Defining Paternalism

Much of the philosophical engagement with the issue of paternalism, especially in the last couple of decades, has focused on important normative issues such as: 'what, if anything, is morally problematic about paternalism?', 'when is paternalism justified?', and 'how concerned should we be, morally speaking, with paternalism?'. My thesis seeks to take a step back and asks a more fundamental, conceptual question, upon which these more practical, normative issues supervene: What precisely defines an act of paternalism? To this end, this thesis is divided into five parts; an introduction followed by four chapters. As well as setting out the aims of the thesis, the introduction outlines some of the basic, uncontroversial features of paternalism. Chapters 1, 2, and 3 then examine the rich philosophical literature on defining paternalism; each chapter examining a different approach to defining paternalism. Through the outlining of some of the uncontroversial features of paternalism, and subsequent investigation of where philosophers have gone wrong in defining paternalism, I develop seven 'Challenges' an accurate definition of paternalism must meet. I also argue that no definition of paternalism currently in the philosophical literature, can meet each of these Challenges (or even just meet Challenges 5, 6, and 7; three connected Challenges that are particularly important). Finally, in Chapter 4, I present an original definition of paternalism consisting of three individually necessary, and together sufficient conditions. I argue that this definition can in fact meet each of the seven 'Challenges'

Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.

BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700

Design of CD40 Agonists and Their Use in Growing B Cells for Cancer Immunotherapy

CD40 stimulation has produced impressive results in early-stage clinical trials of patients with cancer. Further progress will be facilitated by a better understanding of how the CD40 receptor becomes activated and the subsequent functions of CD40-stimulated immune cells. This review focuses on two aspects of this subject. The first is the recent recognition that signaling by CD40 is initiated when the receptors are induced to cluster within the membrane of responding cells. This requirement for CD40 clustering explains the stimulatory effects of certain anti-CD40 antibodies and the activity of many-trimer, but not one-trimer, forms of CD40 ligand (CD40L, CD154). The second topic is the use of these CD40 activators to expand B cells (“CD40-B cells”). As antigen-presenting cells (APCs), CD40-B cells are as effective as dendritic cells, with the important difference that CD40-B cells can be induced to proliferate in vitro whereas DCs proliferate poorly if at all. As a result, the use of CD40-B cells as antigen-presenting cells (APCs) promises to streamline the generation of anti-tumor CD8+ T cells for the adoptive cell therapy (ACT) of cancer