Clinical ethics revisited

A decade ago, we reviewed the field of clinical ethics; assessed its progress in research, education, and ethics committees and consultation; and made predictions about the future of the field. In this article, we revisit clinical ethics to examine our earlier observations, highlight key developments, and discuss remaining challenges for clinical ethics, including the need to develop a global perspective on clinical ethics problems

Developing a placebo-controlled trial in surgery:issues of design, acceptability and feasibility

BACKGROUND: Surgical placebos are controversial. This in-depth study explored the design, acceptability, and feasibility issues relevant to designing a surgical placebo-controlled trial for the evaluation of the clinical and cost effectiveness of arthroscopic lavage for the management of people with osteoarthritis of the knee in the UK. METHODS: Two surgeon focus groups at a UK national meeting for orthopaedic surgeons and one regional surgeon focus group (41 surgeons); plenary discussion at a UK national meeting for orthopaedic anaesthetists (130 anaesthetists); three focus groups with anaesthetists (one national, two regional; 58 anaesthetists); two focus groups with members of the patient organisation Arthritis Care (7 participants); telephone interviews with people on consultant waiting lists from two UK regional centres (15 participants); interviews with Chairs of UK ethics committees (6 individuals); postal surveys of members of the British Association of Surgeons of the Knee (382 surgeons) and members of the British Society of Orthopaedic Anaesthetists (398 anaesthetists); two centre pilot (49 patients assessed). RESULTS: There was widespread acceptance that evaluation of arthroscopic lavage had to be conducted with a placebo control if scientific rigour was not to be compromised. The choice of placebo surgical procedure (three small incisions) proved easier than the method of anaesthesia (general anaesthesia). General anaesthesia, while an excellent mimic, was more intrusive and raised concerns among some stakeholders and caused extensive discussion with local decision-makers when seeking formal approval for the pilot.Patients were willing to participate in a pilot with a placebo arm; although some patients when allocated to surgery became apprehensive about the possibility of receiving placebo, and withdrew. Placebo surgery was undertaken successfully. CONCLUSIONS: Our study illustrated the opposing and often strongly held opinions about surgical placebos, the ethical issues underpinning this controversy, and the challenges that exist even when ethics committee approval has been granted. It showed that a placebo-controlled trial could be conducted in principle, albeit with difficulty. It also highlighted that not only does a placebo-controlled trial in surgery have to be ethically and scientifically acceptable but that it also must be a feasible course of action. The place of placebo-controlled surgical trials more generally is likely to be limited and require specific circumstances to be met. Suggested criteria are presented. TRIAL REGISTRATION NUMBER: The trial was assigned ISRCTN02328576 through http://controlled-trials.com/ in June 2006. The first patient was randomised to the pilot in July 2007

Über eine Klasse polynomialer Scharen selbstadjungierter Operatoren im Hilbertraum

HEK293A cells expressing either mouse MOG (mMOG) or rat MOG (rMOG) C terminally tagged with EGFP. (DOCX 2792 kb

3D Multi-Cell Simulation of Tumor Growth and Angiogenesis

We present a 3D multi-cell simulation of a generic simplification of vascular tumor growth which can be easily extended and adapted to describe more specific vascular tumor types and host tissues. Initially, tumor cells proliferate as they take up the oxygen which the pre-existing vasculature supplies. The tumor grows exponentially. When the oxygen level drops below a threshold, the tumor cells become hypoxic and start secreting pro-angiogenic factors. At this stage, the tumor reaches a maximum diameter characteristic of an avascular tumor spheroid. The endothelial cells in the pre-existing vasculature respond to the pro-angiogenic factors both by chemotaxing towards higher concentrations of pro-angiogenic factors and by forming new blood vessels via angiogenesis. The tumor-induced vasculature increases the growth rate of the resulting vascularized solid tumor compared to an avascular tumor, allowing the tumor to grow beyond the spheroid in these linear-growth phases. First, in the linear-spherical phase of growth, the tumor remains spherical while its volume increases. Second, in the linear-cylindrical phase of growth the tumor elongates into a cylinder. Finally, in the linear-sheet phase of growth, tumor growth accelerates as the tumor changes from cylindrical to paddle-shaped. Substantial periods during which the tumor grows slowly or not at all separate the exponential from the linear-spherical and the linear-spherical from the linear-cylindrical growth phases. In contrast to other simulations in which avascular tumors remain spherical, our simulated avascular tumors form cylinders following the blood vessels, leading to a different distribution of hypoxic cells within the tumor. Our simulations cover time periods which are long enough to produce a range of biologically reasonable complex morphologies, allowing us to study how tumor-induced angiogenesis affects the growth rate, size and morphology of simulated tumors

Ethical issues in epidemiologic research and public health practice

A rich and growing body of literature has emerged on ethics in epidemiologic research and public health practice. Recent articles have included conceptual frameworks of public health ethics and overviews of historical developments in the field. Several important topics in public health ethics have also been highlighted. Attention to ethical issues can facilitate the effective planning, implementation, and growth of a variety of public health programs and research activities. Public health ethics is consistent with the prevention orientation of public health. Ethical concerns can be anticipated or identified early and effectively addressed through careful analysis and consultation

The human body at cellular resolution: the NIH Human Biomolecular Atlas Program

Abstract: Transformative technologies are enabling the construction of three-dimensional maps of tissues with unprecedented spatial and molecular resolution. Over the next seven years, the NIH Common Fund Human Biomolecular Atlas Program (HuBMAP) intends to develop a widely accessible framework for comprehensively mapping the human body at single-cell resolution by supporting technology development, data acquisition, and detailed spatial mapping. HuBMAP will integrate its efforts with other funding agencies, programs, consortia, and the biomedical research community at large towards the shared vision of a comprehensive, accessible three-dimensional molecular and cellular atlas of the human body, in health and under various disease conditions

Nuclear Fission: : A Review of Experimental Advances and Phenomenology

In the last two decades, through technological, experimental and theoretical advances, the situation in experimental fission studies has changed dramatically. With the use of advanced production and detection techniques both much more detailed and precise information can now be obtained for the traditional regions of fission research and, crucially, new regions of nuclei have become routinely accessible for fission studies.
 This work first of all reviews the recent developments in experimental fission techniques, in particular the resurgence of transfer-induced fission reactions with light and heavy ions, the emerging use of inverse-kinematic approaches, both at Coulomb and relativistic energies, and of fission studies with radioactive beams.
 The emphasis on the fission-fragment mass and charge distributions will be made in this work, though some of the other fission observables, such as prompt neutron and γ-ray emission will also be reviewed.
 A particular attention will be given to the low-energy fission in the so far scarcely explored nuclei in the very neutron-deficient lead region. They recently became the focus for several complementary experimental studies, such as β-delayed fission with radioactive beams at ISOLDE(CERN), Coulex-induced fission of relativistic secondary beams at FRS(GSI), and several prompt fusion-fission studies. The synergy of these approaches allows a unique insight in the new region of asymmetric fission around <sup>180</sup>Hg, recently discovered at ISOLDE. Recent extensive theoretical efforts in this region will also be outlined.
 The unprecedented high-quality data for fission fragments, completely identified in <i>Z</i> and <i>A</i>, by means of reactions in inverse kinematics at FRS(GSI) and VAMOS(GANIL) will be also reviewed. These experiments explored an extended range of mercury-to-californium elements, spanning from the neutron-deficient to neutron-rich nuclides, and covering both asymmetric, symmetric and transitional fission regions.
 Some aspects of heavy-ion induced fusion-fission and quasifission reactions will be also discussed, which reveal their dynamical features, such as the fission time scale. The crucial role of the multi-chance fission, probed by means of multinucleon-transfer induced fission reactions, will be highlighted.
 The review will conclude with the discussion of the new experimental fission facilities which are presently being brought into operation, along with promising 'next-generation' fission approaches, which might become available within the next decade