In the past two decades, reinforcement learning has become a popular framework for understanding brain function. A key component of RL models, prediction error, has been associated with neural signals throughout the brain, including subcortical nuclei, primary sensory cortices, and prefrontal cortex. Depending on the location in which activity is observed, the functional interpretation of prediction error may change: Prediction errors may reflect a discrepancy in the anticipated and actual value of reward, a signal indicating the salience or novelty of (...) a stimulus, and many other interpretations. Anterior cingulate cortex has long been recognized as a region involved in processing behavioral error, and recent computational models of the region have expanded this interpretation to include a more general role for the region in predicting likely events, broadly construed, and signaling deviations between expected and observed events. Ongoing modeling work investigating the interaction between ACC and additional regions involved in cognitive control suggests an even broader role for cingulate in computing a hierarchically structured surprise signal critical for learning models of the environment. The result is a predictive coding model of the frontal lobes, suggesting that predictive coding may be a unifying computational principle across the neocortex. (shrink)

Before the development of the nuclear shell model estimates of the strength of the nuclear spin-orbit interaction varied widely. Wheeler was the first to conclude that the nuclear spin-orbit interaction produces splittings of several MeV. This conclusion appeared, however, to be inconsistent with some experimental results that later turned out to be faulty.

The medial prefrontal cortex (mPFC) has been the subject of intense interest as a locus of cognitive control. Several computational models have been proposed to account for a range of effects, including error detection, conflict monitoring, error likelihood prediction, and numerous other effects observed with single-unit neurophysiology, fMRI, and lesion studies. Here, we review the state of computational models of cognitive control and offer a new theoretical synthesis of the mPFC as signaling response–outcome predictions. This new synthesis has two interacting (...) components. The first component learns to predict the various possible outcomes of a planned action, and the second component detects discrepancies between the actual and intended responses; the detected discrepancies in turn update the outcome predictions. This single construct is consistent with a wide array of performance monitoring effects in mPFC and suggests a unifying account of the cognitive role of medial PFC in performance monitoring. (shrink)

Science fiction is often held up as a particularly philosophical genre. For, beyond actualising mind-experiment-like fantasies, science fiction films also commonly toy with speculative ideas, or else engineer encounters with the strange and unknown. Denis Villeneuve's Arrival is a contemporary science fiction film that does exactly this, by introducing Lovecraft-esque tentacular aliens whose arrival on Earth heralds in a novel, but ultimately paralysing, inhuman perspective on the nature of time and reality. This article shows how this cerebral film invites viewers (...) to confront a counterintuitive model of time that at once recalls and reposes what Gilles Deleuze called a “third synthesis” of time, and that which J. M. E. McTaggart named the a-temporal “C series” of “unreal” time. We finally suggest that Arrival's a-temporal conception of the future as having already happened can function as a key to understanding the fate of humanity as a whole as we pass from the anthropocene, in which humans have... (shrink)

Is consolidation needed to account for retroactive interference in free recall? Interfering mental activity during the retention interval of a memory task impairs performance, in particular if the interference occurs in temporal proximity to the encoding of the to-be-remembered information. There are at least two rival theoretical accounts of this temporal gradient of retroactive interference. The cognitive neuroscience literature has suggested neural consolidation is a pivotal factor determining item recall. According to this account, interfering activity interrupts consolidation processes that would (...) otherwise stabilize the memory representations of TBR items post-encoding. Temporal distinctiveness theory, by contrast, proposes that the retrievability of items depends on their isolation in psychological time. According to this theory, information processed after the encoding of TBR material will reduce the temporal distinctiveness of the TBR information. To test between these accounts, implementations of consolidation were added to the SIMPLE model of memory and learning. We report data from two experiments utilizing a two-list free recall paradigm. Modeling results imply that SIMPLE was able to model the data and did not benefit from the addition of consolidation. It is concluded that the temporal gradient of retroactive interference cannot be taken as evidence for memory consolidation. (shrink)

A cut or crush injury to a peripheral nerve results in the degeneration of that portion of the axon isolated from the cell body. The rapid degeneration of this distal segment was for many years believed to be a process intrinsic to the nerve. It was believed that Schwann cells both phagocytosed degenerating axons and myelin sheaths and also provided growth factors to promote regeneration of the damaged axons. In recent years, it has become apparent that the degenerating distal segment (...) is invaded by monocytes from the blood. We will review the evidence that these recruited macrophages play a role in both degeneration and regeneration of peripheral nerve axons after injury and consider whether the slow degeneration and poor monocyte recruitment in the central nervous system may contribute to the poor regeneration there. (shrink)

Taking a schizoanalytic approach to audio-visual images, this article explores some of the radical potentia for deterritorialisation found within David Fincher's Fight Club (1999). The film's potential for deterritorialisation is initially located in an exploration of the film's form and content, which appear designed to interrogate and transcend a series of false binaries between mind and body, inside and outside, male and female. Paying attention to the construction of photorealistic digital spaces and composited images, we examine the actual (and possible) (...) ways viewers relate to the film, both during and after screenings. Recognising the film as an affective force performing within our world, we also investigate some of the real-world effects the film catalysed. Finally, we propose that schizoanalysis, when applied to a Hollywood film, suggests that Deleuze underestimated the deterritorialising potential of contemporary, special effects-driven cinema. If schizoanalysis has thus been reterritorialised by mainstream products, we argue that new, ‘post-Deleuzian’ lines of flight are required to disrupt this ‘de-re-territorialisation’. (shrink)

Objectives—To evaluate a departmental computer system.Design—a. Direct comparison of the time taken to use a manual system with the time taken to use a computer system for lung function evaluation, loan of equipment and production of correspondence. b. Analysis of the accuracy of data capture before and after the introduction of the computer system. c. Analysis of the comparative running costs of the manual and computer systems.Setting—Within a department of respiratory medicine serving a hospital of 1323 beds.Main Outcome Measures—a. Time (...) taken to perform functions with the assistance of computerised methods, in comparison to the manual method used alone. b. Accuracy of data capture. c. Relative running costs.Results—a. The computer system was significantly faster than the manual system for lung function evaluation, loan of equipment, and checking for overdue equipment. The production of correspondence was slightly slower with the computer. b. All outpatient episodes, but only 43 of 65 of inpatient episodes, were captured. Lung function and managerial report data were accurate using both manual and computerised methods. The manual system for equipment loans was inefficient, and use of the computer resulted in the recovery of 221 nebulisers. c. Development costs for 1988–1990 were high. Only £1200 to £1845 per year was recovered directly from staff time saved by the computer but larger savings resulted from changes in work practice. After 10 years the projected deficit is £10 000 per annum in running costs.Conclusions—In comparison with the manual methods, the computer system has shown significant advantages which provide accurate information, with significant favourable effects on working practices. In evaluating computer systems used in clinical practice it is essential to ensure that the projected work practice benefits are achieved without unacceptable costs in staff time, inaccurate data and high financial outlay. (shrink)

Objectives—To evaluate a departmental computer system.Design—a. Direct comparison of the time taken to use a manual system with the time taken to use a computer system for lung function evaluation, loan of equipment and production of correspondence. b. Analysis of the accuracy of data capture before and after the introduction of the computer system. c. Analysis of the comparative running costs of the manual and computer systems.Setting—Within a department of respiratory medicine serving a hospital of 1323 beds.Main Outcome Measures—a. Time (...) taken to perform functions with the assistance of computerised methods, in comparison to the manual method used alone. b. Accuracy of data capture. c. Relative running costs.Results—a. The computer system (CS) was significantly faster than the manual system (MS) for lung function evaluation (CS=7.63 min/test, MS=12.25 min/test), loan of equipment (CS=0.40 min/loan, MS=2.07 min/loan), and checking for overdue equipment (CS=0.49 s/record, MS=9 s/record). The production of correspondence was slightly slower with the computer (CS=9.30 min/letter, MS=8.54 min/letter). b. All outpatient episodes, but only 43 of 65 (66%) of inpatient episodes, were captured. Lung function and managerial report data were accurate using both manual and computerised methods. The manual system for equipment loans was inefficient, and use of the computer resulted in the recovery of 221 nebulisers. c. Development costs for 1988–1990 were high (£72 178). Only £1200 to £1845 per year was recovered directly from staff time saved by the computer but larger savings resulted from changes in work practice (£4049–4765). After 10 years the projected deficit is £10 000 per annum in running costs.Conclusions—In comparison with the manual methods, the computer system has shown significant advantages which provide accurate information, with significant favourable effects on working practices. In evaluating computer systems used in clinical practice it is essential to ensure that the projected work practice benefits are achieved without unacceptable costs in staff time, inaccurate data and high financial outlay. (shrink)

The participation of vulnerable patients in clinical research poses apparent ethical dilemmas. Depending on the nature of the vulnerability, their participation may challenge the ethical principles of autonomy, non-maleficence, or justice. On the other hand, non-participation may preclude the building of a knowledge base that is a prerequisite for defining the optimal clinical management of vulnerable patients. Such clinical uncertainty may also incur substantial economic costs. We present the participation of pre-menopausal women with atrial fibrillation in trials of novel oral (...) anticoagulant drugs as a case study. Due to their non-participation in pivotal trials, it is uncertain whether for them, the risks that are associated with these drugs are outweighed by the advantages compared with conventional treatment. We addressed the question whether research of this new class of drugs in this subgroup would be appropriate from both, an ethical as well an economic perspective. We used the method of specifying norms as a wider framework to resolve the apparent ethical dilemma, while incorporating the question whether research of oral anticoagulants in premenopausal women with atrial fibrillation can be justified on economic grounds. For the latter, the results of a value-of-information analysis were used. Further clinical research on NOACs in premenopausal women with atrial fibrillation can be justified on both, ethical and economic grounds. Addressing apparent ethical dilemmas by invoking a method such as specifying norms can improve the quality of public practical reasoning. As such, the method should also prove valuable to committees that have formally been granted the authority to review trial protocols and proposals for scientific research. (shrink)

Cultural differences occur in the use of categories to aid accurate recall of information. This study investigated whether culture also contributed to false (erroneous) memories, and extended cross-cultural memory research to Turkish culture, which is shaped by Eastern and Western influences. Americans and Turks viewed word pairs, half of which were categorically related and half unrelated. Participants then attempted to recall the second word from the pair in response to the first word cue. Responses were coded as correct, as blanks, (...) or as different types of errors. Americans committed more categorical errors than did Turks, and Turks mistakenly recalled more non-categorically related list words than did Americans. These results support the idea that Americans use categories either to organize information in memory or to support retrieval strategies to a greater extent than Turks and suggest that culture shapes not only accurate recall but also erroneous distortions of memory. (shrink)

This manuscript explores the argument for lower student-to-school counselor ratios in U.S. public education. Drawing upon a comprehensive historical review and existing research, we establish the integral role of school counselors and the notable benefits of reduced student-to-counselor ratios. Our analysis of national data exposes marked disparities across states and districts, with the most underfunded often serving higher percentages of low-income students and students of color. This situation raises significant ethical concerns, prompting a call for conscientious policy reform and targeted (...) investment. Informed by emerging best practices, we propose recommendations for enhancing counselor staffing and ultimately student outcomes. This ethical argument underscores the need for proactive actions and provides a basis for future research to further delineate the impact of school counselor ratios on educational equity and student success. (shrink)

From David Hume's famous puzzle about 'the missing shade of blue' to current research into the science of colour, the topic of colour is an incredibly fertile region of study and debate, cutting across philosophy of mind, epistemology, metaphysics and aesthetics as well as psychology. Debates about the nature of our experience of colour and the nature of colour itself are central to contemporary discussion and argument in philosophy of mind and psychology, and philosophy of perception. This outstanding Handbook contains (...) twenty-nine specially commissioned contributions by leading philosophers and examines the most important aspects of philosophy of colour. It is organised into six parts: The Importance of Colour to Philosophy The Science and Spaces of Colour Colour Phenomena Colour Ontology Colour Experience and Epistemology Language, Categories and Thought. The Routledge Handbook of Philosophy of Colour is essential reading for students and researchers in philosophy of mind and psychology, epistemology, metaphysics and aesthetics, as well as for those interested in conceptual issues in the psychology of colour. (shrink)

I defend the thesis that most or all perceptual experiences are infused with imaginative contributions. While the idea is not new, it has few supporters. I begin by developing a framework for the underlying debate. Central to that framework is the claim that a perceptual experience is infused with imagination if and only if there are self-generated contributions to that experience that have ampliative effect on its phenomenal and directed elements. Self-generated ingredients to experience are produced by the subject as (...) opposed to being received from the world. Some form of stored content is an obvious starting point. Ampliative effects are aspects of perceptual experience that outstrip the content the senses get from the world. This conceptual framework is applied to three case studies: object-sameness and object-kind recognition (section 2), memory colour (section 3), and perceptual constancy and amodal completion (section 4). If the three cases and my overall analysis are accepted (a substantive if), then we have a forceful inductive argument for perception being infused with imagination. (shrink)

The 1940s and 1950s were marked by intense debates over the origin of drug resistance in microbes. Bacteriologists had traditionally invoked the notions of ‘training’ and ‘adaptation’ to account for the ability of microbes to acquire new traits. As the field of bacterial genetics emerged, however, its participants rejected ‘Lamarckian’ views of microbial heredity, and offered statistical evidence that drug resistance resulted from the selection of random resistant mutants. Antibiotic resistance became a key issue among those disputing physiological vs. genetic (...) explanations of variation in bacteria. Postwar developments connected with the Lysenko affair gave this debate a new political valence.Proponents of the neo-Darwinian synthesis weighed in with support for the genetic theory. However, certain features of drug resistance seemed inexplicable by mutation and selection, particularly the phenomenon of ‘multiple resistance’—the emergence of resistance in a single strain against several unrelated antibiotics. In the late 1950s, Tsutomu Watanabe and his collaborators solved this puzzle by determining that resistance could be conferred by cytoplasmic resistance factors rather than chromosomal mutation. These R factors could carry resistance to many antibiotics and seemed able to promote their own dissemination in bacterial populations. In the end, the vindication of the genetic view of drug resistance was accompanied by a recasting of the ‘gene’ to include extrachromosomal hereditary units carried on viruses and plasmids. (shrink)

This paper examines the US Atomic Energy Commission’s radioisotope distribution program, established in 1946, which employed the uranium piles built for the wartime bomb project to produce specific radioisotopes for use in scientific investigation and medical therapy. As soon as the program was announced, requests from researchers began pouring into the Commission’s office. During the first year of the program alone over 1000 radioisotope shipments were sent out. The numerous requests that came from scientists outside the United States, however, sparked (...) a political debate about whether the Commission should or even could export radioisotopes. This controversy manifested the tension between the aims of the Marshall Plan and growing US national security concerns after World War II. Proponents of international circulation of radioisotopes emphasized the political and scientific value of collaborating with European scientists, especially biomedical researchers. In the end, radioisotopes were shipped from the Commission’s Oak Ridge facility to many laboratories in England and continental Europe, where they were used in biochemical research on animals, plants, and microbes. However, the issue of radioisotope export continued to draw political fire in the United States, even after the establishment of national atomic energy facilities elsewhere. (shrink)

This Handbook is the first comprehensive survey of a rapidly expanding sub-field in archaeology, the study of the present and recent past. It seeks to explore the boundaries of this emerging area, to develop a tool-kit of concepts and methods, which are applicable to this new sub-field, and to suggest important future trajectories for research.

The recent historiography of molecular biology features key technologies, instruments and materials, which offer a different view of the field and its turning points than preceding intellectual and institutional histories. Radioisotopes, in this vein, became essential tools in postwar life science research, including molecular biology, and are here analyzed through their use in experiments on bacteriophage. Isotopes were especially well suited for studying the dynamics of chemical transformation over time, through metabolic pathways or life cycles. Scientists labeled phage with phosphorus-32 (...) in order to trace the transfer of genetic material between parent and progeny in virus reproduction. Initial studies of this type did not resolve the mechanism of generational transfer but unexpectedly gave rise to a new style of molecular radiobiology based on the inactivation of phage by the radioactive decay of incorporated phosphorus-32. These ‘suicide experiments’, a preoccupation of phage researchers in the mid-1950s, reveal how molecular biologists interacted with the traditions and practices of radiation geneticists as well as those of biochemists as they were seeking to demarcate a new field. The routine use of radiolabels to visualize nucleic acids emerged as an enduring feature of molecular biological experimentation. (shrink)

ABSTRACT Rosalind Franklin is best known for her informative X-ray diffraction patterns of DNA that provided vital clues for James Watson and Francis Crick's double-stranded helical model. Her scientific career did not end when she left the DNA work at King's College, however. In 1953 Franklin moved to J. D. Bernal's crystallography laboratory at Birkbeck College, where she shifted her focus to the three-dimensional structure of viruses, obtaining diffraction patterns of Tobacco mosaic virus (TMV) of unprecedented detail and clarity. During (...) the next five years, while making significant headway on the structural determination of TMV, Franklin maintained an active correspondence with both Watson and Crick, who were also studying aspects of virus structure. Developments in TMV research during the 1950s illustrate the connections in the emerging field of molecular biology between structural studies of nucleic acids and of proteins and viruses. They also reveal how the protagonists of the “race for the double helix” continued to interact personally and professionally during the years when Watson and Crick's model for the double-helical structure of DNA was debated and confirmed. (shrink)

ABSTRACT Rosalind Franklin is best known for her informative X-ray diffraction patterns of DNA that provided vital clues for James Watson and Francis Crick's double-stranded helical model. Her scientific career did not end when she left the DNA work at King's College, however. In 1953 Franklin moved to J. D. Bernal's crystallography laboratory at Birkbeck College, where she shifted her focus to the three-dimensional structure of viruses, obtaining diffraction patterns of Tobacco mosaic virus (TMV) of unprecedented detail and clarity. During (...) the next five years, while making significant headway on the structural determination of TMV, Franklin maintained an active correspondence with both Watson and Crick, who were also studying aspects of virus structure. Developments in TMV research during the 1950s illustrate the connections in the emerging field of molecular biology between structural studies of nucleic acids and of proteins and viruses. They also reveal how the protagonists of the “race for the double helix” continued to interact personally and professionally during the years when Watson and Crick's model for the double-helical structure of DNA was debated and confirmed. (shrink)

The widespread adoption of radioisotopes as tools in biomedical research and therapy became one of the major consequences of the "physicists' war" for postwar life science. Scientists in the Manhattan Project, as part of their efforts to advocate for civilian uses of atomic energy after the war, proposed using infrastructure from the wartime bomb project to develop a government-run radioisotope distribution program. After the Atomic Energy Bill was passed and before the Atomic Energy Commission was formally established, the Manhattan Project (...) began shipping isotopes from Oak Ridge. Scientists and physicians put these reactor-produced isotopes to many of the same uses that had been pioneered with cyclotron-generated radioisotopes in the 1930s and early 1940s. The majority of early AEC shipments were radioiodine and radiophosphorus, employed to evaluate thyroid function, diagnose medical disorders, and irradiate tumors. Both researchers and politicians lauded radioisotopes publicly for their potential in curing diseases, particularly cancer. However, isotopes proved less successful than anticipated in treating cancer and more successful in medical diagnostics. On the research side, reactor-generated radioisotopes equipped biologists with new tools to trace molecular transformations from metabolic pathways to ecosystems. The U.S. government's production and promotion of isotopes stimulated their consumption by scientists and physicians, such that in the postwar period isotopes became routine elements of laboratory and clinical use. In the early postwar years, radioisotopes signified the government's commitment to harness the atom for peace, particularly through contributions to biology, medicine, and agriculture. (shrink)

Scientists and historians have often presumed that the divide between biochemistry and molecular biology is fundamentally epistemological.100 The historiography of molecular biology as promulgated by Max Delbrück's phage disciples similarly emphasizes inherent differences between the archaic tradition of biochemistry and the approach of phage geneticists, the ur molecular biologists. A historical analysis of the development of both disciplines at Berkeley mitigates against accepting predestined differences, and underscores the similarities between the postwar development of biochemistry and the emergence of molecular biology (...) as a university discipline. Stanley's image of postwar biochemistry, with its focus on viruses as key experimental systems, and its preference for following macromolecular structure over metabolism pathways, traced the outline of molecular biology in 1950.Changes in the postwar political economy of research universities enabled the proliferation of disciplines such as microbiology, biochemistry, biophysics, immunology, and molecular biology in universities rather than in medical schools and agricultural colleges. These disciplines were predominantly concerned with investigating life at the subcellular level-research that during the 1930s had often entailed collaboration with physicists and chemists. The interdisciplinary efforts of the 1930s (many fostered by the Rockefeller Foundation) yielded a host of new tools and reagents that were standardized and mass-produced for laboratories after World War II. This commercial infrastructure enabled “basic” researchers in biochemistry and molecular biology in the 1950s and 1960s to become more independent from physics and chemistry (although they were practicing a physicochemical biology), as well as from the agricultural and medical schools that had previously housed or sponsored such research. In turn, the disciplines increasingly required their practitioners to have specialized graduate training, rather than admitting interlopers from the physical sciences.These general transitions toward greater autonomy for biochemistry and allied disciplines should not mask the important particularities of these developments on each campus. At the University of Caliornia at Berkeley, agriculture had provided, with medicine, significant sponsorship for biochemistry. The proximity of Lawrence and his cyclotrons supported the early development of Berkeley as a center for the biological uses of radioisotopes, particularly in studies of metabolism and photosynthesis. Stanley arrived to establish his department and virus institute before large-scale federal funding of biomedical research was in place, and he courted the state of California for substantial backing by promising both national prominence in the life sciences and virus research pertinent to agriculture and public health. Stanley's venture benefited significantly from the expansion of California's economy after World War II, and his mobilization against viral diseases resonated with the concerns of the Cold War, which fueled the state's rapid growth. The scientific prominence of contemporary developments at Caltech and Stanford invites the historical examination of the significance of postwar biochemistry and molecular biology within the political and cultural economy of the Golden State.In 1950, Stanley presented a persuasive picture of the power of biochemistry to refurbish life science at Berkeley while answering fundamental questions about life and infection. In the words of one Rockefeller Foundation officer,There seems little doubt in [my] mind that as a personality Stanley will be well able to dominate the other personalities on the Berkeley campus and will be able to drive his dream through to completion, which, incidentally, leaves Dr. Hubert [sic] Evans and the whole ineffective Life Sciences building in the somewhat peculiar position of being by-passed by much of the truly modern biochemistry and biophysics research that will be carried out at Berkeley. Furthermore, it seems likely that Dr. S's show will throw Dr. John Lawrence's Biophysics Department strongly in the shade both figuratively and literally, but should make the University of California pre-eminent not only in physics but in biochemistry as well.101Stanley, Sproul, Weaver, and this officer (William Loomis) all testified to a perceptible postwar opportunity to capitalize on public support for biological research that relied on the technologies from physics and chemistry without being captive to them, and that addressed issues of medicine and agriculture without being institutionally subservient. What is striking, given the expectation by many that Stanley would ‘be able to drive his dream through to completion,” was that in fact he did not. Biochemists who had succeeded in making their expertise valued in specialized niches were resistant to giving up their affiliations to joint Stanley's “liberated” organization. Stanley's failure was not simply due to institutional factors: researchers as well as Rockefeller Foundation officers faulted him for his lack of scientific imagination, which made it difficult for him to gain credibility in leading the field. Moreover, many biochemists did not share Stanley's commitment to viruses as the key material for the “new biochemistry.”In the end, Stanley's free-standing department did become a first-rate department of biochemistry, but only after freeing itself from Stanley's leadership and his single-minded devotion to viruses. Nonetheless, the falling-out with the Berkeley biochemists was rapidly followed by the establishment of a Department of Molecular Biology, attesting to the unabating economic and institutional possibilities for an authoritative “general biology” (or two, for that matter) to take hold. In each case, following Stanley's dream sheds light on how the possible and the real shaped the (re)formation of biochemistry and molecular biology as postwar life sciences. (shrink)

When the Toxic Substances Control Act was passed by the US Congress in 1976, its advocates pointed to new generation of genotoxicity tests as a way to systematically screen chemicals for carcinogenicity. However, in the end, TSCA did not require any new testing of commercial chemicals, including these rapid laboratory screens. In addition, although the Environmental Protection Agency was to make public data about the health effects of industrial chemicals, companies routinely used the agency’s obligation to protect confidential business information (...) to prevent such disclosures. This paper traces the contested history of TSCA and its provisions for testing, from the circulation of the first draft bill in the Nixon administration through the debates over its implementation, which stretched into the Reagan administration. The paucity of publicly available health and environmental data concerning chemicals, I argue, was a by-product of the law and its execution, leading to a situation of institutionalized ignorance, the underside of regulatory knowledge. (shrink)