An Evaluation of Web Browsers

Many computational biologists would agree that, had it not been for multi-processors, the construction of multi- processors might never have occurred. In this position paper, we argue the exploration of interrupts. We present a novel heuristic for the visualization of Scheme, which we call YAWN

CNH: Fine-Scale Dynamics of Human Adaptation in Coupled Natural and Social Systems: An Integrated Computational Approach Applied to Three Fisheries

The purpose of this project is to gain a better understanding of the way competition between individual fishermen lead to the emergence of private incentives and informal social arrangements that are (or are not) consistent with conservation of the resource. These informal arrangements and incentives are important because they help us understand the extent to which private interests might strengthen or weaken on-going resource management and, consequently, the sustainability of coupled human and natural systems. The broad hypothesis driving the study is that the informal social structure that emerges from competitive interactions among fishermen reflects the particular circumstances of the natural system. In some cases, successful competition requires secretive non-cooperative behavior; in others, cooperation tends to yield better competitive results. These different outcomes have different, and not always obvious, impacts on the feasibility and effectiveness of resource management. We think of the relevant human social process as one in which individuals compete with one another through time-consuming and costly acquisition of valuable knowledge about a complex resource. To compete successfully, individuals must balance the immediate benefits that come from exploiting knowledge they currently hold with the costly need to explore for new knowledge; additionally, when seeking new knowledge, individuals must balance the costs and benefits of acquiring knowledge through cooperation or through autonomous search. In order to model this kind of competitive process, we employ a significantly modified version of a technique borrowed from computer science called a learning classifier system (LCS). LCS uses a genetic algorithm to mimic the way an agent (here a fisherman) uses his experience to continuously refine his knowledge and decisions about his natural and social environment. The importance of LCS is that it permits simulation of the co-evolving strategic interactions of self-interested fishermen who are only partially informed about the state of the resource they are exploiting and the fishermen with whom they compete. The problem of understanding these kinds of competitive dynamics is evident in almost all coupled natural and human systems. We apply the approach to a comparative study of three Gulf of Maine fisheries which are characterized by significantly different temporal and spatial dynamics - sea urchins, lobster and cod. Each fishery will be modeled using a biophysical simulator of the natural system and a tightly integrated multi-agent learning classifier system that simulates the learning and interactions of fishermen. The design of each model will be based in part on extensive interviews with fishermen about their knowledge of the dynamics of the fisheries in which they work. We will use these models to explore past and prospective policy problems in each fishery. Beyond the immediate applicability of these explorations, we expect this project will provide a foundation for the wider use of multi-agent learning models in other coupled systems. Project outcomes will be transmitted regularly to industry and managers. Principal investigators include economists, biologists, anthropologists and computer scientists. All the PIs have years of experience in the fisheries of the Gulf of Maine and have well developed relationships with individual fishermen and managers. A masters level student in marine policy, a Ph.D. student in computer or marine science and a post-doctoral researcher in computer science will be employed on the project. In addition, the project will develop an undergraduate course in complex adaptive social-ecological systems and a graduate student/faculty workshop in the same area

Effect of empiric antiarrhythmic therapy in resuscitated out-of-hospital cardiac arrest victims with coronary artery disease

The effect of empiric antiarrhythmic therapy with quindine and procainamide on long-term mortality was examined in 209 patients with coronary artery disease resuscitated after out-of-hospital cardiac arrest. The antiarrhythmic agent used was determined by the patient's private physician without knowledge of the study ambulatory electrocardiogram. Of the 209 patients, procainamide was prescribed in 45 (22%), qiinidine in 48 (23%) and no antiarrhythmic therapy in 116 (55%). Digoxin therapy was initiated in 101 patients. The 2-year total survival rate for the quinidine, procainamide and nontreated patients was 61, 57 and 71% (p < 0.05), and for sudden death was 69, 69 and 89% (p < 0.01), respectively. These observations suggest that empiric antiarrhythmic therapy in survivors of out-of-hospital cardiac arrest did not affect total mortality and was associated with an increased frequency of sudden death.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/28573/1/0000376.pd

Evaluation of a 'virtual' approach to commissioning health research

BACKGROUND: The objective of this study was to evaluate the implementation of a 'virtual' (computer-mediated) approach to health research commissioning. This had been introduced experimentally in a DOH programme – the 'Health of Londoners Programme' – in order to assess whether is could enhance the accessibility, transparency and effectiveness of commissioning health research. The study described here was commissioned to evaluate this novel approach, addressing these key questions. METHODS: A naturalistic-experimental approach was combined with principles of action research. The different commissioning groups within the programme were randomly allocated to either the traditional face-to-face mode or the novel 'virtual' mode. Mainly qualitative data were gathered including observation of all (virtual and face-to-face) commissioning meetings; semi-structured interviews with a purposive sample of participants (n = 32/66); structured questionnaires and interviews with lead researchers of early commissioned projects. All members of the commissioning groups were invited to participate in collaborative enquiry groups which participated actively in the analysis process. RESULTS: The virtual process functioned as intended, reaching timely and relatively transparent decisions that participants had confidence in. Despite the potential for greater access using a virtual approach, few differences were found in practice. Key advantages included physical access, a more flexible and extended time period for discussion, reflection and information gathering and a more transparent decision-making process. Key challenges were the reduction of social cues available in a computer-mediated medium that require novel ways of ensuring appropriate dialogue, feedback and interaction. However, in both modes, the process was influenced by a range of factors and was not technology driven. CONCLUSION: There is potential for using computer-mediated communication within the research commissioning process. This may enhance access, effectiveness and transparency of decision-making but further development is needed for this to be fully realised, including attention to process as well as the computer-mediated medium

Screening Patients with a Family History of Colorectal Cancer

OBJECTIVES: To compare screening practices and beliefs in patients with and without a clinically important family history. DESIGN: We mailed a brief questionnaire asking about family history and a second, longer survey asking about knowledge of and beliefs about colorectal cancer to all respondents with a family history and a random sample of respondents without a family history of colorectal cancer. We reviewed electronic medical records for screening examinations and recording of family history. PARTICIPANTS: One thousand eight hundred seventy of 6,807 randomly selected patients ages 35–55 years who had been continuously enrolled in a large multispecialty group practice for at least 5 years. MEASUREMENTS: Recognition of increased risk, screening practices, and beliefs—all according to strength of family history and patient’s age. RESULTS: Nineteen percent of respondents reported a family history of colorectal cancer. In 11%, this history was strong enough to warrant screening before age 50 years. However, only 39% (95% CI 36, 42) of respondents under the age of 50 years said they had been asked about family history and only 45% of those with a strong family history of colorectal cancer had been screened appropriately. Forty-six percent of patients with a strong family history did not know that they should be screened at a younger age than average risk people. Medical records mentioned family history of colorectal cancer in 59% of patients reporting a family history. CONCLUSIONS: More efforts are needed to translate information about family history of colorectal cancer into the care of patients

Pathogenic <i>NR2F1</i> variants cause a developmental ocular phenotype recapitulated in a mutant mouse model.

Funder: National Institute of Health Research Biomedical Research Centre at Moorfields Eye Hospital and UCL Institute of OphthalmologyPathogenic NR2F1 variants cause a rare autosomal dominant neurodevelopmental disorder referred to as the Bosch-Boonstra-Schaaf Optic Atrophy Syndrome. Although visual loss is a prominent feature seen in affected individuals, the molecular and cellular mechanisms contributing to visual impairment are still poorly characterized. We conducted a deep phenotyping study on a cohort of 22 individuals carrying pathogenic NR2F1 variants to document the neurodevelopmental and ophthalmological manifestations, in particular the structural and functional changes within the retina and the optic nerve, which have not been detailed previously. The visual impairment became apparent in early childhood with small and/or tilted hypoplastic optic nerves observed in 10 cases. High-resolution optical coherence tomography imaging confirmed significant loss of retinal ganglion cells with thinning of the ganglion cell layer, consistent with electrophysiological evidence of retinal ganglion cells dysfunction. Interestingly, for those individuals with available longitudinal ophthalmological data, there was no significant deterioration in visual function during the period of follow-up. Diffusion tensor imaging tractography studies showed defective connections and disorganization of the extracortical visual pathways. To further investigate how pathogenic NR2F1 variants impact on retinal and optic nerve development, we took advantage of an Nr2f1 mutant mouse disease model. Abnormal retinogenesis in early stages of development was observed in Nr2f1 mutant mice with decreased retinal ganglion cell density and disruption of retinal ganglion cell axonal guidance from the neural retina into the optic stalk, accounting for the development of optic nerve hypoplasia. The mutant mice showed significantly reduced visual acuity based on electrophysiological parameters with marked conduction delay and decreased amplitude of the recordings in the superficial layers of the visual cortex. The clinical observations in our study cohort, supported by the mouse data, suggest an early neurodevelopmental origin for the retinal and optic nerve head defects caused by NR2F1 pathogenic variants, resulting in congenital vision loss that seems to be non-progressive. We propose NR2F1 as a major gene that orchestrates early retinal and optic nerve head development, playing a key role in the maturation of the visual system

Early Initiation of Colorectal Cancer Screening in Individuals with Affected First-degree Relatives

BACKGROUND: Several guidelines recommend initiating colorectal cancer screening at age 40 for individuals with affected first-degree relatives, yet little evidence exists describing how often these individuals receive screening procedures. OBJECTIVES: To determine the proportion of individuals in whom early initiation of colorectal cancer screening might be indicated and whether screening disparities exist. DESIGN: Population-based Supplemental Cancer Control Module to the 2000 National Health Interview Survey. PARTICIPANTS: Respondents, 5,564, aged 40 to 49 years were included within the analysis. MEASUREMENTS: Patient self-report of sigmoidoscopy, colonoscopy, or fecal occult blood test. RESULTS: Overall, 279 respondents (5.4%: 95% C.I., 4.7, 6.2) reported having a first-degree relative affected with colorectal cancer. For individuals with a positive family history, 67 whites (27.9%: 95% C.I., 21.1, 34.5) and 3 African American (9.3%: 95% C.I., 1.7, 37.9) had undergone an endoscopic procedure within the previous 10 years (P-value = .03). After adjusting for age, family history, gender, educational level, insurance status, and usual source of care, whites were more likely to be current with early initiation endoscopic screening recommendations than African Americans (OR = 1.38: 95% C.I., 1.01, 1.87). Having an affected first-degree relative with colorectal cancer appeared to have a stronger impact on endoscopic screening for whites (OR = 3.21: 95% C.I., 2.31, 4.46) than for African Americans (OR = 1.05: 95% C.I., 0.15, 7.21). CONCLUSIONS: White participants with a family history are more likely to have endoscopic procedures beginning before age 50 than African Americans

Pathogenic NR2F1 variants cause a developmental ocular phenotype recapitulated in a mutant mouse model.

Pathogenic NR2F1 variants cause a rare autosomal dominant neurodevelopmental disorder referred to as the Bosch-Boonstra-Schaaf Optic Atrophy Syndrome. Although visual loss is a prominent feature seen in affected individuals, the molecular and cellular mechanisms contributing to visual impairment are still poorly characterized. We conducted a deep phenotyping study on a cohort of 22 individuals carrying pathogenic NR2F1 variants to document the neurodevelopmental and ophthalmological manifestations, in particular the structural and functional changes within the retina and the optic nerve, which have not been detailed previously. The visual impairment became apparent in early childhood with small and/or tilted hypoplastic optic nerves observed in 10 cases. High-resolution optical coherence tomography imaging confirmed significant loss of retinal ganglion cells with thinning of the ganglion cell layer, consistent with electrophysiological evidence of retinal ganglion cells dysfunction. Interestingly, for those individuals with available longitudinal ophthalmological data, there was no significant deterioration in visual function during the period of follow-up. Diffusion tensor imaging tractography studies showed defective connections and disorganization of the extracortical visual pathways. To further investigate how pathogenic NR2F1 variants impact on retinal and optic nerve development, we took advantage of an Nr2f1 mutant mouse disease model. Abnormal retinogenesis in early stages of development was observed in Nr2f1 mutant mice with decreased retinal ganglion cell density and disruption of retinal ganglion cell axonal guidance from the neural retina into the optic stalk, accounting for the development of optic nerve hypoplasia. The mutant mice showed significantly reduced visual acuity based on electrophysiological parameters with marked conduction delay and decreased amplitude of the recordings in the superficial layers of the visual cortex. The clinical observations in our study cohort, supported by the mouse data, suggest an early neurodevelopmental origin for the retinal and optic nerve head defects caused by NR2F1 pathogenic variants, resulting in congenital vision loss that seems to be non-progressive. We propose NR2F1 as a major gene that orchestrates early retinal and optic nerve head development, playing a key role in the maturation of the visual system

The Dopamine Augmenter L-DOPA Does Not Affect Positive Mood in Healthy Human Volunteers

Dopamine neurotransmission influences approach toward rewards and reward-related cues. The best cited interpretation of this effect proposes that dopamine mediates the pleasure that commonly accompanies reward. This hypothesis has received support in some animal models and a few studies in humans. However, direct assessments of the effect of transiently increasing dopamine neurotransmission have been largely limited to the use of psychostimulant drugs, which elevate brain levels of multiple neurotransmitters in addition to dopamine. In the present study we tested the effect of more selectively elevating dopamine neurotransmission, as produced by administration of the immediate dopamine precursor, L-DOPA (0, 100/25, 200/50 mg, Sinemet), in healthy human volunteers. Neither dose altered positive mood. The results suggest that dopamine neurotransmission does not directly influence positive mood in humans

Nonpulmonary Outcomes of Asbestos Exposure

The adverse pulmonary effects of asbestos are well accepted in scientific circles. However, the extrapulmonary consequences of asbestos exposure are not as clearly defined. In this review the potential for asbestos to produce diseases of the peritoneum, immune, gastrointestinal (GIT), and reproductive systems are explored as evidenced in published, peer-reviewed literature. Several hundred epidemiological, in vivo, and in vitro publications analyzing the extrapulmonary effects of asbestos were used as sources to arrive at the conclusions and to establish areas needing further study. In order to be considered, each study had to monitor extrapulmonary outcomes following exposure to asbestos. The literature supports a strong association between asbestos exposure and peritoneal neoplasms. Correlations between asbestos exposure and immune-related disease are less conclusive; nevertheless, it was concluded from the combined autoimmune studies that there is a possibility for a higher-than-expected risk of systemic autoimmune disease among asbestos-exposed populations. In general, the GIT effects of asbestos exposure appear to be minimal, with the most likely outcome being development of stomach cancer. However, IARC recently concluded the evidence to support asbestos-induced stomach cancer to be “limited.” The strongest evidence for reproductive disease due to asbestos is in regard to ovarian cancer. Unfortunately, effects on fertility and the developing fetus are under-studied. The possibility of other asbestos-induced health effects does exist. These include brain-related tumors, blood disorders due to the mutagenic and hemolytic properties of asbestos, and peritoneal fibrosis. It is clear from the literature that the adverse properties of asbestos are not confined to the pulmonary system