Morphine Tolerance As A Function Of Ratio Schedule: Response Requirement Or Unit Price?

Key pecking by 3 pigeons was maintained by a multiple fixed-ratio 10, fixed-ratio 30, fixed-ratio 90 schedule of food presentation. Components differed with respect to amount of reinforcement, such that the unit price was 10 responses per 1-s access to food. Acute administration of morphine, l-methadone, and cocaine dose-dependently decreased overall response rates in each of the components. When a rate decreasing dose of morphine was administered daily, tolerance, as measured by an increase in the dose that reduced response rates to 50% of control (i.e., the ED50 value), developed in each of the components; however, the degree of tolerance was smallest in the fixed-ratio 90 component (i.e., the ED50 value increased the least). When the l-methadone dose-effect curve was redetermined during the chronic morphine phase, the degree of cross-tolerance conferred to l-methadone was similar across components, suggesting that behavioral variables may not influence the degree of cross-tolerance between opioids. During the chronic phase, the cocaine dose-effect curve shifted to the right for 2 pigeons and to the left for 1 pigeon, which is consistent with predictions based on the lack of pharmacological similarity between morphine and cocaine. When the morphine, l-methadone, and cocaine dose-effect curves were redetermined after chronic morphine administration ended, the morphine and l-methadone ED50s replicated those obtained prior to chronic morphine administration. The morphine data suggest that the fixed-ratio value (i.e., the absolute output) determines the degree of tolerance and not the unit price

What controls submarine channel development and the morphology of deltas entering deep-water fjords?

River deltas and associated turbidity current systems produce some of the largest and most rapid sediment accumulations on our planet. These systems bury globally significant volumes of organic carbon and determine the runout distance of potentially hazardous sediment flows and the shape of their deposits. Here we seek to understand the main factors that determine the morphology of turbidity current systems linked to deltas in fjords, and why some locations have well developed submarine channels whilst others do not. Deltas and associated turbidity current systems are analysed initially in five fjord systems from British Columbia in Canada, and then more widely. This provides the basis for a general classification of delta and turbidity current system types, where rivers enter relatively deep (>200 m) water. Fjord-delta area is found to be strongly bimodal. Avalanching of coarse-grained bedload delivered by steep mountainous rivers produces small Gilbert-type fan- deltas, whose steep gradient (11°-25°) approaches the sediment’s angle of repose. Bigger fjord-head deltas are associated with much larger and finer-grained rivers. These deltas have much lower gradients (1.5°-10°) that decrease offshore in a near exponential fashion. The lengths of turbidity current channels are highly variable, even in settings fed by rivers with similar discharges. This may be due to resetting of channel systems by delta-top channel avulsions or major offshore landslides, as well as the amount and rate of sediment supplied to the delta front by rivers

The hearing of fitness to practice cases by the General Medical Council: Current trends and future research agendas

Over the last three decades a risk-based model of medical regulation has emerged in the United Kingdom. To promote a risk-averse operational culture of transparency and professional accountability the regulatory state has intervened in medical governance and introduced best-evidenced practice frameworks, audit and performance appraisal, Against this background the paper analyses descriptive statistical data pertaining to the General Medical Council’s management of the process by which fitness to practice complaints against doctors are dealt with from initial receipt through to subsequent investigative and adjudication stages. Statistical trends are outlined regarding complaint data in relation to a doctor’s gender and race and ethnicity. The data shows that there has been an increase in rehabilitative and/or punitive action against doctors. In light of its findings the paper considers what the long-term consequences may be, for both patients and doctors, of the increasing use of risk-averse administrative systems to reform medical regulation and ensure professional accountability

Observation-based modeling of ozone chemistry in the Seoul metropolitan area during the Korea-United States Air Quality Study (KORUS-AQ)

The Seoul Metropolitan Area (SMA) has a population of 24 million and frequently experiences unhealthy levels of ozone (O3). In this work, measurements taken during the Korea-United States Air Quality Study (KORUS-AQ, 2016) are used to explore regional gradients in O3 and its chemical precursors, and an observationally-constrained 0-D photochemical box model is used to quantify key aspects of O3 production including its sensitivity to precursor gases. Box model performance was evaluated by comparing modeled concentrations of select secondary species to airborne measurements. These comparisons indicate that the steady state assumption used in 0-D box models cannot describe select intermediate species, highlighting the importance of having a broad suite of trace gases as model constraints. When fully constrained, aggregated statistics of modeled O3 production rates agreed with observed changes in O3, indicating that the box model was able to represent the majority of O3 chemistry. Comparison of airborne observations between urban Seoul and a downwind receptor site reveal a positive gradient in O3 coinciding with a negative gradient in NOx, no gradient in CH2O, and a slight positive gradient in modeled rates of O3 production. Together, these observations indicate a radical-limited (VOC-limited) O3 production environment in the SMA. Zero-out simulations identified C7+ aromatics as the dominant VOC contributors to O3 production, with isoprene and anthropogenic alkenes making smaller but appreciable contributions. Simulations of model sensitivity to decreases in NOx produced results that were not spatially uniform, with large increases in O3 production predicted for urban Seoul and decreases in O3 production predicted for far-outlying areas. The policy implications of this work are clear: Effective O3 mitigation strategies in the SMA must focus on reducing local emissions of C7+ aromatics, while reductions in NOx emissions may increase O3 in some areas but generally decrease the regional extent of O3 exposure

Near-Infrared Molecular Hydrogen Emission from the Central Regions of Galaxies: Regulated Physical Conditions in the Interstellar Medium

The central regions of many interacting and early-type spiral galaxies are actively forming stars. This process affects the physical and chemical properties of the local interstellar medium as well as the evolution of the galaxies. We observed near-infrared H2 emission lines: v=1-0 S(1), 3-2 S(3), 1-0 S(0), and 2-1 S(1) from the central ~1 kpc regions of the archetypical starburst galaxies, M82 and NGC 253, and the less dramatic but still vigorously star-forming galaxies, NGC 6946 and IC 342. Like the far-infrared continuum luminosity, the near-infrared H2 emission luminosity can directly trace the amount of star formation activity because the H2 emission lines arise from the interaction between hot and young stars and nearby neutral clouds. The observed H2 line ratios show that both thermal and non-thermal excitation are responsible for the emission lines, but that the great majority of the near-infrared H2 line emission in these galaxies arises from energy states excited by ultraviolet fluorescence. The derived physical conditions, e.g., far-ultraviolet radiation field and gas density, from [C II] and [O I] lines and far-infrared continuum observations when used as inputs to photodissociation models, also explain the luminosity of the observed H2 v=1-0 S(1) line. The ratio of the H2 v=1-0 S(1) line to far-IR continuum luminosity is remarkably constant over a broad range of galaxy luminosities; L_H2/L_FIR = about 10^{-5}, in normal late-type galaxies (including the Galactic center), in nearby starburst galaxies, and in luminous IR galaxies (LIRGs: L_FIR > 10^{11} L_sun). Examining this constant ratio in the context of photodissociation region models, we conclude that it implies that the strength of the incident UV field on typical molecular clouds follows the gas density at the cloud surface.Comment: Accepted for ApJ, 24 pages, 17 figures, for complete PDF file, see http://kao.re.kr/~soojong/mypaper/2004_pak_egh2.pd

Thinking like a man? The cultures of science

Culture includes science and science includes culture, but conflicts between the two traditions persist, often seen as clashes between interpretation and knowledge. One way of highlighting this false polarity has been to explore the gendered symbolism of science. Feminism has contributed to science studies and the critical interrogation of knowledge, aware that practical knowledge and scientific understanding have never been synonymous. Persisting notions of an underlying unity to scientific endeavour have often impeded rather than fostered the useful application of knowledge. This has been particularly evident in the recent rise of molecular biology, with its delusory dream of the total conquest of disease. It is equally prominent in evolutionary psychology, with its renewed attempts to depict the fundamental basis of sex differences. Wars over science have continued to intensify over the last decade, even as our knowledge of the political, economic and ideological significance of science funding and research has become ever more apparent

Traces of Fallback Breccia on the Rim of Barringer Meteorite Crater (a.k.a. Meteor Crater), Arizona

Barringer Meteorite Crater (a.k.a. Meteor Crater), Arizona, is one of the youngest and best preserved impact craters on Earth. For that rea-son, it provides a baseline for similar craters formed in the geologic past, formed elsewhere in the Solar Sys-tem, and illuminates the astronomical and geological processes that produce them. The crater has not, how-ever, escaped erosion completely. While Shoemaker [1] mapped a breccia with fallback components inside the crater, he did not locate it beyond the crater rim. He only found remnants of that type of debris in re-worked alluvium [1; see also 2]. Fallback breccia and any base-surge deposits have, thus, been missing components in studies of material ejected beyond the transient crater rim

Factor structure and construct validity of the Adult Social Care Outcomes Toolkit for Carers (ASCOT-Carer)

Background: The ASCOT-Carer is a self-report instrument designed to measure social care-related quality of life (SCRQoL). This article presents the psychometric testing and validation of the ASCOT-Carer four response-level interview (INT4) in a sample of unpaid carers of adults who receive publicly-funded social care services in England. Methods: Unpaid carers were identified through a survey of users of publicly-funded social care services in England. 387 carers completed a face-to-face or telephone interview. Data on variables hypothesised to be related to SCRQoL (for example, characteristics of the carer, cared-for person and care situation) and measures of carer experience, strain, health-related quality of life and overall QoL were collected. Relationships between these variables and overall SCRQoL score were evaluated through correlation, ANOVA and regression analysis to test the construct validity of the scale. Internal reliability was assessed using Cronbach’s alpha and feasibility by the number of missing responses. Results: The construct validity was supported by statistically significant relationships between SCRQoL and scores on instruments of related constructs, as well as with characteristics of the carer and care recipient in univariate and multivariate analyses. A Cronbach’s alpha of 0.87 (7 items) indicates that the internal reliability of the instrument is satisfactory and a low number of missing responses (<1%) indicates a high level of acceptance. Conclusions: The results provide evidence to support the construct validity, factor structure, internal reliability and feasibility of the ASCOT-Carer INT4 as an instrument for measuring social care-related quality of life of unpaid carers who care for adults with a variety of long-term conditions, disability or problems related to old age