Definitive diagnosis of malaria requires the demonstration through laboratory tests of the presence within the patient of malaria parasites or their components. Since malaria parasites can be present even in the absence of malaria manifestations, and since symptoms of malaria can be manifested even in the absence of malaria parasites, malaria diagnosis raises important issues for the adequate understanding of disease, etiology and diagnosis. One approach to the resolution of these issues adopts a realist view, according to which the (...) needed clarifications will be derived from a careful representation of the entities on the side of the patient which form the ultimate truthmakers for clinical statements. We here address a challenge to this realist approach relating to the diagnosis of malaria, and show how this challenge can be resolved by appeal to Basic Formal Ontology (BFO) and to the Ontology for General Medical Science (OGMS) constructed in its terms. (shrink)

Definitive diagnosis of malaria requires the demonstration through laboratory tests of the presence within the patient of malaria parasites or their components. Since malaria parasites can be present even in the absence of malaria manifestations, and since symptoms of malaria can be manifested even in the absence of malaria parasites, malaria diagnosis raises important issues for the adequate understanding of disease, etiology and diagnosis. One approach to the resolution of these issues adopts a realist view, according to which the (...) needed clarifications will be derived from a careful representation of the entities on the side of the patient which form the ultimate truthmakers for clinical statements. We here address a challenge to this realist approach relating to the diagnosis of malaria, and show how this challenge can be resolved by appeal to Basic Formal Ontology (BFO) and to the Ontology for General Medical Science (OGMS) constructed in its terms. (shrink)

There has always been an intimate and complex relationship between the diagnosis of a disease and its treatment. The approach dubbed theranostics aims to combine diagnostic techniques with therapeutic ones by deploying the same molecule in two roles, exploiting the specificity of its function to render disease treatment more effective. Does this technical development have the potential to change our conception of disease diagnosis? With the treatment approach so intimately linked to the diagnostic tool, might it be possible to treat (...) a disease without having first made an independent clinical or laboratory diagnosis? Here we discuss medical diagnosis, arguing for three categories of diagnosis, before presenting an example of a theranostic approach using radioactive prostate-specific membrane antigen ligands. This example allows us to envision a form of theranostic agent that would be able to diagnose a cancer, for example, and engage directly in its treatment, opening up the possibility of treating patients at risk of developing this cancer without any other clinical diagnostic steps. Would it be a problem if these approaches eventually became independent of any specialist clinical diagnostic supervision? If a theranostic technique is shown to work, following its own logic, do we still need an independent ‘traditional’ diagnosis prior to its use? We argue that such a diagnosis would no longer be necessary provided certain conditions are fulfilled. (shrink)

Medical diagnosis has been traditionally recognized as a privileged field of application for so called probabilistic induction. Consequently, the Bayesian theorem, which mathematically formalizes this form of inference, has been seen as the most adequate tool for quantifying the uncertainty surrounding the diagnosis by providing probabilities of different diagnostic hypotheses, given symptomatic or laboratory data. On the other side, it has also been remarked that differential diagnosis rather works by exclusion, e.g. by modus tollens, i.e. deductively. By drawing on (...) a case history, this paper aims at clarifying some points on the issue. Namely: 1) Medical diagnosis does not represent, strictly speaking, a form of induction, but a type, of what in Peircean terms should be called ‘abduction’ (identifying a case as the token of a specific type); 2) in performing the single diagnostic steps, however, different inferential methods are used for both inductive and deductive nature: modus tollens, hypothetical-deductive method, abduction; 3) Bayes’ theorem is a probabilized form of abduction which uses mathematics in order to justify the degree of confidence which can be entertained on a hypothesis given the available evidence; 4) although theoretically irreconcilable, in practice, both the hypothetical- deductive method and the Bayesian one, are used in the same diagnosis with no serious compromise for its correctness; 5) Medical diagnosis, especially differential diagnosis, also uses a kind of “probabilistic modus tollens”, in that, signs (symptoms or laboratory data) are taken as strong evidence for a given hypothesis not to be true: the focus is not on hypothesis confirmation, but instead on its refutation [Pr (¬ H/E1, E2, …, En)]. Especially at the beginning of a complicated case, odds are between the hypothesis that is potentially being excluded and a vague “other”. This procedure has the advantage of providing a clue of what evidence to look for and to eventually reduce the set of candidate hypotheses if conclusive negative evidence is found. 6) Bayes’ theorem in the hypothesis-confirmation form can more faithfully, although idealistically, represent the medical diagnosis when the diagnostic itinerary has come to a reduced set of plausible hypotheses after a process of progressive elimination of candidate hypotheses; 7) Bayes’ theorem is however indispensable in the case of litigation in order to assess doctor’s responsibility for medical error by taking into account the weight of the evidence at his disposal. (shrink)

In recent years physicians have used a variety of laboratory studies as confirmatory tests in the diagnosis of brain death. The most widely used test has been the EEG. However, with the development of newer technologies capable of measuring other parameters of brain functions, other laboratory studies are playing an increasingly important role in confirming brain death. In this article, we discuss the role of one of these newer tests, the radioactive brain scan, and compare its advantages and (...) limitations with the EEG. (shrink)

With technical sophistication and innovation in the field of medical science, a considerable proportion of medical diagnosis now rely on laboratory analyses, which emphasises the crucial role of laboratory physicians in patient care. Sustaining high ethical standards remains crucial in both clinical biochemistry and laboratory medicine, and several ethical dilemmas are faced by laboratory physicians in day-to-day practice. In a low-resource country like Bangladesh, formal ethics education or ethical framework in laboratory practice is still absent; (...) ethics has not received that much attention it this field. This paper has considered ethical issues encountered during the daily routine work of laboratory physicians and specially focused on the ethical issues encountered during the pre-analytical, analytical and post-analytical phases of laboratory medicine practice and discuss those issues in light of ‘The Belmont Report’ (1978) perspective. It is not intended to be a comprehensive one, rather it aims to complement existing guidelines and documents that are available in some institutions and to offer a framework for addressing ethical issues encountered in the practice of clinical biochemistry and laboratory medicine in Bangladesh. (shrink)

Scientific and medical practice both relate to and differ from each other, as do discussions of how to handle decisions under uncertainty in the laboratory and clinic respectively. While studies of science have pointed out that scientific practice is more complex and messier than dominant conceptions suggest, medical practice has looked to the rigour of scientific and statistical methods to address clinical uncertainty. In this article, we turn to epistemological studies of the laboratory to highlight how clinical practice (...) already has strategies for dealing with messiness. We draw on Hans-Jo ̈rg Rheinberger’s Toward a History of Epistemic Things, in which he invokes the metaphor of a spider’s web to explain the role of tacit practices in experimental biochemistry for helping practitioners manage messiness. We argue that diagnostic practices in clinical medicine employ similar, albeit codified, procedures to evaluate epistemic significance, ensure sensitivity to the unforeseen, and allow focused grounds for action. We consider three practices: (a) the pre-set structure of medical records, ensuring broad coverage in initial anamnesis, (b) the use of lists of differential diagnoses and ongoing ‘anchoring and adjusting’ as inquiry progresses, and (c) shared decision-making as an occasion to synthesize empirical evidence and reopen inquiry for potential missed information. We end by suggesting that while philosophy of medicine may learn from laboratory epistemology, the sciences may learn something from medical practice. (shrink)

Nucleic acid hybridization is being increasingly used in viral diagnosis. Most of the assays described so far for this purpose require the use of radioactive probes. Their replacement by Non‐radioactive assays has many advantages and makes the technique feasible in routine diagnostic work. Non‐radioactive assays have had limited use but their diagnostic value has been demonstrated for a number of virus infections. They have the main advantages of employing stable probes, of avoiding safety hazards and of being easy and rapid (...) to perform with limited laboratory facilities. Their main disadvantage compared to radioactive assays is in having relatively low sensitivity. Improvements in probe construction, in labelling and detecting methods, in sample treatment and in hybridization conditions may well increase their usefulness. (shrink)

The use of preimplantation genetic diagnosis, the powerful technique employed during fertility treatment to select embryos based on their genes, is currently unregulated in the United States—unlike in nearly all other countries where PGD is available. Of course, the analytical quality of the genetic tests, the laboratories where they are performed, and the technicians who carry them out are subject to the Clinical Laboratory Improvement Amendment requirements. And as the Food and Drug Administration prepares to begin regulating laboratory‐developed (...) tests, including many genetic tests, the clinical validity of the tests may also need to be demonstrated. But neither CLIA nor the U.S. Food and Drug Administration is responsible for governing medical practice, and state law and the relevant medical associations have largely fallen silent on the questions of when and why PGD ought to be performed. The result of this regulatory lacuna is that while PGD was originally intended for screening embryos for severe heritable disorders, it is now also employed for a variety of more controversial purposes. (shrink)

When a person at risk of having a child with a genetic illness or disease wishes to have an unaffected child, this can involve difficult choices. If the pregnancy is established by sexual intercourse, the fetus can be tested early in pregnancy, and if affected a decision can be made to abort in the hope that a future pregnancy with an unaffected fetus ensures. Alternatively, preimplantation genetic diagnosis can be used after in vitro fertilisation to select and implant an unaffected (...) embryo that hopefully will proceed to term and produce a healthy baby. We are aware that many individuals at risk regard the latter as ethically more acceptable than the former, and examine whether there is an ethical difference between these options. We conclude that PGD and implantation of an unaffected embryo is a more acceptable choice ethically than prenatal diagnosis followed by abortion for the following reasons: Choice after PGD is seen as ethically neutral because a positive result balances a negative result simultaneously . While there is usually the intention to establish a healthy pregnancy after an abortion, this is not simultaneous; A woman sees abortion as a personal physical violation of her integrity, and as the pregnancy proceeds she increasingly identifies with and gives ethical status to the embryo/fetus as it develops in utero and not in the laboratory; Many people see aborting a fetus as “killing”, whereas in the case of PGD the spare embryos are “allowed to die”. We argue that this difference of opinion gives further weight to our conclusion, but note that this has been addressed and debated at length by others. (shrink)

In many cases medical diagnosis is based on information obtained through a process involving the emission of different forms of ionizing radiation. The safety of the medical staff and patients exposed to ionizing radiation is highly dependent on the proper design of the shielding used in the laboratory. Therefore, the authors propose a multi-platform application supporting such a design through the computation of the critical parameters of shielding. The specific requirements for shielding are defined by government authorities so the (...) algorithm must comply with all the written standards. The application was implemented using Xamarin. Forms for cross-platform development. The results obtained with the use of the developed tool were compared with those calculated manually for the design of stationary shields developed, deployed, and validated by local inspection. (shrink)

Psychiatric disorders present distinct clinical challenges which are partly attributable to their multifactorial aetiology and the absence of laboratory tests that can be used to confirm diagnosis or predict risk. Psychiatric disorders are highly heritable, but also polygenic, with genetic risk conferred by interactions between thousands of variants of small effect that can be summarized in a polygenic risk score. We discuss four areas in which the use of polygenic risk scores in psychiatric research and clinical contexts could have (...) ethical implications. First, there is concern that clinical use of polygenic risk scores may exacerbate existing health inequities. Second, research findings regarding polygenic risk could be misinterpreted in stigmatising or discriminatory ways. Third, there are concerns associated with testing minors as well as eugenics concerns elicited by prenatal polygenic risk testing. Fourth, potential challenges that could arise with the feedback and interpretation of high polygenic risk for a psychiatric disorder would require consideration. While there would be extensive overlap with the challenges of feeding back genetic findings in general, the potential clinical use of polygenic risk scoring warrants discussion in its own right, given the recency of this possibility. To this end, we discuss how lay interpretations of risk and genetic information could intersect. Consideration of these factors would be necessary for ensuring effective and constructive communication and interpretation of polygenic risk information which, in turn, could have implications for the uptake of any therapeutic recommendations. Recent advances in polygenic risk scoring have major implications for its clinical potential, however, care should be taken to ensure that communication of polygenic risk does not feed into problematic assumptions regarding mental disorders or support reductive interpretations. (shrink)

Decision making is the physician's major activity. Every day, in doctors' offices throughout the world, patients describe their symptoms and com plaints while doctors perform examinations, order tests, and, on the basis of these data, decide what is wrong and what should be done. Although the process may appear routine-even to the physicians in volved-each step in the sequence requires skilled clinical judgment. Physicians must decide: which symptoms are important, whether any laboratory tests should be done, how the various (...) items of clinical data should be combined, and, finally, which of several treatments (including doing nothing) is indicated. Although much of the information used in clinical decision making is objective, the physician's values (a belief that pain relief is more important than potential addiction to pain-killing drugs, for example) and subjectivity are as much a part of the clinical process as the objective findings of laboratory tests. In recent years, both physicians and psychologists have come to realize that patient management decisions are not only subjective but also prob abilistic (although this is not always acknowledged overtly). When doc tors argue that an operation is fairly safe because it has a mortality rate of only 1 %, they are at least implicitly admitting that the outcome of their decision is based on probability. (shrink)

This guest editorial opens with a brief overview of the transformations of medicine and mental health that can be observed since the second half of the twentieth century. New genetics and biotechnologies hold out the promise of overcoming presumed limitations in the field of mental health care, that is, the fact that diagnostic procedures in psychiatry and clinical psychology still largely rely on the narratives of patients and questionnaires, supposedly subjective assessments by physicians and psychologists. It is envisioned that innovative (...) genetic and proteomic tools, imaging technologies, and objective laboratory tests for blood biomarkers will enable better diagnosis and treatment of mental diseases. We argue that emerging biotechnologies do not revolutionize mental health, despite their promise to do so. Instead, we observe a pluralization of research and treatment approaches in the domain of mental health. The second part of this editorial discusses the contributions to this special issue on emerging biotechnologies and mental health and outlines how they address some of the gaps in social studies of psychiatry and mental health in the twenty-first century. (shrink)

Emerging genomic technologies promise more efficient infectious disease control. Whole genome sequencing is increasingly being used in tuberculosis diagnosis, surveillance, and epidemiology. However, while the use of WGS by public health agencies may raise ethical, legal, and socio-political concerns, these challenges are poorly understood. Between November 2017 and April 2018, we conducted semi-structured interviews with 22 key stakeholders across the fields of governance and policy, public health, and laboratory sciences representing the major jurisdictions currently using WGS in national TB (...) programs. Thematic analysis of the interviews was conducted using NVivo 11. Respondents identified several ethical and practical challenges associated with WGS in TB care and surveillance, all related to issues of trust, including: 1) the power of public health; 2) data sharing and profits derived from surveillance efforts; and 3) concerns regarding who has access to, and can benefit from, the technology. Additional challenges included: the potential utility that WGS adds to a public health program, the risks associated with linking necessary epidemiological metadata to the genomic data, and challenges associated with jurisdictional capacity to implement the technology. Successful implementation of WGS is dependent on fostering relationships of trust between those working with genomics technology and those directly impacted by it, including clinicians. Building trust between the public and the public health agencies and within public health agencies themselves is critical due to the inherent complexity of WGS and its implementation for communicable disease control purposes. (shrink)

Many years ago, the esteemed patriarch of bioethics, Joseph Fletcher, spoke loud and clear in favor of rationality in reproduction. By rationality, he meant not merely limiting population growth, which he certainly favored, but bringing to bear human analytic and creative intelligence on the random and instinctive activities of sexual intercourse and procreation that we share with all mammals. In his 1974 book, The Ethics of Genetic Control: Ending Reproductive Roulette, he foresaw most of the issues that we are facing (...) today. He reflected on artificial insemination, prenatal diagnosis, cloning, eugenics, ectogenesis, ovum transfers, and genetic engineering. He examined these innovations to the extent that he felt that each of them represents a way of exercising rational and responsible control over life and reproduction. The subtitle of his book, “Ending Reproductive Roulette,” proclaims his faith. Dr. Fletcher's dedication to rationality led him to make the astonishing statement, “Man is a maker and the more rationally contrived and deliberate anything is, the more human it is. Therefore, laboratory reproduction is radically human compared to conception by ordinary heterosexual intercourse.”. (shrink)

Face perception and emotion categorization are widely investigated under laboratory conditions that are devoid of real social interaction. Using mobile eye-tracking glasses in a standardized diagnostic setting while applying the Autism Diagnostic Observation Schedule, we had the opportunity to record gaze behavior of children and adolescents with and without Autism Spectrum Conditions during social interaction. The objective was to investigate differences in eye-gaze behavior between three groups of children and adolescents either with ASC or with unconfirmed diagnosis of ASC (...) or with neurotypical development during social interaction with an adult interviewer in a diagnostic standard situation using the ADOS-2. In a case control study, we used mobile eye-tracking glasses in an ecologically valid and highly standardized diagnostic interview to investigate suspected cases of ASC. After completion of the ASC diagnostic gold standard including the ADOS-2, the participants were assigned to two groups based on their diagnosis and compared with a matched group of neurotypically developed controls. The primary outcome measure is the percentage of total dwell times assessed for different areas of interest with regard to the face and body of a diagnostic interviewer and the surrounding space. Overall, 65 children and adolescents within an age range of 8.3–17.9 years were included in the study. The data revealed significant group differences, especially in the central-face area. Previous investigations under laboratory conditions gave preferential attention to the eye region during face perception to describe differences between ASC and NTD. In this study – using an ecologically valid setting within a standard diagnostic procedure – the results indicate that neurotypically developed controls seem to process faces and facial expressions in a holistic manner originating from the central-face region. Conversely, participants on the Autism Spectrum seem to avoid the central-face region and show unsystematic gaze behavior, not using the preferred landing position in the central-face region as the Archimedean point of face perception. This study uses a new approach, and it will be important to replicate these preliminary findings in future research. (shrink)

ABSTRACT: GEORGES CANGUILHEM’S BIOPHILOSOPHY The eminent French biologist and historian of biology, François Jacob, once notoriously declared «On n’interroge plus la vie dans les laboratoires»: laboratory research no longer inquires into the notion of “Life”. Certain influential French philosophers of science of the mid‐century such as Georges Canguilhem would disagree, or at least seek to resist some of Jacob’s diagnosis. Not by imposing a different kind of research program in laboratories, but by an unusual combination of historical and philosophical (...) inquiry into the foundations of the life sciences. Canguilhem speaks of «defending vitalist biology» and declares that Life cannot be grasped by logic. Is this history and philosophy of biology? Is it vitalism? It definitely is a different project from current philosophy of biology. One short‐lived term for it was “biophilosophy”. In this paper I explore the content of this term as it relates to the above questions. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Genetic Testing and Genetic ScreeningPat Milmoe McCarrick (bio)In recent years there has been an enormous expansion in the knowledge that may be gleaned from the testing of an individual's genetic material to predict present or future disability or disease either for oneself or one's offspring. The Human Genome Project, which is currently mapping the entire human gene system, is identifying progressively more genetic sequencing information (see Scope Note 17, (...) The Human Genome Project). Information obtained from genetic testing raises ethical and legal questions about its uses by society. The ethical dilemmas were foreseen two decades ago by bioethicists who asked whether questionable applications could stop "legitimate pursuits" (IV, Gaylin 1972) and whether genetic disease might come to be viewed as "transmissible" in the sense of being contagious (IV, Veatch 1974).Not only has knowledge expanded, but the practice of genetic testing and screening has greatly increased as well. For example, in the case of testing for cystic fibrosis (CF), the U.S. Congress' Office of Technology Assessment (OTA) estimates that instances of screening jumped from 9310 tests in 1991 to 63,000 tests in 1992 (I, OTA [Cystic Fibrosis] 1992). In addition, the OTA estimates that within the next few years, the six million women who become pregnant each year routinely will be informed of available CF carrier tests (I, OTA [Cystic Fibrosis] 1992).Following the recent identification of a gene linked to breast cancer, Dr. Francis Sellers Collins, director of the National Center for Human Genome Research, said that "it is not inconceivable that every woman in America may want to be screened for this gene. The economic, ethical, and counseling issues will be very daunting." Dr. Collins opines that in the near future physical examinations for 18-year-olds will include DNA testing for diseases with genetic components and that physicians, in the interests of preventive medicine, will make risk-based recommendations for a healthy life-style (IV, Breo 1993). The U.S. President's Commission for the Study of Ethical Problems in Medicine and Biomedical and Behavioral Research predicted as early as 1983 that before the end of the century genetic screening and counseling would become major components of both public health and individual medical care (I, U.S. President's Commission 1983). [End Page 333]The OTA defines genetic testing as "the use of specific assays to determine the genetic status of individuals already suspected to be at high risk for a particular inherited condition. The terms genetic test, genetic assay, and genetic analysis are used interchangeably to mean the actual laboratory examination of samples." In contrast, genetic screening usually uses the same assays employed for genetic testing but is distinguished from genetic testing by its target population (I, OTA [Genetic Monitoring] 1990). The National Academy of Sciences (NAS) defines screening as the systematic search of populations for persons with latent, early, or asymptomatic disease (III, NAS 1975). Some of the literature annotated for this Scope Note appears to use the terms "testing" and "screening" interchangeably.Philip Boyle of the Hastings Center points out that the language used to describe genetic variation is important and asks what words should be used: "Defects, flaws, deleterious genes, disorders, or the more neutral conditions? Using words such as normal—and its corollary, abnormal—is likely to foster stigmatization and discrimination" (III, Genetic Grammar, Boyle 1992).Areas of focus in genetic testing include: prenatal diagnosis, newborn screening, carrier screening, forensic screening, and susceptibility screening.Prenatal diagnosis discerns whether a fetus is at risk for various identifiable genetic diseases or traits. Prenatal diagnosis is made using amniotic fluid, fetal cells, and fetal or maternal blood cells obtained during amniocentesis testing; alpha fetoprotein assays or chorionic villus sampling; or ultrasound tomography, which creates fetal images on a screen. Another method, known as fetoscopy, uses a camera on a needle inserted in the uterus to view the fetus. Since prenatal screening began in 1966 (I, U.S. President's Commission 1983), the number of metabolic defects and genetic disorders that can be diagnosed prenatally has expanded greatly. There is also discussion of requiring testing for parents who are participating in an in vitro fertilization program and are at genetic... (shrink)

In light of Perry Anderson's recent re-Iaunch of New Left Review, and the publication of Gregory Elliott's Perry Anderson: The Merciless Laboratory of History, it is perhaps an opportune moment for Marxists to assess Anderson's contribution to socialist strategic thought. At the heart of Anderson's manifesto is the claim that the principal aspect of the past decade ‘can be defined as the virtually uncontested consolidation, and universal diffusion, of neoliberalism'. There is, obviously, something in this claim. However, Anderson also (...) briefly notes, amongst other counter-currents, the labour upsurge in France in 1995, but dismisses the significance of these events with the claim that ‘capital has comprehensively beaten back all threats to its rule'. Anderson compares the context of the launch of the first New Left Review with that of the present day. He writes that, back then, a third of the planet had broken with capitalism, the discrediting of Stalinism in 1956 had unleashed a vital process of the rediscovery of authentic Marxism, while, culturally, there had been a qualitative break with the conformism of the 1950s. Today, by contrast, American capitalism has reasserted its international primacy, European social-democratic governments are implementing policies designed to follow the American model, Japan is suffering from a slump, while the Russian catastrophe has produced no popular backlash. Moreover, the Western powers have recently asserted themselves successfully in the Balkans, and, despite upsurges against capital in the 1990s, ‘no collective agency able to match the power of capital is yet on the horizon’. How are socialists to respond to this diagnosis? In this essay, I want to locate the logic of Anderson's interpretation of the present conjuncture within the context of his previous strategic claims. I will argue that, while socialists will always have much to learn from Anderson, strategically his thought has systematically suffered from a form of political impressionism. This suggests that his interpretation of the present conjuncture may fail the test of history. (shrink)

A political discourse of peace marked the distribution and use of radioisotopes in biomedical research and in medical diagnosis and therapy in the post-World War II period. This occurred during the era of expansion and strengthening of the United States' influence on the promotion of sciences and technologies in Europe as a collaborative effort, initially encouraged by the policies and budgetary distribution of the Marshall Plan. This article follows the importation of radioisotopes by two Spanish research groups, one in experimental (...) endocrinology and one in molecular biology. For both groups foreign funds were instrumental in the early establishment of their laboratories. The combination of funding and access to previously scarce radioisotopes helped position these groups at the forefront of research in Spain. (shrink)

In‐vitro fertilization clinics across the world currently use the body mass index (BMI) to assess risk for and determine access to in‐vitro fertilization (IVF); however, clinics vary widely in both setting specific BMI limits for access to IVF and articulating the reasons for their policies. Given that scholars have begun to question the usefulness of BMI for individual health risk assessment, it is striking that ethicists have not yet systematically evaluated the reasons given for using BMI in assessing individuals' risk (...) in IVF treatments. In this paper, I provide the first systematic analysis of the chief arguments currently offered by IVF programs for using BMI as a criterion for risk assessment. Specifically, I articulate empirical concerns about the success of IVF in high‐BMI patients, practical concerns about the ability of high‐BMI patients to safely undergo procedures associated with IVF, and ethical concerns about the risk‐to‐reward ratio for high‐BMI patients and their potential children. I advance a series of objections to those arguments, using empirical data regarding IVF procedures and analogies with other high‐risk conditions including systemic lupus erythematosus, and science regarding the diagnosis of BMI‐correlated comorbidities such as high blood pressure or diabetes to argue that BMI alone is not a reasonable criterion for risk assessment in IVF; moreover, the usage of BMI may involve unacceptable violations of the bioethical principles of justice and respect for autonomy. Instead, I hold that IVF programs should rely on more precise laboratory and clinical measurements to evaluate risk in IVF. (shrink)

Tremendous development in recent medical science and the consequent discoveries resulting in successful prevention and also cure of different diseases are shared by clinical research involving the human volunteers. Preceding the trials in the human subjects, and to ensure safety, the proposed drug and other interventions are either tested in animals (vivo) or in laboratory (vitro) to evaluate initial safe starting dose for the human beings and to key out the benchmarks for the clinical monitoring for the potential unfavorable (...) effects. These pre human trials might not necessarily protect against the untoward effects in the human beings as happened in the case of thalidomide tragedy, which caused disability and killed thousands of babies born to the mothers, those who took this medicine. Use of healthy human volunteers in the preliminary experiments or phase I clinical trials either reduces or excludes risks of subsequent undesirable effects in the future trails (1). Phase-1 trials are conducted in order to test the safety, reactions and immunogenicity of vaccines in volunteers. Novel treatments for the cancer are first tested in phase 1 trials enrolling the patients with advanced disease, who have exhausted the standard treatment options. Phase-1 oncology trials are the pivot point in the translation of new cancer therapies from bench to bedside. Nevertheless, these trials remain ethically controversial. The controversy stems from the fact that, classically, phase-1 oncology clinical trials involve first-in-human testing of experimental treatment candidates in patients with a terminal diagnosis, who typically have exhausted standard treatment options. Commentators on the ethics of phase-1 clinical trials make diametrically opposed claims about the prospect of direct medical benefit from participation in these trials-benefits that can be attributed to receiving the experimental treatment intervention. One camp of benefit skeptics, inhabited mainly by bioethicists, characterizes this form of research as lacking any reasonable prospect of direct medical benefit. They see an ethical cloud hovering over phase-1 trials, because the vast majority of patients volunteer for phase-1 trials out of a motivation to receive medical benefit. In the view of these skeptics, such patients therefore harbor a ‘therapeutic misconception’ about research participation. This misconception calls into question the validity of informed consent and thereby undercuts the ethical basis of these trials (2). In this paper, I will discuss the ethical justification of the participation of human volunteers in phase-1 trials. (shrink)

Over the last three decades, an escalating portion of U.S. school children has been classified for special education; those with diagnoses entitled to services now number 15 percent of all public school pupils. At the same time, American scientists have focused increasingly on juvenile brains, studying what one psychiatric epidemiologist labeled ‘‘social incapacities.’’ This article reports on the laboratory labors of two scientific groups: neuroscientists who scan children’s brains in search of resting state differences according to diagnosis and psychiatric (...) epidemiologists who look to epigenetics to distinguish differential diagnostic populations. The article focuses on the medicalization of childhood differences and the harmonies and discordances between what researchers and parents understand to be at the root of children’s learning and social capacities. (shrink)

Cytogenetic research has had a major impact on the field of reproductive medicine, providing an insight into the frequency of chromosomal abnormalities that occur during gametogenesis, embryonic development and pregnancy. In humans, aneuploidy has been found to be relatively common during fetal life, necessitating prenatal screening of high‐risk pregnancies. Aneuploidy rates are higher still during the preimplantation stage of development. An increasing number of IVF laboratories have attempted to improve pregnancy rates by using preimplantation genetic diagnosis (PGD) to ensure that (...) the embryos transferred to the mother are chromosomally normal. This paper reviews some of the techniques that are key to the detection of aneuploidy in reproductive samples including comparative genomic hybridization (CGH). CGH has provided an unparalleled insight into the nature of chromosome imbalance in human embryos and polar bodies. The clinical application of CGH for the purposes of PGD and the future extensions of the methodology, including DNA microarrays, are discussed. BioEssays 25:289–300, 2003. © 2003 Wiley Periodicals, Inc. (shrink)

It is widely argued that the final decades of the twentieth century saw a fundamental change, marked by terms such as biomedicalization and geneticization, within the biomedical sciences. What unites these concepts is the assertion that a vast array of emerging technologies—in genomics, bioengineering, information technology, and so forth—are transforming understandings of disease, diagnosis, therapeutics, and working practices. While clearly important, these analyses have been accused of perpetuating theoretical trends that attribute primacy to the new over the old, discontinuity over (...) continuity, and the laboratory over the field. In this paper, I show that in the case of autism, the effects of genomic technologies can only be understood by simultaneously examining the role of questionnaires. Due to shortcomings in clinical diagnoses, genomic analyses could only progress once questionnaires had been developed to address a “reverse salient” within the “technological system.” Furthermore, I argue that questionnaires such as the Autism Quotient have a significance that surpasses the genomic classifications they were designed to undergird. I argue that to neglect the role of mundane technologies such as questionnaires in contemporary biomedicine is to miss complexity, bifurcate old and new, and do a disservice to innovation. (shrink)

Schizophrenia is a serious mental disease whose pathogenesis has not been fully elucidated. Its clinical evaluation and diagnosis still highly depend on the clinical experience of doctors. It is of great scientific value and clinical significance to study the inducing factors and neuropathological mechanism of schizophrenia. Based on the four research problems of schizophrenia, this paper analyzes the data types that need to be stored in clinical trials and scientific research, including basic information, case report data, neuropsychological and cognitive function (...) evaluation, magnetic resonance data, electroencephalogram data, and intestinal flora data. Through the demand analysis of the system, including the data management part, data analysis part, the functional demand of the system management part, and the overall nonfunctional demand of the system, the overall architecture design, functional module division, and database table structure design of the system are completed. Adopting Browser/Server architecture and front-end and back-end separation mode and applying Java and Python programming language, based on spring framework and database, a multidimensional information management system for schizophrenia is designed and implemented, which includes four modules: data analysis, data management, system management, and security control. In addition, each functional module of the system is designed and implemented in detail, and the software operation flow of each module is illustrated with the sequence diagram. Finally, the multidimensional data of schizophrenia collected in our laboratory were used for system test to verify whether the system can meet the needs of clinical big data management of schizophrenia and the multidimensional information management system of schizophrenia can meet the needs of clinical big data management. The information management system helps schizophrenic researchers to carry out data management and data analysis. It also has advantages that are easy to use, safe, and efficient and has strong scalability in data management, data analysis, and scalability. It reflects the innovation of the system and provides a good platform for the management, research, and analysis of clinical big data of schizophrenia. (shrink)

Alongside the renowned male pioneers of medical cytogenetics, many women participated in investigations at the laboratory bench and the bedside, both in Europe and the Americas. These women were committed to this new biological and clinical practice—cytogenetics, the origins of contemporary genetic diagnosis—and contributed to the creation of new biological concepts and settings centered on the study of chromosome imaging. This paper will review the contributions made by a group of woman scientists from a wide geographical distribution, situating their (...) names and research agendas within the history of a field dating back to early plant and insect cytogenetics. Rather than an exhaustive compendium of women geneticists, this essay presents a kind of historical reconstruction that can be achieved by placing women at center stage in their geographies and networks of circulating cytogenetic knowledge and practices thereby relating a history of genetic images though the work carried out by women, retrieving their agency and constructing an inclusive history of an influential contemporary biomedical practice as it gained increasing influence in the laboratory and the clinic. (shrink)

The size and organization of the brain are determined by the activity of progenitor cells early in development. Key mechanisms regulating progenitor cell biology involve miRNAs. These small noncoding RNA molecules bind mRNAs with high specificity, controlling their abundance and expression. The role of miRNAs in brain development has been studied extensively, but their involvement at early stages remained unknown until recently. Here, recent findings showing the important role of miRNAs in the earliest phases of brain development are reviewed, and (...) it is discussed how loss of specific miRNAs leads to pathological conditions, particularly adult and pediatric brain tumors. Let‐7 miRNA downregulation and the initiation of embryonal tumors with multilayered rosettes (ETMR), a novel link recently discovered by the laboratory, are focused upon. Finally, it is discussed how miRNAs may be used for the diagnosis and therapeutic treatment of pediatric brain tumors, with the hope of improving the prognosis of these devastating diseases. (shrink)

Inborn errors of vitamin B12 (cobalamin) metabolism are associated with homocystinuria and methylmalonic aciduria, either alone or in combination. A number of these disorders have provided the first evidence for the existence of important steps in the transport or metabolism of cobalamin in eukaryotic cells. Eight complementation classes have been defined on the basis of somatic cell hybridization studies. Although the majority of patients present in infancy or early childhood, some are not diagnosed until adolescence or later. For some of (...) these disorders, prenatal diagnosis and therapy with cobalamin during pregnancy has been attempted. Although only males have been described with cblE disease, all of these disorders are presumed to be autosomal recessive in inheritance. The clinical and laboratory aspects of the different complementation classes (cblA–cblG) are reviewed here. (shrink)

In this article, I examine reproductive travel for sex selection with reference to two distinct technologies—MicroSort and preimplantation genetic diagnosis. Available since the 1990s for sex-linked disease avoidance, I focus here on their imbrication in an emerging global form of nonmedical, lifestyle sex selection that elicits movements of information, biomaterial, patients, providers, and equipment across borders. This web of cross-border, interclinical, and laboratory transactions raises issues highly relevant to a feminist approach to the bioethics of sex selection. International documents, (...) however, have yet to account for their implication in an increasingly stratified system of global sex selection practices. (shrink)

In the years around 1900 one of the most significant practical consequences of new styles of bacteriological thought and practice was the development of preventive vaccines and therapeutic sera. Historical scholarship has highlighted how approaches rooted in the laboratory methods of Robert Koch, Louis Pasteur and their collaborators were transformed in local contexts and applied in diverse ways to enable more effective disease identification, prevention and treatment. Amongst these, the anti-anthrax serum developed by the Italian physician Achille Sclavo (1861–1930) (...) has received little to no attention from historians. This article positions Sclavo's serum as a neglected but significant presence in British microbiology, which achieved widespread uptake amidst a wave of optimism, despite prolonged uncertainty about its mechanism of action and dosage. After being introduced to Britain in 1904 by the enterprising first medical inspector of factories Thomas Morison Legge, within a matter of months the serum became regarded by medical practitioners as an effective treatment of cutaneous anthrax, though access to ‘fresh’ serum and the necessary speedy diagnosis remained problematic. Like the disease anthrax itself, discussion of ‘Sclavo's serum’ was out of all proportion to the relatively low number of cases, reflecting a deep-seated fascination with the wider possibilities afforded by effective serum therapy. (shrink)

Biotechnology is the use of living systems and organisms to develop or make products, or any technological application that uses biological systems, living organisms or derivatives to make or modify products or processes for specific use. Biotechnology is a constantly evolving field of modern science. New tools and products developed by biotechnologists are useful in research, agriculture, industry and healthcare. Although it has many benefits including lowering our environmental footprint, and helping in diagnosis and treatment of diseases, it comes with (...) its all-possible disadvantages. The four main societal concerns revolve around are ethical, safety, bioterrorism and environmental issues. This paper aims to describe those societal concerns raised by applications of biotechnology and possible regulations related to biotech innovations and policy implementation. (shrink)

A political discourse of peace marked the distribution and use of radioisotopes in biomedical research and in medical diagnosis and therapy in the post-World War II period. This occurred during the era of expansion and strengthening of the United States' influence on the promotion of sciences and technologies in Europe as a collaborative effort, initially encouraged by the policies and budgetary distribution of the Marshall Plan. This article follows the importation of radioisotopes by two Spanish research groups, one in experimental (...) endocrinology and one in molecular biology. For both groups foreign funds were instrumental in the early establishment of their laboratories. The combination of funding and access to previously scarce radioisotopes helped position these groups at the forefront of research in Spain. (shrink)

Newton's bucket, Einstein's elevator, Schrödinger's cat – these are some of the best-known examples of thought experiments in the natural sciences. But what function do these experiments perform? Are they really experiments at all? Can they help us gain a greater understanding of the natural world? How is it possible that we can learn new things just by thinking? In this revised and updated new edition of his classic text _The Laboratory of the Mind_, James Robert Brown continues to (...) defend apriorism in the physical world. This edition features two new chapters, one on “counter thought experiments” and another on the development of inertial motion. With plenty of illustrations and updated coverage of the debate between Platonic rationalism and classic empiricism, this is a lively and engaging contribution to the field of philosophy of science. (shrink)

The laboratory animal environment: room for concern.

We develop an account of laboratory models, which have been central to the group selection controversy. We compare arguments for group selection in nature with Darwin's arguments for natural selection to argue that laboratory models provide important grounds for causal claims about selection. Biologists get information about causes and cause-effect relationships in the laboratory because of the special role their own causal agency plays there. They can also get information about patterns of effects and antecedent conditions in (...) nature. But to argue that some cause is actually responsible in nature, they require an inference from knowledge of causes in the laboratory context and of effects in the natural context. This process, cause detection, forms the core of an analogical argument for group selection. We discuss the differing roles of mathematical and laboratory models in constructing selective explanations at the group level and apply our discussion to the units of selection controversy to distinguish between the related problems of cause determination and evaluation of evidence. Because laboratory models are at the intersection of the two problems, their study is crucial for framing a coherent theory of explanation for evolutionary biology. (shrink)

Chapter 1 FROM ORDER TO DISORDER 5 mins. John enters and goes into his office. He says something very quickly about having made a bad mistake. He had sent the review of a paper. . . . The rest of the sentence is inaudible. 5 mins.

A diagnostic process is an investigative process that takes a clinical picture as input and outputs a diagnosis. We propose a method for distinguishing diagnoses that are warranted from those that are not, based on the cognitive processes of which they are the outputs. Processes designed and vetted to reliably produce correct diagnoses will output what we shall call ‘warranted diagnoses’. The latter are diagnoses that should be trusted even if they later turn out to have been wrong. Our work (...) is based on the recently developed Cognitive Process Ontology and further develops the Ontology of General Medical Science. It also has applications in fields such as intelligence, forensics, and predictive maintenance, all of which rely on vetted processes designed to secure the reliability of their outputs. (shrink)

Clinical decisionmaking includes reasoning from prescientific or scientific theories, reasoning from uncontrolled or controlled experience, and reasoning based on empathic understanding and moral beliefe. The development of contemporary clinical thinking is discussed, and it is found that successive generations of medical practitioners have had different views of the rationality and relative importance of these modes of reasoning: that which is considered rational by one generation of doctors is sometimes denounced by the next. The author's book, Rational Diagnosis and Treatment , (...) which is an example of clinical thinking in the 1960s and early 70s, is used to illustrate one particular view of clinical decisionmaking. Keywords: rational, clinical decisionmaking, biological theory, controlled clinical studies, empathic understanding, ethical reasoning CiteULike Connotea Del.icio.us What's this? (shrink)

Now in its fourth edition, Rational Diagnosis and Treatment: Evidence-Based Clinical Decision - Making is a unique book to look at evidence-based medicine and the difficulty of applying evidence from group studies to individual patients._ The book analyses the successive stages of the decision process and deals with topics such as the examination of the patient,_the reliability of clinical data, the logic of diagnosis, the fallacies of uncontrolled therapeutic experience and the need for randomised clinical trials and meta-analyses. It is (...) the main theme of the book that, whenever possible, clinical decisions must be based on the evidence from clinical research, but the authors also explain the pitfalls of such research and the problems involved in applying evidence from groups of patients to the individual patient._ For this new edition, the sections on placebo and meta-analysis and on alternative medicine have been thoroughly updated, and there is more focus on insufficient reporting of harms of interventions. The sections on different research designs describe advantages and limitations, and the increased medicalisation and the effects of cancer screening on health people are noted. A section on academic freedom when clinicians collaborate with industry and ghost authors is added._ This essential reference work integrates the science and statistical approach of evidence-based medicine with the art and humanism of medical practice; distinguishing between data, sets of data, knowledge and wisdom, and their application. Such an intellectually challenging book is ideal for both medical students and doctors who require theoretical and practical clinical skills to help ensure that they apply theory in practice. (shrink)

ABSTRACTMedical diagnosis is sometimes used by critical realists and others as an exemplar of a form of inference across time in which a current empirical observation points backwards to the conditions of its emergence and forwards to a possible future outcome or progression. Accordingly, its practice warrants critical exploration to confirm its legitimacy as a philosophical reference point. The strengths and weakness of the exemplar are appraised using case brief case studies. The limitations of medical diagnosis are discussed in the (...) wider context of the sociology of medical knowledge, the social determinants of ill-health and the role of commercial interests in shaping diagnostic practice. The conclusion is cautious, not nihilistic. Diachronic inference in medicine, as in other disciplines working in and with open systems, can be respected for its advantages to humanity. However, this brings with it the perennial caution of epistemic humility and a needed tolerance of uncertainty.. (shrink)

The aim of this essay is to elaborate philosophical and ethical underpinnings of posthumous diagnosis of famous historical figures based on literary and artistic products, or commonly called retrospective diagnosis. It discusses ontological and epistemic challenges raised in the humanities and social sciences, and attempts to systematically reply to their criticisms from the viewpoint of clinical medicine, philosophy of medicine, particularly the ontology of disease and the epistemology of diagnosis, and medical ethics. The ontological challenge focuses on the doubt about (...) the persistence of a disease over historical time, whereas the epistemic challenge disputes the inaccessibility of scientific verification of a diagnosis in the past. I argue that the critics are in error in conflating the taxonomy of disease and the act of diagnosing a patient. Medical diagnosis is fundamentally a hypothesis-construction and an explanatory device that can be generated under various degrees of uncertainty and limited amount of information. It is not an apodictic judgment as the critics presuppose, but a probabilistic judgment with varying degrees of plausibility under uncertainty. In order to avoid this confusion, I propose that retrospective diagnosis of a historical figure be syndromic without identifying underlying disease, unless there is justifiable reason for such specification. Moreover it should be evaluated not only from the viewpoint of medical science but also in a larger context of the scholarship of the humanities and social sciences by its overall plausibility and consistency. On the other hand, I will endorse their concerns regarding the ethics and professionalism of retrospective diagnosis, and call for the need for situating such a diagnosis in an interdisciplinary scope and the context of the scholarship of the historical figure. I will then enumerate several important caveats for interdisciplinary retrospective diagnosis using an example of the retrospective diagnosis of Socrates for his life-long intermittent neurologic symptoms. Finally, I will situate the present argument in a larger context of the major debate among the historians of medicine and paleopathologists, and discuss the similarities and differences. (shrink)

UK science policy now includes ‘upstream public engagement’ as an element in the responsible development of nanotechnology. This paper explores different understandings of the term upstream engagement before discussing in more detail a laboratory-based collaboration between social science and nanoscience aimed at exploring the social dimensions of nanotechnology. The paper concludes that concern with defining what counts as ‘upstream’ can obscure more critical questions about how to make public, and therefore accountable, deliberations about the interrelated social and technical aspects (...) of nanoscience. (shrink)

In clinical medicine, a diagnosis can offer an explanation of a patient's symptoms by specifying the pathology that is causing them. Diagnoses in psychiatry are also sometimes presented in clinical texts as if they pick out pathological processes that cause sets of symptoms. However, current evidence suggests the possibility that many diagnostic categories in psychiatry are highly causally heterogeneous. For example, major depressive disorder may not be associated with a single type of underlying pathological process, but with a range of (...) different causal pathways, each involving complex interactions of various biological, psychological, and social factors. This paper explores the implications of causal heterogeneity for whether psychiatric diagnoses can be said to serve causal explanatory roles in clinical practice. I argue that while they may fall short of picking out a specific cause of the patient's symptoms, they can nonetheless supply different sorts of clinically relevant causal information. In particular, I suggest that some psychiatric diagnoses provide negative information that rules out certain causes, some provide approximate or disjunctive information about the range of possible causal processes, and some provide causal information about the relations between the symptoms themselves. (shrink)

1. GENERAL The term "diagnostics" refers to the general theory of diagnosis, not to the study of specific diagnoses but to their general framework. It borrows from different sciences and from different philosophies. Traditionally, the general framework of diagnostics was not distinguished from the framework of medicine. It was not taught in special courses in any systematic way; it was not accorded special attention: students absorbed it intuitively. There is almost no comprehensive study of diagnostics. The instruction in diagnosis provided (...) in medical schools is exclusively specific. Clinical instruction includes (in addition to vital background information, such as anatomy and physiology) specific instruction in nosology, the theory and classification of diseases, and this includes information on diagnoses and prognoses of diverse diseases. What is the cause of the neglect of diagnostics, and of its integrated teaching? The main cause may be the prevalence of the view of diagnostics as part-and parcel of nosology. In this book nosology is taken as a given, autonomous field of study, which invites almost no comments; we shall freely borrow from it a few important general theses and a few examples. We attempt to integrate here three studies: ll of the way nosology is used in the diagnostic process; of the diagnostic process as a branch of applied ethics; ~ of the diagnostic process as a branch of social science and social technology. (shrink)

In this chapter, our focus is the role played by notions of rationality in the diagnosis of mental disorders, and in the practice of overriding patient autonomy in psychiatry. We describe and evaluate different hypotheses concerning the relationship between rationality and diagnosis, raising questions about what features underpin psychiatric categories. These questions reinforce widely held concerns about the use of diagnosis as a justification for overriding autonomy, which have motivated a shift to mental incapacity as an alternative justification. However, this (...) approach too has recently been criticized from a mental disability rights perspective. Our analysis of the relationship between mental capacity and rationality is used to illuminate these concerns, and to investigate further the relationship between rationality and psychiatric diagnosis. (shrink)