Analytical and behavioral characterization of 1-hexanoyl-LSD (1H-LSD)

The development of lysergic acid diethylamide (LSD) derivatives and analogs continues to inform the design of novel receptor probes and potentially new medicines. On the other hand, a number of newly developed LSD derivatives have also emerged as recreational drugs, leading to reports of their detection in some countries. One position in the ergoline scaffold of LSD that is frequently targeted is the N1-position; numerous N1-alkylcarbonyl LSD derivatives have been reported where the acyl chain is attached to the indole nitrogen, for example, in the form of linear n-alkane substituents, which represent higher homologs of the prototypical 1-acetyl-N,N-diethyllysergamide (1A-LSD, ALD-52). In this study, 1-hexanoyl-LSD (1H-LSD, SYN-L-027), a novel N1-acyl LSD derivative, was characterized analytically using standard techniques, followed by evaluation of its in vivo behavioral effects using the mouse head-twitch response (HTR) assay in C57BL/6J mice. 1H-LSD induced the HTR, with a median effective dose (ED50) of 192.4 μg/kg (equivalent to 387 nmol/kg), making it roughly equipotent to ALD-52 when tested previously under similar conditions. Similar to other N1-acylated analogs, 1H-LSD is anticipated to by hydrolyzed to LSD in vivo and acts as a prodrug. It is currently unknown whether 1H-LSD has appeared as on the research chemical market or is being used recreationally

Understanding barriers and outcomes of unspecified (non-directed altruistic) kidney donation from both professional's and patient's perspectives: research protocol for a national multicentre mixed-methods prospective cohort study.

INTRODUCTION: Living donation accounts for over one-third of all kidney transplants taking place in the UK. 1 The concept of anonymously donating a kidney to a stranger (non-directed altruistic or unspecified kidney donation (UKD)) remains uncomfortable for some clinicians, principally due to concerns about the motivations and long-term physical and psychological outcomes in this donor group. AIMS: The research programme aims to provide a comprehensive assessment of the unspecified donor programme in the UK. It aims to identify reasons for variations in practice across centres, explore outcomes for donors and ascertain barriers and facilitators to UKD, as well as assess the economic implications of unspecified donation. METHODS: The research programme will adopt a mixed-methods approach to assessing UKD nationally using focus groups, interviews and questionnaires. Two study populations will be investigated. The first will include transplant professionals involved in unspecified kidney donation. The second will include a 5-year prospective cohort of individuals who present to any of the 23 UK transplant centres as a potential unspecified living kidney donor. Physical and psychological outcomes will be followed up to 1 year following donation or withdrawal from the donation process. A matched sample of specified donors (those donating to someone they know) will be recruited as a control group. Further qualitative work consisting of interviews will be performed on a purposive sample of unspecified donors from both groups (those who do and do not donate). DISSEMINATION: The findings will be reported to NHS Blood and Transplant and the British Transplant Society with a view to developing national guidelines and a protocol for the management of those presenting for unspecified donation. TRIAL REGISTRATION NUMBER: ISRCTN23895878, Pre-results

Application of Respondent Driven Sampling to Collect Baseline Data on FSWs and MSM for HIV Risk Reduction Interventions in Two Urban Centres in Papua New Guinea

The need to obtain unbiased information among hard–to-reach and hidden populations for behavioural and biological surveillance, epidemiological studies, and intervention program evaluations has led researchers to search for a suitable sampling method. One method that has been tested among IDU and MSM recently is respondent-driven sampling (RDS). We used RDS to conduct a behavioural survey among FSWs and MSM in two urban centres in Papua New Guinea (PNG). In this paper we present the lessons learned implementing RDS in a developing country setting. We also present comparisons of RDSAT-adjusted versus unadjusted crude estimates of some key socio-demographic indicators as well as comparisons between the estimates from RDS and a hypothetical time–location sample (TLS). Overall, the use of RDS among the MSM and FSWs in PNG had numerous advantages in terms of collecting a required sample size in a short time period, minimizing costs and maximising security for staff and respondents. Although there were a few problems these were easily remedied and we would recommend RDS for other similar studies in PNG and other developing countries

Stepping Beyond the Newtonian Paradigm in Biology. Towards an Integrable Model of Life: Accelerating Discovery in the Biological Foundations of Science

The INBIOSA project brings together a group of experts across many disciplines who believe that science requires a revolutionary transformative step in order to address many of the vexing challenges presented by the world. It is INBIOSA’s purpose to enable the focused collaboration of an interdisciplinary community of original thinkers. This paper sets out the case for support for this effort. The focus of the transformative research program proposal is biology-centric. We admit that biology to date has been more fact-oriented and less theoretical than physics. However, the key leverageable idea is that careful extension of the science of living systems can be more effectively applied to some of our most vexing modern problems than the prevailing scheme, derived from abstractions in physics. While these have some universal application and demonstrate computational advantages, they are not theoretically mandated for the living. A new set of mathematical abstractions derived from biology can now be similarly extended. This is made possible by leveraging new formal tools to understand abstraction and enable computability. [The latter has a much expanded meaning in our context from the one known and used in computer science and biology today, that is "by rote algorithmic means", since it is not known if a living system is computable in this sense (Mossio et al., 2009).] Two major challenges constitute the effort. The first challenge is to design an original general system of abstractions within the biological domain. The initial issue is descriptive leading to the explanatory. There has not yet been a serious formal examination of the abstractions of the biological domain. What is used today is an amalgam; much is inherited from physics (via the bridging abstractions of chemistry) and there are many new abstractions from advances in mathematics (incentivized by the need for more capable computational analyses). Interspersed are abstractions, concepts and underlying assumptions “native” to biology and distinct from the mechanical language of physics and computation as we know them. A pressing agenda should be to single out the most concrete and at the same time the most fundamental process-units in biology and to recruit them into the descriptive domain. Therefore, the first challenge is to build a coherent formal system of abstractions and operations that is truly native to living systems. Nothing will be thrown away, but many common methods will be philosophically recast, just as in physics relativity subsumed and reinterpreted Newtonian mechanics. This step is required because we need a comprehensible, formal system to apply in many domains. Emphasis should be placed on the distinction between multi-perspective analysis and synthesis and on what could be the basic terms or tools needed. The second challenge is relatively simple: the actual application of this set of biology-centric ways and means to cross-disciplinary problems. In its early stages, this will seem to be a “new science”. This White Paper sets out the case of continuing support of Information and Communication Technology (ICT) for transformative research in biology and information processing centered on paradigm changes in the epistemological, ontological, mathematical and computational bases of the science of living systems. Today, curiously, living systems cannot be said to be anything more than dissipative structures organized internally by genetic information. There is not anything substantially different from abiotic systems other than the empirical nature of their robustness. We believe that there are other new and unique properties and patterns comprehensible at this bio-logical level. The report lays out a fundamental set of approaches to articulate these properties and patterns, and is composed as follows. Sections 1 through 4 (preamble, introduction, motivation and major biomathematical problems) are incipient. Section 5 describes the issues affecting Integral Biomathics and Section 6 -- the aspects of the Grand Challenge we face with this project. Section 7 contemplates the effort to formalize a General Theory of Living Systems (GTLS) from what we have today. The goal is to have a formal system, equivalent to that which exists in the physics community. Here we define how to perceive the role of time in biology. Section 8 describes the initial efforts to apply this general theory of living systems in many domains, with special emphasis on crossdisciplinary problems and multiple domains spanning both “hard” and “soft” sciences. The expected result is a coherent collection of integrated mathematical techniques. Section 9 discusses the first two test cases, project proposals, of our approach. They are designed to demonstrate the ability of our approach to address “wicked problems” which span across physics, chemistry, biology, societies and societal dynamics. The solutions require integrated measurable results at multiple levels known as “grand challenges” to existing methods. Finally, Section 10 adheres to an appeal for action, advocating the necessity for further long-term support of the INBIOSA program. The report is concluded with preliminary non-exclusive list of challenging research themes to address, as well as required administrative actions. The efforts described in the ten sections of this White Paper will proceed concurrently. Collectively, they describe a program that can be managed and measured as it progresses

Analytic philosophy for biomedical research: the imperative of applying yesterday's timeless messages to today's impasses

The mantra that "the best way to predict the future is to invent it" (attributed to the computer scientist Alan Kay) exemplifies some of the expectations from the technical and innovative sides of biomedical research at present. However, for technical advancements to make real impacts both on patient health and genuine scientific understanding, quite a number of lingering challenges facing the entire spectrum from protein biology all the way to randomized controlled trials should start to be overcome. The proposal in this chapter is that philosophy is essential in this process. By reviewing select examples from the history of science and philosophy, disciplines which were indistinguishable until the mid-nineteenth century, I argue that progress toward the many impasses in biomedicine can be achieved by emphasizing theoretical work (in the true sense of the word 'theory') as a vital foundation for experimental biology. Furthermore, a philosophical biology program that could provide a framework for theoretical investigations is outlined

Gaia Data Release 2: Calibration and mitigation of electronic offset effects in the data

The European Space Agency Gaia satellite was launched into orbit around L2 in December 2013. This ambitious mission has strict requirements on residual systematic errors resulting from instrumental corrections in order to meet a design goal of sub-10 microarcsecond astrometry. During the design and build phase of the science instruments, various critical calibrations were studied in detail to ensure that this goal could be met in orbit. In particular, it was determined that the video-chain offsets on the analogue side of the analogue-to-digital conversion electronics exhibited instabilities that could not be mitigated fully by modifications to the flight hardware. We provide a detailed description of the behaviour of the electronic offset levels on microsecond timescales, identifying various systematic effects that are known collectively as offset non-uniformities. The effects manifest themselves as transient perturbations on the gross zero-point electronic offset level that is routinely monitored as part of the overall calibration process. Using in-orbit special calibration sequences along with simple parametric models, we show how the effects can be calibrated, and how these calibrations are applied to the science data. While the calibration part of the process is relatively straightforward, the application of the calibrations during science data processing requires a detailed on-ground reconstruction of the readout timing of each charge-coupled device (CCD) sample on each device in order to predict correctly the highly time-dependent nature of the corrections. We demonstrate the effectiveness of our offset non-uniformity models in mitigating the effects in Gaia data. We demonstrate for all CCDs and operating instrument and modes on board Gaia that the video-chain noise-limited performance is recovered in the vast majority of science samples

Moving towards public policy-ready science: philosophical insights on the social-ecological systems perspective for conservation science

The social-ecological systems (SES) perspective stems from the need to rethink the ways humans relate to the environment, given the evidence that conventional conservation and management approaches are often ineffective in dealing with complex socio-environmental problems. The SES approach conceives non-scientific and scientific knowledge as equally necessary in the process of management and public policy formation. Thus, the adoption of the SES approach must also serve to make better decisions about what kind of science and technology would be ‘public policy-ready’ (as well as also ‘policy-relevant’); that is, a science oriented and conceived to provide concrete solutions to societal needs and demands. Here we review and reinterpret the SES perspective as a real paradigm change for conservation science. Under the lenses of philosophy, we try to untangle some weak points of the SES approach in order to advance to a conservation science closer to the process of science-based public policy creation and to enhance the intertwining with other types of knowledge. In this sense, we discuss how co-production of knowledge and decision-making process under the SES perspective are a huge step forward towards fulfilling the need to bring increasingly closer the spheres of science and policy, narrowing its interface.Fil: Sala, Juan Emilio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico. Instituto de Biología de Organismos Marinos; Argentina. Universidad Nacional de la Patagonia "San Juan Bosco"; ArgentinaFil: Torchio, Gabriela María. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico. Instituto de Biología de Organismos Marinos; Argentin

Investigation into the cause of spontaneous emulsification of a free steel droplet : validation of the chemical exchange pathway

Small Fe-based droplets have been heated to a molten phase suspended within a slag medium to replicate a partial environment within the basic oxygen furnace (BOF). The confocal scanning laser microscope (CSLM) has been used as a heating platform to interrogate the effect of impurities and their transfer across the metal/slag interface, on the emulsification of the droplet into the slag medium. The samples were then examined through X-ray computer tomography (XCT) giving the mapping of emulsion dispersion in 3D space, calculating the changing of interfacial area between the two materials, and changes of material volume due to material transfer between metal and slag. Null experiments to rule out thermal gradients being the cause of emulsification have been conducted as well as replication of the previously reported study by Assis et al.[1] which has given insights into the mechanism of emulsification. Finally chemical analysis was conducted to discover the transfer of oxygen to be the cause of emulsification, leading to a new study of a system with undergoing oxygen equilibration

Noncompliance in people living with HIV: accuracy of defining characteristics of the nursing diagnosis

ABSTRACT Objective: to evaluate the accuracy of the defining characteristics of the NANDA International nursing diagnosis, noncompliance, in people with HIV. Method: study of diagnostic accuracy, performed in two stages. In the first stage, 113 people with HIV from a hospital of infectious diseases in the Northeast of Brazil were assessed for identification of clinical indicators of noncompliance. In the second, the defining characteristics were evaluated by six specialist nurses, analyzing the presence or absence of the diagnosis. For accuracy of the clinical indicators, the specificity, sensitivity, predictive values and likelihood ratios were measured. Results: the presence of the noncompliance diagnosis was shown in 69% (n=78) of people with HIV. The most sensitive indicator was, missing of appointments (OR: 28.93, 95% CI: 1.112-2.126, p = 0.002). On the other hand, nonadherence behavior (OR: 15.00, 95% CI: 1.829-3.981, p = 0.001) and failure to meet outcomes (OR: 13.41; 95% CI: 1.272-2.508; P = 0.003) achieved higher specificity. Conclusion: the most accurate defining characteristics were nonadherence behavior, missing of appointments, and failure to meet outcomes. Thus, in the presence of these, the nurse can identify, with greater security, the diagnosis studied