Search

We present an implementation of the Yennie--\-Frautschi--\-Suura (YFS) scheme for the all-orders resummation of logarithms from the emission of soft real and virtual photons in processes that are critical for future lepton colliders. They include, in particular, $e^-e^+\to f\bar{f}$ and $e^-e^+\to W^-W^+$, where we validate the results of our implementation, improved with fixed-order corrections, with those obtained from the most precise calculations. We also show, for the first time, results for the Higgs-Strahlungs process, $e^-e^+\to ZH$, in YFS resummation including fixed-order improvements up to order $\alpha^3L^3$., Comment: Submission to SciPost. 25 pages, 9 figures. v2 Minor corrections

Diarrhoea remains one of the leading causes of childhood mortality globally. Recent epidemiological studies conducted in low-middle income countries (LMICs) identified Shigella spp. as the first and second most predominant agent of dysentery and moderate diarrhoea, respectively. Antimicrobial therapy is often necessary for Shigella infections; however, we are reaching a crisis point with efficacious antimicrobials. The rapid emergence of resistance against existing antimicrobials in Shigella spp. poses a serious global health problem. Here, aiming to identify alternative antimicrobial chemicals with activity against multi-drug resistant (MDR) Shigella, we initiated a collaborative academia-industry drug discovery project, applying high throughput phenotypic screening across broad chemical diversity. We identified several suitable compounds with antibacterial activity against Shigella. These compounds included the oral carbapenem tebipenem, which was found to be highly potent against broadly susceptible Shigella and contemporary MDR variants. Additional in vitro screening demonstrated that tebipenem had activity against a wide range of other non-Shigella enteric bacteria. Cognisant of the risk for the development of resistance against monotherapy, we identified synergistic behaviour of two different drug combinations incorporating tebipenem. The orally bioavailable prodrug (tebipenem pivoxil) effectively cleared the gut of infecting organisms when administered in physiological doses to Shigella-infected mice and gnotobiotic piglets. Our data highlight the utility of broad compound screening for tackling the emerging antimicrobial resistance crisis and shows that tebipenem pivoxil (licenced for paediatric respiratory tract infections in Japan) could be repurposed as an effective treatment for severe diarrhoea caused by MDR Shigella and other enteric pathogens in LMICs.

This paper argues that Philippe Van Parijs’s original arguments for an unconditional basic income, while representing a distinctive proposal, rest on flawed assumptions. A contrast is drawn between Rawls’s anti-capitalism and Van Parijs’s defence of an optimised capitalism. His UBI proposal leaves in place the social power of the rentier-investor class and undermines effective political agency. This poses a problem for achieving a sufficient level of a UBI given its grounding on gifts and rents. The innovation of treating labour market rents as the source of a UBI involves a tension between full employment policy and that which a liberal state may promote. A UBI is also likely to be inflationary in a self-stultifying way. An alternative view, drawing on the work of Keynes, Kalecki and Minsky, is developed. Ultimately Van Parijs’s “Left Rawlsianism” collapses into Rawls’s anti-capitalist conception of a property-owning democracy.

Background People live socially complex lives and have different health care needs influenced by socio-economic factors such as deprivation, unemployment, and poor housing. Lack of access to community based social care results in people seeking social support from health care services. This study explores the Life Rooms as a social prescribing model addressing the social determinants of mental health by providing support and access to resources in a local community setting. With an aim to identify key elements that contribute toward enhancing the effectiveness of the Life Rooms social prescribing approach. Methods Data were obtained through six semi-structured focus groups with mental health service users from two locations in the North West of the UK. Postcode data was collected to generate an Index for Multiple Deprivation (IMD) score, to understand their socio-economic background. Data were analysed using thematic analysis. Results A total of 18 participants took part in the study. The majority of participants came from disadvantaged backgrounds; 14 participants measuring 3 and below in terms of overall IMD scores and 9 participants belonged to the poorest decile (IMD score = 1). Participants reported on different elements of the Life Rooms which they found as an effective approach to care. Four main themes emerged from the data: 1) social belonging: being able to just ‘be’ 2) resourceful and accessible; 3) social inclusion and connectedness; and 4) moving forward: self-development and independence. Conclusion Findings support the need and benefit social prescribing to improve mental health wellbeing and reduce the burden of mental illness.

William Edmundson defines a neo-liberal view as one which is liberal but does not guarantee the fair value of political liberty. The advantage of the view is putatively higher overall welfare. This paper questions whether this trade off is genuine and argues that it is not.

Objective: We propose a computational framework for integrating diverse patient measurements into an aggregate health score and applying it to patient stability prediction. Materials and Methods: We mapped retrospective patient data from the Multiparameter Intelligent Monitoring in Intensive Care (MIMIC) II clinical database into a discrete multidimensional space, which was searched for measurement combinations and trends relevant to patient outcomes of interest. Patient trajectories through this space were then used to make outcome predictions. As a case study, we built AutoTriage, a patient stability prediction tool to be used for discharge recommendation. Results: AutoTriage correctly identified 3 times as many stabilizing patients as existing tools and achieved an accuracy of 92.9% (95% CI: 91.6–93.9%), while maintaining 94.5% specificity. Analysis of AutoTriage parameters revealed that interdependencies between risk factors comprised the majority of each patient stability score. Discussion: AutoTriage demonstrated an improvement in the sensitivity of existing stability prediction tools, while considering patient safety upon discharge. The relative contributions of risk factors indicated that time-series trends and measurement interdependencies are most important to stability prediction. Conclusion: Our results motivate the application of multidimensional analysis to other clinical problems and highlight the importance of risk factor trends and interdependencies in outcome prediction.

This invited journal article discusses the arguments of Thomas Nagel's latest and most controversial book, Mind and Cosmos. It contextualises its arguments in Nagel's overall approach to philosophy and considers early criticism of the book and how it may be addressed.

No Abstract

This paper considers an argument that justice as fairness requires liberal socialism as opposed to a property-owning democracy. It analyses the arguments for departing from Rawls’s principled agnosticism over the choice between liberal market socialism and property owning democracy. It questions the extension of Rawls’s fair value guarantee for the political liberties to all liberty and suggests an alternative interpretation of the kind of predistributive egalitarianism represented by a property-owning democracy.

ObjectiveTo develop high-performance early sepsis prediction technology for the general patient population. MethodsRetrospective analysis of adult patients admitted to the intensive care unit (from the MIMIC II dataset) who were not septic at the time of admission. ResultsA sepsis early warning algorithm, InSight, was developed and applied to the prediction of sepsis up to three hours prior to a patient's first five hour Systemic Inflammatory Response Syndrome (SIRS) episode. When applied to a never-before-seen set of test patients, InSight predictions demonstrated a sensitivity of 0.90 (95% CI: 0.89-0.91) and a specificity of 0.81 (95% CI: 0.80-0.82), exceeding or rivaling that of existing biomarker detection methods. Across predictive times up to three hours before a sustained SIRS event, InSight maintained an average area under the ROC curve of 0.83 (95% CI: 0.80-0.86). Analysis of patient sepsis risk showed that contributions from the coevolution of multiple risk factors were more important than the contributions from isolated individual risk factors when making predictions further in advance. ConclusionsSepsis can be predicted at least three hours in advance of onset of the first five hour SIRS episode, using only nine commonly available vital signs, with better performance than methods in standard practice today. High-order correlations of vital sign measurements are key to this prediction, which improves the likelihood of early identification of at-risk patients.

Introduction:\ud \ud Radiotherapy is often used to treat pain in malignant pleural mesothelioma (MPM), although there is limited evidence to support this. The aim of this trial was to assess the role of radiotherapy for the treatment of pain in MPM.\ud \ud Methods:\ud \ud A multicentre, single arm phase II trial was conducted. Eligible patients fulfilled the following criteria: pathological or radiological diagnosis of MPM; pain secondary to MPM; radiotherapy indicated for pain control; and more than 18 years of age. Patients had assessments of pain and other symptoms at baseline and then received 20 Gy in five daily fractions. Key follow-up points were 5 and 12 weeks posttreatment. The primary end point measure was assessment of pain at the site of radiotherapy at 5 weeks. Secondary end points included effects on quality of life, breathlessness, fatigue, mood, toxicity, and the radiological response.\ud \ud Results:\ud \ud Forty patients were recruited from three UK oncology centers. Fourteen patients had a clinically meaningful improvement in their pain 5 weeks post radiotherapy (intention to treat), with five patients having a complete improvement. On the basis of a complete case analysis of the 30 patients assessable at week 5, 47% (confidence intervals, 28.3–65.7) of patients alive at week 5 had an improvement in their pain. There was no improvement in other key symptoms or quality of life.\ud \ud Conclusions:\ud \ud Radiotherapy for pain control in MPM is an effective treatment in a proportion of patients. Future studies examining differing radiotherapy regimens with a view to improving response rates are warranted.

Political realism criticises the putative abstraction, foundationalism and neglect of the agonistic dimension of political practice in the work of John Rawls. This paper argues that had Rawls not fully specified the implementation of his theory of justice in one particular form of political economy then he would be vulnerable to a realist critique. But he did present such an implementation: a property-owning democracy. An appreciation of Rawls s specificationist method undercuts the realist critique of his conception of justice as fairness.

BACKGROUND Surgical resection is the recognised treatment of choice for patients with stage I or II non-small cell lung cancer (NSCLC). In the UK surgical resection rates have remained far lower ( 20%), despite the recent introduction of fast access investigation units. It remains unclear therefore why UK surgical resection rates lag so far behind those of other countries. METHODS A new quick access two stop investigation service was established at Papworth in November 1995 to investigate all patients presenting to any of three surrounding health districts with suspected lung cancer. Once staging was complete, all patients with confirmed lung cancer were reviewed by a multidisciplinary team which included an oncologist and a thoracic surgeon. Time from presentation to definitive treatment and surgical resection rates were reviewed. RESULTS Two hundred and nine (76%) of a total of 275 consecutive patients investigated had confirmed lung cancer (28 small cell, 181 non-small cell). Of the remainder, eight patients (2%) had metastatic disease, four (1%) had other thoracic malignancy (thymoma, mesothelioma), four patients (1%) had benign thoracic tumours, and 50 (18%) had other non-malignant diseases. Of the 181 patients with non-small cell primary lung cancer, 47 (25%) underwent successful surgical resection, of whom 59% had stage I and 21% stage II disease. The failed thoracotomy rate was 11%. Median time from presentation at the peripheral clinic to surgical resection was 5 weeks (range 1–13). CONCLUSION Quick access investigation, high histological confirmation rates, routine CT scanning, and review of every patient with confirmed lung cancer by a thoracic surgeon led to a substantial increase in the successful surgical resection rate. These results support the growing concern that many patients with operable tumours are being denied the chance of curative surgery in our present system.

While our Y2K worries about old computers "retiring" at midnight captured the television and news media attention, a more significant "old age" phenomenon snuck onto the scene with hardly a headline: the dawn of the age of the aged. (1) The over burdened health care system will face a worldwide wave of retirees who will live longer, cost more to treat, and demand new goods and services to help them stay healthy, active, and independent. Research in persuasive technologies and the associated usage of a computing system, device, or application intentionally designed to change a person's attitude or behavior in a predetermined way is showing the potential to assist in improving healthy living, reduce the costs on the health care system, and allow the aged to maintain a more independent life. This article gives a deeper insight into the evolution of persuasive technologies and presents a framework that can guide a researcher or practitioner in comprehending more effectively the work being done in this novel research field. It also provides categories of domains within health care in which these technologies are used and surveys exemplars from published literature. The article's goal is to provide greater understanding by addressing the challenges that lie ahead for all key stakeholders that design and/or use persuasive technologies in health care.

Background Tuberculous infections in patients with hematological disorders and hematopoietic stem cell transplant vary in incidence, complications and response to treatment. Methods and materials A retrospective study of patients with various benign and malignant hematological disorders and recipients of hematopoietic stem cell transplant who were treated at Riyadh Armed Forces Hospital, Saudi Arabia between January 1991 and December 2002 and who developed tuberculous infections was conducted. Results Tuberculous infections occurred in eighteen patients with hematological disorders and hematopoietic stem cell transplant. The main associated factors were: reduced immunity due to the primary hematological disorder, age more than 50 years and the administration of cytotoxic chemotherapy, steroids or radiotherapy. These infections frequently involved the lungs and predominantly occurred in males and in patients with chronic myeloproliferative disorders, myelodysplastic syndrome and acute myeloid leukemia. In patients treated with intravenous cytotoxic chemotherapy, tuberculous infections tended to occur earlier and also tended to be more disseminated compared to infections occurring in patients treated with oral chemotherapy. Anti-tuberculous treatment was given to 16 patients and it was successful in 15 of these patients. Conclusion Tuberculous infections cause significant morbidity and mortality in patients with various hematological disorders and in recipients of hematopoietic stem cell transplant. The early administration of anti-tuberculous therapy and compliance with drug treatment are associated with successful outcomes while delayed management, drug resistance and the presence of miliary infections are associated with poor prognosis and high mortality rates.

Empire of Sleep is an interactive virtual environment installation viewed in stereoscopic 3D on a large rear projection screen. Participants interact using a hand-held camera to take photographs of the scene, triggering the virtual camera to move to new points of interest. A group of surreal-looking figures, clothed in early 20th century bathing suits, are scattered about on several isolated sand bars somewhere on an open and calm body of water. They first appear as if there for recreation, but there is a pensive mood, as if some unusual event is taking place unknown to the viewer.

Horace Judson’s new historical commentary, The great betrayal: fraud in science, is a stimulating and thoughtful book for readers interested in science, publication ethics, and research misconduct. He writes with his typical flair, drawing on interviews with famous scientists. His premise is that scrutiny of the nature of fraud and other misconduct will reach to the pulse of what the sciences are and what scientists do. The book offers little, however, for readers whose principal interest is clinical research. Judson is a respected modern historian of science, perhaps best known for his history of molecular biology, The eighth day of creation: makers of the revolution in biology (S1). Most of the citations in this new book precede 1996, except for references to stories of misconduct among businessmen, historians, and journalists that have filled the press since 2000. In fact, the 35 “Recent Cases” are almost the same set of cases (late 1800s-late 1900s) previously described in Betrayers of the truth (S2) and False prophets (S3), neither of which is referenced in this new book. The newest cases cited in Judson’s book involve major scandals in a German and an American laboratory, heavily covered in the recent science press. Nonetheless, Judson does profitably draw on the classical cases noted in these earlier books, drawing analogies with cases of scientific fraud during the past decade. Also missing is a discussion of the findings of scientific misconduct in clinical cases made between 1992 and 2004 by the Office of Research Integrity (ORI), part of the United States Public Health Service (PHS) in the Department of Health and Human Services (HHS), which would have been of interest to JCI readers. About 40 of the 150 findings have involved clinical or related nonclinical research with human subjects (S4, S5). The only such case described by Judson is a clinical trial on the use of mastectomy versus lumpectomy to treat breast cancer, conducted at St. Luc’s Hospital, Montreal, and coordinated by the University of Pittsburgh, in which the investigator falsified records to make more patients eligible for the study. However, Judson includes a long, solid chapter on “The Baltimore Affair,” dealing with the allegations of falsification of data on the part of a Massachusetts Institute of Technology scientist and the overturning of the ORI’s 1994 finding against her in 1996 by the HHS appeals board. This case had been discussed in detail in 2 previous books, Science on trial: the whistle blower, the accused, and the Nobel laureate (S6), and The Baltimore case: a trial of politics, science, and character (S7), which also are not cited in Judson’s new book. To his credit, Judson personally reviewed records and interviewed witnesses, describing both in much the same style as he used in The eighth day of creation (S1), which makes the new book a fascinating read. Also striking is Judson’s initial chapter, “A Culture of Fraud,” describing public cases of fraud by businessmen, social scientists, clergy, and others. The conclusion is obvious: a few scientists are likely no better and no worse than the few members of the general population who are crooks and charlatans. His epilogue includes a plea to restore high standards to the conduct of scientific research. Several interesting chapters, titled “The problems of peer review,” “Authorship, ownership: problems of credit, plagiarism, and intellectual property,” and “Laboratory to law: the problems of institutions when misconduct is charged” will be enlightening and challenging to readers who deal with such problems and try to teach students how to avoid them in the responsible conduct of research. Judson examines self-governance in science and whether officials, editors, and peers can deal effectively, without conflicts of interest, with deviations from appropriate standards in conducting, reporting, and reviewing research. He focuses as well on the important role of whistle-blowers or complainants in challenging some reports for reasons of integrity. Judson’s book is accurate and timely, in that in 2000, the US Office of Science and Technology developed a uniform policy for dealing with allegations and investigations for all federal agencies. Each agency has since been publishing new policies or regulations; the revised HHS regulation should soon be finalized. In response, universities, research hospitals, and institutes are updating their policies and procedures, at least to address the federal government’s new definition: “Research misconduct is defined as fabrication, falsification, or plagiarism in proposing, performing, or reviewing research, or in reporting research results . . . [A] finding . . . requires that: there be a significant departure from accepted practices of the relevant research community; and the misconduct be committed intentionally, or knowingly, or recklessly; and the allegation be proven by a preponderance of evidence.” Judson has provided a nice history of the public debate over this definition through the 1990s and the creation of the ORI. His book accomplishes its goal, to describe and analyze the history of fraud in science and its impact on the scientific and public communities, and he examines what contributes to fraud. The book is recommended to readers interested in fundamental research ethics and their historical and political context in the new millennium. This review represents the personal views of the author and not necessarily any position of the ORI, PHS, or HHS. References are available online with this article; doi:10.1172/JCI200524343DS1.