The solution structures of several small proteins have recently been determined from high‐resolution nuclear magnetic resonance data. The principal features of the methods available to do this are outlined here, together with the advantages, limitations and future prospects of the technique.

This case describes an adolescent in a crisis of a chronic medical condition whose situation is complicated by substance abuse and mental illness. D. Micah Hester provides an analytic approach, teasing apart the multiple layers of medical, developmental, and moral issues at hand and describing possible responses and outcomes. Amy T. Campbell examines existing legal guidelines for adolescent decision making, arguing that greater space exists for clinical discretion in these matters than commonly thought. Cheryl D. Lew discusses the development (...) of agency in adolescent patients, the ideal of autonomous decision making in the context of impairment and chronic illness, and the obligation of healthcare teams to examine an adolescent patient’s decisions in relation to her identity. (shrink)

Nanomedicine is yielding new and improved treatments and diagnostics for a range of diseases and disorders. Nanomedicine applications incorporate materials and components with nanoscale dimensions where novel physiochemical properties emerge as a result of size-dependent phenomena and high surface-to-mass ratio. Nanotherapeutics and in vivo nanodiagnostics are a subset of nanomedicine products that enter the human body. These include drugs, biological products, implantable medical devices, and combination products that are designed to function in the body in ways unachievable at larger scales. (...) Nanotherapeutics andin vivonanodiagnostics incorporate materials that are engineered at the nanoscale to express novel properties that are medicinally useful. These nanomedicine applications can also contain nanomaterials that are biologically active, producing interactions that depend on biological triggers. Examples include nanoscale formulations of insoluble drugs to improve bioavailability and pharmacokinetics, drugs encapsulated in hollow nanoparticles with the ability to target and cross cellular and tissue membranes and to release their payload at a specific time or location, imaging agents that demonstrate novel optical properties to aid in locating micrometastases, and antimicrobial and drug-eluting components or coatings of implantable medical devices such as stents. (shrink)

Book reviewed in this article: In That Case: Medical Ethics in Everyday Practice. By Alastair Campbell and Roger Higgs. Medical Genetics Casebook: A Clinical Introduction to Medical Ethics Systems Theory. By Colleen D. Clements. Cases in Bioethics from the Hastings Center Report. Edited by Carol Levine and Robert M. Veatch. Hastings‐on‐Hudson.

BackgroundRandomized controlled trials (RCTs) are often complex and expensive to perform. Less than one third achieve planned recruitment targets, follow-up can be labor-intensive, and many have limited real-world generalizability. Designs for RCTs conducted using cohorts and routinely collected health data, including registries, electronic health records, and administrative databases, have been proposed to address these challenges and are being rapidly adopted. These designs, however, are relatively recent innovations, and published RCT reports often do not describe important aspects of their methodology in (...) a standardized way. Our objective is to extend the Consolidated Standards of Reporting Trials (CONSORT) statement with a consensus-driven reporting guideline for RCTs using cohorts and routinely collected health data.MethodsThe development of this CONSORT extension will consist of five phases. Phase 1 (completed) consisted of the project launch, including fundraising, the establishment of a research team, and development of a conceptual framework. In phase 2, a systematic review will be performed to identify publications (1) that describe methods or reporting considerations for RCTs conducted using cohorts and routinely collected health data or (2) that are protocols or report results from such RCTs. An initial “long list” of possible modifications to CONSORT checklist items and possible new items for the reporting guideline will be generated based on the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) and The REporting of studies Conducted using Observational Routinely-collected health Data (RECORD) statements. Additional possible modifications and new items will be identified based on the results of the systematic review. Phase 3 will consist of a three-round Delphi exercise with methods and content experts to evaluate the “long list” and generate a “short list” of key items. In phase 4, these items will serve as the basis for an in-person consensus meeting to finalize a core set of items to be included in the reporting guideline and checklist. Phase 5 will involve drafting the checklist and elaboration-explanation documents, and dissemination and implementation of the guideline.DiscussionDevelopment of this CONSORT extension will contribute to more transparent reporting of RCTs conducted using cohorts and routinely collected health data. (shrink)

D. M. Armstrong is an eminent Australian philosopher whose work over many years has dealt with such subjects as: the nature of possibility, concepts of the particular and the general, causes and laws of nature, and the nature of human consciousness. This collection of essays explores the many facets of Armstrong's work, concentrating on his more recent interests. There are four sections to the book: possibility and identity, universals, laws and causality, and philosophy of mind. The contributors comprise an international (...) group of philosophers from the United States, England and Australia. An interesting feature of the volume is that Armstrong himself has written responses to each of the essays. There is also a complete bibliography of Armstrong's writings. (shrink)

Background Informed consent is an integral component of good medical practice. Many researchers have investigated measures to improve the quality of informed consent, but it is not clear which techniques work best and why. To address this problem, we propose developing a core outcome set to evaluate interventions designed to improve the consent process for surgery in adult patients with capacity. Part of this process involves reviewing existing research that has reported what is important to patients and doctors in the (...) informed consent process. Methods This qualitative synthesis comprises four phases: identification of published papers and determining their relevance; appraisal of the quality of the papers; identification and summary of the key findings from each paper while determining the definitiveness of each finding against the primary data; comparison of key themes between papers such that findings are linked across studies. Results Searches of bibliographic databases returned 11,073 titles. Of these, 16 studies met the inclusion criteria. Studies were published between 1996 and 2016 and included a total of 367 patients and 74 health care providers. Thirteen studies collected data using in-depth interviews and constant comparison was the most common means of qualitative analysis. A total of 94 findings were extracted from the primary papers and divided into 17 categories and ultimately 6 synthesised findings related to: patient characteristics, knowledge, communication, the model patient, trust and decision making. Conclusions This qualitative meta-aggregation is the first to examine the issue of informed consent for surgery. It has revealed several outcomes deemed important to capture by patients and clinicians when evaluating the quality of a consent process. Some of these outcomes have not been examined previously in research comparing methods for informed consent. This review is an important step in the development of a COS to evaluate interventions designed to improve the consent process for surgery. Registration The study protocol was registered on the international prospective register for systematic reviews. (shrink)

Randomized controlled trial trial designs exist on an explanatory-pragmatic spectrum, depending on the degree to which a study aims to address a question of efficacy or effectiveness. As conceptualized by Schwartz and Lellouch in 1967, an explanatory approach to trial design emphasizes hypothesis testing about the mechanisms of action of treatments under ideal conditions, whereas a pragmatic approach emphasizes testing effectiveness of two or more available treatments in real-world conditions. Interest in, and the number of, pragmatic trials has grown substantially (...) in recent years, with increased recognition by funders and stakeholders worldwide of the need for credible evidence to inform clinical decision-making. This increase has been accompanied by the onset of learning healthcare systems, as well as an increasing focus on patient-oriented research. However, pragmatic trials have ethical challenges that have not yet been identified or adequately characterized. The present study aims to explore the views of key stakeholders with respect to ethical issues raised by the design and conduct of pragmatic trials. It is embedded within a large, four-year project that seeks to develop guidance for the ethical design and conduct of pragmatic trials. As a first step, this study will address important gaps in the current empirical literature with respect to identifying a comprehensive range of ethical issues arising from the design and conduct of pragmatic trials. By opening up a broad range of topics for consideration within our parallel ethical analysis, we will extend the current debate, which has largely emphasized issues of consent, to the range of ethical considerations that may flow from specific design choices. Semi-structured interviews with key stakeholders, across multiple jurisdictions, identified based on their known experience and/or expertise with pragmatic trials. We expect that the study outputs will be of interest to a wide range of knowledge users including trialists, ethicists, research ethics committees, journal editors, regulators, healthcare policymakers, research funders and patient groups. All publications will adhere to the Tri-Agency Open Access Policy on Publications. (shrink)

BackgroundAlthough patient advocates have developed templates for standard consent forms, evaluating patient preferences for first in human (FIH) and window of opportunity (Window) trial consent forms is critical due to their unique risks. FIH trials are the initial use of a novel compound in study participants. In contrast, Window trials give an investigational agent over a fixed duration to treatment naïve patients in the time between diagnosis and standard of care (SOC) surgery. Our goal was to determine the patient-preferred presentation (...) of important information in consent forms for these trials.MethodsThe study consisted of two phases: (1) analyses of oncology FIH and Window consents; (2) interviews of trial participants. FIH consent forms were analyzed for the location(s) of information stating that the study drug has not been tested in humans (FIH information); Window consents were analyzed for the location(s) of information stating the trial may delay SOC surgery (delay information). Participants were asked about their preferred placement of the information in their own trial’s consent form. The location of information in the consent forms was compared to the participants’ suggestions for placement. Results34 [17 FIH; 17 Window] of 42(81%) cancer patients approached participated. 25 consents [20 FIH; 5 Window] were analyzed. 19/20 FIH consent forms included FIH information, and 4/5 Window consent forms included delay information. 19/20(95%) FIH consent forms contained FIH information in the risks section 12/17(71%) patients preferred the same. Fourteen (82%) patients wanted FIH information in the purpose, but only 5(25%) consents mentioned it there. 9/17(53%) Window patients preferred delay information to be located early in the consent, before the “Risks” section. 3/5(60%) consents did this.ConclusionsDesigning consents that reflect patient preferences more accurately is essential for ethical informed consent; however, a one-size fits all approach will not accurately capture patient preferences. We found that preferences differed for FIH and Window trial consents, though for both, patients preferred key risk information early in the consent. Next steps include determining if FIH and Window consent templates improve understanding. (shrink)

Editors of Pliny's Naturalis Historia have not had to deplore the paucity of the MS. tradition, but rather its value; while MSS. belonging to the ordo recentiorum are numerous and fairly complete, those of the ordo uetustiorum are very few, and never contain more than a few books, often with considerable gaps. They are A ii 196–vi 51, M xi–xv, P and H parts of xviii, I xxiii, xxv, B xxxii–xxxvii . There are also some scattered fragments. Detlefsen indeed claimed (...) that the restoration of the original text of the N.H. is more difficult than that of any other Latin author owing to the mutilated and defective transmission of considerable parts. (shrink)

— No 1, mars : S. Chollet et D. Valentin, Le degré d’expertise a-t-il une influence sur la perception olfactive ? Quelques éléments de réponse dans le domaine du vin ; G. Molina et J.-M. Fabre, Norme et contexte : influence d’une dichotomisation du matériel et de l’évaluation sur la contextualisation de jugements catégoriels ; S. Nicolas, J. Ségui..

Moral theories which, like those of Plato, Aristotle and Aquinas, give a central place to the virtues, tend to assume that as traits of character the virtues are mutually compatible so that it is possible for one and the same person to possess them all. This assumption—let us call it the compatibility thesis—does not deny the existence of painful moral dilemmas: it allows that the virtues may conflict in particular situations when considerations associated with different virtues favour incompatible courses of (...) action, but holds that these conflicts occur only at the level of individual actions. Thus while it may not always be possible to do both what would be just and what would be kind or to act both loyally and honestly, it is possible to be both a kind and a just person and to have both the virtue of loyalty and the virtue of honesty. (shrink)

The traditional empiricist view of perception is that in perception we receive information through the senses of the so-called external world. This idea is reflected in the notions of the ‘given’ and of 1‘data’ which have figured so largely in theories of perception. Even if philosophers of this persuasion have gone on to say something about what we do with the data, it remains true that at rock bottom and in the last resort perception is thought of as something passive. (...) I have tried to chart the historical issues elsewhere, and I shall not repeat anything about them here. That is not my concern. I am here interested in the question whether the notion of a purely passive perceiver makes any sense in itself. That it does not has been suggested by philosophers on occasion. There are some brief remarks to that effect in G.E.M. Anscombe’s Intention ; and Stuart Hampshire’s Thought and Action lays great weight on action in connection with our awareness of the world, although I do not myself believe that the exact nature of the connection is clearly worked out by him. Some aspects of his views, however, have been taken up by Campbell Garnett with explicit reference to perception in his The Perceptual Process, with a resulting theory that bears more than a superficial resemblance to that of Maine de Biran. (shrink)

The role of the environment in producing the correct classical limit in the Bohm interpretation of quantum mechanics is investigated, in the context of a model of quantum Brownian motion. One of the effects of the interaction is to produce a rapid approximate diagonalisation of the reduced density matrix in the position representation. This effect is, by itself, insufficient to produce generically quasi-classical behaviour of the Bohmian trajectory. However, it is shown that, if the system particle is initially in an (...) approximate energy eigenstate, then there is a tendency for the Bohmian trajectory to become approximately classical on a longer time-scale. The relationship between this phenomenon and the behaviour of the Wigner function post-decoherence is discussed. (shrink)