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PubMed1994

A history of the origin, evolution, and impact of electrocardiography.

The invention of the electrocardiograph by Dutch physiologist Willem Einthoven in 1902 gave physicians a powerful tool to help them diagnose various forms of heart disease, especially arrhythmias and acute myocardial infarction. The discovery of x-rays in 1895 and the invention of the electrocardiograph 7 years later inaugurated a new era in which various machines and technical procedures gradually replaced the physician's unaided senses and the stethoscope as the primary tools of cardiac diagnosis. These sophisticated new approaches provided objective information about the structure and function of the heart in health and disease. This review summarizes the origins and development of electrocardiography and addresses its role in defining cardiology as a specialty.

Angina Pectoris↗

PubMed1983

The phylogenetic distribution of electroreception: evidence for convergent evolution of a primitive vertebrate sense modality.

Specializations for electroreception in sense organs and brain centers are found in a wide variety of fishes and amphibians, though probably in a small minority of teleost taxa. No other group of vertebrates or invertebrates is presently suspected to have adaptations for electroreception in the definition given here. The distribution among fishes is unlike any other sense modality in that it has apparently been invented, lost completely and reinvented several times independently, using distinct receptors and central nuclei in the medulla. There are so far no clearly borderline or transitional fishes, either physiologically or anatomically. We rather expect a few new electroreceptive taxa to be found. The evoked potential method and the newly validated central anatomical criteria provide two useful tools for searching. Although Myxiniformes probably lack electroreception, it is well developed in Petromyzoniformes and in all other non-teleost fishes except Holostei. Thus Elasmobranchia, Holocephala, Dipneusti, Crossopterygii, Polypteriformes and Chondrostei have the physiological and anatomical specializations in a common form consistent with a single origin in primitive vertebrates. Amphibian ancestors probably inherited the system from a stem similar to one of these and passed it on at least to the ambystomatoid and salamandroid urodeles, apparently after losing the kinocilium of the sense cell. The suggestion of electroreception in ichthyophid apodans from skin histology has not been confirmed physiologically, behaviorally or by brain anatomy. With respect to more advanced fishes the most parsimonious interpretation is that the entire system, peripheral and central was lost in ancestors of holostean and teleostean fishes and new systems reinvented in Siluriformes, in Gymnotiformes, in Xenomystinae and in Mormyriformes. These 4 taxa must represent at least two, and probably 3 or 4 independent inventions, presumably from mechanoreceptive lateral line organs and brain centers.

Afferent Pathways↗

PubMed2004

Biotechnology--a challenge to the patent system.

Biotechnology inventions raise both moral and technical dilemmas. The patent system was developed to protect inventions such as the Spinning Jenny and Stevenson's Rocket. This article looks at how this long-established and slow-moving system is coping with a modern, highly sophisticated and swiftly moving field of science. It looks at specific areas of the technology--research tools and claims that reach to the products produced using those tools, genes, stem cells and bioinformatics. It concludes that the system is having to adapt, but that it will cope.

Biomedical Research↗

PubMedDate not supplied

Patentability of life and ethics.

Patent law has relied in part on ethical considerations since its inception in Europe. Such considerations have been introduced more recently in the United States. Whereas the EU Directive on the protection on the occasion of the Human Genome Project of biotechnological inventions was intended to foster economic development in Europe, its implementation is outweighted by controversy about patenting life and commercialization of science. The confusion created must be cleared at the international level through harmonization of patent office policies preventing abusive commercial practices in the absence of inventiveness.

Biotechnology↗

PubMed2006

Linnaeus' herbarium cabinet: a piece of furniture and its function.

The Swedish 18th-century naturalist Carolus (Carl) Linnaeus is habitually credited with laying the foundations of modern taxonomy through the invention of binominal nomenclature. However, another innovation of Linnaeus' has largely gone unnoticed. He seems to have been one of the first botanists to leave his herbarium unbound, keeping the sheets of dried plants separate and stacking them in a purpose built-cabinet. Understanding the significance of this seemingly mundane and simple invention opens a window onto the profound changes that natural history underwent in the 18th century.

Botany↗

PubMed2005

A new weighted scoring system for Subjective Global Assessment.

OBJECTIVE: Subjective Global Assessment (SGA) is a widely used and validated method for identifying and classifying malnutrition. Recently, in effort to assess nutritional status more accurately, quantitative systems have been devised in which scores are assigned for items or components of the SGA. In addition to validation of conventional SGA in our patient population, this prospective study investigated the association of a recently devised quantitative SGA (Q-SGA) method and an invented modified Q-SGA (MQ-SGA) scoring system with conventional SGA. METHODS: A total of 2197 patients was evaluated. Each subject was assessed for malnutrition by SGA, anthropometric measurements, and laboratory testing. The items of SGA were scored by assigning 1 point for each increasing severity level to obtain the Q-SGA score. In the invented MQ-SGA system, the items were entered into the logistic regression model and weighted scores were calculated according to the weighted effect of the SGA items. The efficiencies of Q-SGA and MQ-SGA were compared to predict malnutrition according to SGA. RESULTS: Eighty-nine percent of patients were classified as well nourished according to conventional SGA, whereas 27 patients (1.2%) were classified as severely malnourished. When patients were grouped according to binary SGA outcome (well nourished versus malnourished), receiver operating characteristics curve areas for the Q-SGA and MQ-SGA scores were 0.897 (95% confidence interval = 0.875-0.919) and 0.952 (95% confidence interval = 0.939-0.964), respectively. The cutoff points for Q-SGA and MQ-SGA were identified as 10 and 18, respectively. Although the sensitivity of these systems in identifying malnutrition were similar (90.0% and 90.9%, respectively), the specificity of MQ-SGA was greater than that of Q-SGA (85.6% versus 67.0%). CONCLUSIONS: The findings suggest that MQ-SGA outperforms Q-SGA in identifying malnutrition according to SGA. Future nutrition scoring studies need to take into account the weighted effects of items on outcome.

Anthropometry↗

PubMed1996

The early years with Hal Anger.

In the course of your day, when you interpret or count a radioimmunoassay or a sample of blood or body fluid, you will probably use a variant of the well counter invented by Hal O. Anger in the early 1950s. If you obtain or read a patient image, it probably came from some type of his gamma camera. If yoy do or see a single photon emission computed tomography study, Hal Anger showed the feasibility. Even if you are working with positrons, some of the early imaging work was done by devices Hal Anger invented. This article deals primarily with the years I spent with Hal, 1962 to 1964. I was fortunate to have the opportunity to spend this time with him when he had just completed the development of his 11-in gamma camera, the first multipurpose camera suitable for diverse clinical examinations. In retrospect, it is easy to see why Hal was honored by the Society of Nuclear Medicine as one of its pioneers and why he was the first recipient of the Ben Cassen Prize. However, it was not always clear that Hal's creative road would lead to such deserved distinction. I have tried to portray the beginnings of this journey to the best of my recollections.

History, 20th Century↗

PubMed2003

The evolution of gene patents viewed from the United States Patent Office.

In my remarks here, I have necessarily limited myself to general principles of patent law that are applicable to a consideration of gene-related inventions. Were I still Commissioner of Patents and Trademarks, I would not let electrical engineers anywhere near the examination of applications for patents for gene-related inventions, just as I would not let the USPTO's many Ph.D.s in microbiology or genetics near the examination of complex applications on computer architecture or programming. The same should hold true for attorneys who prosecute patent applications. That is why the U.S. patent system works so well. There can be no discrimination in the system by the field of technology--a principle enshrined in Article 27 of the World Trade Organization's Trade-Related Aspects of Intellectual Property. But we quite properly depend upon specialists to apply across-the-board general principles to very specialized technological fields of endeavor. This works very well in a system in which in the U.S., "everything under the sun made by humans" is patentable.

Creativity↗

PubMed2003

Competition policy in patent cases and antitrust.

The article that follows examines the competition policy reflected in the decisions of the Court of Appeals for the Federal Circuit in its patent cases. The court's views on this subject have been manifested most plainly in decisions that have transformed the law concerning infringement under the doctrine of equivalents and claim construction. In both categories, the court narrowed patent scope by reason of its desire to protect competitors. The article argues that the court's premise in prescribing narrower claim scope reflected an incomplete view of competition policy. The court's analysis overlooked the benefits to competition provided by patents, which stimulate inventions and their development. The article traces the development of antitrust jurisprudence and demonstrates how respect for the contribution of patents to competition and skepticism of free-riding has evolved, particularly beginning in the 1970s. The article draws a parallel between the Court's reasoning about competition policy, on the one hand, and the rejected views of Justices Hugo Black and William O. Douglas and abandoned patent-antitrust jurisprudence, on the other. The Federal Circuit's decision in Festo Corp. v. Shoketsu Kinzoku Kogyo Kabushiki Co., Ltd., 234 F.3d 558 (Fed. Cir. 2000), on the subject of equivalents is considered in the paper. In that decision, the majority adopted a new rule that completely barred infringement under the doctrine of equivalents of any claim limitation where, in prosecution, there had been a narrowing amendment relating to patentability. In the past, prosecution estoppel foreclosing equivalents had been subject to a "flexible bar," which, in some circumstances, allowed for equivalence notwithstanding such an amendment. The article points out that because almost all patents are amended during prosecution, the effect would be to allow widespread copying of patented inventions by trivial modifications of any narrowed claim limitation. The incentive to innovate in the future would be correspondingly diminished and the expectations of past patentees would be correspondingly altered.

Antitrust Laws↗

PubMed2002

Pharmaceutical patents and price controls.

BACKGROUND: Since 1995, every member-country of the World Trade Organization (WTO) has agreed to honor a 20-year patent-life, from the date of a pharmaceutical company's application for the patent, in the country of application. Patent protection retards competitive imitation of an invented product. This kind of protection is particularly important for pharmaceuticals, because pharmaceuticals that are not derived from biotechnology can be imitated easily and inexpensively. The economic function of a patent is to allow a period of above-normal profits for a technically and commercially successful product; these profits stimulate further investment and invention. However, direct price controls, or permutations of direct price controls on pharmaceutical compounds, can fully or partially circumvent the economic intent of patent agreements. OBJECTIVE: This paper formulates an economic model that takes into account demand and cost/supply dimensions of the output and pricing of a hypothetical pharmaceutical, extrapolating about the respective effects of direct price controls and lack of price controls, and describing permutations of direct price controls in different countries. RESULTS: The pharmaceutical industry depends on patents to fund the development and introduction of new products. A country can indirectly circumvent the economic logic of a patent by using price controls, but it cannot shift the economic costs of such a policy to another country that does not use price controls. Instead, less money is available for research and development (R&D). CONCLUSIONS: Pharmaceutical price controls allow some countries to avoid the constraints of patent agreements without breaking those agreements outright. This, in turn, reduces the amount of profit available for further R&D, which is a detriment to consumers worldwide.

Commerce↗

PubMed2000

The bicentennial of the Voltaic battery (1800-2000): the artificial electric organ.

Alessandro Volta invented the electric battery at the end of 1799 and communicated his invention to the Royal Society of London in 1800. The studies that led him to develop this revolutionary device began in 1792, after Volta read the work of Luigi Galvani on the existence of an intrinsic electricity in living organisms. During these studies, Volta obtained a series of results of great physiological relevance, which led him to anticipate some important ideas that marked the inception of modern neuroscience. These results have been obscured by a cultural tradition that has seen Volta exclusively as a physicist, lacking interest for biological problems and opposed in an irreversible way to the physiologist, Luigi Galvani.

Animals↗

PubMed2003

[Auguste Lumière, pioneer of the modern cicatrization].

At the "Grand Café" in Paris, on december 28, 1895 Louis and Auguste Lumiere displayed the cinematograph, a technical innovation that revolutionized the nascent motion picture. It was the first public projection of a film. While Louis continues his work on pictures and invents autochrome plates for colour photography, Auguste focused his interests on biology and medicine. Since Ambroise Paré, few doctors have been interested in the healing process. Although Carrel and Lecomte Du Nouy published the first studies in the early twentieth century, Auguste Lumière was a pioneer in the modern research and treatment of wounds. He applied the principles of experimental medicine. In his research he used 44 dogs to study the healing speed and the scar quality in certain areas and under general conditions. In the winter of 1914-1915 he studied in Lyon several hundred wounds of war casualties. In 1922 he established and published in a marvellous book the principles of normal healing. In the department of Pr Leon Bérard he was shocked by the fetidness of the wards where the dried bandages were changed once a week. In 1915 he perfected a revolutionary sterilized "treatment-bandage" consisting of 2 mm stitched gauze saturated with Vaseline and Perou's balsam: the "Tulle Gras. In order to disinfect wounds, he used an iodized solution, sprayed in little droplets. The lives of Auguste and Louis Lumière were full of projects and inventions. When Auguste died in 1954 he had registered more than one hundred patents.

Cicatrix↗

PubMed1999

Europe says 'hello Dolly' to the biotech directive.

Nearly a decade after it was first proposed, the European Biotechnology Directive has finally been passed into law. The main purpose of the Directive is to provide a uniform set of legal rules that will apply to biotechnology patents throughout the 15 countries of the European Union. The authors describe how the Directive confirms that, subject to meeting the normal criteria, patents can be granted for inventions involving DNA, cell lines, microorganisms, plants, animals and human-derived material. However, on moral grounds, patents will not be allowed for certain inventions involving human cloning, germ-line gene therapy, human embryos or transgenic animals.

Journal Article↗

PubMed2003

Oral cancer: reviewing the present understanding of its molecular mechanism and exploring the future directions for its effective management.

The present review aims to analyze the information available regarding the molecular mechanisms of Oral Carcinogenesis and explore the future directions where the field of Cancer Biology is venturing. Oncologists have excellently followed the proverb "Necessity is the mother of Invention". The desire to be more precise and comprehensive in their studies has led to the invention of some of the most innovative techniques like laser capture microdissection, comparative genomic hybridization, microarrays, and protein chips etc. Various Biotech companies and Cancer Institutes are on a hunt for anti-cancer drugs and molecular markers for cancers. These revolutionary approaches and the new breed of Oncologists have made the field very exciting and have generated the hope that finally the war against cancer would be won. In the end it is urged that the lead taken in other cancers like colon, breast, leukemia will be emulated in oral cancer. This is expected to provide a molecular blueprint for HNSCC, thus helping to identify suitable markers for the early detection of pre-neoplastic lesions, as well as novel targets for its pharmacological intervention.

Carcinoma, Squamous Cell↗

PubMed2003

The evolution of cell death programs as prerequisites of multicellularity.

One of the hallmarks of multicellularity is that the individual cellular fate is sacrificed for the benefit of a higher order of life-the organism. The accidental death of cells in a multicellular organism results in swelling and membrane-rupture and inevitably spills cell contents into the surrounding tissue with deleterious effects for the organism. To avoid this form of necrotic death the cells of metazoans have developed complex self-destruction mechanisms, collectively called programmed cell death, which see to an orderly removal of superfluous cells. Since evolution never invents new genes but plays variations on old themes by DNA mutations, it is not surprising, that some of the genes involved in metazoan death pathways apparently have evolved from homologues in unicellular organisms, where they originally had different functions. Interestingly some unicellular protozoans have developed a primitive form of non-necrotic cell death themselves, which could mean that the idea of an altruistic death for the benefit of genetically identical cells predated the invention of multicellularity. The cell death pathways of protozoans, however, show no homology to those in metazoans, where several death pathways seem to have evolved in parallel. Mitochondria stands at the beginning of several death pathways and also determines, whether a cell has sufficient energy to complete a death program. However, the endosymbiotic bacterial ancestors of mitochondria are unlikely to have contributed to the recent mitochondrial death machinery and therefore, these components may derive from mutated eukaryotic precursors and might have invaded the respective mitochondrial compartments. Although there is no direct evidence, it seems that the prokaryotic-eukaryotic symbiosis created the space necessary for sophisticated death mechanisms on command, which in their distinct forms are major factors for the evolution of multicellular organisms.

Animals↗

PubMed1987

Autonomous languages of twins.

Twins are regularly reported to invent languages of their own, unintelligible to others. These languages are known as autonomous languages, cryptophasia or idioglossia. Despite current belief, this is not a rare phenomenon. Autonomous languages exist in about 40% of all twins, but often disappear soon. In this study, nine autonomous languages are compared: the circumstances in which they emerge, how these languages relate to the parents' language (the model language) and how they are structured. The prototypical situation is one in which two or more close siblings (not necessarily twins) grow up closely together during the language acquisition period. If an adult model language is frequently absent, the children use each other as a model and acquire the language imperfectly. The language may stabilise at that level. If a model is completely absent, the children probably do not create a language. In all cases known, the language consists of onomatopoeic expressions, some invented words, but for the greatest part of words from the adult language adopted to the constrained phonological possibilities of young children. These words being hardly recognizable, the language may turn out to be completely unintelligible to speakers of the model languages, but they resemble each other in that they lack morphology and that word order is based on pragmatic principles such as saliency and the semantic scope of words. Neither the structure of the languages nor its emergence can be explained by other than situational factors.

Child Language↗

PubMed2003

Effect of government actions on technological innovation for SO2 control.

The relationship between government actions and innovation in environmental control technology is important for the design of cost-effective policies to achieve environmental goals. This paper examines such relationships for the case of sulfur dioxide control technology for U.S. coal-fired power plants. The study employs several complementary research methods, including analyses of key government actions, technology patenting activity, technology performance and cost trends, knowledge transfer activities, and expert elicitations. Our results indicate that government regulation appears to be a greater stimulus to inventive activity than government-sponsored research support alone, and that the anticipation of regulation also spurs inventive activity. Regulatory stringency focuses this activity along particular technical pathways and is a key factor in creating markets for environmental technologies. We also find that with greater technology adoption, both new and existing systems experience notable efficiency improvements and capital cost reductions. The important role of government in fostering knowledge transfer via technical conferences and other measures is also seen as an important factor in promoting environmental technology innovation.

Air Pollutants↗

PubMed2000

Do clinical databases render population-based cancer registers obsolete? The example of breast cancer in Denmark.

OBJECTIVE: Clinical databases have been invented to monitor treatment outcomes, therapies or diseases, often in great detail. The traditional population-based cancer registry has been invented to collect a minimum of information about all incident cancers. Do clinical databases render population-based cancer registers obsolete as sources of cancer cases for epidemiological study? METHODS: We compared the study base of first incident breast cancer cases in Denmark in 1978-1994 known from the national cancer register and from the national clinical database on breast cancer patients. The clinical database is used for monitoring protocoled treatment. RESULTS: Combining the two data sources we found 48,522 first primary breast cancers in Denmark 1978-1994. Of these, 37,640 were included in both data sources, 2151 were included only in the clinical database, and 8731 were included only in the cancer register. A major part of the difference between the two data sources was due to treatment-focused data collection in the clinical database, and a minor part due to differences in the registration of second primaries, date of diagnosis and invasiveness. CONCLUSIONS: Cancer incidence data are sensitive to registration procedures and definitions. Clinical cancer databases cannot generally replace the traditional cancer register as a reliable data source for incident cancer cases in a national population.

Adult↗