Summary While historians have dealt with the origins of the concept of drug receptors in the work of Paul Ehrlich (1854–1915) and John N. Langley (1852–1925) as well as with some of its applications in modern pharmaceutical research, the history of the receptor theory as such has been neglected. Discussing major developments and conceptual changes in receptor theory between about 1910 and 1960 (including relevant contributions by A. V. Hill, A. J. Clark, J. H. Gaddum, E. J. Ariëns and (...) others), this paper attempts to fill this gap in historiography. It provides a case study of the unfolding of research under a new paradigm, but it considers also contemporary criticism and scepticism. By the early 1960s, quantitative investigations of drug action and interpretations of the experimental findings in terms of the receptor concept had become constitutive of the emerging field of ‘molecular pharmacology’. Even then, however, receptors were still hypothetical entities. (shrink)

In this article, the authors explore the impact of a potential future regulatory decision by FDA whether or not to continue its enforcement discretion policy allowing physicians to perform, and stool banks to sell, stool product for fecal microbiota transplantation as a treatment for recurrent Clostridium Difficile infection without an Investigative New Drug application. The paper looks at the Agency's regulatory options in light of the current gut microbiota based products that are in the FDA pipeline for (...) class='Hi'>drug approval and the potential impact and repercussions of their approval on FDA action. In laying out FDA's options we consider the implications of market exclusivity and off-label use of newly approved drugs. Ultimately, we explore the potential impact of FDA's decision on patients, research, and innovation. (shrink)

There are many kinds of clinical trials. The regulatory framework within which most drug development takes place appears to be the one that is to be applied to the development of novel stem cell-based clinical trials. In the standard drug development model, appropriate pre-clinical research is conducted, and investigators or research sponsors submit an investigational new drug application to the Food and Drug Administration.If approved, typical clinical trials start with Phase I, which is usually (...) a trial to determine the maximum tolerable dose of a drug. Phase I trials are often referred to as “safety studies” because the primary goal of Phase I research is to determine if an intervention is safe. (shrink)

The clinical Bioresearch Monitoring (BIMO) oversight program of the US Food and Drug Administration (FDA) assesses the quality and integrity of data submitted to the FDA for new product approvals and human subjects protection during clinical studies. A comprehensive program of on-site inspections and data verification, the BIMO program routinely performs random inspections to verify studies submitted to the FDA to support a marketing application. On occasion the FDA will conduct a directed inspection of a specific site or (...) study to look for problems that may have previously been identified. The inspection of a clinical study sometimes uncovers evidence of research fraud or misconduct and it must be decided how to deal with the investigator and the suspect data. The prevention of [or] decreasing the incidence of fraud and misconduct through monitoring by the sponsor is one way to manage compliance issues and can help prevent misconduct. A training program is another way to manage compliance issues in clinical research. While training does not guarantee quality, it does help to ensure that all individuals involved understand the rules and the consequences of research misconduct. (shrink)

Do terminally ill patients who have exhausted all other available, government-approved treatment options have a constitutional right to experimental treatment that may prolong their lives? On May 2, 2006, a divided panel of the U.S. Court of Appeals for the District of Columbia, in a startling opinion, Abigail Alliance for Better Access to Developmental Drugs v. Von Eschenbach, held “Yes.” The plaintiffs, Abigail Alliance for Better Access to Developmental Drugs and Washington Legal Foundation, sought to enjoin the Food and (...) class='Hi'>Drug Administration from refusing to allow the sale of investigational new drugs that had not yet received FDA approval. The terminally ill plaintiffs contended that they quite literally could not wait that long for the drugs. With no other treatment options available, the plaintiffs urged the court to recognize a fundamental, constitutional right to take potentially life-saving or life-prolonging drugs, even though the treatment had not been fully tested through human trials for safety and effectiveness and could not be legally marketed to the public. (shrink)

The patient wished to receive an experimental drug that she was instrumental in developing. After her diagnosis, she had investigated treatments that might help her condition and discovered that a specific compound could be beneficial. To further the development of this potential drug, she obtained preclinical data, founded a company, and sought investment from venture capitalists. The company was about to begin phase I testing, but the clinical trial had not yet opened. In addition, she would not have (...) been a candidate for the study, as it excluded patients with advanced disease. To be able to administer this drug to her, the patient's team of oncologists was in the process of drafting an individual patient investigational new drug application, including the protocol for the drug's delivery, to the Food and Drug Administration. The company developing the drug had preliminarily agreed to provide it. This protocol was also under review by the institutional review board of the university, and the ethics committee was consulted to determine whether she should receive the drug. (shrink)

Although applications are being developed and have reached the market, nanopharmacy to date is generally still conceived as an emerging technology. Its concept is ill-defined. Nanopharmacy can also be construed as a converging technology, which combines features of multiple technologies, ranging from nanotechnology to medicine and ICT. It is still debated whether its features give rise to new ethical issues or that issues associated with nanopharma are merely an extension of existing issues in the underlying fields. We argue here that, (...) regardless of the alleged newness of the ethical issues involved, developments occasioned by technological advances affect the roles played by stakeholders in the field of nanopharmacy to such an extent that this calls for a different approach to responsible innovation in this field. Specific features associated with nanopharmacy itself and features introduced to the associated converging technologies- bring about a shift in the roles of stakeholders that call for a different approach to responsibility. We suggest that Value Sensitive Design is a suitable framework to involve stakeholders in addressing moral issues responsibly at an early stage of development of new nanopharmaceuticals. (shrink)

The transition of novel and potentially promising medical therapies into their initial human clinical trials can engender conflicting pressures. On the one side, because Phase I trials raise greater ethical and human protection challenges than later stage clinical trials, there is a need to proceed cautiously. This is particularly the case for Phase I trials with a novel therapy being tested in humans for the first time, usually termed first-in-human (FIH) trials, especially if the FIH trial involves significant risks. On (...) the other side, scientists interested in having their research validated, corporations with a financial interest in the field, and potential patients and patient support groups desirous of having .. (shrink)

Many commentators have expressed concern that large investments in biomedical research over the past two decades have not been translated effectively into clinical applications. In its Critical Path Report, the Food and Drug Administration characterized the problem as a “technological disconnect between discovery and the product development process,” and documented that the number of investigational new drugs submitted to the agency had declined “significantly” since 2000. Along a similar vein, another study found that only five of 101 basic (...) science studies showing significant therapeutic promise were successfully translated into clinical applications.This perceived translational lag is stimulating a shift toward human testing of study interventions earlier in the drug development process. One indication of this trend is a recent guidance encouraging sponsors to pursue human “exploratory” studies before embarking on phase I trials. (shrink)

As an EU state, Lithuania has become an active member of the eEurope 2005 initiative, implementing the goals set forth in the strategic plan for the development of information society in Lithuania. Information technologies introduced into various areas of life open up new, more convenient opportunities to receive services and information. The modernization of state management becomes an integral factor for ensuring continuous social development. The objective of this paper is to study practical aspects of the application of specialized (...) knowledge in the investigation of crimes on electronic data and information systems security and to offer some recommendations for the investigation and prevention of such crimes. This article is the first of a two part study. In the next article, the authors intend to present aspects of prevention in crimes against electronic data and information systems security. The authors used statistical data, results of a survey of experts—investigators of crimes on electronic data and information system security, experts of information technology (IT) forensics. (shrink)

The Food and Drug Administration, as a matter of long-standing policy, does not inform the public of instances whereby applications for new drugs or new indications for existing drugs have been rejected by the agency or withdrawn from consideration, nor does it disclose the agency’s analyses of the data submitted with such applications. This lack of transparency is unjustified and prevents patients, researchers, and healthcare providers from gaining insight into why a drug’s application was not approved. The (...) FDA’s policy is particularly troubling in cases where the agency has found a currently marketed drug to be ineffective or unsafe for a newly proposed indication. Disclosure of the FDA’s findings in such cases would promote public health by encouraging healthcare providers to avoid prescribing drugs for unapproved uses that the agency has deemed to be potentially dangerous or ineffective. The FDA’s counterpart agencies in Europe and Canada have demonstrated the feasibility of disclosing information on rejected and withdrawn drug marketing applications. The FDA should follow suit and allow the American public to know when a drug is deemed unsafe or ineffective for a certain use. (shrink)

Traditional multiple-group confirmatory factor analysis is usually criticized for having too restrictive model assumption, namely the scalar measurement invariance. The new multiple-group analysis methodology, alignment, has become an effective alternative. The alignment evaluates measurement invariance and more importantly, permits factor mean comparisons without requiring scalar invariance which is usually required in traditional multiple-group CFA. Some simulation studies and empirical studies have investigated the applicability of alignment under different conditions, but some areas remain unexplored. Based on the simulation studies of Asparouhov (...) and Muthén and of Flake and McCoach, this current simulation study is broken into two sections. The first study investigates the minimal group sizes required for alignment in three-factor models. The second study compares the performance of multiple-group CFA, multiple-group exploratory structural equation model, and alignment by including different proportions and magnitudes of cross-loadings in the models. Study 1 shows that when the model has no noninvariant parameters, the alignment requires relatively lower group sizes. Explicitly, the minimal group size required for alignment was 250 when the amount of groups was three, the minimal group size was 150 when the amount of groups was nine, and 200 when the amount of groups was 15. When there are noninvariant parameters in the model and the amount of groups is low, a group size of 350 is a safe rule of thumb. When there are noninvariant parameters in the model and the amount of groups is high, a group size of 250 is required for trustworthy results. The magnitude of noninvariance and the noninvariance rate do not affect the minimal group size required for alignment. Study 2 shows that multiple-group CFA provides accurate factor mean estimates when each factor had 20% factor loading with small-sized cross-loading. Multiple-group ESEM provides accurate factor mean estimates when the magnitude of cross-loading is small or when each factor had 20% factor loading with medium-sized cross-loading. Alignment provides accurate factor mean estimates when there are only small-sized cross-loadings in the model. The parameter estimates, coverage rates and ratios of average standard error to standard deviation for each methodology are not influenced by the amount of groups. Recommendations are concluded for using multiple-group CFA, multiple-group ESEM, traditional alignment and aligned ESEM based on the results. Multiple-group CFA is more suitable for use when scalar invariance is established. Multiple-group ESEM works best when there are small-sized or only a few medium-sized cross-loadings in the model. Traditional alignment allows for small-sized cross-loadings and a few noninvariant parameters in the model. AESEM integrates the advantages of alignment and ESEM, can provide accurate estimates when noninvariant parameters and cross-loadings both exist in the model. Compared to multiple-group CFA, multiple-group ESEM, the alignment methodology performs well in more situations. (shrink)

It has become essential to create and apply new media in visual communication design due to social media existence. This study aims to investigate the role of innovative applications of new media in visual communication design in educational institutions. Traditional media design in visual communication lacks to disseminate information more effectively, which requires innovative change. Therefore, this study attempts to highlight the role of innovative application of new media in visual communication by considering visual expression design with information technology, (...) flexible layout, diversified modes of transmission, and interactivity of integration. For this purpose, this study adopted a quantitative research approach in which a cross-sectional research design is followed. A questionnaire survey is carried out to collect data from educational institutions in China. Partial Least Square-Structural Equation Modeling is used for data analysis. Results of the study indicated that innovative applications of new media have central importance in visual communication. However, resistance to innovative change has a negative role in the relationship between innovative applications of new media and visual communication design. Results of the study highlighted that visual expression design with IT, flexible layout, diversified modes of transmission, and interactivity of integration have a positive effect on visual communication design. Therefore, among the educational intuitions of China, implementing innovative applications related to the new media can lead to visual communication design. The results of this study provided several insights for the practitioners to promote communication methods among educational institutions. (shrink)

Assume this hypothetical situation: an American pharmaceutical company, Maxwell Fisch Pharmaceuticals, Inc., wishes to perform clinical trials involving a new antipsychotic medication, Klezac. Klezac is in its third phase of the clinical stage of the drug research process. Once the testing is complete, Maxwell plans to submit a New Drug Application, the official request to begin marketing Klezac, to the Food and Drug Administration. The new drug is expected to receive FDA approval in 2 or (...) more years. The company decides to shift its research and development activities to Z, a small, developing country. In doing so, Maxwell is following the course taken by numerous other drug companies who wish to take advantage of faster governmental approval in foreign sites and ensuing cheaper research costs. (shrink)

New technologies regularly bring about profound changes in our daily lives. Romantic relationships are no exception to these transformations. Some philosophers expect the emergence in the near future of love drugs: a theoretically achievable biotechnological intervention that could be designed to strengthen and maintain love in romantic relationships. We investigated laypeople’s resistance to the use of such technologies and its sources. Across two studies (Study 1, French and Peruvian university students, N after exclusion = 186; Study 2, Amazon Mechanical Turk (...) sample, N after exclusion = 693, pre-registered), we found that the use of love drugs designed to strengthen and maintain love in romantic relationships are considered as more morally problematic than psychological therapy with the same aim. In Study 2, we show that this last effect is partially due to the fact that the love resulting from the use of love drugs is perceived as less authentic, intense, and durable. We discuss the specific role of authenticity in the relative moral disapproval of love drugs. (shrink)

The VOICES study involved at least one radical move in the decades-old debates about attention deficit hyperactivity disorder diagnosis and stimulant drug treatments: to systematically investigate young people's perspectives and experiences so that these could be included as evidence in social, ethical and policy deliberations about the benefits and risks of these interventions. The findings reported in this article were both surprising and unsurprising to us as researchers. We were surprised at the consistency of children's positive responses to stimulant (...) medication, and at the robustness of the experience of increased capacity for moral agency with medication. We were unsurprised at the insights many young people have into their own behaviours and that of others.I am hopeful that the perspectives of children reported in this article will inspire a fresh public conversation about the ethics of stimulant drug treatments, as well as further research with children. In order to believe that children's perspectives add something new and valuable to the social discourse, one must first view children as capable of reliably reporting their own experiences as part of a well-designed research study. It seems that Steven Rose does …. (shrink)

Multi-space is the notion combining different fields in to a unifying field, which is more applicable in our daily life. In this paper, we introduced the notion of multi-soft space which is the approximated collection of the multi-subspaces of a multi-space . Further, we defined some basic operations such as union, intersection, AND, OR etc. We also investigated some properties of multi-soft spaces.

The study of the chaotic dynamics in fractional-order discrete-time systems has received great attention over the last years. Some efforts have been also devoted to analyze fractional maps with special features. This paper makes a contribution to the topic by introducing a new fractional map that is characterized by both particular dynamic behaviors and specific properties related to the system equilibria. In particular, the conceived one dimensional map is algebraically simpler than all the proposed fractional maps in the literature. Using (...) numerical simulation, we investigate the dynamic and complexity of the fractional map. The results indicate that the new one-dimensional fractional map displays various types of coexisting attractors. The approximate entropy is used to observe the changes in the sequence sequence complexity when the fractional order and system parameter. Finally, the fractional map is applied to the problem of encrypting electrophysiological signals. For the encryption process, random numbers were generated using the values of the fractional map. Some statistical tests are given to show the performance of the encryption. (shrink)

Probability distributions play an essential role in modeling and predicting biomedical datasets. To have the best description and accurate prediction of the biomedical datasets, numerous probability distributions have been introduced and implemented. We investigate a novel family of lifetime probability distributions to represent biological datasets in this paper. The proposed family is called a new flexible logarithmic- X family. The suggested NFLog- X family is obtained by applying the T- X method together with the exponential model having the PDF m (...) t = e − t. Based on the NFLog- X approach, a three parameters probability distribution, namely, a new flexible logarithmic-Weibull distribution is introduced. The method of maximum likelihood estimation is adopted for estimating the parameters of the NFLog- X family. In the end, we examine three different biological datasets in order to give a thorough numerical research that illustrates the NFLog-Wei distribution. Comparisons are made between the analytical goodness-of-fit metrics of the suggested distribution. We made comparison with the alpha power transformed Weibull, exponentiated Weibull, Weibull, flexible reduced logarithmic-Weibull, and Marshall–Olkin Weibull distributions. After performing the analyses, we observe that the proposed method outclassed other competitive distributions. (shrink)

Treating physicians have key roles to play in expanded access to investigational drugs, by identifying investigational treatment options, assessing the balance of risks and potential benefits, informing their patients, and applying to the regulatory authorities. This study is the first to explore physicians’ experiences and moral views, with the aim of understanding the conditions under which doctors decide to pursue expanded access for their patients and the obstacles and facilitators they encounter in the Netherlands. In this mixed-methods study, (...) semi-structured interviews and a questionnaire were conducted with medical specialists across the country and analysed thematically. Typically, our respondents pursue expanded access in “back against the wall” situations and broadly support its classic requirements. They indicate practical hurdles related to reimbursement, the amount of time and effort required for the application, and unfamiliarity with the regulatory process. Some physicians are morally opposed to expanded access, with an appeal to safety risks, lack of evidence, and “false hope.” Some of these moral concerns and practical obstacles may be essential targets for change, if expanded access to unapproved drugs is to become available for wider groups of patients for whom standard treatment options are not—or no longer—available, on a more consistent and equal basis. (shrink)

The Food and Drug Administration and the European Medicines Agency have launched a recent initiative to enhance collaboration in research, with the intent to “ensure that clinical trials submitted in drug marketing applications in the United States and European Union are conducted uniformly, appropriately, and ethically.” This initiative recalls efforts from two decades ago when the United States, the European Union and Japan formed the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (...) as a mechanism for harmonizing clinical research regulations. The intent of harmonization was to improve patients’ “access to new drugs, to prevent unnecessary global development delays and to avoid animal and human study duplications” through policy reconciliation.FDA/EMA efforts at collaboration call for a reassessment of past harmonization efforts: to what extent are ICH member policies already synchronized and to what extent can they be harmonized in the future? This paper will focus on these questions through the lens of pediatric investigation. (shrink)

Drug phenomenon is relatively new in our country; it became relevant only in the ninth decade of the last century. A new phenomenon or a process is usually dynamic in the initial stages and only later does it acquire features of stability and the main trends that have become prominent several years ago remain unchanged. The author shows the data of drugs crime and other indicators and the aspects of their perspectives. In the article, a question about drug (...) crimes in Lithuania is considered in all aspects. The author maintains that the rapid emergence of many new non‑controlled psychoactive substances represents an increasing challenge for current models of drug control. (shrink)

Aphasia is a language disorder that occurs after a stroke and impairs listening, speaking, reading, writing, and calculation skills. Patients with post-stroke aphasia in Japan are increasing due to population aging and the advancement of medical treatment. Opportunities for adequate speech therapy in chronic stroke are limited due to time constraints. Recent studies have reported that intensive speech therapy for a short period of time or continuous speech therapy using high-tech equipment, including speech applications (apps, can improve aphasia even in (...) the chronic stage. However, its underlying mechanism for improving language function and its effect on other cognitive functions remains unclear. In the present study, we investigated whether intensive speech therapy using a newly developed speech support app could improve aphasia and other cognitive functions in patients with chronic stroke. Furthermore, we examined whether it can alter the brain network related to language and other cortical areas. Thus, we conducted a prospective, single-comparison study to examine the effects of a new speech support app on language and cognitive functions and used resting state functional MRI (rs-fMRI) regions of interest (ROI) to ROI analysis to determine changes in the related brain network. Two patients with chronic stroke participated in this study. They used the independent speech therapy system to perform eight sets of 20 randomly presented words/time (taking approximately 20 min), for 8 consecutive weeks. Their language, higher cognitive functions including attention function, and rs-fMRI, were evaluated before and after the rehabilitation intervention using the speech support app. Both patients had improved pronunciation, daily conversational situations, and attention. The rs-fMRI analysis showed increased functional connectivity of brain regions associated with language and attention related areas. Our results show that intensive speech therapy using this speech support app can improve language and attention functions even in the chronic stage of stroke, and may be a useful tool for patients with aphasia. In the future, we will conduct longitudinal studies with larger numbers of patients, which we hope will continue the trends seen in the current study, and provide even stronger evidence for the usefulness of this new speech support app. (shrink)

This volume is intended for professional philosophers and laymen with an interest in East-West studies and comparative philosophy and religion. The central focus is the concept of comparing perspectives from both the Eastern and the Western philosophical traditions on harmony and strife. The unique and happy result is an East-West anthology which is directed at analyzing a single philosophical problem which is of importance to both traditions. Unlike many anthologies which tend to be collections of isolated and unrelated essays, the (...) Editors' focus on a single theme has resulted in a unified volume which maintains a high continuity of interest throughout. The Editors have carefully culled and organized essays from a select group of philosophers from the United States, West Germany, Japan, Australia, Beijing, Taipei and Hong Kong. Harmony and strife are analyzed as systematic concepts in Western philosophy, as parts of classical Chinese thought, as central concepts in Buddhism, as metaphysical concepts, as dialectical concepts and even as null concepts. The Editors have taken great care so that a continuity and a coherence of presentation is achieved despite the striking variety of perspectives from which harmony and strife are analyzed. It is both unusual and important to have such a systematic and thorough investigation of a topic of paramount social and philosophical significance by some of the leading minds of the day. Besides, the essays included are eminently readable. The volume is likely to become a standard work in this area for some years to come. (shrink)

Despite their crucial role in the translation of pre-clinical research into new clinical applications, phase 1 trials involving patients continue to prompt ethical debate. At the heart of the controversy is the question of whether risks of administering experimental drugs are therapeutically justified. We suggest that prior attempts to address this question have been muddled, in part because it cannot be answered adequately without first attending to the way labor is divided in managing risk in clinical trials. In what follows, (...) we approach the question of therapeutic justification for phase 1 trials from the viewpoint of five different stakeholders: the drug regulatory authority, the IRB, the clinical investigator, the referring physician, and the patient. Our analysis shows that the question of therapeutic justification actually raises multiple questions corresponding to the roles and responsibilities of the different stakeholders involved. By attending to these contextual differences, we provide more coherent guidance for the ethical negotiation of risk in phase 1 trials involving patients. We close by discussing the implications of our argument for various perennial controversies in phase 1 trial practice. (shrink)

The assessment of nanotechnology applications such as nanocarrier-based targeted drug delivery has historically been based mostly on toxicological and safety aspects. The use of nanocarriers for TDD, a leading-edge nanomedical application, has received little study from the angle of experts’ perceptions and acceptability, which may be reflected in how TDD applications are developed. In recent years, numerous authors have maintained that TDD assessment should also take into account impacts on ethical, environmental, economic, legal, and social issues in order (...) to lead to socially responsible innovation. Semi-structured interviews were conducted with French and Canadian researchers and research trainees with diverse disciplinary backgrounds and involved in research related to emerging technologies. The interviews focussed on scenarios presenting two types of TDD nanocarriers in two contexts of use. Content and inductive analyses of interviews showed how facets of perceived impacts such as health, environment, social cohabitation, economy, life and death, representations of the human being and nature, and technoscience were weighed in acceptability judgments. The analyses also revealed that contextual factors related to device, to use, and to user influenced the weighting assigned to perceived impacts and thus contributed to variability in interviewees’ judgments of acceptability. Giving consideration to researchers’ perspective could accompany first steps of implementation and development of nanomedicine by producing a first, but wide, picture of the acceptability of nanocarrier-based TDD. (shrink)

With the introduction of new information communication technologies, employers are increasingly engaging in social media screening, also known as cybervetting, as part of their hiring process. Our research, using an online survey with 482 participants, investigates young people’s concerns with their publicly available social media data being used in the context of job hiring. Grounded in stakeholder theory, we analyze the relationship between young people’s concerns with social media screening and their gender, job seeking status, privacy concerns, and social media (...) use. We find that young people are generally not comfortable with social media screening. A key finding of this research is that concern for privacy for public information on social media cannot be fully explained by some “traditional” variables in privacy research. The research extends stakeholder theory to identify how social media data ethics should be inextricably linked to organizational practices. The findings have theoretical implications for a rich conceptualization of stakeholders in an age of social media and practical implications for organizations engaging in cybervetting. (shrink)

Objective Compare outcome of dogs that did and did not receive fresh frozen plasma (FFP) for treatment of pancreatitis. Design Retrospective case series between 1995 and 2005. Setting University referral hospital. Animals Seventy-four dogs were enrolled with a total of 77 Cases as 2 dogs had repeat episodes of pancreatitis. Diagnosis of pancreatitis was based on clinical signs, physical examination, and abdominal ultrasonographic examination. Interventions The medical database was searched for dogs with a diagnosis of pancreatitis. Information collected included signalment, (...) vital signs, CBC, use of FFP, length of stay, use of antimicrobials and supplemental nutrition, surgical intervention, preexisting illness, evidence of a coagulopathy and outcome. Outcome was compared between those patients that did and did not receive FFP. Measurements and Main Results Fifty-nine dogs survived to discharge. Two dogs with repeat pancreatitis survived to discharge after each episode. Thirteen dogs died and 2 were euthanized. FFP was administered to 20 dogs. Two dogs that were hospitalized for repeat pancreatitis did not receive FFP. Seven of 20 (35%) cases that received plasma died or were euthanized compared with 6 of 57 (12%) cases that did not receive plasma. Plasma administration was significantly related to outcome (P<0.001). Severity of illness scores were difficult to assign, however, dogs meeting criteria for systemic inflammatory response syndrome were not more likely to receive FFP. Other therapies included supplemental nutrition, antimicrobials, and surgical intervention, which did not affect outcome. Conclusions Mortality rate for those dogs receiving plasma was higher than those that did not. Severity of illness scores were difficult to assign; however, preexisting illness, evidence of systemic inflammatory response syndrome, and presence of a coagulopathy were not significantly different between the groups that did and did not receive FFP. No benefit for administration of FFP was noted. Additional investigation should be performed to confirm this result. 2009 Veterinary Emergency and Critical Care Society. (shrink)

Children who experience well-being are engaging more confidently and positively with their caregiver and peers, which helps them to profit more from available learning opportunities and support current and later life outcomes. The goodness-of-fit theory suggests that children’s well-being might be a result of the interplay between their temperament and the environment. However, there is a lack of studies that examined the association between children’s temperament and well-being in early childhood education and care, and whether this association is affected by (...) ECEC process quality. Using a multilevel random coefficient approach, this study examines the association between toddlers’ temperament and well-being in Norwegian ECEC and investigates whether process quality moderates this association. Results reveal an association between temperament and well-being. Staff-child conflict moderates the association between shyness and well-being, and between activity and well-being. Moreover, high emotional behavioral support moderates the association between activity and well-being. Extra attention should be paid by the staff to these children’s needs. (shrink)

Each of the antiretroviral drugs that are currently used to stop the progression of HIV infection causes its own specific side effects. Despite the expansion, multiplication, and simplification of treatment options over the past decade, side effects continue to affect people living with HIV. Yet, we see a clear disconnect between the way side effects are normalized, routinized, and framed in clinical practice and the way they are experienced by people living with HIV. This paper builds on the premise that (...) new approaches are needed to understand side effects in a manner that is more reflective of the subjective accounts of people living with HIV. Drawing on the work of Deleuze and Guattari, it offers an original application of the theory of ‘assemblage’. This theory offers a new way of theorizing side effects, and ultimately the relationship between the body and antiretroviral drugs (as technologies). Combining theory with examples derived from empirical data, we examine the multiple ways in which the body connects not only to the drugs but also to people, things, and systems. Our objective is to illustrate how this theory dares us to think differently about side effects and allows us to originally (re)think the experience of taking antiretroviral drugs. (shrink)

This paper builds on previous work that investigated anticancer drugs as ‘informed materials’, i.e., substances that undergo an informational enrichment that situates them in a dense relational web of qualifications and measurements generated by clinical experiments and clinical trials. The paper analyzes the recent transformation of anticancer drugs from ‘informed’ to ‘informing material’. Briefly put: in the post-genomic era, anti-cancer drugs have become instruments for the production of new biological, pathological, and therapeutic insights into the underlying etiology and evolution of (...) cancer. Genomic platforms characterize individual patients’ tumors based on their mutational landscapes. As part of this new approach, drugs targeting specific mutations transcend informational enrichment to become tools for informing their targets, while also problematizing the very notion of a ‘target’. In other words, they have become tools for the exploration of cancer pathways and mechanisms. While several studies in the philosophy and history of biomedicine have called attention to the heuristic relevance and experimental use of drugs, few have investigated concrete instances of this role of drugs in clinical research. (shrink)

This research is part of the last study Drugs and School IX developed in the Basque Country (Spain) by the Instituto Deusto de Drogodependencias (Deusto Institute of Drug Addiction) of the University of Deusto and the data gathered by means of cluster sampling in two stages. The sample is made up of N= 6.007 girls and boys ranging from 12 to 22 years of age in Secondary Education and the aim is to answer the following new research questions based (...) on those parameters: (1) describe the reality of drug consumption and some psychosocial variables in this sample, as well as analyse several relations between variables; (2) analysing the role of school well-being, self-esteem and self-concept regarding consumption; (3) taking a close look at the moderating role of age and gender on the relationship of school well-being, self-concept and self-esteem with consumption; and (4) understand the existing interaction between all these variables, studying the moderating role of self-esteem and self-concept in the influence of school well-being on consumption. Using a correlation, hierarchical regression and mediation analysis with SPSS (v. 26) and Amos (v. 26) applications, three main conclusions were reached. Firstly, that educational and academic well-being, academic self-concept and self-esteem seem to play the role of protecting factors in adolescence, while assertiveness is linked to a higher consumption level. Secondly, that academic self-concept has a mediating effect between well-being and consumption. Some of these relations are moderated by the variables of gender and age. Thirdly, that age and gender are very relevant sociodemographic variables that must be taken into account in order to understand this phenomenon. Age has shown its covariant effect, which is especially relevant in the influence of academic well-being measured as being held back years. It has also proved to be important in order to understand its experiential or experimental and transitory character. Moreover, significant differences in consumptions have been found based on gender. (shrink)

The facilitation of tight regulatory frameworks necessary to ensure that new drugs are safe and effective have yet to be effectively applied within the paediatric population. Utilization of unlicensed and off-label drugs in children results in a variety of problems ranging from inefficacy, adverse reactions and in some cases death. This ethically questionable behaviour has led the European government to legally force pharmaceutical companies to propose paediatric applications and carry out clinical studies at early stages of drug development. The (...) new European Paediatric Regulation implemented in 2007 opens a new era of paediatric drug development and will offer the opportunity to vastly improve children's health. However, this brighter outlook for the paediatric community might encourage potentially unethical behaviour in a pharmaceutical industry that finds itself in economically unstable times. The article records the gradual evolution of the US Paediatric Exclusivity Plan and the underlying principle of the newly introduced European Paediatric Regulation. It discusses some of the potential drawbacks and detrimental consequences of implementing the new European regulation, and the prospects of avoiding these by critically evaluating the difficulties experienced by the US. (shrink)

In this article, we develop a new approach to integrating philosophical phenomenology with qualitative research. The approach uses phenomenology’s concepts, namely existentials, rather than methods such as the epoché or reductions. We here introduce the approach to both philosophers and qualitative researchers, as we believe that these studies are best conducted through interdisciplinary collaboration. In section 1, we review the debate over phenomenology’s role in qualitative research and argue that qualitative theorists have not taken full advantage of what philosophical phenomenology (...) has to offer, thus motivating the need for new approaches. In section 2, we introduce our alternative approach, which we call Phenomenologically Grounded Qualitative Research (PGQR). Drawing parallels with phenomenology’s applications in the cognitive sciences, we explain how phenomenological grounding can be used to conceptually front-load a qualitative study, establishing an explicit focus on one or more structures of human existence, or of our being in the world. In section 3, we illustrate this approach with an example of a qualitative study carried out by one of the authors: a study of the existential impact of early parental bereavement. In section 4, we clarify the kind of knowledge that phenomenologically grounded studies generate and how it may be integrated with existing approaches. (shrink)

There is an increasing interest in expanding the one-parameter Lindley distribution to two-parameter, three-parameter, and five-parameter. The univariate one-parameter Lindley distribution is still one of the most applicable distributions in data analysis especially in lifetime data. Modeling dependent random quantities required bivariate parametric probability distributions. This study presents a new bivariate three-parameter probability distribution called bivariate modified Lindley distribution. The one-parameter modified Lindley distribution is used as a base line to construct the new model. Its statistical properties including cumulative function, (...) density function, marginals, moments, conditional distributions, and copula are discussed. Simulation is constructed to declare theoretical properties, to show the flexibility of the new model and to investigate the goodness of fit. Two sets of real data, financial data and UEFA Champion’s League data, are used to show the applicability of the proposed model for different types of data. (shrink)

The recent development of the research field of Computing and Philosophy has triggered investigations into the theoretical foundations of computing and information. This thesis consists of two parts which are the result of studies in two areas of Philosophy of Computing and Philosophy of Information regarding the production of meaning and the value system with applications. The first part develops a unified dual-aspect theory of information and computation, in which information is characterized as structure, and computation is the information dynamics. (...) This enables naturalization of epistemology, based on interactive information representation and communication. In the study of systems modeling, meaning, truth and agency are discussed within the framework of the PI/PC unification. The second part of the thesis addresses the necessity of ethical judgment in rational agency illustrated by the problem of information privacy and surveillance in the networked society. The value grounds and socio-technological solutions for securing trustworthiness of computing are analyzed. Privacy issues clearly show the need for computing professionals to contribute to understanding of the technological mechanisms of Information and Communication Technology. The main original contribution of this thesis is the unified dual-aspect theory of computation/information. Semantics of information is seen as a part of the data-information-knowledge structuring, in which complex structures are self-organized by the computational processing of information. Within the unified model, complexity is a result of computational processes on informational structures. The thesis argues for the necessity of computing beyond the Turing-Church limit, motivated by natural computation, and wider by pancomputationalism and paninformationalism, seen as two complementary views of the same physical reality. Moreover, it follows that pancomputationalism does not depend on the assumption that the physical world on some basic level is digital. Contrary to many believes it is entirely compatible with dual quantum-mechanical computing. (shrink)

When you type the word “serendipity” in a word-processor application such as Microsoft Word, the autocorrection engine suggests you choose other words like “luck” or “fate”. This correcting act turns out to be incorrect. However, it points to the reality that serendipity is not a familiar English word and can be misunderstood easily. Serendipity is a very much scientific concept as it has been found useful in numerous scientific discoveries, pharmaceutical innovations, and numerous humankind’s technical and technological advances. Therefore, (...) there have been many books written around the concept. So why do we need this additional book? This is not just another book about serendipity. It has evolved from the Editor’s question lingering for a decade after finishing his widely cited article (coauthored with Prof. Nancy K. Napier of Boise State University, ID, USA) “Serendipity as a strategic advantage?” in T. Wilkinson’s edited volume Strategic Management in the 21st Century, published by Praeger. The Editor and contributing authors have tried to achieve the following in this title. Demystifying the Serendipity Myth The phenomenon of serendipity has always been thought of as a “miracle”. It is the mystery of human innovation and one of the ultimate secrets of our society. But serendipity is not just a lucky coincidence nor any hidden conspiracy. This book explores the science of the information process behind this seemingly miraculous phenomenon. It connects human society with nature, going back to the root of our existence and looking at the flame of survival to discover the harmony in making creativity. Presenting the nuts and bolts of being an adventurer of science The authors present their conceptual investigations into serendipity’s nature and its mechanism by examining interesting real events and stories. The content is thought-provoking, and readers are led to question and explore their own life stories and problems along the journey of reading this book. Catching an elusive high-value target requires great strategies and efforts. But there are no dark secrets here because this is the “way of nature” – how we humans have always strived for innovation without realizing the blueprints behind such processes. Unlike other books on serendipity, this book will show you that a powerful “secret” is closer than you think. Delivering practical uses for different audiences By understanding the conditionality and survival drivers of serendipity, individuals or organizations can make better decisions on creating the right environment to facilitate the encounter and attainment of this valuable phenomenon. For scientists: With clear explanations of the information processes underlying serendipity, flexible theoretical frameworks of mindsponge and the 3D principle of creativity, researchers are provided with the tools they need to dig deeper into their own fields of study and find practical applications, be it psychology, economics, sociology, or anything that involves innovation (which is, in fact, every scientific discipline). For curious casual readers: Everybody needs innovation to make breakthroughs or spice up one’s life. If you think great ideas come to people randomly from an unknown fairy place, this book will convince you otherwise without taking away that awe and wonder. But above all, you will know how to become more creative, scientifically and straightforwardly, with no snake oil and no weird tricks. For ambitious business people: The flame that brought about great successes throughout human history is within you. But you can only use it if you understand it. While others wait for serendipity to come, you will be able to actively hunt for those precious moments. As it has always been: the best hunters triumph, not the passive wanderers. And in this age of information chaos, finding the golden fruits is not easy. Those from information technology know this problem well, and this book is the treasure map that they have been seeking to navigate that stormy ocean looking for jewels. Like a kingfisher tracking its prey through the water, waiting to gracefully strike, with serendipity, a person seizes the prize of creativity amid the chaos of life. ¤ ¤ ¤ Official introduction: The book explores the nature, underlying causes, and the information processing mechanism of serendipity. It proposes that natural or social survival demands drive serendipity, and serendipity is conditional on the environment and the mindset, on both individual and collective levels. From Darwin's evolution theory to Sun Tzu's war tactics, major innovations throughout human history are unified by this key concept. In the rapidly changing world, information is abundant but rather chaotic. The adaptive power of serendipity allows people to notice treasures within this wild sea, but only for those who understand how it works. To increase the probability of encountering and attaining serendipity, one should employ the mindsponge mechanism and the 3D process of creativity, for without these frameworks, serendipity is truly an elusive target. The book also discusses methods to build environments and cultures rich in navigational and useful information to maximize the chance of finding and capitalizing on serendipity. As a skill, serendipity has a resemblance to how kingfishers observe and hunt their prey. (shrink)

Following the studies of Araujo et al. (AI Soc 35:611–623, 2020) and Lee (Big Data Soc 5:1–16, 2018), this empirical study uses two scenario-based online experiments. The sample consists of 221 subjects from Germany, differing in both age and gender. The original studies are not replicated one-to-one. New scenarios are constructed as realistically as possible and focused on everyday work situations. They are based on the AI acceptance model of Scheuer (Grundlagen intelligenter KI-Assistenten und deren vertrauensvolle Nutzung. Springer, Wiesbaden, 2020) (...) and are extended by individual descriptive elements of AI systems in comparison to the original studies. The first online experiment examines decisions made by artificial intelligence with varying degrees of impact. In the high-impact scenario, applicants are automatically selected for a job and immediately received an employment contract. In the low-impact scenario, three applicants are automatically invited for another interview. In addition, the relationship between age and risk perception is investigated. The second online experiment tests subjects’ perceived trust in decisions made by artificial intelligence, either semi-automatically through the assistance of human experts or fully automatically in comparison. Two task types are distinguished. The task type that requires “human skills”—represented as a performance evaluation situation—and the task type that requires “mechanical skills”—represented as a work distribution situation. In addition, the extent of negative emotions in automated decisions is investigated. The results are related to the findings of Araujo et al. (AI Soc 35:611–623, 2020) and Lee (Big Data Soc 5:1–16, 2018). Implications for further research activities and practical relevance are discussed. (shrink)

Definition of the problem Compassionate use is the use of unapproved drugs in groups of patients suffering from a disease that, in the absence of an alternative treatment option, is life-threatening or leads to severe disability. Physicians are not in charge because access to the drug is only granted by pharmaceutical companies, which comes along with many ethical issues. Launched in 2020, the program of Onasemnogenum abeparvovecum against spinal muscular atrophy in children reached a new dimension. The intent of (...) this drug is to stop the progression of the disease with just a single dose, but the company limited the doses in the program to only 100. The global allocation was by lottery, which was considered a novelty in compassionate use history and therefore widely criticized. This paper investigates alternative allocation principles. Arguments Each possible principle is accompanied by many aspects that need to be considered with regard to urgency and global distribution. This makes some principles like first-come-first-served seem negligible. Remaining principles are ordered hierarchically to derive an algorithm that can represent an alternative to a lottery. A combination of willingness to participate in research, urgency, and likelihood of success (relative to the availability of supportive treatment options) may be considered in similar cases in future global compassionate use programs with children. Conclusion Since universal algorithms are difficult to define, allocation criteria should always be discussed by an independent panel of experts. Both the constitution of such a panel and its mandatory consultation are necessary in order to decrease the burden for all those involved and to prevent arbitrariness. (shrink)

New genetic technologies and their applications in biomedicine have important implications for social identities in contemporary societies. In medicine, new genetics is increasingly important for the identification of health and disease, the imputation of personal and familial risk, and the moral status of those identified as having genetic susceptibility for inherited conditions. There are also consequent transformations in national and ethnic collective identity, and the body and its investigation is potentially transformed by the possibilities of genetic investigations and modifications (including (...) the highly controversial terrains of reproductive technologies and the use of human embryos in biomedical research). The papers in this volume, drawn from an international array of authors, address these issues from a variety of national, disciplinary and empirical standpoints. An informative read for postgraduates and professionals in the fields of sociology, social anthropology, science and technology studies, and environmental studies, the chapters comprise empirically based and theoretically informed discussions of key sociological, anthropological, political and ethical issues. Using the resources of a wide range of social science disciplines to provide a comparative approach to complex issues, this superb collection explores the local and global consequences of the new genetics, and analyzes the social implications of these advances for identity formation in a period of rapid social change. (shrink)

Over the past decade, the management of clinical trials of pharmaceuticals has become a veritable industry, as evidenced by the emergence and proliferation of contract research organizations (CROs) that co‐ordinate and monitor trials. This article focuses on work performed by one CRO involved in the introduction of new software, modelled on industrial production processes, into clinical trial practices. It investigates how this new management technique relates to the work performed in the clinic to ensure that trial participants comply with the (...) protocol. Using an analytical distinction between ‘classical’ management work and invisible work, the article contextualizes the meaning of compliance in the clinic and suggests that the work involved in producing compliance should be taken into consideration by those concerned with validity of trials, as clinical trials are put under private industrial management. The article builds on participant observation at a Swedish university hospital and interviews the nurses, dieticians, doctors and a software engineer, all part of a team involved in pharmaceutical drug trials on a potential obesity drug. (shrink)

ObjectiveTo identify the ethical challenges associated with the development and implementation of new tuberculosis drugs and diagnostics.MethodsTwenty-three semi-structured qualitative interviews conducted between December 2015 and September 2016 with programme administrators, healthcare workers, advocates, policymakers, and funders based in the Americas, Europe, and Africa. Interviews were analysed using thematic analysis.ResultsDivergent interests and responsibilities, coupled with power imbalances, are a primary source of ethical challenges; the uncertain risk profiles of new drugs present an additional one. Although this challenge can be partially mitigated (...) through stringent pharmacovigilance, respondents highlighted that high-burden countries tend to lack the resources to facilitate safe implementation. Increased advocacy and community engagement are considered an ethical imperative for future TB development and implementation.ConclusionsThis project helps identify some of the ethical challenges of new TB technologies. It demonstrates that investigating ethical challenges through qualitative research is one way to apprehend the difficulty of implementing new TB technologies. Addressing this difficulty will require that those in positions of power reconsider their interests in relation to disempowered communities.Policy implicationsEfforts to build consensus regarding what values should underpin the global governance of TB research, prevention, and care are essential to facilitate the ethical implementation of new TB technologies. (shrink)

The genetic component of variations in human responses to pharmacological agents is called pharmacogenetics while the molecular basis for these variations are most often identified as pharmacogenomics. Pharmacogenomics as a field of scientific endeavor is so new that in the scientific literature the two terms are often used interchangeably. In fact, the search for new drugs at the molecular level start with the identification of variations in DNA sequences whose products produce alterations in the amino acid structure of the active (...) portion of a protein which are then identified with the clinical disorder in question. This process is just the reverse of standard pharmaceutical approaches which begin with exploration of the physiological and potentially the biochemical basis of the specific disorder under study. The completion of the first draft of the human genome in the first months of the new millenium has increased expectations that molecular genetic approaches to drug disovery and development will significantly shorten the time-frame of new drug testing, significantly reduce the level of adverse events and anable the design of drugs to treat those with unique disorders.Based on such rosy expectations and the potential economic opportunities afforded by those who obtain such patents, there has been a rush of patent applications both in the United States and in Europe by private industry and university laboratories conducting genomic research to secure the rights to specific DNA sequences and federal agencies attempting to place the control of such information in the public domaine. This paper will document and discuss from a historic prospective the public policy and bioethical issues associated with the availability of patents for drug development. (shrink)

Artificial intelligence is the new technological buzzword. Everything from camera apps on your mobile phone to medical diagnosis algorithms to expert systems are now claiming to be ‘AI’, and many more facets of our lives are being colonized by the application of AI/ML systems (henceforth, ‘AI’). But what does this entail to designers, users and to society at large? Most of the philosophical discourse in this context has focused on the analysis and clarification of the epistemological claims of intelligence (...) within AI and on the moral implications of AI. Philosophical critiques of the plausibility of artificial intelligence do not have much to say about the real-world repercussions of introducing AI systems into every possible domain in the name of automation and efficiency; similarly, most of the moral misgivings about AI have to do with conceiving them as autonomous agents beyond the control of human actors. These discussions have clarified the debate surrounding AI to a great extent; however, certain crucial questions remain outside the ambit of these debates. Arguments in support of AI often take advantage of this void by emphasizing that AI systems are no different than previously existing ‘unintelligent’ technologies, thereby implying that the economic, existential, and ethical threats posed by these systems are either similar in kind as those posed by any other technology or grossly misplaced and exaggerated. In this chapter, we shall think through this assumption by investigating into the ontology of AI systems vis-à-vis ordinary (non-AI) technical artefacts to see wherein lies the distinction between the two. I shall examine how contemporary ontologies of technical artefacts (e.g., intentionalist and non-intentionalist theories of function) apply to AI. Hence, clarifying the ontology of AI is crucial to understand their normative and moral significance and the implications therefrom. (shrink)

The genetic component of variations in human responses to pharmacological agents is called pharmacogenetics while the molecular basis for these variations are most often identified as pharmacogenomics. Pharmacogenomics as a field of scientific endeavor is so new that in the scientific literature the two terms are often used interchangeably. In fact, the search for new drugs at the molecular level start with the identification of variations in DNA sequences whose products produce alterations in the amino acid structure of the active (...) portion of a protein which are then identified with the clinical disorder in question. This process is just the reverse of standard pharmaceutical approaches which begin with exploration of the physiological and potentially the biochemical basis of the specific disorder under study. The completion of the first draft of the human genome in the first months of the new millenium has increased expectations that molecular genetic approaches to drug disovery and development will significantly shorten the time-frame of new drug testing, significantly reduce the level of adverse events and anable the design of drugs to treat those with unique disorders.Based on such rosy expectations and the potential economic opportunities afforded by those who obtain such patents, there has been a rush of patent applications both in the United States and in Europe by private industry and university laboratories conducting genomic research to secure the rights to specific DNA sequences and federal agencies attempting to place the control of such information in the public domaine. This paper will document and discuss from a historic prospective the public policy and bioethical issues associated with the availability of patents for drug development. (shrink)

Parkinson’s Disease can be treated with the use of microelectrode recording and stimulation. This paper presents a data stream classifier that analyses raw data from micro-electrodes and decides whether the measurements were taken from the subthalamic nucleus (STN) or not. The novelty of the proposed approach is based on the fact that distances based on raw data are used. Two distances are investigated in this paper, i.e. Normalized Compression Distance (NCD) and Lempel-Ziv Jaccard Distance (LZJD). No new features needed to (...) be extracted due to the fact that in the case of high-dimensional data the process is extremely time-consuming. The k-nearest neighbour (k-NN) was chosen as the classifier due to its simplicity, which is essential in data stream classification. Results obtained from classifiers based on k-NN: k-NN, k-NN were compared with Probabilistic Approximate Window (k-NN with PAW); k-NN with Probabilistic Approximate Window and Adaptive Windowing (k-NN with PAW and ADWIN); and Self Adjusting Memory k-NN (SAM k-NN), which use the proposed distances, with the performance of the same classifiers but using standard Euclidean distance. Prequential accuracy was chosen as the performance measure. The results of the experiments performed with the described approach are in most cases better, i.e. the performance measures for kNN classifiers that use NCD and LZJD distances are better by up to 8.5 per cent and 14 per cent, respectively. Moreover, the proposed approach performs better when compared with other stream classification algorithms, i.e. Hoeffding Tree, Naive Bayes, and Leveraging Bagging. In the discussed case, an improvement of classification rate of up to 17.9 per cent when using Lempel-Ziv Jaccard Distance instead of the Euclidean was noted. (shrink)

Considerable hope surrounds the use of disease‐specific pluripotent stem cells to generate models of human disease allowing exploration of pathological mechanisms and search for new treatments. Disease‐specific human embryonic stem cells were the first to provide a useful source for studying certain disease states. The recent demonstration that human somatic cells, derived from readily accessible tissue such as skin or blood, can be converted to embryonic‐like induced pluripotent stem cells (hiPSCs) has opened new perspectives for modelling and understanding a larger (...) number of human pathologies. In this review, we examine the opportunities and challenges for the use of disease‐specific pluripotent stem cells in disease modelling and drug screening. Progress in these areas will substantially accelerate effective application of disease‐specific human pluripotent stem cells for drug screening. (shrink)

In applying statutory safeguards, the FDA must not regulate investigational new products so stringently that a life‐saving therapy is unavailable. But the agency must also protect dying patients from exploitation by unscrupulous or overzealous researchers. The balance between individual choice and public protection has been questioned in cases involving experimental AIDS drugs and an artificial heart.