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Andrew Stirling, Josie Coburn
The purpose of this essay is to critically review the design of methods for ethically robust forms of technology appraisal in the regulation of research and innovation in synthetic biology. It will focus, in particular, on the extent to which cost-benefit analysis offers a basis for informing decisions about which technological pathways to pursue and which to discourage. A further goal is to consider what (if anything) the precautionary principle might offer in enabling better decisions. And this, in turn, raises questions about why mention of precaution can excite accusations of unscientific bias or irrational, "anti-innovation" extremism...
January 2018: Hastings Center Report
Jun Hosogi, Rui Ohashi, Hiroshi Maeda, Kazuhiro Fujita, Junko Ushiki, Takashi Kuwabara, Yorihiro Yamamoto, Toru Imamura
We previously reported that KW-2449, (E)-1-{4-[2-(1H-Indazol-3-yl)vinyl]benzoyl}piperazine, a novel multikinase inhibitor developed for the treatment of leukemia patients, was oxidized to an iminium ion intermediate by monoamine oxidase B (MAO-B) and then converted to its oxo-piperazine form (M1) by aldehyde oxidase (AO). However, we found that the significant decrease in the pharmacologically active metabolite M1 following repeated administration of KW-2449 in primates might hamper the effectiveness of the drug...
February 16, 2018: Biopharmaceutics & Drug Disposition
Sandro Claudio Lera, Didier Sornette
A model that combines economic growth rate fluctuations at the microscopic and macroscopic levels is presented. At the microscopic level, firms are growing at different rates while also being exposed to idiosyncratic shocks at the firm and sector levels. We describe such fluctuations as independent Lévy-stable fluctuations, varying over multiple orders of magnitude. These fluctuations are aggregated and measured at the macroscopic level in averaged economic output quantities such as GDP. A fundamental question is thereby to what extent individual firm size fluctuations can have a noticeable impact on the overall economy...
January 2018: Physical Review. E
Robert Hosfield, James Cole, John McNabb
Corbey et al. (2016) propose that the Acheulean handaxe was, at least in part, under genetic control. An alternative perspective is offered here, focusing on the nature of the Acheulean handaxe and the archaeological record, and re-emphasizing their status as cultural artefacts. This is based on four main arguments challenging the proposals of Corbey et al. Firstly, handaxes do not have to track environmental variation to be a cultural artefact, given their role as a hand-held butchery knife or multi-purpose tool...
January 2018: Evolutionary Anthropology
Astrid M L Kappers
Many studies have already shown that a large idiosyncratic orientation difference is needed to perceive two bars that are far apart as haptically parallel. There exist also strong indications that if such bars are imagined to be minute hands of clocks, errors made in clock time estimates and clock time settings are much smaller. The current study investigated this seemingly discrepancy. Participants partook in three experiments: parallel setting, clock time estimate and clock time setting, in this order. As the individual parallel settings were used in the subsequent clock time estimate experiment, and the estimated clock times in the clock time setting experiment, the deviations could be compared directly...
February 14, 2018: Scientific Reports
Patrick Gary Rose, Robert Seabury, Gregory Cwikla
Dofetilide's hepatotoxicity is not well described. In this case report, we describe acute hepatocellular jaundice related to dofetilide use in a 33-year-old male being treated for atrial fibrillation. Both viral and ischemic causes of hepatocellular damage were ruled out as unlikely in this case. This case report outlines a rare yet probable report of idiosyncratic dofetilide-induced liver injury.
February 2018: Hospital Pharmacy
Laia Sans-Atxer, Dominique Joly
Standard of care therapies for autosomal dominant polycystic kidney disease (ADPKD) may limit morbidity and mortality due to disease-related complications, but they do not delay disease progression. Tolvaptan, a selective vasopressin V2 receptor antagonist, delays the increase in kidney volume (a surrogate marker for disease progression), slows the decline in renal function, and reduces pain in ADPKD patients with relatively preserved renal function. The most common adverse events of tolvaptan are linked to its aquaretic effect, and rare cases of idiosyncratic hepatitis were observed...
2018: International Journal of Nephrology and Renovascular Disease
Lawrence P L Iu, Michelle C Y Fan, Wai-Ching Lam, Ian Y H Wong
BACKGROUND: Cytomegalovirus (CMV) retinitis is an opportunistic infection that primarily affects immunocompromised individuals. Intravitreal ganciclovir injection monotherapy or in combination with systemic anti-CMV therapy are effective treatments for CMV retinitis. Crystallization of ganciclovir after intravitreal injection is extremely rare. Only two cases had been reported in literature. Crystallization in only one eye after bilateral injections had not been reported before. We hereby report a case of intraocular ganciclovir crystallization in one eye after bilateral intravitreal injections, and repeated crystallization in the same eye after repeated injections...
February 9, 2018: BMC Ophthalmology
Joachim Sicking, Thomas Guhr, Rudi Schäfer
We consider the problem of concurrent portfolio losses in two non-overlapping credit portfolios. In order to explore the full statistical dependence structure of such portfolio losses, we estimate their empirical pairwise copulas. Instead of a Gaussian dependence, we typically find a strong asymmetry in the copulas. Concurrent large portfolio losses are much more likely than small ones. Studying the dependences of these losses as a function of portfolio size, we moreover reveal that not only large portfolios of thousands of contracts, but also medium-sized and small ones with only a few dozens of contracts exhibit notable portfolio loss correlations...
2018: PloS One
Joseph Bernstein, James J Bernstein, Samir Mehta, Eric L Hume, Mara L Schenker, Jaimo Ahn
INTRODUCTION: The American College of Surgeons' Statements on Principles requires attending surgeons to be present for the "key parts" of surgical procedures, but the term is not defined. The research question addressed in this study is whether a functional definition of the critical or key steps of common orthopaedic surgical procedures can be reliably constructed. We used the examples of hip and knee arthroplasty because these procedures are highly structured and divisible into distinct subroutines...
February 15, 2018: Journal of the American Academy of Orthopaedic Surgeons
Andrey G Tereshchenkov, Malgorzata Dobosz-Bartoszek, Ilya A Osterman, James Marks, Vasilina A Sergeeva, Pavel Kasatsky, Ekaterina S Komarova, Andrey A Stavrianidi, Igor A Rodin, Andrey L Konevega, Petr V Sergiev, Natalia V Sumbatyan, Alexander S Mankin, Alexey A Bogdanov, Yury S Polikanov
Antibiotic chloramphenicol (CHL) binds with a moderate affinity at the peptidyl transferase center of the bacterial ribosome and inhibits peptide bond formation. As an approach for modifying and potentially improving properties of this inhibitor, we explored ribosome binding and inhibitory activity of a number of amino-acid analogues of CHL. The L-histidyl analogue binds to the ribosome with the affinity exceeding that of CHL by 10 fold. Several of the newly synthesized analogues were able to inhibit protein synthesis and exhibited the mode of action that was distinct from the action of CHL...
February 1, 2018: Journal of Molecular Biology
Dwayne Van Eerd, Era Mae Ferron, Teresa D'Elia, Derek Morgan, Frances Ziesmann, Benjamin C Amick
BACKGROUND: Long-term care (LTC) workers are at significant risk for occupational-related injuries. Our objective was to evaluate the implementation process of a participatory change program to reduce risk. METHODS: A process evaluation was conducted in three LTC sites using a qualitative approach employing structured interviews, consultant logs and a focus group. RESULTS: Findings revealed recruitment/reach themes of being "voluntold", using established methods, and challenges related to work schedules...
April 2018: Applied Ergonomics
Justin Barr
In the first half of the twentieth century, the training of American surgeons changed from an idiosyncratic, often isolated venture to a standardized, regulated, and mandated regimen in the form of the surgical residency. Over the three critical decades between 1930 and 1960, these residencies developed from an extraordinary, unique opportunity for a few leading practitioners to a widespread, uniform requirement. This article explores the transformation of surgical education in the United States, focusing on the standardization and dissemination of residencies during this key period...
February 2, 2018: Journal of the History of Medicine and Allied Sciences
Nipun Verma, Pramod Kumar, Suvradeep Mitra, Sunil Taneja, Sahajal Dhooria, Ashim Das, Ajay Duseja, Radha Krishan Dhiman, Yogesh Chawla
Idiosyncratic drug-induced liver injury (DILI) is ranked among the top most common etiologies of acute liver failure (ALF). It carries poor transplant-free survival. Pirfenidone is an anti-inflammatory and antifibrotic drug that is commonly used for the treatment of idiopathic pulmonary fibrosis (IPF). Hepatotoxicity due to pirfenidone is rare and generally manifests as a mild rise in serum aminotransferases. In this mini-review, we report an unusual case of idiosyncratic DILI due to pirfenidone presenting as ALF, with emphasis on the definition, classification, diagnostic criteria, histopathology, molecular markers, and treatment options for DILI and related ALF...
February 2018: Hepatology communications
Yo-Ichi Yamashita, Katsunori Imai, Kosuke Mima, Shigeki Nakagawa, Daisuke Hashimoto, Akira Chikamoto, Hideo Baba
Idiosyncratic drug-induced liver injury (iDILI) is a rare adverse drug reaction that occasionally leads to acute liver failure or even death. An aging population that uses more drugs, a constant influx of newly developed drugs, and a growing risk from herbal and dietary supplements of uncertain quality can lead to an increase in iDILI. Antimicrobials, central nervous system agents, and herbal and dietary supplements are the most common causes of iDILI in developed countries. iDILI is still a diagnosis of exclusion, and thus careful history taking and thorough work-ups for competing etiologies, such as acute viral hepatitis, autoimmune hepatitis, and others, are essential...
August 2017: Hepatology communications
Yoh Zen, Matthew M Yeh
The adverse effects of immune checkpoint inhibitors in various organs may be attributed to immune-mediated processes triggered by disrupted self-tolerance; however, it remains unclear whether they are similar or dissimilar to classic organ-specific autoimmune diseases. The present study aimed to compare clinicopathologic features between checkpoint inhibitor-induced liver injury and acutely presenting autoimmune hepatitis or idiosyncratic drug-induced liver injury. Seven patients treated with nivolumab (n = 5) or ipilimumab (n = 2) presented with liver dysfunction a median of 41 days (range 21-120) after the initiation of immunotherapy...
February 5, 2018: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
George Van Den Driessche, Denis Fourches
BACKGROUND: Idiosyncratic adverse drug reactions have been linked to a drug's ability to bind with a human leukocyte antigen (HLA) protein. However, due to the thousands of HLA variants and limited structural data for drug-HLA complexes, predicting a specific drug-HLA combination represents a significant challenge. Recently, we investigated the binding mode of abacavir with the HLA-B*57:01 variant using molecular docking. Herein, we developed a new ensemble screening workflow involving three X-ray crystal derived docking procedures to screen the DrugBank database and identify potentially HLA-B*57:01 liable drugs...
January 30, 2018: Journal of Cheminformatics
Guilian Zhang, Tao Li, Heying Wang, Jiao Liu
RELATION: Iodide mumps is an uncommon condition, induced by iodide-containing contrast, and is characterized by a rapid, painless enlargement of the bilateral or unilateral salivary gland. At present, the pathogenesis of iodide mumps is not yet clear. It may be related to an idiosyncratic reaction, a toxic accumulation of iodine in the gland duct, or renal function damage leading to an iodine excretion disorder. This paper reports the clinical manifestations and magnetic resonance imaging results of one case of iodide mumps, which occurred after digital subtraction angiography...
November 2017: Medicine (Baltimore)
Giulio Giustarini, Laura Kruijssen, Manon van Roest, Rob Bleumink, Richard J Weaver, Marianne Bol-Schoenmakers, Joost Smit, Raymond Pieters
Idiosyncratic drug-induced liver injury (iDILI) has a poorly understood pathogenesis. However, iDILI is often associated with inflammatory stress signals in human patients as well as animal models. Tumor necrosis factor (TNF) and neutrophils play a key role in onset of trovafloxacin (TVX)-induced iDILI, but the exact role of neutrophils and other leukocytes remains to be defined. We therefore set out to study the kinetics of immunological changes during the development of TVX-induced iDILI in the established murine model of acute liver injury induced by administration of TVX and TNF...
January 26, 2018: Journal of Applied Toxicology: JAT
Emily R Thompson, Sarah A Hosgood, Michael L Nicholson, Colin H Wilson
BACKGROUND: Kidney transplantation is the treatment of choice for patients with end-stage kidney disease. In a previous review we concluded that the routine use of ureteric stents in kidney transplantation reduces the incidence of major urological complications (MUC). Unfortunately, this reduction appears to lead to a concomitant rise in urinary tract infections (UTI). For kidney recipients UTI is now the commonest post-transplant complication. This represents a considerable risk to the immunosuppressed transplant recipient, particularly in the era of increased immunologically challenging transplants...
January 29, 2018: Cochrane Database of Systematic Reviews
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