but it is important to remember that beginning students are struggling to embrace simplicity.

On Clinical rotations

One important precept is that incorporating basic science training into the clinical years may need faculty development for teachers, so that the link between science and the clinical decisions is “made explicit, concise and clear”.11 Employing Ericsson’s concept of deliberate practice – repetition with feedback from a master teacher – a best practice would be the teacher who asks and expects students to have asked themselves “why?” this patient has the symptoms at hand. This teacher makes the articulation of mechanism in explanation and therapy a routine practice.25 This, too, will often require a faculty development effort, since this not habitual with faculty who are often supervising residents and patient care at the same time, and so naturally focus on action rather than understanding.

Many schools have incorporated early clinical contact with patients in the first year of medical school, and now a growing number have a formal return to science during the clinical years. A formal return to science may now be considered a “best practice”. The “double helix” curriculum of the University of Rochester is one model that articulates the close relationship of these two domains of knowledge throughout the four years.26

Spencer and others provide a comprehensive summary of formal basic science education in US medical schools based on the AAMC curriculum directory and each school’s own website.27 As of 2007, 19% of US schools (up from 13% in 1985) included basic science after the clerkships for an average duration of four weeks. Specific formats and sessions are described as well as some common content areas (advanced pharmacology and pathology; resuscitation, neoplasia and molecular medicine).

In such a “formal return” to the study of basic science, there is some support for allowing the curriculum to meet the needs and desires of individual students, giving more flexibility and allowing more interdisciplinary work. For instance, from a selective panel of basic science senior seminars or mini-courses, a student going into surgery might choose three modules from anatomy and one from physiology; a student going into pediatrics might choose three from physiology at one from anatomy.

The recent HHMI report prefers to formulate learning objectives for students as “competencies” which are demonstrable by students rather than as areas to be covered by faculty.3 Such phrasing moves the pedagogy from teacher-centered (what was presented) to student-centered (what skills were acquired), and may also be considered a best practice. This report also provides “eleven overarching principles” to inform science teaching, among which are that students should have not just a grounding in knowledge but, as importantly, in how that knowledge evolves; the report endorses the role of science in forming professional values such as curiosity, skepticism, objectivity and scientific reasoning. The HHMI report does not propose increasing the number of requirements for entry to medical school; instead it recommends substituting more relevant requirements for others that are less relevant to the practice of medicine”.

New Developments

Educators should be aware that a revised standard for accreditation (ED 11) requires that “the curriculum of the educational program must include content from the biomedical sciences that supports students’ mastery of the contemporary scientific knowledge, concepts and methods fundamental to acquiring and applying science to the health of people had to the contemporary practice of medicine”.28 It is the new annotation for this requirement that is remarkable in its phrasing to make it clear that departmental a (or scientist-based) approach to syllabus should not be a barrier to integrated learning all “it is expected that the curriculum will be guided by clinically-relevant biomedical content from, among others, the disciplines that have been traditionally titled anatomy, biochemistry, genetics, immunology, microbiology, pathology, pharmacology, physiology, and public health sciences”.28

CONCLUSION

Teaching basic science should be incorporated into a larger concept of progress toward independence than that ‘knowledge is an essential competence’. Educational leaders should be aware that a growing body of evidence supports the teaching of basic science as an essential step in solving complicated or unusual clinical problems, and not be discouraged by the fact that clinicians do not routinely mention the basic science facts that underlie our diagnostic reasoning. Little attention has yet been paid to articulating the role of basic science in teaching therapeutic management, but this author believes that teachers should continue to insist on an understanding of mechanisms as at least as important as epidemiologic studies and EBM. We should be aware that students are often still achieving understanding in a setting in which their teachers are focused on action (whether or not understanding is complete). Successful incorporation of science into medical practice through education depends on the effort to make this step an explicit priority.

REFERENCES

  1. Finnerty EP, Chauvin S, Bonaminio G, Andrews M, Carroll RG, Pangaro LN. Flexner revisited: the role and value of the basic sciences in medical education. Acad Med. 2010 Feb;85(2):349-55
  2. Weatherall DJ, Science in the undergraduate curriculum during the20th century, Medical Education, 2006, 40, 195 – 201.
  3. Howard Hughes Medical Institute, Scientific Foundations for Future Physicians, AAMC, 2009.
  4. Sweeney G, The challenge for basic science education in problem-based medical education”, Clin Inest Med, (1999), 22, 1v-22.
  5. Epstein RM, Hundert EM, Defining and Assessing Professional Competence, J Amer Med Assoc, 2002, 287, 226 -235.
  6. Accreditation Council for Graduate Medical Education, http://www.acgme.org/outcome/comp/compmin.asp, accessed 11April 2010.xxix
  7. Pangaro L, A New Vocabulary and Other Innovations for Improving Descriptive In-training Evaluations, Academic Medicine, 74: 1203-1207, 1999.
  8. Pangaro L, Investing in Descriptive Evaluation: a vision for the future of assessment. Medical Teacher. 22(5), 478 -481, 2000.
  9. Patel VL, Evans DA, Groen GJ, Reconciling basic sciences and clinical reasoning, Teach Learn Med, 1989, 1: 116-121.
  10. Patel VL, Yoskowitz NA, Arocha JF, Shortliffe EH, J Biomedical Informatics, 2009, 42, 176 – 197.
  11. Woods NN, Medical Education, 2007, 41, 1173 – 1177.
  12. Bordage G. Elaborated knowledge: a key to successful diagnostic thinking. Acad Med 1994;69:883–
  13. Schmidt HG, Rikers RMJP, Medical Education, 2007, 41, 1133-1139.
  14. Patel VL, Groen GJ, Arocha JF, Memory and Cognition, 1990, 18, 394 – 406
  15. Pangaro LN, A Primer of Evaluation, Guidebook for Clerkship Directors, 3rd edition, Fincher RM, Alliance for Clinical Education, 2005.
  16. Bacon F, “Novum Organum”, Francis Bacon: Novum Organum -With Other Parts of The Great Instauration, Paul Carus Student Editions) [Paperback, Carus, 1994
  17. Cook DA, Bordage G, Schmidt HG. Description, justification and clarification: a framework for classifying the purposes of research in medical education. Med Educ. 2008 Feb;42(2):128-33.
  18. Woods NN, Brooks LR, Norman GR, The role of biomedical knowledge in diagnosis of difficult cases, Adv in Health Sci EDuc, 2007, 12:417-426.
  19. USMLE Website http://www.usmle.org/
  20. Torre DM, Daley BJ, Sebastian JL, Elnicki DM, Overview of Current Learning Theories for Medical Educators, Amer J of Medicine 2006, 119, 903 – 907.
  21. Bloom, B.S. (Ed.) (1956) Taxonomy of educational objectives: The classification of educational goals: Handbook I, cognitive domain. New York; Toronto: Longmans, Green.
  22. Pangaro LN, A Shared Professional Framework for Anatomy and Clinical Clerkships, Clinical Anatomy, 2006, 91: 419-428.
  23. Woods NN, Neville AJ, Levinson AJ, Howley EHA, Oczkowski WJ, Norman GR, The value of basic science in clinical diagnosis, Acad Med, 2006, 81, S124-S127.
  24. Lambert DR, Lurie SJ, Lynes JM, Ward DS, Acad Med, 2010, 85, 356 – 362.
  25. Ericsson, K Anders, Deliberate Practice and the Acquisition and Maintenance of Expert Performance in Medicine and Related Domains. Academic Medicine. Research in Medical Education Proceedings of the Forty-Third Annual Conference November 7¬10, 2004. 79(10) (Supplement):S70-S81, October 2004.
  26. University of Rochester website, http://www.urmc.rochester.edu/education/md/prospect ive-students/curriculum/, accessed 15 July 2010
  27. Spencer AL, Brosenitsch T, Levine AS, Kanter SL, Back to the basic sciences: An innovative approach to teaching senior medical students how best to integrate basic science and clinical medicine, Acad Med, 2008, 83, 662 – 669.
  28. Liason Committee on Medical Education, The structure and Function of a Medical School, http://www.lcme.org/functions2010jun.pdf

Published Page Numbers: 307 - 313