The history of physics ranges from antiquity to modern string theory. Since early times, human beings have sought to understand the workings of nature--why unsupported objects drop to the ground, why different materials have different properties, and so forth. The emergence of physics as a science, distinct from natural philosophy, began with the scientific revolution of the 16th and 17th centuries when the scientific method came into vogue. Speculation was no longer acceptable; research was required. The beginning of the 20th (...) century marks the start of a more modern physics. Physicists began to study the atom, with its electrons and its nucleus. Then they began to look at the fundamental question of the forces that hold the nucleus together and the particles that account for the natural forces. This book approaches the history of physics from a biographical point of view, considering people to be more interesting than things, and the combination of the two more interesting than the sum of the individual parts. After a brief overview of classical and modern physics, 336 one-page biographies of individuals who have made significant contributions to the field of physics are presented. (shrink)

The levels of different classes of mitochondrially encoded transcripts are developmentally regulated in sea urchin embryos, as a result of selection between mutually exclusive synthetic pathways. I propose a simple model to explain these observations, based on a dual role for mitochondrial ribosomes and translation factors in RNA synthesis as well as in translation. This effect may be exerted either at the transcriptional or post‐transcriptional level (or both), and is potentially generalizable to mammalian mtDNA and to other systems.

Last year, we reported a new mechanism of DNA replication in mammals. It occurs inside mitochondria and entails the use of processed transcripts, termed bootlaces, which hybridize with the displaced parental strand as the replication fork advances. Here we discuss possible reasons why such an unusual mechanism of DNA replication might have evolved. The bootlace mechanism can minimize the occurrence and impact of single‐strand breaks that would otherwise threaten genome stability. Furthermore, by providing an implicit mismatch recognition system, it should (...) limit the occurrence of replication‐dependent deletions and insertions, and defend against invading elements. Such a mechanism may also limit attempts to manipulate the mammalian mitochondrial genome. (shrink)

The internet is widely used for health information and support, often by vulnerable people. Internet-based research raises both familiar and new ethical problems for researchers and ethics committees. While guidelines for internet-based research are available, it is unclear to what extent ethics committees use these. Experience of gaining research ethics approval for a UK study (SharpTalk), involving internet-based discussion groups with young people who self-harm and health professionals is described. During ethical review, unsurprisingly, concerns were raised about the vulnerability of (...) potential participants. These were dominated by the issue of anonymity, which also affected participant safety and consent. These ethical problems are discussed, and our solutions, which included: participant usernames specific to the study, a closed website, private messaging facilities, a direct contact email to researchers, information about forum rules displayed on the website, a ‘report’ button for participants, links to online support, and a discussion room for forum moderators. This experience with SharpTalk suggests that an approach to ethics, which recognises the relational aspects of research with vulnerable people, is particularly useful for internet-based health research. The solutions presented here can act as guidance for researchers developing proposals and for ethics committees reviewing them. (shrink)

Copyright © 2015 by the Society of Criti. Objective: Global lung stress varies considerably with low tidal volume ventilation for acute respiratory distress syndrome. High stress despite low tidal volumes may worsen lung injury and increase risk of death. No widely available parameter exists to assess global lung stress. We aimed to determine whether the volume delivered during a recruitment maneuver is inversely associated with lung stress and mortality in acute respiratory distress syndrome. Design: Substudy of an acute respiratory distress (...) syndrome clinical trial on esophageal pressure-guided positive end-expiratory pressure titration. Setting: U.S. academic medical center. Patients: Forty-two patients with acute respiratory distress syndrome in whom airflow, airway pressure, and esophageal pressure were recorded during the recruitment maneuver. Interventions: A single recruitment maneuver was performed before initiating protocol-directed ventilator management. Recruitment maneuvers consisted of a 30-second breath hold at 40 cm H2O airway pressure under heavy sedation or paralysis. VRM was calculated by integrating the flow-time waveform during the maneuver. End-inspiratory stress was defined as the transpulmonary pressure during end-inspiratory pause of a tidal breath and tidal stress as the transpulmonary pressure difference between end-inspiratory and end-expiratory pauses. Measurements and Main Results: VRM ranged between 7.4 and 34.7 mL/kg predicted body weight. Lower VRM predicted high end-inspiratory and tidal lung stress. After adjusting for Pao2/Fio2 and either driving pressure, tidal volume, or plateau pressure and positive end-expiratory pressure, VRM remained independently associated with both end-inspiratory and tidal stress. In unadjusted analysis, low VRM predicted increased risk of death. VRM remained significantly associated with mortality after adjusting for study arm. Conclusions: Low VRM independently predicts high lung stress and may predict risk of death in patients with acute respiratory distress syndrome. (shrink)

Ethical decision-making frameworks assist in identifying the issues at stake in a particular setting and thinking through, in a methodical manner, the ethical issues that require consideration as well as the values that need to be considered and promoted. Decisions made about the use, sharing, and re-use of big data are complex and laden with values. This paper sets out an Ethics Framework for Big Data in Health and Research developed by a working group convened by the Science, Health and (...) Policy-relevant Ethics in Singapore Initiative. It presents the aim and rationale for this framework supported by the underlying ethical concerns that relate to all health and research contexts. It also describes a set of substantive and procedural values that can be weighed up in addressing these concerns, and a step-by-step process for identifying, considering, and resolving the ethical issues arising from big data uses in health and research. This Framework is subsequently applied in the papers published in this Special Issue. These papers each address one of six domains where big data is currently employed: openness in big data and data repositories, precision medicine and big data, real-world data to generate evidence about healthcare interventions, AI-assisted decision-making in healthcare, public-private partnerships in healthcare and research, and cross-sectoral big data. (shrink)

Superoxide is produced by a NADPH oxidase of phagocytic cells and contributes to their microbicidal activities. The oxidase is activated when receptors in the neutrophil plasma membrane bind to the target microbe. These receptors recognise antibodies and complement fragments which coat the target cell. The oxidase electron transport chain, located in the plasma membrane, comprises a low potential cytochrome b heterodimer (gp 91‐phox and p22‐phox) associated with FAD. It is non‐functional until at least three proteins, p67‐phox, p47‐phox and p21rac (and (...) possibly others), move from the cytosol to dock on the cytochrome b. The docking involves the interaction of SH3 domains may become exposed follwoing phosphorylation of p47‐phox by protein kinase C or, in model systems, by addition of arachidonic acid to reconstitution mixtures. Following the docking process the electron‐transporting component is able to transfer electrons from NADPH to oxygen. This electrogenic event is charge‐compensated by the opening of a prton channel. Components of the oxidase are expressed in non‐phagocytes, where their function is uncretain but could be related to some signal function of superoxide. (shrink)

U.S. Department of Health and Human Services (HHS) federal regulations pertaining to the protection of human subjects at Title 45 of the Code of Federal Regulations, Part 46, Subpart A (“the Common Rule”), refer to the need for special precautions when persons characterized as vulnerable are used as human research subjects. Under the Common Rule, persons considered “vulnerablae” are those who are likely to be susceptible to coercive or undue influence; the term “vulnerable” includes “children, prisoners, pregnant women, mentally disabled (...) persons,” or those who are “economically or educationally disadvantaged.” The need for special precautions with some of these vulnerable persons in the context of research has long been addressed by both mandatory additional protections found in Subparts B through D of 45 C.F.R. pt. 46 (that arenot, coincidentally, part of the Common Rule) and additional detailed guidance documents provided by HHS or its components to investigators and their respective institutions. (shrink)

Routledge is now re-issuing this prestigious series of 204 volumes originally published between 1910 and 1965. The titles include works by key figures such as C.G. Jung, Sigmund Freud, Jean Piaget, Otto Rank, James Hillman, Erich Fromm, Karen Horney and Susan Isaacs. Each volume is available on its own, as part of a themed mini-set, or as part of a specially-priced 204-volume set.

Heidegger’s position on the relation of the holy and the divine to the truth of being and the possible signification of the word ‘God’ is internally related to his understanding of truth as a double-concealment. Formal indication holds the key to this internal relation. The question of how the deity enters into philosophy forms the framework within which these thoughts are developed.

We discuss our surgical philosophy concerning the subtle interplay between the size of the surgical margin taken and the resultant morbidity from ablative oncological. procedures, which is ever more evident in the treatment of head and neck malignancy. The extent of tissue resection is determined by the "trade off" between cancer control and the perioperative, functional and aesthetic morbidity and mortality of the surgery. We also discuss our dilemmas concerning recent minimally invasive endoscopic microsurgical. techniques for the trans-oral laser removal. (...) or co-ablation of aero-digestive tract tumours, which result in a minimal. surgical margin of oncological clearance. By a process of inductive argument as to the nature of the surgical margin, we consider whether the risks of taking a lesser margin with adjuvant therapy is justified by the attendant gain in reduced surgical morbidity and the possible costs in tumour control. (c) 2006 Elsevier Ltd. All rights reserved. (shrink)

In what is clearly an important development related to research integrity and the protection of human research subjects, the U.S. government has instituted two new training requirements as a condition of receiving federal financial support. First, the National Institutes of Health is requiring, as a condition of funding, that key research personnel involved in human subject research complete education “in the protection of human subjects.” Evidence that key personnel have completed this training must be provided in NIH grant applications or (...) contract proposals.The NIH education policy will eventually be superseded by a more broadly applicable instructional policy for the “responsible conduct of research,” which will be promulgated by the Department of Health and Human Service's Office of Research Integrity and the Public Health Service. The instructional policy will apply to all persons engaged in any research or research training with PHS support. Presently, the only version of the policy is in draft form. (shrink)

In addition to considering sociocultural, political, economic, and ethical factors, effectively engaging socioscientific issues requires that students understand and apply scientific explanations and the nature of science. Promoting such understandings can be achieved through immersing students in authentic real-world contexts where the SSI impacts occur and teaching those students about how scientists comprehend, research, and debate those SSI. This triangulated mixed-methods investigation explored how 60 secondary students’ trophic cascade explanations changed through their experiencing place-based SSI instruction focused on the Yellowstone (...) wolf reintroduction, including scientists’ work and debates regarding that issue. Furthermore, this investigation determined the association between the students’ post place-based SSI instruction trophic cascade explanations and NOS views. Findings from this investigation demonstrate that through the place-based SSI instruction students’ trophic cascade explanations became significantly more accurate and complex and included more ecological causal mechanisms. Also, significant and moderate to moderately large correlations were found between the accuracy and contextualization of students’ post place-based SSI instruction NOS views and the complexity of their trophic cascade explanations. Empirical substantiation of the association between the complexity of students’ scientific explanations and their NOS views responds to an understudied area in the science education research. It also encourages the consideration of several implications, drawn from this investigation’s findings and others’ prior work, which include the need for NOS to be forefront alongside and in connection with science content in curricular standards and through instruction focused on relevant and authentic place-based SSI. (shrink)

The increasing availability of passively observed data has yielded a growing interest in “data fusion” methods, which involve merging data from observational and experimental sources to draw causal conclusions. Such methods often require a precarious tradeoff between the unknown bias in the observational dataset and the often-large variance in the experimental dataset. We propose an alternative approach, which avoids this tradeoff: rather than using observational data for inference, we use it to design a more efficient experiment. We consider the case (...) of a stratified experiment with a binary outcome and suppose pilot estimates for the stratum potential outcome variances can be obtained from the observational study. We extend existing results to generate confidence sets for these variances, while accounting for the possibility of unmeasured confounding. Then, we pose the experimental design problem as a regret minimization problem subject to the constraints imposed by our confidence sets. We show that this problem can be converted into a concave maximization and solved using conventional methods. Finally, we demonstrate the practical utility of our methods using data from the Women’s Health Initiative. (shrink)

During the past decade and a half, the field of family literacy has gone from its infancy on the educational periphery toward a position closer to the mainstream. Characteristic ofthe field’s growth is the nation’s largest endeavor in family literacy, the federal Even Start program, which began from scratch in the late 1980s and now claims more than 800 local programs in 50 states and Puerto Rico.Despite several national evaluations of Even Start, no comprehensive study in the family literacy literature (...) specifically focuses on this quarter-billion dollar program’s attempts to measure the progress of its adult students. Accordingly, this study sought to discover the ways in which adult assessment is performed by Even Start programs.This essay emphasizes critical thinking with regards to assessment in Even Start programs Critical thought and reflection drive the exploration of several themes in the study’s data that carry itnplications for the families served by Even Start. These implications, gleaned from what Brookfield (1987) calls “reflective skepticism” and careful study of the data, bring the survey’s numbers to life and ultimately yield useful, potentially program-enhancing information.The article offers background on family literacy and Even Start programs and briefly illustrates the study’s methodology. Then follows a discourse that views the study’s findings through the lens of critical thought, drawing meaning from selected findings that contain repercussions for Even Start families. The piece concludes with recommendations for the improvement of Even Start programs through enhanced assessment and continued study. (shrink)

In this article, we propose the Fair Priority Model for COVID-19 vaccine distribution, and emphasize three fundamental values we believe should be considered when distributing a COVID-19 vaccine among countries: Benefiting people and limiting harm, prioritizing the disadvantaged, and equal moral concern for all individuals. The Priority Model addresses these values by focusing on mitigating three types of harms caused by COVID-19: death and permanent organ damage, indirect health consequences, such as health care system strain and stress, as well as (...) economic destruction. It proposes proceeding in three phases: the first addresses premature death, the second long-term health issues and economic harms, and the third aims to contain viral transmission fully and restore pre-pandemic activity. -/- To those who may deem an ethical framework irrelevant because of the belief that many countries will pursue "vaccine nationalism," we argue such a framework still has broad relevance. Reasonable national partiality would permit countries to focus on vaccine distribution within their borders up until the rate of transmission is below 1, at which point there would not be sufficient vaccine-preventable harm to justify retaining a vaccine. When a government reaches the limit of national partiality, it should release vaccines for other countries. -/- We also argue against two other recent proposals. Distributing a vaccine proportional to a country's population mistakenly assumes that equality requires treating differently situated countries identically. Prioritizing countries according to the number of front-line health care workers, the proportion of the population over 65, and the number of people with comorbidities within each country may exacerbate disadvantage and end up giving the vaccine in large part to wealthy nations. (shrink)