The seventh "Oxford Conference" on Modeling and Control of Ventilation was held in the beautiful setting of Northem Ontario at the Grandview Inn in Hunstville. This meet- ing was called the Canadian Conference on Modeling and Control ofVentilation (CCMCV) to follow on LCMCV held in London, England, three years ago. The beautiful view over Fairy Lake greeted everyone in the moming and provided an ideal setting for many discus- sions about respiratory physiology and modeling. The Oxford Conferences began in 1971 when Dr. Richard Hercynski (a mathematical modeler with an interest in respiratory physiology) and Dr. Dan Cunningham (a respiratory physiologist with an interest in modeling) decided to organize a meeting "Modelling of a Biological Control System: Tbe Regulation of Breathing" in Oxford, England, in 1978. The meeting was a success, and it spawned aseries of meetings that have continued to today. A second conference was organized at Lake Arrowbead, Califomia, in 1982. After tbis, con- ferences were repeated at tbree-year intervals. My first Oxford Conference was at tbe abbey in Solignac, France, in 1985. Next, we met in tbe cabins overlooking Grand Lake, Colorado, in 1988. In 1991, we traveled to the training institute at the base ofMt. Fuji (or at least they tell us Mt. Fuji was out there--we never saw it because of a typhoon rolling through). Our last meeting was at Royal Holloway College (University of London) where we got to dine in a castle among artwork that required guards and an electronic security system.

This is the premier evidence-based textbook in critical care medicine. The Third Edition features updated and revised chapters, numerous new references, streamlined content, and new chapters on key topics such as the new paradigm in critical care medicine, cardiac output monitoring, surgical optimization, vital signs, and arterial blood gas analysis. The book maintains the author's trademark humor and engaging writing style and is suitable for a broad and diverse audience of medical students, residents, fellows, physicians, nurses, and respiratory therapists who seek the latest and best evidence in critical care. From reviews of previous editions: "This is an excellent introduction to the concept of evidence-based medicine...The writing is clear, logical, and highly organized, which makes for fast and enjoyable reading. I believe this book will get daily use in most intensive care units, by a wide range of readers." -Respiratory Care "This is one of the most comprehensive handbooks on critical care medicine with a strong emphasis on evidence base...Overall, this book should be useful for junior doctors or intensive care trainees who are starting their term in an intensive care unit." -Anaesthesia and Intensive Care

When I first proposed this book, one of the hopes was that it would be the stage upon which would be conducted a quiet, well reasoned discussion of the various techniques of stereotactic radio surgery. At that time, there was quite a bit of rancorous debate that tended to obscure the scientific and medical merits of each of the separate methods. At the present time, I am happy to report that the field of stereotactic radiosurgery is much less riven by such inappropriate posturing. The field has taken many steps towards maturity, both technically and medically. In the course of this mat uration process, there have been many grandiose plans and speeches made on behalf of stereotactic radiosurgery. Inevitably, the reality will not live up to the hype, but such is the natural course of devel opment in these sorts of matters. However, even though events may not match our hopes, we should keep in mind the words of Herbert Parker. Recognizing that new modalities for the treatment of cancer do not stand much chance of revolutionary success, nevertheless, he quite correctly pointed out that " . . . with any type of radiatiQn, the margin between success and failure is small. If the chance of success is a little greater . . . thi~ might well be classed as a great advance. " Mark H.

This book is the first of four books on the core principles of acute neurology. This book is a primer - and a great deal more - on how to clinically recognize acute brain injury and to treat its consequences. Acute brain injury often changes the dynamics of cerebral blood flow, cerebrospinal fluid mechanics and eventually intracranial pressure. And furthermore, acute brain and spine injury impacts on heart function, blood pressure control, breathing regulation and even gastric and bladder function. It is necessary to not only understand these fundamentals but also how certain measures could influence or correct these manifestations. Major concepts are illustrated to facilitate understanding. Each chapter concludes with a section that explains its relevance to clinical practice.The book truly combines basic neuroscience with practical know- how in an easy to read prose useful for both the novice and expert.

Ability to learn from errors is an essential aspect of the quest to improve treatment quality and patient safety. This book consists of 33 cases in anesthesiology that is based on real life situations and illuminate avoidable complications and mishaps. The cases are presented in a novel manner in that they are embedded within narratives. The reader comes to each case "cold", without any clue as to the content, and each case comprises a narrative and a factual component that are interwoven. The narrative parts provide the reader with information and tips regarding the clinical problems and tasks that the protagonist must face and try to solve. The idea is to engage the reader emotionally while reading and to entertain him or her while learning. All cases conclude with short debriefing sections which include possible strategies to prevent similar errors or mishaps.

The International Hypoxia Symposium convenes biannually to bring together international experts from many fields to explore the state of the art in normal and pathophysiological responses to hypoxia. Representatives from five continents and 32 countries joined together in February 2003 for four days in the dramatic mountains of Banff, Alberta. As editors of the Proceedings of the International Hypoxia Symposia, we strive to maintain a 26 six year tradition of presenting a stimulating blend of clinical and basic science papers focused on hypoxia. Topics covered in 2003 include hibernation and hypoxia, hypoxia and fetal development and new advances in high altitude pathophysiology, oxidative stress and membrane damage, hypoxic regulation of blood flow, heat shock proteins in hypoxia, and future directions in hypoxia research. In 2003 we also had the privilege ofhonoring John W. Severinghaus as a friend, colleague, mentor and inspiration to many in the field. Tom Hornbein's personal tribute to John Severinghaus is the first chapter in this volume, followed by an entertaining update of the history of the discovery of oxygen written by John Severinghaus.

Cardiac Pacement has undergone a rapid development in technique and application in the last years. Methods of cardiac pacement have become more successful but also more complicated. This book is written for internists in their practice and also for the specialists in cardiology to improve their therapeutic measures being informed about specific problems in cardiac pacement. Apart from the basics of cardiac pacement also indications, selection of pacers, implantation methods and complications are described. A special focus is on postoperative monitoring of the patient. A vast amount of illustrations is combined with very instructive text. This book is for daily practice and desk reference for practicioners and clinicians.

Despite numerous reports of cerebral damage in cardiac surgery, the subject has not been given the attention it requires. This book, with a preface by Torkel Aberg, will remedy that situation. The causes and incidence of pre- and post-operative cerebral damage are considered in the first section. Cardiac surgery patients frequently have preoperative cerebral impairment, not suprising when one considers the impaired circulation from a damaged heart and the brain's prodigious need for blood. Moreover, several perioperative aspects of surgical procedures have been considered as possible causes of cerebral dysfunction, for example: microbubbles, toxic by-products, non-pulsatile blood flow. The second section describes how imaging techniques (CT scan, MRI, regional cerebral blood flow imaging), and functional assessment techniques. (PET scan, EEG, BEAM and evoked potentials) can be used to measure cerebral damage. In the third section, psychometric and neuropsychological techniques are used to assess impaired mental abilities (abstract thinking, language, memory, visuo-spatial ability, mental flexibility, attention and concentration). The final section explores the relationship between cerebral dysfunction and psychopathology (several types of depression, anxiety, and aspects of organic brain syndrome, delirium and dementia).

This volume contains selected works from the 25th Anniversary of the International Conference on Intracranial Pressure (ICP) held in Williamsburg, Virginia. The theme of the meeting was Intracranial Pressure and Neuromonitoring and focused on all the current state of the art brain monitoring methodologies and their application to brain injury. The brain monitoring techniques covered a wide spectrum from neurochemical monitoring of the injured brain to specialized techniques for assessing shunt function in normal pressure hydrocephalus. It also includes the most recent advances in monitoring of the brain oxygen levels using electrodes or the less invasive Near Infrared Sprectroscopy devices. Controversial issues regarding the management of ICP and CPP or both are also addressed and there are several works dealing with this topic. Of particular interest is the group of papers describing diagnosis and outcome in normal pressure hydrocephalus. It is the first compilation of papers which covers all the latest brain monitoring studies in both ischemia, trauma and hydrocephalus. The manuscripts in this volume have been selected from over 300 abstracts submitted to this international symposium. The abstracts are also published in order to provide the most comprehensive view of the progress made in brain injury research.

Charles Ernest Overton's 1901 monograph Studien aber die Narkose has become a scientific classic in a number of different fields. This book represents the first English translation, and in fact the first translation into any other language, of the original German work. In addition to. the edited translation, this volume contains introductory chapters by Keith Miller, Peter Winter and Leonard Firestone and myself. As editor, I have attempted above all else to ensure that the translation faithfully represents Overton's ideas and data, while making the material readily understandable to the modem scientific reader. This has frequently required that extremely long sentences, common in turn-of the-century German but considered cumbersome today, be simplified into two or even three sentences. In addition, I have paid particular attention to the correct translation of scientific terms, and I accept complete responsibility for any inaccuracies in this area. Overton's original contents list included headings and subheadings, but only a fraction of these appear in the original text. For the sake of clarity they have all been included in the body of the translated work. Also included is an index containing all chemicals mentioned in the book, along with their Chemical Abstracts System Registry Numbers for un ambiguous identification, a complete list of Overton's publications (Appendix B), and a list of all biographical articles about Overton and articles dealing specifically with analyses of his data (Appendix C)."

Drug dosage in renal insufficiency has become an toxication. In 1975, his Poison Index was pub important facet of nephrology, a subspeciality of lished, first in German, and two years later in internal medicine which is only 30 years young but English, with supplements in 1979 and 1983. This constantly growing in scope and importance. Two volume has become an obligatory reference in more thirds of all drugs are partially, mainly, or exclu than 2500 dialysis units. sively excreted by the kidneys. In the presence of Based on GOnter Seyffart's experience and renal insufficiency, dose adjustments are therefore knowledge in this field, the plans for this book obligatory. In patients on dialysis, drug elimination matured in 1984, a logical step in view of his by this route must also be considered. untiring effort and diligence. In order to deal with As the reader of this book will discover, 20 more than 1200 different drugs and almost 4000 percent of currently used drugs are contraindicated references, 21 contributors were sollicited, while it where there is any degree of renal insufficiency, took six years to complete the work. The major and for at least another 60 percent a dose reduc share of the effort was thus left to the main author tion is required. It is obvious, therefore, that the and editor and he has produced a concise work of detailed knowledge required can never be com impressive clarity.

Anesthesia and the Central Nervous System is a textbook for a postgraduate course as well as a reference for all anesthesiologists which presents many of the latest concepts in anesthesiology within a brief formal presentation. An outstanding faculty presents topics relating to the biochemistry, physiology, and pharmacology of the nervous system, the anesthetic management of intracranial and spinal cord surgery, and the intensive care management of central nervous system disease. Each chapter is a brief but sharply focused glimpse of the interests in anesthesia. This textbook is the eleventh in a continuing series documenting the proceedings of the Postgraduate Course in Salt Lake City.

Neuroanesthesia contains the edited presentations of the 42nd Annual Postgraduate Course in Anesthesiology given by the Department of Anesthesiology at the University of Utah School of Medicine, February 1997. The chapters reflect recent advances in neurophysiology, pharmacology and monitoring related to the practice of neuroanesthesiology. The sections on central nervous system trauma, intraoperative management, brain protection and postoperative care provide a conceptual framework for current clinical practices. This textbook is the fifteenth in a continuing series documenting the proceedings of the Postgraduate Course of the Department of Anesthesiology of the University of Utah School of Medicine. It reflects, as well as past and future volumes, the rapid and continuing evolution of anesthesia in the last years of the twentieth century.

Since its launch in 1998 the European Society for Intravenous Anaesthesia (EuroSIVA) has come a long way in providing educational material and supporting the research and clinical application of intravenous anaesthesia. After the first two annual meetings held in Barcelona and Amsterdam in 1998 and 1999, three other successful meetings took place in Vienna, Gothenburg and Nice in 2000, 2001 and 2002. Next to these main meetings, starting in the year 2000, a smaller winter meeting has been organised every last week of January in Crans Montana, Switzerland. Both the main summer and the winter meetings breathe the same atmosphere of sharing the latest on intravenous anaesthesia research in the presence of a friendly environment and good company. Since the first meetings the educational tools of EuroSIVA have increased in quantity and technical quality allowing digital slide and video presentation along with the use of the computer simulation program TIVAtrainer during the speaker sessions and the workshops. Furthermore, EuroSIVA now exploits a website www. eurosiva. org that allows for continuous exchange of information on intravenous anaesthesia, the TIVAtrainer, the EuroSIVA meetings and online registration for these meetings. The EuroSIVA is currently engaged in friendly contacts with the Asian Oceanic Society for Intravenous Anaesthesia (AOSIVA), the United Kingdom Society for Intravenous Anaesthesia (UKSIVA), the Korean Society for Intravenous Anaesthesia (KSIVA), the European Society of Anaesthesiology (ESA) and the International Society for Applied Pharmacology (ISAP).

On 15 November 1997, the first international symposium "Neural and Chemical Control of Breathing: Pharmacological and Clinical Aspects" was held at Leiden University Medical Center on the occasion of the retirement of one of the members of the Control of Breathing Research Group of the Departments of Physiology and Anesthesiology, Dr. Aad Berkenbosch. Among others, Dr. Berkenbosch, played an important role in this research group, which made a large and significant contribution to scientific research on the regulation of breathing. This book presents the proceedings of that meeting together with papers of several authors who have strong bonds with the Leiden Departments of Physiology and Anesthesiology. All studies represent state of the art work on the subject of respiratory control and cardiovascular medicine, with emphasis on the physiological, pharmacological and anesthesiological aspects of both fields. The book is divided in several sections: Oxygen Physiology. Prof. John Severinghaus presents among other things his ideas on oxygen sensing and high altitude related diseases. Prof. Honda gives results from studies in a unique set of subjects without carotid bodies. The findings of Honda's group support the idea that an intact hypoxic drive from the carotid bodies is necessary for the generation of central hypoxic depression. Dr. Hans van Beek discusses the effects of hypoxia and hypercapnia on cardiac contractility in animal models. Prof. Oeseburg demonstrates the feasibility of Near Infra Red Oximetry for monitoring tissue oxygenation in patients. Central Chemoreception.

The small neck of the aneurysm afforded an easy surgical attack. An ordinary flat silver clip was placed over the sac and tightly compressed obliterated it completely. The clip was flush with the wall of the carotid artery. The sac, lateral to the silver clip, was then picked up with the forceps and thrombosed by the electocautery. Walter Dandy reporting his successful operation of a posterior communicating aneurysm on March 23, 1937. Walter Dandy's patient left the hospital in good health 2 weeks later, and from his report one may gain the impression that the operation was an easy task. Despite continuous developments during the following decades, it was not until the introduction of the operating microscope and microsurgical techniques that surgical treatment was generally accepted. During the microsurgical era surgical results have continued to improve due to diagnostical, neuroanaesthesi ological, and microsurgical refinements, and improved neurointensive care. Endovascular obliteration has become an important treatment alternative but this has not been included in this particular volume. The purpose of the present supplement of the ACTA NEUROCHIRURGICA is to review some of the elements in the neurosurgical management of patients with aneurysmal subarachnoid haemorrhage that are important for a successful outcome. Professor Helge Nornes has been a major force in the development of new techniques and research strategies in this area for a number of years and has recently retired from the National Hospital in Oslo."

PROFESSOR SIR KENNETH L. STUART Pain control has become one ofmedicine's most rapidly growing disciplines, and Iwelcome the opportunity to write this foreword to abook that Iam sure will make its own unique contribution to advancing this discipline. My pleasure in writing it is heightened by my pride in the fact that its editor was at one time an undergraduate student of mine at the University of the West Indies in Jamaica. One of the uncertainties teachers always face is that they can never predict how their charges will turn out. This uncertainty has been happily resolved. Dr. Parris' professional career has been marked by the same dedication and commitment that characterized his undergraduate days and that clearly has been brought to the preparation of this scholarly and practical work. Pain reliefhas been until recently acomparatively neglected field. Its neglect was determined not so much by lack ofprofessional awareness ofits import ance but mainly because so little could be done about it in the past.

The topics in this book represent the presentations given at the First and Second Annual Meetings entitled "Critical Issues in Surgery" held at the Frenchman's Reef Beach Resort, st. Thomas, U.S. Virgin Islands, November 1992 and 1993. This symposium was sponsored by the Department of Surgery, and the Department of Nursing Education and Quality Assurance of Cooper Hospital/University Medical Center, the University of Medicine and Den tistry of New Jersey, Robert Wood Johnson Medical School, Camden, New Jersey, as well as the Academy of Medicine of New Jersey. Chapter authors were charged with the task of writing brief overviews of major issues related to the field of general surgery and critical care medicine. The book is specifically tailored to the needs of general surgeons, allied health professionals and nursing personnel involved in all phases of caring for the surgical patient. Although intended as a reference source with emphasis on up-dated approaches applied in general surgery, it is hoped that the discussion of these topics will compliment other texts and manuscripts. Obviously, a book of this length cannot cover the whole multidiSCiplinary and complex field of surgery. However, the co-editors are certain that the annual appearance of this text will highlight comprehensive, new and interesting approaches to the field of surgery."

Currently blood is a volatile issue. The safety of blood and the quantification of transfusion risks have been dominant themes that have stimulated the development of alternative approaches in this rapidly developing area. In clinical medicine conventional blood and its components are used in supportive therapies dependent on the choice of apparent uncritical trigger factors. A compounding factor is depth of prospective clinical trials for evidence. Such trials in critical care areas would be of enormous value, not only in recording adverse effects and under-transfusion, but also indicating the value of decision analysis and cost-effectiveness in transfusion practice. Alternative approaches include the use of cytokines, growth factors, humanised monoclonal antibodies, recombinant plasma factors, and buffy coat derived natural human interferons. These are being increasingly implemented in the clinic. Solutions for oxygen transport are being developed and fibrinogen coated microcapsules are being investigated for thrombocytopenia. In surgical patients, various crystalloid and colloid combinations are explored as volume replacements. To avoid allogeneic transfusions, beneficial blood saving methods include various strategies, such as autologous deposits, normovolemic haemodilution and various agents including aprotinin, tranecamic acid, desmopressin and erythropoietin, but their use in hospital shows considerable variations. That umbilical cord blood could be a significant source of allogeneic stem cells in related and unrelated transplantation is illustrated by the increasing number of cord blood banks in Europe and elsewhere. Future blood resources are likely to face several challenges: immediate challenges relate to increased regulatory and political oversights; intermediate solutions would offer some improvements in public health and alleviate public fear but probably not address the economic challenges thrust upon the medical care system. As we approach the year 2000, the major concerns about transfusion medicine remain its logistics, safety and effectiveness. This theme is presented in the proceedings of the 22nd International Symposium on Blood Transfusion, developed in 21 up-to-date topics, collected and discussed in four sections. This book will be of timely value to students, professionals and all others interested or involved in the field of transfusion medicine, whether clinical or related.

Foreword by Walter J. Freeman.

The induction of unconsciousness using anesthetic agents demonstrates that the cerebral cortex can operate in two very different behavioral modes: alert and responsive vs. unaware and quiescent. But the states of wakefulness and sleep are not single-neuron properties---they emerge as bulk properties of cooperating populations of neurons, with the switchover between states being similar to the physical change of phase observed when water freezes or ice melts. Some brain-state transitions, such as sleep cycling, anesthetic induction, epileptic seizure, are obvious and detected readily with a few EEG electrodes; others, such as the emergence of gamma rhythms during cognition, or the ultra-slow BOLD rhythms of relaxed free-association, are much more subtle. The unifying theme of this book is the notion that all of these bulk changes in brain behavior can be treated as phase transitions between distinct brain states.

Modeling Phase Transitions in the Brain contains chapter contributions from leading researchers who apply state-space methods, network models, and biophysically-motivated continuum approaches to investigate a range of neuroscientifically relevant problems that include analysis of nonstationary EEG time-series; network topologies that limit epileptic spreading; saddle--node bifurcations for anesthesia, sleep-cycling, and the wake--sleep switch; prediction of dynamical and noise-induced spatiotemporal instabilities underlying BOLD, alpha-, and gamma-band Hopf oscillations, gap-junction-moderated Turing structures, and Hopf-Turing interactions leading to cortical waves.

Anesthesiology: A Comprehensive Review for the Written Boards and Recertification is a high-yield, streamlined study aid. It contains more than 1000 updated, realistic multiple-choice questions tailored to the question content of recent American Board of Anesthesiology (ABA) exams. To maximize reading efficiency, key messages are repeated and highlighted in the bullets. While focusing on most-frequently tested keywords by the ABA, this book also covers new "emerging" topics such as patient safety, statistics, and ethics. Well-chosen illustrations and graphs are used to enhance the learning experience. Also novel is a high-yield summary of the 60 most frequently tested topics and concepts to be reviewed just before taking the boards. With this book as guidance, readers will be able to efficiently prepare for the written primary certification or recertification anesthesiology board exam.

Brain resuscitation is the therapeutic intervention for critically ill patients with severe brain damage, particularly the types caused by ischemia and hypoxia. The The objective of the International Symposium on Brain Resuscitation held in Ube, Yamaguchi Japan October 31 to November 2 1988, and sponsored by Yamaguchi University and the Japanese Ministry of Education, was to review our recent progress in brain resuscitation and to discuss controversies both basic and clinical. To my knowledge, this symposium was the first held in Japan. Our understanding of neuronal dysfunction due to ischemic/hypoxic insults at organ, cellular, and molecular levels has advanced significantly in the last two decades. We had therefore intended that this international symposium should broadly cover the topics which are of interest to both basic researchers and clinicians. Three hundred and twenty-five attendants, including twenty scientists from eight different countries, actively participated in discussion and exchange of new ideas and thoughts concerning brain resuscitation. This book comprises the re ports presented during the symposium which consisted of two main parts: basic and clinical. Although one single meeting can never be expected to solve any problems, meetings often highlight areas of ignorance and problems which are ripe for solving. It has been hard to review all the papers because of the multi plicity of the discussed topics, but the overview on brain resuscitation by Profes sor Bo K. Siesjo and the summary by Professor J."

The past few years have seen the publication of a large number of articles and not a few books on the subject of relief of intractable pain. New ideas have been put forward on pain mechanisms, new methods of treatment have been reported and improved results c1aimed, and a growing catalogue of complications oftreatment has been recorded. The vast and expanding literature on the subject poses for the reader the dual problems of surveil lance and of assessment. The object of the present book is to provide a critical and constructive review of current writings and ideas on a wide range of aspects of the nature of intractable pain, particularly of present day practice and new ideas on treatment. Each chapter is written by an acknowledged authority and the approach throughout is practical rather than academic. In editing the individual chapters an effort was made to achieve a contemporary approach and to eliminate material which was unduly historicalor retrospective in content. At the same time the individ ual style of the authors was retained as far as possible. For decades chronic pain has been a therapeutic 'no man's land'. For the surgeon pain was an unfortunate complication wh ich not infrequently followed surgery; for the physician it was a distressing symptom in a number of disease syndromes; to the psychiatrist it was one of a number of features in many cases of mental illness."

Neurophysiological recording is the major neuromonitoring technique employed in ICU. In addition, continuous recording of intracranial pressure has proved to provide infomation useful for critical care of the patient with severe brain damage. It is, however, difficult to assess neurochemical and/or metabolic environments of the brain with these conventional neuromoni toring techniques. Information regarding these changes, if available on a real-time basis, is undoubtedly useful for patient care. Many important developments in bedside techniques to monitor these changes have been achieved during the last few years. It was the consensus of the editors that a symposium to exchange knowledge concerning recent advances in such techniques would be valuable. With this background, the First International Symposium of Neuro chemical Monitoring in ICU held May 20-21, 1994, in Tokyo, Japan. It was not the intention of the organizers that this symposium should survey the whole field of neuromonitoring in ICU. The symposium was thus focused on clinical application of microdialysis, jugular venous oximetry, and near infrared spectroscopy, which currently appear to be the most promising techniques for monitoring neurochemical and metabolic changes in the brain in a clinical setting. We termed these techniques collectively as neuro chemical monitoring, contrasting them with neurophysiological monitoring in ICU. The concept that has motivated this symposium was to provide an opportunity to exchange up-to-date summaries on issues currently debated for these techniques. This volume is based on the papers presented at the symposium."

This aim of this book is to focus on a very common situation seen in medical practice, the acute catabolic state. This pathophysiological sit uation is rarely discussed as a separate entity, possibly because it is seen in all specialties of medicine and results from a great diversity of agents, insults, and diseases. It thus seemed to be high time to gather the most important and up-to-date knowledge on this entity, and the primary aim of the book is to offer a collection of updated information on the acute catabolic state. Another objective of the book is to make clear that, apart from the general response of the whole organism during the acute catabolic state, a series of organ-specific responses will also take place, which must also be considered during treatment. It has become very clear of these organ-spe from working on this book that current knowledge cific responses is very sparse and in some areas almost nonexistent; this book thus also focuses on the responses and changes which take place in different organs during the acute catabolic state and the inter action between these organs and their responses.