Challenges in Biomedical Instrumentation A Birds eye view

About population
According to WHO, the global population was 2.8 billion in 1955 may reach 5.8 billion by the year 2025. The proportion of older people requiring support from adults of working age will increase from 10.5% in 1955 to 17.2% in 2025. By 2025 the strength of senior citizens may rise up to 300% mostly in many developing countries, especially in Latin America and Asia. Average life expectancy at birth in 1955 was just 48 years and in 2025 it will reach 73 years.

What is biomedical Instrumentation

Biomedical Instrumentation is a multi disciplinary approach meant for well being of human kind in the areas including medical imaging, biological signal analysis, medical informatics, clinical engineering, biomechanics, rehabilitation engineering, prosthetic devices and artificial organs, biomaterials, biosensors, cellular and tissue engineering, biological transport phenomena, physiological modelling, biological effects of electromagnetic fields.

Impact of BMI on human life

The instruments used in the hospitals now a days range from the drug administrating pumps, heartbeat monitors, sccnners, implanted pace makers, artificial joints Progress in medical Instrumentation revolutionized the medical facilities The basic biomedical Instrumentation can broadly be categorized mainly in to two categories 1. Indirect interactive instrumentation ex: Pharmaceutical Instrumentation for the preparation of medicines 2. Direct interactive instrumentation a. Diagnostic b. Maintenance c. Surgical 1. Diseases Trends in 21st century Infectious diseases 1

Futures visions
People will store their genetic profile an accessible database . They live in smart houses equipped with sensors to monitor their health status.

Everyone will have access to regular screening so that many diseases will effectively be preventable by early detection and treatment Noninvasive sensor-based procedures will be designed to monitor and evaluate health status of citizens. It will be an unusual and perhaps a foolish person whose genetic profile is not stored in an accessible database. People will be able to live in smart houses equipped with sensors to monitor the status of their health. Everyone will have access to regular screening so that many diseases will effectively be preventable by early detection and treatment. Efficient noninvasive sensor-based procedures will be designed to monitor and evaluate health status of citizens and, particularly, their cardiovascular and locomotor systems. Gait and motion analysis is an area in which sophisticated new procedures will be developed and introduced into clinical practice. These technologies will also be applicable in sports medicine, to aid athletes to reach their full potential. On the other hand, those with disabilities will be assisted by unobtrusive and intelligent devices to help with their mobility and dexterity and to compensate for deficient cognitive and physiological functions.

Access to the virtual world will be easy and intuitive, so that the "cyberphysician" will largely be able to undertake many of the functions currently in the realm of the general practitioner. The cyberphysician will be able to guide patients through the management of their illnesses while in their homes, arranging for the timely provision of the appropriate medicines. If a patient needs to go by ambulance to hospital as the result of an accident or an emergency, the vehicle will be equipped to initiate an accurate diagnosis so that no time will be wasted on arrival. The scanners in the hospital will make clear and realistic pictures

of the inside of the body, supplemented by information from laboratory tests using automated analysers.

The treatment which the patient receives will be determined by computer, balancing the costs against the benefits, and following evidence-based ethical protocols. Internal and external sensors will be able continuously to measure the response to treatment. Many of the people who look after the patient will not be medically qualified but will be highly skilled practitioners trained in specialised diagnostic and therapeutic procedures. The doctors and all the other staff will have access to clinical data on a need-to-know basis through hand-held wireless personal digital assistants, thus avoiding information overload and protecting the confidentiality of the patients. Similar processes will take place within the teams of professionals concerned with conducting training of athletes, often in outdoor field conditions. This will improve the training process significantly, since it will be based at a more quantitative level using physiological feed-back information from sensors, unavailable previously. All this will significantly and positively influence the broad field of sports medicine.

If anything other than the simplest surgical intervention should be necessary, this will be performed by image-guided instruments, which, in the most complex procedures, will be operated by robots. The air in the operating room will be virtually free from bacteria so that the risk of infection will be trivial. The anaesthetic agents will be automatically delivered to maintain the patient at the optimal level of awareness by feedback control from sensors in and on the body. If body parts need to be replaced, this will be with biologically-

compatible engineered systems made either from living tissue or from artificial materials. Many interventional procedures will be virtually without trauma to the patient, who will not even have to stay in the hospital overnight. Back home, the patient will be empowered to manage recovery and convalescence, both of which will be rapid, again often in the care of the cyberphysician. Following this, rehabilitation will frequently depend on the provision and maintenance of appropriate assistive technologies.

At the other end of the healthcare spectrum, in the developing world, the potential exists greatly to improve diagnosis and therapy and to increase access to appropriate technologies. Clearly, in such countries, there will never be sufficient resources to emulate what will happen in the developed world. The mainstay of diagnosis will likely still be simple X-ray and ultrasonic imaging, both of which are relatively inexpensive but which need to be adapted for the local environment. There will be a limited range of inexpensive but effective medicines. The operating room will be equipped with general-purpose anaesthetic facilities and simple and reliable instruments.

Outside the hospital, there are often strong support groups, but appropriate assistive technologies, such as artificial limbs and wheelchairs, still need to be improved. For all this to be effective, the training and mentoring of the medical and quasimedical, nursing and technical staff will perhaps be the most vital component. Although national self-sufficiency will be desirable, the great distances from the specialist centres to the smaller townships and the need for appropriate tuition and advice from centres in the developed world will mean that telemedicine and ICT systems will be absolutely indispensable. Telemedicine

and e-health are powerful tools increasingly used by health practitioners around the world. Irrespective of distance and the availability of medical specialists on site, these technologies will facilitate medical care, particularly in developing countries. Five issues, however, are unresolved in telemedicine. These are: clinical expectations and medical effectiveness; matching technology to medical needs; economics of telemedicine; legal and social issues; and organisational factors. Despite these problems, however, telemedicine continues to be an essential element in health services delivery in the twenty-first century and significant growth is certain.

Some medical challenges to which engineering might provide solutions

Medical progress is driven both by the identification of problems that need to be solved "clinical pull" - or by the invention of new devices or processes, the application of which may move medical practice into radically new areas - "technology push". History provides many examples: to choose but two from engineering, the plethora of paperwork has led to the development of the electronic patient record and the invention of the laser has made possible previously undreamt-of surgical procedures. In the following paragraphs, just a few of the vast number of future challenges for engineering are discussed. They have been selected at random: they could have been drawn from vascular diseases, cancer, mental health, diabetes and so on. The purpose is to give a flavour of the excitement and potential of biomedical engineering, not to be comprehensive.

The Human Genome Project was one of the most significant scientific endeavours in the world in the 1990s. The objective was to discover the entire sequence of the genetic code that is the key to health and disease. This massive task involved the identification of all the approximately 30000 genes in human DNA and the determination of the three billion chemical base pairs of which it is composed. The result of this research is that it is now becoming possible to diagnose and predict diseases, all of which, to a greater or lesser extent, have a genetic component, and to develop new and effective methods of combating them. Vital to this effort has been the development of devices including automatic sequencers, robotic liquid-handling equipment and software for databasing and sequence assembly.

The challenge for engineering is now to devise novel and cost-effective approaches to enable the benefits of this new knowledge to extend to individuals, whether to predict their susceptibility to diseases, to diagnose the nature of diseases or to treat them by genetic means. For example, successful therapy may require the delivery of healthy genes into the individual cells within the patient's body: a bioengineering technique that promises to make this possible involves localised exposure to ultrasonic waves in the presence of tiny precision encapsulated gas bubbles which can make the cell walls temporarily porous to the ingress of the genetic material.

Aging and disability pose what will arguably become the most pressing sociomedical problem in the coming century. Today, younger people globally predominate, with a fairly steady reduction in population with age and very few living beyond 100 years. By 2050, in

the least developed regions, there will be approximately equal numbers in all age ranges up to about 40 years and this will extend up to about 60 years in less developed regions. In the more developed regions, the population will peak in numbers at around 65 years, with progressively fewer people of younger ages. Nevertheless, even in more developed regions, overall longevity will seldom exceed 100 years.

It is a fact that, in Europe, the upper limit of compulsory working age will need to be raised to 75 years in order to obtain in 2050 the same potential support ratio as that existing in 1995, that is, 4.8 persons of working age per older person. An inevitable corollary of this is that people will have to remain fit enough to engage in productive work for 10 years more than they do today and this will only be achievable if they have access to appropriate assistive technologies. The intelligent systems and technologies in rehabilitation engineering represent a dynamic field which is evolving tremendously. These systems are essential components in increasing the well-being of people with disabling conditions around the world. The challenge for bioengineering will be to develop these technologies, which will include telecare, aids and devices for people with visual and communication impairments, tissue engineering approaches to repairing brain damage after stroke and nerve regeneration after spinal cord and other injuries, and functional electrical stimulation for the maintenance of continence. Repairing worn out joints has become a routine surgical procedure with the development of mechanical devices and new bone surface treatments. The main goal is to relieve the pain in the joint following damage, which is most often the result of arthritis. Joints commonly affected are those in the hip, knee, shoulder, elbow, wrist, finger and ankle. Although the

present procedures are successful in around 90 per cent of cases, problems may arise due to infection, blood clots, loosening, dislocation, wear, breakage and nerve injury. Some of these problems may make it necessary for the artificial joint to be replaced after a period which, in younger and more active people, may currently be significantly less than a decade.

The trends in the use and development of new technologies must also be oriented toward noninvasive or, at least, minimally-invasive diagnosis and therapy. These techniques and devices will lead to more comfortable lives for patients, as well as their faster rehabilitation and shorter stay in hospitals, including reduction of health care costs. The challenge for bioengineering in this field is, for example, to reduce the trauma of the surgical procedure so that the patient can leave the hospital quickly and return rapidly to normal life, to minimise the immediate postoperative complications and to extend the life of the new joint so that it never needs to be replaced. The achievement of these objectives will require the development of better techniques for accessing the diseased joint and performing the surgery, more reliable fixation of the artificial joint and better mechanical reliability. It may even become possible to dispense with mechanical artificial joints and to regrow the worn out joints by using the techniques of tissue engineering. Various engineering prostheses will evolve from interdisciplinary research based on new technologies, such as, for instance, those restoring lost or damaged sight or impaired motor function.

Understanding the structure and function of the human body will be advanced by the development of more and more powerful computers joined together by vast

telecommunications networks based on internet protocol technology. The idea is that it will soon be possible to create a conceptual model of the entire biological continuum of the human organism (that is, physiological systems, organs, cells, proteins and genes), based on imaging and visualisation information. The scale of the information will range from the whole body (metres) down to the subcellular structures of which it is composed (nanometres and less).

In addition to imaging, other engineering methods, such as systems theory, control theory and signal processing, will be used to build models of, for example, how cells communicate and how they regulate the production of different proteins. Once the way in which cells function is known, it may be possible to grow replacement organs and other body parts from an individual's own genome. This would be a much more effective approach than current forms of tissue engineering.

Imaging techniques are generally aimed at seeing inside the intact human body. This first became possible with the discovery of X-rays more than a century ago. Since then, techniques using radioactive tracers, ultrasonic waves and nuclear magnetic resonance have become commonplace. All these different methods have their own advantages, disadvantages, costs and benefits. The scanners that produce and display the images are engineering systems based on mechanics, electronics and computing. Generally, except for simple X-ray equipment and ultrasonic scanners, the machinery is large and expensive. In almost every case, the images can only properly be interpreted by medical experts and this is a serious limitation. As far as image acquisition is concerned, current research is

concentrated in the areas of optical, electrical and magnetic approaches, as well as in seeking to extend the capabilities of the mainstream technologies. The images are usually displayed as two-dimensional cross-sections or as three-dim ensional volumes, and some systems can operate in real time. An important use of threedimensional body imaging is in the realisation of faithful musculoskeletal models of human extremities. Such models, incorporating biomechanical models of muscles, are applicable, for instance, in orthopaedics, enabling simulations of planned surgical procedures. Two particularly challenging possibilities for engineers are that the current displays might be replaced by pictorial representations of what would be seen under direct vision, and that a compact ultrasonic scanner could be developed to fit in every doctor's pocket, alongside the stethoscope and other medical paraphernalia.

Biomedical Engineering in Perspective

Biomedical engineering has come a long way since Leonardo da Vinci, who lived from 1452 to 1519, drew his revolutionary pictures of the skeleton and its musculature and studied the mechanics of the flight of birds. The modern era has seen the application of engineering in almost every branch of biomedicine, so that much of the practice of medicine is now completely dependent on the work and support of engineers. The pace of progress is accelerating and tremendous challenges lie ahead for engineers working in this field.

The introduction of electronic patient records, complex and extremely powerful

electromedical equipment and devices, minimally invasive technologies, new possibilities of providing telemedicine and e-health services, new ways of home self-care, sophisticated new sensors, new ways of care and heath care for older persons are only some of possibilities, which, on the other hand, are challenges as well, that are opened up by the introduction of new technologies. Among such problems, there is certainly the one related to adequate education of new generations of medical professionals. It is illustrative, in this context, to mention the opinion that future orthopaedic surgeons might in fact become biomedical engineers of a kind.

The grasp for what could be done by and through biomedical engineering far exceeds the reach that is constrained by the limited availability of resources. There seems to be no limit to what engineering could do further to revolutionise medical practice and many of these challenges will have to be met to enable society to cope with the imperatives of demography, the changing pressures of disease and the rising aspirations of patients and the public.

FUTURE CHALLENGES IN BIOMEDICAL ENGINEERING What is biomedical engineering? Astounding progress has been made in medical science over the last half-century. At the same time, remarkable advances have taken place in electronic and mechanical engineering, computer science and engineering, and in information and communication

technologies (ICT). It is not always realised that this medical progress has been, and continues to be, absolutely dependent on these engineering advances. This linkage is exemplified by the introduction of an increasing number of the most varied, frequently extraordinarily complex and sophisticated, electromedical devices and equipment into everyday medical practice. There has also been an explosive growth in ICT, firstly in the administrative and financial areas of management and, most recently, in medical practice as well. Biomedical engineering is the application of the principles of engineering to the solution of problems in biology and medicine, with particular reference to the techniques, devices and procedures used to diagnose and treat patients with disease. In this definition, the distinction between engineering and physics is far from clear: at the very least, biomedical engineering involves both engineering and applied physics. Moreover, the field is exceptionally highly multidisciplinary. Examples of this multidisciplinarity include biomedical instrumentation, medical imaging, biological signal analysis, medical informatics, clinical engineering, biomechanics, rehabilitation engineering, prosthetic devices and artificial organs, biomaterials, biosensors, cellular and tissue engineering, biological transport phenomena, physiological modelling, biological effects of electromagnetic fields, to name but a few. A well-trained biomedical engineer is ideally suited to work at the intersection of engineering with mathemat ical and physical sciences, biology and medicine, in order to solve real clinical problems. Although biomedical engineers are primarily engineers, they need to have a firm grasp of the biology and medicine that is relevant to their work. Sometimes, their knowledge of the particular medical processes with which they happen to be concerned can be as detailed as that of any medical doctor. Nowadays, medical practice in developed countries is often completely dependent on engineering. Modern hospitals are full of devices, instruments and machines that have been designed and produced by engineers, usually working in collaboration with other healthcare professionals including doctors, nurses, biochemists, physicists, microbiologists and technologists of various specialties. Examples range from the pumps that administer drugs to patients, through the instruments that monitor heart beats and other vital functions, to the hugely complicated scanners that produce detailed three-dimensional images of the internal body structures. Engineering devices are also essential for many kinds of treatments: examples include implanted pacemakers that maintain the function of the heart, artificial joints that replace those damaged by disease, and synthetic blood vessels. Progress in medical engineering has never been more rapid than it is today. Medical engineering innovations will continue to revolutionise clinical practice whether by providing solutions to the challenges of obtaining fast and reliable diagnosis, providing effective and less traumatic therapies, managing the burgeoning volumes of data, or by the discovery and development of radically new technologies leading to completely novel procedures. Visions of the future

It will be an unusual and perhaps a foolish person whose genetic profile is not stored in an accessible database. People will be able to live in smart houses equipped with sensors to monitor the status of their health. Everyone will have access to regular screening so that many diseases will effectively be preventable by early detection and treatment. Efficient noninvasive sensor-based procedures will be designed to monitor and evaluate health status of citizens and, particularly, their cardiovascular and locomotor systems. Gait and motion analysis is an area in which sophisticated new procedures will be developed and introduced into clinical practice. These technologies will also be applicable in sports medicine, to aid athletes to reach their full potential. On the other hand, those with disabilities will be assisted by unobtrusive and intelligent devices to help with their mobility and dexterity and to compensate for deficient cognitive and physiological functions. Access to the virtual world will be easy and intuitive, so that the "cyberphysician" will largely be able to undertake many of the functions currently in the realm of the general practitioner. The cyberphysician will be able to guide patients through the management of their illnesses while in their homes, arranging for the timely provision of the appropriate medicines. If a patient needs to go by ambulance to hospital as the result of an accident or an emergency, the vehicle will be equipped to initiate an accurate diagnosis so that no time will be wasted on arrival. The scanners in the hospital will make clear and realistic pictures of the inside of the body, supplemented by information from laboratory tests using automated analysers. The treatment which the patient receives will be determined by computer, balancing the costs against the benefits, and following evidence-based ethical protocols. Internal and external sensors will be able continuously to measure the response to treatment. Many of the people who look after the patient will not be medically qualified but will be highly skilled practitioners trained in specialised diagnostic and therapeutic procedures. The doctors and all the other staff will have access to clinical data on a need-to-know basis through hand-held wireless personal digital assistants, thus avoiding information overload and protecting the confidentiality of the patients. Similar processes will take place within the teams of professionals concerned with conducting training of athletes, often in outdoor field conditions. This will improve the training process significantly, since it will be based at a more quantitative level using physiological feed-back information from sensors, unavailable previously. All thi s will significantly and positively influence the broad field of sports medicine. If anything other than the simplest surgical intervention should be necessary, this will be performed by image-guided instruments, which, in the most complex procedures, will be operated by robots. The air in the operating room will be virtually free from bacteria so that the risk of infection will be trivial. The anaesthetic agents will be automatically delivered to maintain the patient at the optimal level of awareness by feedback control from sensors in and on the body. If body parts need to be replaced, this will be with biologicallycompatible engineered systems made either from living tissue or from artificial materials. Many interventional procedures will be virtually without trauma to the patient, who will not even have to stay in the hospital overnight. Back home, the patient will be empowered to manage recovery and convalescence, both of which will be rapid, again often in the care

of the cyberphysician. Following this, rehabilitation will frequently depend on the provision and maintenance of a ppropriate assistive technologies. At the other end of the healthcare spectrum, in the developing world, the potential exists greatly to improve diagnosis and therapy and to increase access to appropriate technologies. Clearly, in such countries, there will never be sufficient resources to emulate what will happen in the developed world. The mainstay of diagnosis will likely still be simple X-ray and ultrasonic imaging, both of which are relatively inexpensive but which need to be adapted for the local environment. There will be a limited range of inexpensive but effective medicines. The operating room will be equipped with general-purpose anaesthetic facilities and simple and reliable instruments. Outside the hospital, there are often strong support groups, but appropriate assistive technologies, such as artificial limbs and wheelchairs, still need to be improved. For all this to be effective, the training and mentoring of the medical and quasimedical, nursing and technical staff will perhaps be the most vital component. Although national self-sufficiency will be desirable, the great distances from the specialist centres to the smaller townships and the need for appropriate tuition and advice from centres in the developed world will mean that telemedicine and ICT systems will be absolutely indispensable. Telemedicine and e-health are powerful tools increasingly used by health practitioners around the world. Irrespective of distance and the availability of medical specialists on site, these technologies will facilitate medical care, particularly in developing countries. Five issues, however, are unresolved in telemedicine. These are: clinical expectations and medical effectiveness; matching technol ogy to medical needs; economics of telemedicine; legal and social issues; and organisational factors. Despite these problems, however, telemedicine continues to be an essential element in health services delivery in the twenty-first century and significant growth is certain. Some medical challenges to which engineering might provide solutions Medical progress is driven both by the identification of problems that need to be solved "clinical pull" - or by the invention of new devices or processes, the application of which may move medical practice into radically new areas - "technology push". History provides many examples: to choose but two from engineering, the plethora of paperwork has led to the development of the electronic patient record and the invention of the laser has made possible previously undreamt-of surgical procedures. In the following paragraphs, just a few of the vast number of future challenges for engineering are discussed. They have been selected at random: they could have been drawn from vascular diseases, cancer, mental health, diabetes and so on. The purpose is to give a flavour of the excitement and potential of biomedical engineering, not to be comprehensive. The Human Genome Project was one of the most significant scientific endeavours in the world in the 1990s. The objective was to discover the entire sequence of the genetic code

that is the key to health and disease. This massive task involved the identification of all the approximately 30000 genes in human DNA and the determination of the three billion chemical base pairs of which it is composed. The result of this research is that it is now becoming possible to diagnose and predict diseases, all of which, to a greater or lesser extent, have a genetic component, and to develop new and effective methods of combating them. Vital to this effort has been the development of devices including automatic sequencers, robotic liquid-handling equipment and software for databasing and sequence assembly. The challenge for engineering is now to devise novel and cost-effective approaches to enable the benefits of this new knowledge to extend to individuals, whether to predict their susceptibility to diseases, to diagnose the nature of diseases or to treat them by genetic means. For example, successful therapy may require the delivery of healthy genes into the individual cells within the patient's body: a bioengineering technique that promises to make this possible involves localised exposure to ultrasonic waves in the presence of tiny precision encapsulated gas bubbles which can make the cell walls temporarily porous to the ingress of the genetic material. Aging and disability pose what will arguably become the most pressing sociomedical problem in the coming century. Today, younger people globally predominate, with a fairly steady reduction in population with age and very few living beyond 100 years. By 2050, in the least developed regions, there will be approximately equal numbers in all age ranges up to about 40 years and this will extend up to about 60 years in less developed regions. In the more developed regions, the population will peak in numbers at around 65 years, with progressively fewer people of younger ages. Nevertheless, even in more developed regions, overall longevity will seldom exceed 100 years. It is a fact that, in Europe, the upper limit of compulsory working age will need to be raised to 75 years in order to obtain in 2050 the same potential support ratio as that existing in 1995, that is, 4.8 persons of working age per older person. An inevitable corollary of this is that people will have to remain fit enough to engage in productive work for 10 years more than they do today and this will only be achievable if they have access to appropriate assistive technologies. The intelligent systems and technologies in rehabilitation engineering represent a dynamic field which is evolving tremendously. These systems are essential components in increasing the well-being of people with disabling conditions around the world. The challenge for bioengineering will be to develop these technologies, which will include telecare, aids and devices for people with visual and communication impairments, tissue engineering approaches to repairing brain damage after stroke and nerve regeneration after spinal cord and other injuries, and functional electrical stimulation for the maintenance of continence. Repairing worn out joints has become a routine surgical procedure with the development of mechanical devices and new bone surface treatments. The main goal is to relieve the pain in the joint following damage, which is most often the result of arthritis. Joints commonly affected are those in the hip, knee, shoulder, elbow, wrist, finger and ankle. Although the present procedures are successful in around 90 per cent of cases, problems may arise due to infection, blood clots, loosening, dislocation, wear, breakage and nerve injury. Some of

these problems may make it necessary for the artificial joint to be replaced after a period which, in younger and more active people, may currently be significantly less than a decade. The trends in the use and development of new technologies must also be oriented toward noninvasive or, at least, minimally-invasive diagnosis and therapy. These techniques and devices will lead to more comfortable lives for patients, as well as their faster rehabilitation and shorter stay in hospitals, including reduction of health care costs. The challenge for bioengineering in this field is, for example, to reduce the trauma of the surgical procedure so that the patient can leave the hospital quickly and return rapidly to normal life, to minimise the immediate postoperative complications and to extend the life of the new joint so that it never needs to be replaced. The achievement of these objectives will require the development of better techniques for accessing the diseased joint and performing the surgery, more reliable fixation of the artificial joint and better mechanical reliability. It may even become possible to dispense with mechanical artificial joints and to regrow the worn out joints by usin g the techniques of tissue engineering. Various engineering prostheses will evolve from interdisciplinary research based on new technologies, such as, for instance, those restoring lost or damaged sight or impaired motor function. Understanding the structure and function of the human body will be advanced by the development of more and more powerful computers joined together by vast telecommunications networks based on internet protocol technology. The idea is that it will soon be possible to create a conceptual model of the entire biological continuum of the human organism (that is, physiological systems, organs, cells, proteins and genes), based on imaging and visualisation information. The scale of the information will range from the whole body (metres) down to the subcellular structures of which it is composed (nanometres and less). In addition to imaging, other engineering methods, such as systems theory, control theory and signal processing, will be used to build models of, for example, how cells communicate and how they regulate the production of different proteins. Once the way in which cells function is known, it may be possible to grow replacement organs and other body parts from an individual's own genome. This would be a much more effective approach than current forms of tissue engineering. Imaging techniques are generally aimed at seeing inside the intact human body. This first became possible with the discovery of X-rays more than a century ago. Since then, techniques using radioactive tracers, ultrasonic waves and nuclear magnetic resonance have become commonplace. All these different methods have their own advantages, disadvantages, costs and benefits. The scanners that produce and display the images are engineering systems based on mechanics, electronics and computing. Generally, except for simple X-ray equipment and ultrasonic scanners, the machinery is large and expensive. In almost every case, the images can only properly be interpreted by medical experts and this is a serious limitation. As far as image acquisition is concerned, current research is concentrated in the areas of optical, electrical and magnetic approaches, as well as in

seeking to extend the capabilities of the mainstream technologies. The images are usually displayed as two-dimensional cross-sections or as three-dim ensional volumes, and some systems can operate in real time. An important use of threedimensional body imaging is in the realisation of faithful musculoskeletal models of human extremities. Such models, incorporating biomechanical models of muscles, are applicable, for instance, in orthopaedics, enabling simulations of planned surgical procedures. Two particularly challenging possibilities for engineers are that the current displays might be replaced by pictorial representations of what would be seen under direct vision, and that a compact ultrasonic scanner could be developed to fit in every doctor's pocket, alongside the stethoscope and other medical paraphernalia. Biomedical Engineering in Perspective Biomedical engineering has come a long way since Leonardo da Vinci, who lived from 1452 to 1519, drew his revolutionary pictures of the skeleton and its musculature and studied the mechanics of the flight of birds. The modern era has seen the application of engineering in almost every branch of biomedicine, so that much of the practice of medicine is now completely dependent on the work and support of engineers. The pace of progress is accelerating and tremendous challenges lie ahead for engineers working in this field. The introduction of electronic patient records, complex and extremely powerful electromedical equipment and devices, minimally invasive technologies, new possibilities of providing telemedicine and e-health services, new ways of home self-care, sophisticated new sensors, new ways of care and heath care for older persons are only some of possibilities, which, on the other hand, are challenges as well, that are opened up by the introduction of new technologies. Among such problems, there is certainly the one related to adequate education of new generations of medical professionals. It is illustrative, in this context, to mention the opinion that future orthopaedic surgeons might in fact become biomedical engineers of a kind. The grasp for what could be done by and through biomedical engineering far exceeds the reach that is constrained by the limited availability of resources. There seems to be no limit to what engineering could do further to revolutionise medical practice and many of these challenges will have to be met to enable society to cope with the imperatives of demography, the changing pressures of disease and the rising aspirations of patients and the public.

Robot Robot What is robot?

Human shape dolls have been found in classicalclock in Europe and Karakuri in Japan. We found such dolls in the story of Pinocchio. The word ``Robot came from Czech 1920 Play``Rossums Universal Robot by Karl Capeck, where robotas, robot in Czech, meaning mechanical slaves developed by Rossum revolved against humans. The stories about robots are found in Issac Asimov science fiction to Osamu Tezukas long story manga ``Astro-Boy. They are mechanical men look like and work for humans. Especially in the science fiction ofIssac Asimov(1920-92) ``I, Robot three Laws of Robotics impressed the audience. The three laws are A robot may not injure a human being, or through inaction, allow a human being to come to harm A robot must obey the orders given it by human beings except where such orders would conflict with the First Law. A robot must protect its own existence as long as such protection does not conflict with the First or Second Law. In spite the fact that the science fictions and animated comics have given vivid image of the robots and cyborgs, the robots found in the real life are placed in the factories and they are just arms with end effecter doing repeated simple tasks of moving, assembling, palletizing, painting, cutting and welding. Such robots are said industrial robots. In 1996, Honda Motor Co. announced the first humanoid robot P2 which could autonomously walk with biped, which bought the shock to scientists and engineers who had done researches on walking robot, since Honda had kept the project secret since 1986 from its start. In 1997 the more advanced P3 appeared and in November 2000, the popular Asimo appeared and humanoid researches have been progressed in Japan. Nearly the same time, Sony Co. announced its small autonomous biped robot SDR-3X which uses the similar software architecture with entertaining robot dog AIBO, which is a new robot product to entertain human. When AIBO was sold firstly through the network, it was said that 3,000 units were sold in twenty minutes. Industrial Robot The robots found in the factory floors are consisting of arms and the end effecter and doing simple motion like pick and place following the program mainly used for manufacturing are said industrial robots. Industrial robot is more precisely described by the Robot Institute of America as A robot is a reprogrammable multifunctional manipulator designed to move material, parts, tools, or specialized devices, through variable programmed motions for the performance of a variety of tasks. So the robot is used for a general purpose by changing the program. The industrial robot of the arm shape is designed to achieve general purpose tasks by using appropriate end effecter which is the mechanical instrument to affect the work such as a gripper, spray, welding device and so on. The first industrial robot was built in 1961 by

Unimation, Danbury, Connecticut started by J. Engelberger. Either industrial robot or humanoid robot, they are constructed by the mechanical link structures and joints controlled using sensors and controllers implemented by computers. Robotics is the discipline of the robot, and autonomous vehicles, tele-manipulating mechanism and many other automated machines working for human are considered robots. Robotics is the interdisciplinary subject consisting of the following sciences and engineering disciplines: Mechanism; How to design mechanical structures: Control; Driving actuators to drive joints achieve the tasks following the paths determined based on the sensed information and/or planned motion: Information processing; Software construction of the procedure based on the artificial intelligence to achieve the given tasks by integrating the processing of the sensed information and adapting to the environmental situation. Applications; Tasks robotics depend on application fields such as industries, space, medical surgery tele-operation: Mechanism The basic robot mechanical structures said arms are links and joints. The rotational type joint is said articulate joint and sliding type joint is said prismatic. The revolved joint is usually driven by the motor. The end of the arm is said the wrist or hand and the hand is equipped to the end effecter. To move the hand to the appropriate position with appropriate orientation, the arm should be moved by controlling the joints. The position in the open space is specified by the x, y, z coordinates and specified by the three degrees of freedom. The orientation of the hand is specified by the roll, pitch, and yaw. So the robot needs six degrees of freedom to move to the given position and orientation. For the given joint angels the tip position and orientation are uniquely determined which is said the forward kinematics. The motion of the usual industrial robot is commanded by the position and orientation, and all joint angles should be controlled to follow the command which should solve the inverse kinematics problem of determining angles of the joint for the given position and orientation. To place thing at an arbitrary position with specified orientation in the space, six degrees of freedoms are realized by the six joints. Position in the space is specified by the vector in the three dimensional coordinate space, and the orientation is given by the roll, pitch and yaw. So to place a thing at an arbitrary position, six degrees of freedom are required. One degree of freedom is brought by a joint with a link. There are two kinds of joint. One is revolving and the other is sliding. The number of joints required to place a thing at a given position and orientation in the space is at least six. If the manipulator has more than six joints, there exist several postures of links to place a thing at a given position and attitude in the space. This manipulator is said a redundant manipulator. The joint is driven by a electric motor.

All joint angles are specified, the position and orientation of the tip of the manipulator is uniquely specified. When the position and orientation of the manipulator tip is given, the problem of determining joint angles is difficult problem and is said ``inverse kinematics problem. The problem is known to be treated by Homogenous transformation. The first systematic treatment of the problem is found in the book written by R.P. Paul. Dynamics and control The mechanical systems working for the human muscle power was said the Servo-control, which came from the word meaning service. The fly ball governor installed by James Watt in his steam engine in 1788 for keeping rotational speed of engine constant is said the origin of the control, and the foundation of the control theory was born aiming to solve the stability of this closed loop system by J.C. Maxwell of UK and J.Wischnegradski of Russia. The control has been used in all fields since then such as in ships, airplane and chemical processes. The servo-mechanism had been used in assisting the steering of the ship rudder. Elmer and Lawrence Sperry used the gyroscope to control the attitude of the airplane and demonstrated their autostabiliser in 1914 in Paris. The fire control in the combination of radar had been developed during World War II in Radiation Laboratory. After the war, the project to develop the training simulator for pilots started at MIT under the direction of J. Forrester. The project had brought the digital computer ``Whirlwind. The digital computer later had brought the digital control. The problem of the robot control is how to control the joint angles to have the robot move to the given position and orientation. By the inverse kinematics for the desired position and orientation, the angles are determined. To control the joint angles to be desired ones, the motors at the joint should be controlled to generate the necessary torque to drive joints. The dynamics between the input torque and the joint angles are depending on the attitude of the robot, which are described by the nonlinear differential equations. The development of small computers has made possible to integrate the above three technical ingredients into making robot working for human. The robot appeared was doing simple motion like pick and place following the program mainly used for manufacturing. The conventional industrial robot control the input torque based on PID logic of the error between the joint angles and the reference angles. This control law however is not able to apply to the manipulator in the space shuttle since t he robot dynamics is heavily nonlinear. When the reference joint angles are given, the necessary input torque can be determined. This procedure is said the inverse dynamics. This is equivalent to the nonlinear feedback compensation to make the closed loop of the robot be linear. Such control law has made possible to develop the advanced robot. Intelligent Robot When the computer and sensors are used, the intelligent robot comes to be used. The definition of the intelligence is said the ability to adapt to the varying environment by C. Evans in his book ``Mighty Micros. To have the ability to adapt to the environment, it is necessary to have the following functions:

1, Information and data acquisition using sensors and through communication 2, Data storage in the data base 3, Logics to structure and use the data 4, Interaction with the environment The intelligent robot has the function to adapt to the environment by using sensors information, so the robot can pick up the randomly distributed work pieces, which is said bin picking. Under the structure of intelligent control, many kinds of control realizing robot dexterity have been developed such as the force control, coordination control of multiarms. The sensed data are feed into the computer for storing in the database. The data are structured to form the knowledge and learning ability will be considered. Transfer of pendulum The techniques of robot control are now to aim to make the robot mimic the animals. One of the famous such robots are snake robot developed by S.Hirose. HiroseAnaconda The new Toyota Hybrid automobile has the function to park autonomously in line, which seems to be controlled by robot. Robot arm has equipped actuators at joints, but recently the robot with un-actuated joints called under actuated robot has been developed. One of such robot is the rotating type pendulum called Furuta Pendulum. Furuta Pendulum Future Looking at the history of the robot, as above-mentioned, the robot was first invented as a word used in a play. The robot was described as a machine that will do various tasks in lie of human workers in the factory. In the technology, the robot was also developed as a machine that would do various tasks in lieu of human workers. In 1950s, a robotic system that was called as a manipulator was developed to remotely handle radioactive materials in nuclear power plants. It was a machine that could do a dangerous task in lieu of human workers. It was a machine used to release humans from hazardous and dirty works. Currently, there are many robots that are used in hazardous environment, like for plant maintenance in deep undersea, high voltage power live-line maintenance, exploring space and/or planet as well as nuclear power maintenance. Fig. 1 shows an example of a live-line maintenance robot developing by YASKAWA Electric Corp. This shows a robot that is renewing a worn insulator on a utility pole, this is a typical task required for the live-line maintenance. In order to maintain continuous energy supply it must be done without the power shutdown. It is very dangerous work for human to do it. Currently, the robot is being verified by skilled human workers to release humans from such dangerous works in the actual work field. The manufacturing factory is the other typical place where a lot of robots are employed.

Many industrial robots are working especially at the manufacturing factories for automobile industry, home electronic product industries and so on. In such a factory, there are many repeated and simple tasks that are tedious if human workers will do it. In order to release humans from such tasks, the robot is efficiently employed as a human substitution machine. An important robot application in future will be the one for supporting humans in their daily life. In several countries in the world, a problem in the 21st century is the increase of elderly people population and decrease of labor power enough to keep industrial and social activities high quality. For example, in Japan, there is a prediction in which the rate of elderly people (older than 65) population in the total population will reach to 25% in 2020. It means one of 4 persons will be more than 65 years old. In such a society, it will be supposed that the number of people who need some kinds of assistance in several situations of their daily life will increase. Because of those problems in future society, since the beginning of 1990s, the robot which can work together with human and/or support human in human environment has drawn robotics researchers attention and several contributions have been made in this research area. Such a new area in robotics is called as Human Friendly Robotics. There are several kinds of human friendly robots which support humans, that is, rehabilitation robots, house care robot, information service robot, entertainment robot, and so on. Fig. 2 shows a robot that helps quadriplegics when he/she has a meal by himself, My Spoon developed by SECOM Co., Ltd. It can bring the foods on the table to his/her mouse using a robotic arm according to the command produced by him/her. Fig. 3 shows a robot that looks after the house in anothers absence, a home security robot, Banryu developed by tmsuk Co., Ltd. and SANYO DENKI Co., Ltd. It has a legged mobile robot with obstacle avoidance and a TV camera to monitor the house connected to cellular phone. When the house owner is absent, the robot looks around inside the house and sends the monitored image of the house to the owner. Also, it can provide various security services using several sensory functions installed in the body In robotics, traditionally the robot motions have been used to do some kinds of physical tasks. However, when a robot will exist with human in the same environment and the human can directly see and touch the robot, the human may feel something from the motions of the robot and touching the robot. Using such an emotional effect the human will have from the robot, new several applications of human friendly robot have been proposed for entertainment, mental health care applications and so on. One of the famous examples of such a robot is AIBO developed by Sony Corp.. AIBO is a four-legged robot with vision sensors, auditory sensors and so on. It can do various actions using actuators, responding to the inputs to those sensors. It has also several kinds of intelligence to recognize objects, to understand human voice commands for human-robot communication, and also to express emotion via the behaviors. With those functions, human can play with the robot and feel happiness via communication with it. It is an e fficient mental support device for people who are living alone and feel the loneliness hard in their everyday life. Fig. 4 shows the other example of the mental commit robot, which is called as PARO developed by AIST, Japan. It has a seal shape robot with flexible tactile sensors on the surface, auditory sensors in the head that can detect human voice and proximity sensors in

the face that can detect an approaching object. Also this robot has an emotional behavior generator that is driven by the inputs to the sensors installed in the robot. With those functions, human can enjoy several behaviors of the robot via physically interacting with the robot. Though it can be used as a robot for entertainment for the people who are living alone like AIBO, currently, it is considered to apply it to mental therapy. When the robot lives together with human, humanoid, a robot that has a human shape, will be more suitable rather than other shape robot. Since middle of 1990s, humanoid technology has made remarkable advancements. Currently, there are several practical humanoid developed by several universities, institutions and industries. Fig. 5 is an example of humanoid developed by AIST, Japan and Kawada Industries, Inc. The human shape has a possibility of producing several attractive features in humanrobot communication. For example, even when a humanoid will do a simple repetitive task that a conventional industrial robot also can do, people who will see it will have more attractive impression from the humanoid than from the conventional industrial robot. Because of those effects, humanoid can be considered to be an effective human interface device and several application ideas have been investigated, an example of those applications will be an entertainment robot, Qrio Sony Corporation has developed. It is a machine that can communicate with human and shows an attractive behavior to human, like dancing and so on. Even for robot applications to support human physically, because of the emotional function, humanoid technology will also be important. In future, more number of robots and more kinds of robot will be used in our society and they will play an important role to improve the quality of our life. References 1,Ernest L.Hall, Bettie C. Hall, ``Robotics A User-Friendly Introduction Holt-Saunders International Editions, 1985 2,http://www.honda.co.jp/ASIMO/history/ 3,Mikiko Miyakawa, ``Coexistence of Human and Robots: Robot may storm world-but first, soccer, Daily Yomiuri On-line,http//www.yomiuri.co.jp/dy/special/spe 4, Richard P. Paul `` Robot Manipulators: Mathematics, Programming, and Control, The MIT Press Cambridge Massachusetts, 1981. 5, Willam A. Wolovich, ``Robotics: Basic Analysis and Design, Holt, Rinehart and Winston, 1987 6, S.Bennet, A history of control engineering 1800-1930, IEE,1986 7, http://jin.jcic.or.jp/nipponia/nipponia13/sp01.html, 8, http://www.sony.co.jp/SonyInfo/News/Press

Infectious diseases 1

Among the newer emerging infectious agents and diseases, many have already had great impact, while others show potential for impact in the near future. Agents that have made a significant appearance, particularly in the 21st century, are considered in more depth below. These agents include: Ebola and Marburg hemorrhagic fevers, human monkypox, BSE, SARS, West Nile virus, and avian influenza.
Hemorrhagic Fevers: The Ebola and Marburg Viruses

The Ebola and Marburg viruses are the only known members of the filovirus family. They can cause severe hemorrhagic fever with high fatality rates. There is no specific treatment. Ebola virus is better known to the public as a result of discussion in the popular media, such as in the book by Richard Preston, "The Hot Zone: A Terrifying True Story," (1994), and the movie "Outbreak," starring Dustin Hoffman (Warner Brothers Pictures, 1995). The natural animal reservoir of both is still unknown. Ebola Hemorrhagic Fever. Ebola virus infection was first recognized during a human outbreak in 1976 with almost simultaneous outbreaks in both the Sudan and Zaire (now the Democratic Republic of the Congo). It was named after a river in the Democratic Republic of the Congo (Peters & LeDuc, 1999) The Ebola virus is now known to have four subtypes: Zaire, Sudan, Reston, and Ivory Coast (Pourrut et al., 2005). After an outbreak in 1979 in the Sudan, Ebola appeared relatively quiescent until it appeared among macaque monkeys imported from the Philippines and housed at a primate facility in Reston, Virginia (Peters & LeDuc). In late 1994, a single case in a researcher who performed a necropsy on an ill chimpanzee led to the identification of a new subtype, Ebola-Ivory Coast (Arthur, 2002). In Gabon, Africa, outbreaks of Ebola virus infection occurred from 1994 to 1997 (Georges et al., 1999). Another appearance was in 2000-2001 with an Ebola outbreak in Uganda that resulted in 425 cases with 224 deaths by January 2001 (CDC, 2001). In this outbreak, events and conditions associated with acquired disease were: funeral attendance for those who died with Ebola hemorrhagic fever, intrafamilial contact, and nosocomial infections. Schools were closed and a ban against funerals was enacted (World Health Organization [WHO], 2001). In November, 2001, an Ebola outbreak again occurred in Gabon. and in the Democratic Republic of the Congo, and multiple outbreaks occurred in 2000-2004 in Gabon, the Congo, Sudan, and Uganda. Outbreaks continue in the Congo in 2005. At the same time, it was noted that Ebola outbreaks occurred in large mammals, mainly chimpanzees, duikers (a type of antelope), and gorillas, and that human outbreaks tended to follow those observed in animals. Airborne transmission of the Ebola Zaire strain to monkeys by aerosol has been demonstrated (Johnson, Jaax, White, & Jahrling, 1995) but is not known to occur from human-to-human. To date, no animal reservoir for Ebola virus has been identified (Pourrut et al., 2005). Marburg Hemorrhagic Fever. Marburg virus infection was identified in 1967, when laboratory workers in a pharmaceutical company in Marburg, Germany who were processing tissue from imported African green monkeys began to fall ill. The workers were admitted to the hospital with severe illness. The virus isolated was unrelated to any other known at that time. Other cases occurred at virtually the same time in Frankfurt, Germany and in what was then Belgrade, Yugoslavia (now Serbia) (Peters & LeDuc, 1999). It was determined that the monkeys in all three sites were from the same imported batch from Uganda. The full investigation ultimately led to the recognition of a new family of viruses, the Filoviridiae, of which Marburg virus was the first to be identified (Feldmann & Kiley, 2000). Marburg virus was not recognized again until 1975 when three cases were reported from Johannesburg, South Africa. The index case (initial patient) was a young Australian man who had been on vacation doing a walkabout in what was then Rhodesia (now Zimbabwe) with a female companion. He died, but his companion, and the nurse caring for both of them, recovered (WHO, 2005a). In 1980, Marburg virus infection was next recognized when an index patient became ill in western Kenya, followed by secondary illness of the physician who tried to resuscitate him (Smith et al., 1982). From 1980 until 1998, outbreaks of Marburg virus infection were relatively few and involved a single or a few primary cases.

In 1982, another single case was identified in South Africa. In late 1998, an outbreak of Marburg virus hemorrhagic fever occurred in Durba, in the Democratic Republic of the Congo. Many affected were illegal gold miners in abandoned mines. The remote location and local warfare prevented arrival of experts from the CDC and WHO for months. In October 2004, a very large outbreak began in Angola and was declared over in November 2005. As of November 2005, 374 cases of Marburg hemorrhagic fever were reported, and 329 were fatal (WHO, 2005b; 2005c). Marburg hemorrhagic fever has affected many fewer persons than Ebola virus. Thus, the recent large outbreak that was declared over in November 2005 is of particular interest, especially since before this outbreak, cases in children were rare, and in this outbreak, children account for a high proportion of those affected. Transmission of these viruses occurs by direct contact with infected body fluids from animals and humans, such as blood, saliva, vomitus, respiratory droplets, urine and stool, and contact with virus-contaminated objects (e.g., needles, syringes). Persons who prepare, cook, and eat contaminated animals may become infected. Person-to-person transmission occurs, as does infection from direct inoculation. Transmission via semen may occur weeks after recovery (CDC, 2005a; WHO, 2001). It is extremely important to use proper barrier nursing techniques to prevent secondary cases of Ebola and Marburg virus hemorrhagic fevers to caretakers and families, including use of standard, contact, and airborne isolation precautions. Updated information for infection control for patients with viral hemorrhagic fevers in U.S. hospitals may be found on the CDC website (2005a). There is also concern about use of the filoviruses as bioterror agents, especially if the viruses could be modified to efficiently spread via aerosol from person-to-person.
Monkeypox

Monkeypox results from an orthopoxvirus which has some similarities to the smallpox virus, variola. It is considered to be the most important orthopoxvirus infection in humans outside of smallpox, which has been eradicated in its natural state. Monkeypox was first identified in laboratory monkeys in 1958, and the first human case was reported in 1970 in a child in the Democratic Republic of the Congo. It is now considered endemic in parts of central and western Africa (DiGiulio & Eckburg, 2004a, 2004b). In May of 2003, the first cases in the United States of what was later found to be monkeypox were reported among members of a family in Wisconsin (a woman and man in their early 30s and their young daughter). The family had bought two prairie dogs as pets 11 days before the mother developed fever, headache, sore throat, dyspnea, and malaise along with a small papule. The mother subsequently developed a more severe rash with more than 200 lesions. The outbreak was initially misdiagnosed as a possible staphylococcal infection (CDC, 2003a; Sejvar et al., 2004). The daughter presented with more severe illness that included rash, lymphadenopathy, malaise, enlarged tonsils, and fever. She eventually developed encephalitis, became unresponsive, and required intensive care. Initially it was believed that she might have contracted a viral encephalitis (such as from varicella or herpes simplex virus), but the diagnosis of monkeypox was confirmed. A fourth case was diagnosed in the distributor of exotic animals who had sold the two prairie dogs to the family first affected, thus establishing an epidemiological link between them (Reed et al., 2004). Epidemiological investigation revealed that those two prairie dogs and others were co-housed with an infected Gambian giant rat from Ghana and other exotic rodent species. Additional infected prairie dogs had been sold at swap meets in Illinois, Indiana, and Ohio. In at least one case of monkeypox in this outbreak, an infected prairie dog at an animal clinic transmitted infection to a rabbit, who was the source of primary infection (CDC, 2003a). In this outbreak, 72 cases of monkeypox were reported to the CDC from Illinois, Wisconsin, Indiana, Kansas, Missouri, and Ohio. No specific treatment is known, but supportive and symptomatic care, use of antiviral medications such as cidofovir, and (potentially) vaccinia immune globulin may be useful (Frey & Belshe, 2004). No deaths occurred in this outbreak, and smallpox vaccine was administered both pre-exposure and post-exposure to persons at occupational risk (CDC, 2003b; DiGiulio & Eckburg, 2004b).

This outbreak is an example of how easily a microbe can traverse great distances. It also illustrates a challenge to public health protection, the import of live animals across borders as exotic pets without the necessary oversight (Lashley, 2004). In this outbreak of monkeypox, an embargo on the import, sale, and transport of rodents from Africa and on the sale or movement of prairie dogs was announced on June 11, 2003. However, there is a large illegal trade in animals brought into the United States, and this poses a danger for further instances of transmission of zoonotic diseases (animal diseases that can be transmitted to humans). Another concern is whether or not monkeypox virus has established a reservoir in North America (DiGiulio & Eckburg, 2004a). In Africa, the mortality rate for monkeypox virus infection is between 1% and 10%, and can be higher in children or those who are immunosuppressed (CDC, 2003a). The usual mode of transmission is through the bite of or close contact with an infected animal. Acquisition of monkypox in Africa is associated with preparation and eating of infected rodents and monkeys (Fleischauer et al., 2005). Person-to-person transmission has been previously documented by direct contact and respiratory droplet spread, and there is a theoretical risk for airborne transmission (CDC, 2003d). The risk for person-toperson transmission, while considered rare, is of particular concern to health care workers (Fleischauer et al., 2005). One lesson learned is that when a clinician observes patients with atypical rashes, with or without encephalitis, monkeypox may need to be considered in the differential diagnosis. This is especially true if they have had recent travel to Africa or have exposure to exotic animals or pets (Sejvar et al., 2004). Another lesson is the need for appropriate use of effective infection control. Because severe illness, with no specific treatment, can result from monkeypox virus infection, it is also considered to be a possible agent for use by bioterrorists.
Bovine Spongiform Encephalopathy (BSE)

BSE is a transmissible spongiform encephalopathy (TSE). TSEs are progressively fatal, incurable neurodegenerative diseases that are considered to be prion diseases. Prion proteins that are altered, usually through conformational changes such as misfolding, cause three categories of disease in humans: sporadic, infectious/iatrogenic, and genetic/familial (Glatzel, Stoeck, Seeger, Lhrs, & Azguzzi, 2005). Prion diseases include:

Bovine spongiform encephalopathy (BSE), commonly referred to as "mad cow" disease. Kuru, which was spread horizontally among the Fore people of New Guinea who practiced ritualistic cannibalism, often in conjunction with certain death rituals. Kuru has died out in the Fores born since cannibalism has been banned. Scrapie, a neurological disease in sheep and goats. Creutzfeldt-Jakob disease (CJD) (sporadic, familial or variant), in humans. Chronic wasting disease of certain animals such as elk and mink. Certain genetically determined or familial disorders (e.g., fatal familial insomnia and Gerstmann-StrussslerScheinker syndrome).

Variant Creutzfeldt-Jakob disease (vCJD) is considered to be causally linked to eating beef products contaminated with the prions that cause BSE (Belay et al., 2005). Classic CJD and vCJD are similar but vCJD occurs in younger persons, particularly under 50 years of age. Patients tend to present with behavioral changes or progressive neuropsychiatric symptoms, such as cerebellar ataxia, cognitive impairment, incontinence, dementia, and progression to mutism. The incubation period is long, usually years. Death is inevitable.

Most publicity and lay public concern about the TSEs has related to potential BSE transmission to humans from eating infected meat or meat products. Another area of concern, especially among health care professionals, is the actual and potential transmission through blood transfusions; transmission via corneal, dura mater, and other transplants; or other iatrogenic means (Lashley, 2002a). Concern has also arisen over potential transmission of prion diseases through inadequately sterilized instruments or devices. The current BSE epidemic in the United Kingdom emerged in the 1980s, and epidemics have been reported in many other countries. Linkage to vCJD was first noted in a 1996 report (Will et al., 1996). In the United States, no identified cases of BSE occurred in cows until 2003, when it was identified in a dairy cow in Washington that had been imported from Canada. In June, 2005, BSE was confirmed in a 12 year old cow in Texas that was born in the United States (Belay et al., 2005). In late July, 2005, a third cow was detected in the United States (BSE Update, 2005). The 2003 case of BSE resulted in a number of economic sanctions against U.S. beef. Another result was the implementation of precautions and preventive activities to protect the food supply and enhance surveillance for clinical features of variant Creutzfeldt-Jakob disease (CDC, 2004). As of June 2005, 156 vCJD patients have been reported from the United Kingdom, 13 from France, 3 from Ireland, and one each from Canada, Italy, Japan, Portugal, and the Netherlands (Belay et al., 2005). One vCJD case has been identified in the U.S. This case was in a Florida woman who died in 2004, and who most likely acquired the disease when she lived in Great Britain (Belay et al., 2005).
Severe Acute Respiratory Syndrome (SARS)

Another example of the rapid emergence of a newly recognized human disease agent is the human coronavirus that causes SARS. SARS has been called the first pandemic of the 21st century (Skowronski et al., 2005). In late 2002, reports began to circulate about an "unusual" respiratory disease in southern China, first thought to possibly be an unusual strain of influenza. In February 2003, a physician who was incubating SARS traveled from Guangdong province to Hong Kong. He apparently transmitted SARS to local residents and other travelers, who then returned to their countries of Vietnam, Singapore, Canada, and Taiwan (Breiman et al., 2003). The WHO first reported an outbreak of "acute respiratory syndrome" in China in the February 14, 2003 issue of the Weekly Epidemiological Record, but a period of time passed before international notification occurred (WHO, 2003). The number of reported cases escalated worldwide through May 2003 and then began to decelerate. By mid-July, just under 8, 500 cases had been identified (CDC, 2003c). On July 5, the WHO announced containment of the SARS global outbreak; however, it also warned that SARS was not gone. Rapid scientific attention resulted in the identification of a "novel" coronavirus as the causative agent (Drosten et al., 2003; Ksiazek, Erdman, & Goldsmith, 2003; Peiris et al., 2003). During the SARS outbreak, various definitions of the disease emerged, and a range of infectivity estimates were made. Isolation was deemed important, and it was noted that there was a very high attack rate among health care workers, as well as clustering of cases in community settings such as apartment buildings in Hong Kong. This demonstrated that SARS was highly contagious through close person-to-person contact. Airborne transmission was postulated as possible; SARS was also rapidly spread through air travel. Containment was difficult and it was uncertain whether a seasonal pattern would develop, much like that of influenza. It was believed that the SARS virus may have originated from wildlife, who are often in crowded markets and may be eaten. Effects of this outbreak included uncertainties and fear that, in some cases, resulted in debates and policies against students returning to their U.S. universities from Asia after spring break, and travel restrictions to Hong Kong, parts of China (such as Beijing), Toronto, Canada, and Taiwan. Restrictions had political and economic consequences. Even Asian merchants in unaffected areas experienced a decrease in business, and in other areas, conventions and similar activities were canceled. Identification of SARS cases in Singapore in September 2003 led to concerns about a possible resurgence in the upcoming winter. This concern proved valid. In early January 2004, China announced a case of SARS from Guangdong;

reports of other cases soon followed (WHO, 2004). In response, Chinese health officials slaughtered 10,000 civet cats and other mammals and started a campaign against rats and cockroaches to prevent spread (Normile, 2004; Watts, 2004). On retrospective study, SARS-related virus antibodies were found in serum samples collected in May 2001, indicating that some persons were exposed prior to the 2003 outbreak (Senior, 2004; Zheng, Guan, & Wong, 2004).
West Nile Virus

West Nile virus is a single-stranded RNA flavivirus (Higgs, Schneider, Vanlandingham, Lingler, & Gould, 2005). The most frequent means of transmission is from the bite of an infected mosquito, especially Culex mosquitoes. Mosquitoes may be involved in a complex cycle when they acquire the virus from viremic wild bird reservoirs or other infected vertebrates, including horses and humans. Transmission may also occur through blood transfusion, tissue and organ transplantation, transplacentally from mother to child, and probably through breastfeeding. West Nile virus infection may also occur through direct inoculation, (e.g., among laboratory workers, or those who handle infected animals) (CDC, 2002). A disturbing report also indicates that nonviremic transmission with horizontal transfer of the virus can occur (Higgs, Schneider, Vanlandingham, Lingler, & Gould, 2005). Clinically, there are three basic outcomes following infection with West Nile virus, as follows: 1. 2. No discernable symptoms. This outcome occurs in about 80% of those infected; Development of West Nile fever, a mild illness with flu-like symptoms that is self-limited in immunocompetent individuals. This occurs in approximately 20% of those infected; and Development of central nervous system infection, usually manifested as encephalitis or meningitis. Signs and symptoms include: fever, headache, gastrointestinal symptoms, stiff neck, alterations in consciousness and mental status such as lethargy, seizures, weakness, focal neurological deficits, movement disorders, and others. This outcome occurs in less than 1% of those infected, most frequently in those who are over the age of 50 years (Dean & Palermo, 2005; Granwehr et al., 2004; Watson, Bartt, Houff, Leurgans, & Schneck, 2005).

3.

West Nile virus was first identified in 1937 from a person in the West Nile district of Uganda. Outbreaks were infrequent until 1996 when more significant outbreaks, with hundreds of persons manifesting neurological signs and symptoms, occurred in countries such as Romania, Russia, and Israel (Lashley, 2002b; Smithburn, Hughes, Burke, & Paul, 1940). North America has only really been aware of West Nile virus since 1999, when a cluster of unusual cases of encephalitis in New York City heralded the arrival of West Nile virus in North America (CDC, 1999a; Lashley, 2002b). That year, 62 human cases were identified (CDC, 1999b). This introduction has been called the "perfect microbial storm" because certain factors were present at that point in time (Glaser, 2004, p.557). These factors included large, non-immune animal and human populations; multiple vectors; and a favorable environment for transmission and dissemination. West Nile virus spread quickly across the continent, and within 5 years established itself as endemic in the United States (Glaser, 2004). As of June 21, 2005, the number of human cases of West Nile Virus reported to the CDC was 2,539, with at least one case reported in each state. This is likely an under report, since West Nile virus infection is not a nationally notifiable disease (CDC, 2005b). No specific treatment for West Nile virus is available. Prevention methods center around minimizing the opportunity for mosquito bites through the use of environmental controls, personal protection, surveillance, and reporting activities. "Emerging Infectious Diseases: Trends and Issues," by Lashley and Durham (2002), provides additional details about preventive methods. Personal protective behaviors associated with decreased risk of mosquito bites include wearing long sleeves and long pants, using insect repellant, avoiding exposure to mosquitoes, and avoiding outside leisure activities at dawn and dusk (Loeb et al., 2005). Health care providers should be able to educate consumers about protective measures.

They should also be alert to the possibility of an outbreak of West Nile virus anywhere across North America, in eastern Europe, Israel, Africa, and elsewhere.
Avian Influenza

On the possibility of an avian influenza pandemic arising, Michael Osterholm, director of the Center for Infectious Disease Research at the University of Minnesota, has said "We're screwed" if it hits soon (Querna, 2005, para. 3). To some extent, the influenza virus has excited the imagination to a lesser degree than many other emerging viral diseases. However, it indeed fits into this category because of its ability to genetically change often and rapidly. This ability to mutate is one of the reasons that each year there are seasonal epidemics, and the necessity to produce vaccines targeted for the appropriate strain(s) in the upcoming influenza season. Influenza virus types A and B infect humans and can cause widespread outbreaks. Type A tends to be the most severe. Influenza virus subtypes are referred to by their hemagglutinen (H) and neuraminidase subtypes (N) which are surface glycoproteins of the virus, such as the avian influenza virus subtype H5N1 (Moorman, 2003). The influenza virus is considered to have the potential for use as an agent for bioterrorism, most probably by alteration to a mutated form with greater infectivity, greater virulence, more efficient human-to-human transmission, and antiviral resistance. There have been several great influenza pandemics, notably in the years:

1918-19: "Spanish flu" (caused 20 to 40 million deaths worldwide; a large proportion of deaths occurred in healthy adults 15 to 35 years of age) 1957: "Asian flu" 1968: "Hong Kong flu" 1977: "Russian flu"

In the United States each year, approximately 100,000 people are hospitalized with influenza, and about 36,000 die. Thomas Abraham warned of "a biological tsunami" brewing in regard to avian influenza (Abraham, 2005). There is fear that avian influenza could become pandemic in the very near future. Avian influenza viruses are those carried by birds (usually wild birds)who then shed virus in saliva, nasal secretions, and feces. Birds or fowl become infected when they come into contact with secretions or excretions from infected birds, most often through fecal-oral transmission. Transmission also occurs through contact with surfaces or materials such as feed, water, cages, or dirt that are contaminated with the virus. Contaminated cages, for example, can carry the virus from one place to another. The first documented direct transmission of an avian influenza virus (H5N1) to humans occurred in 1997 in Hong Kong. Limited human-to-human transmission was also thought to occur. Severe respiratory disease occurred in 18 healthy young adults and children and 6 died. Live poultry markets were the source of the virus strain in this outbreak. Many Asian people prefer to buy fresh foods at so-called "wet-markets," which are increasing in number. In both influenza and SARS, wet markets have been implicated as sources of virus transmission. This illustrates a cultural influence on emergence of infectious diseases. Quarantine and depopulation (or culling of birds) are common controls for outbreaks of avian influenza. For example, the 1997 outbreak was controlled by slaughter of the poultry population. More than 1.2 million chickens and 0.3 million other

poultry were killed and imports of chickens from Hong Kong and China were banned by other countries (Bridges et al., 2002). In 1999, avian influenza viruses H9N2 were isolated in Hong Kong from children with mild influenza. One died. In 2003, the avian influenza virus strain H7N7 occurred in poultry farms in the Netherlands, spreading to Germany and Belgium. Infection, mainly conjunctivitis, occurred in humans, with 1 death. The 2003 outbreak was also controlled by the destruction of over 30 million domestic poultry. In British Columbia, Canada, an outbreak of avian influenza H7N3 occurred in poultry; human cases presented with conjunctivitis and mild flu-like symptoms (Monto, 2005; Tweed et al., 2004). In 2003, the avian influenza virus strain, H5N1, emerged in 2 family members in Hong Kong after traveling in China. Also in 2003, an outbreak of avian influenza virus, H5N1, occurred in South Korea, and in 2004, it emerged in Vietnam and Thailand. Many countries banned the import of poultry products from the Asian countries affected. Other countries in which poultry were infected included Canada, Japan, Laos, North Korea, China, Cambodia, Malaysia, Rumania, and Indonesia. Human cases presented with severe respiratory infection and out of 108 known and confirmed cases recognized from January 2004 to June 28, 2005, 54 died. Probable human-to-human transmission was recognized (CDC, 2005c; Ungchusak et al., 2005). In rural Asia, many households maintain poultry for income and food, and increase the opportunity for human exposure (Sthr, 2005). Of concern is the possible mutation of the avian influenza virus to allow sustained person-to-person transmission. Noting the spread of avian influenza in 2004 to 2005, various conferences have addressed plans for surveillance and control, vaccine production, and treatment involving global cooperation among agencies such as the WHO, the Food and Agriculture Organization, and the World Organization for Animal Health (Avian influenza - Eastern Asia, 2005; Knobler, Mack, Mahmoud, & Lemon, 2005; WHO, 2005a). Among the newer emerging infectious agents and diseases, many have already had great impact, while others show potential for impact in the near future. Agents that have made a significant appearance, particularly in the 21st century, are considered in more depth below. These agents include: Ebola and Marburg hemorrhagic fevers, human monkypox, BSE, SARS, West Nile virus, and avian influenza.
Hemorrhagic Fevers: The Ebola and Marburg Viruses

The Ebola and Marburg viruses are the only known members of the filovirus family. They can cause severe hemorrhagic fever with high fatality rates. There is no specific treatment. Ebola virus is better known to the public as a result of discussion in the popular media, such as in the book by Richard Preston, "The Hot Zone: A Terrifying True Story," (1994), and the movie "Outbreak," starring Dustin Hoffman (Warner Brothers Pictures, 1995). The natural animal reservoir of both is still unknown. Ebola Hemorrhagic Fever. Ebola virus infection was first recognized during a human outbreak in 1976 with almost simultaneous outbreaks in both the Sudan and Zaire (now the Democratic Republic of the Congo). It was named after a river in the Democratic Republic of the Congo (Peters & LeDuc, 1999) The Ebola virus is now known to have four subtypes: Zaire, Sudan, Reston, and Ivory Coast (Pourrut et al., 2005). After an outbreak in 1979 in the Sudan, Ebola appeared relatively quiescent until it appeared among macaque monkeys imported from the Philippines and housed at a primate facility in Reston, Virginia (Peters & LeDuc). In late 1994, a single case in a researcher who performed a necropsy on an ill chimpanzee led to the identification of a new subtype, Ebola-Ivory Coast (Arthur, 2002). In Gabon, Africa, outbreaks of Ebola virus infection occurred from 1994 to 1997 (Georges et al., 1999). Another appearance was in 2000-2001 with an Ebola outbreak in Uganda that resulted in 425 cases with 224 deaths by January 2001 (CDC, 2001). In this outbreak, events and conditions associated with acquired disease were: funeral attendance for those who died with Ebola hemorrhagic fever, intrafamilial contact, and nosocomial infections. Schools were closed and a ban against funerals was enacted (World Health Organization [WHO], 2001).

In November, 2001, an Ebola outbreak again occurred in Gabon. and in the Democratic Republic of the Congo, and multiple outbreaks occurred in 2000-2004 in Gabon, the Congo, Sudan, and Uganda. Outbreaks continue in the Congo in 2005. At the same time, it was noted that Ebola outbreaks occurred in large mammals, mainly chimpanzees, duikers (a type of antelope), and gorillas, and that human outbreaks tended to follow those observed in animals. Airborne transmission of the Ebola Zaire strain to monkeys by aerosol has been demonstrated (Johnson, Jaax, White, & Jahrling, 1995) but is not known to occur from human-to-human. To date, no animal reservoir for Ebola virus has been identified (Pourrut et al., 2005). Marburg Hemorrhagic Fever. Marburg virus infection was identified in 1967, when laboratory workers in a pharmaceutical company in Marburg, Germany who were processing tissue from imported African green monkeys began to fall ill. The workers were admitted to the hospital with severe illness. The virus isolated was unrelated to any other known at that time. Other cases occurred at virtually the same time in Frankfurt, Germany and in what was then Belgrade, Yugoslavia (now Serbia) (Peters & LeDuc, 1999). It was determined that the monkeys in all three sites were from the same imported batch from Uganda. The full investigation ultimately led to the recognition of a new family of viruses, the Filoviridiae, of which Marburg virus was the first to be identified (Feldmann & Kiley, 2000). Marburg virus was not recognized again until 1975 when three cases were reported from Johannesburg, South Africa. The index case (initial patient) was a young Australian man who had been on vacation doing a walkabout in what was then Rhodesia (now Zimbabwe) with a female companion. He died, but his companion, and the nurse caring for both of them, recovered (WHO, 2005a). In 1980, Marburg virus infection was next recognized when an index patient became ill in western Kenya, followed by secondary illness of the physician who tried to resuscitate him (Smith et al., 1982). From 1980 until 1998, outbreaks of Marburg virus infection were relatively few and involved a single or a few primary cases. In 1982, another single case was identified in South Africa. In late 1998, an outbreak of Marburg virus hemorrhagic fever occurred in Durba, in the Democratic Republic of the Congo. Many affected were illegal gold miners in abandoned mines. The remote location and local warfare prevented arrival of experts from the CDC and WHO for months. In October 2004, a very large outbreak began in Angola and was declared over in November 2005. As of November 2005, 374 cases of Marburg hemorrhagic fever were reported, and 329 were fatal (WHO, 2005b; 2005c). Marburg hemorrhagic fever has affected many fewer persons than Ebola virus. Thus, the recent large outbreak that was declared over in November 2005 is of particular interest, especially since before this outbreak, cases in children were rare, and in this outbreak, children account for a high proportion of those affected. Transmission of these viruses occurs by direct contact with infected body fluids from animals and humans, such as blood, saliva, vomitus, respiratory droplets, urine and stool, and contact with virus-contaminated objects (e.g., needles, syringes). Persons who prepare, cook, and eat contaminated animals may become infected. Person-to-person transmission occurs, as does infection from direct inoculation. Transmission via semen may occur weeks after recovery (CDC, 2005a; WHO, 2001). It is extremely important to use proper barrier nursing techniques to prevent secondary cases of Ebola and Marburg virus hemorrhagic fevers to caretakers and families, including use of standard, contact, and airborne isolation precautions. Updated information for infection control for patients with viral hemorrhagic fevers in U.S. hospitals may be found on the CDC website (2005a). There is also concern about use of the filoviruses as bioterror agents, especially if the viruses could be modified to efficiently spread via aerosol from person-to-person.
Monkeypox

Monkeypox results from an orthopoxvirus which has some similarities to the smallpox virus, variola. It is considered to be the most important orthopoxvirus infection in humans outside of smallpox, which has been eradicated in its natural state. Monkeypox was first identified in laboratory monkeys in 1958, and the first human case was reported in 1970 in a child in the Democratic Republic of the Congo. It is now considered endemic in parts of central and western Africa (DiGiulio & Eckburg, 2004a, 2004b).

In May of 2003, the first cases in the United States of what was later found to be monkeypox were reported among members of a family in Wisconsin (a woman and man in their early 30s and their young daughter). The family had bought two prairie dogs as pets 11 days before the mother developed fever, headache, sore throat, dyspnea, and malaise along with a small papule. The mother subsequently developed a more severe rash with more than 200 lesions. The outbreak was initially misdiagnosed as a possible staphylococcal infection (CDC, 2003a; Sejvar et al., 2004). The daughter presented with more severe illness that included rash, lymphadenopathy, malaise, enlarged tonsils, and fever. She eventually developed encephalitis, became unresponsive, and required intensive care. Initially it was believed that she might have contracted a viral encephalitis (such as from varicella or herpes simplex virus), but the diagnosis of monkeypox was confirmed. A fourth case was diagnosed in the distributor of exotic animals who had sold the two prairie dogs to the family first affected, thus establishing an epidemiological link between them (Reed et al., 20

2. Management of Diseases 3. Instrumentation approach to manage 4. Conclusions