bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ranking prescribed pharmaceuticals in terms of environmental risk: Inclusion of hospital data and the importance of regular review
Authors: Helwig Karin , Hunter Colin , McNaughtan Moyra , Roberts Joanne , Pahl Ole 
Published: November 2015

Abstract

A newly available dataset on pharmaceuticals used in Scottish hospitals enabled an environmental risk assessment that includes hospital consumption of pharmaceuticals, as previous United Kingdom rankings have been based on community prescriptions only. Although health and the environment are devolved issues for the Scottish government, it is merited to consider a Scottish ranking separately; regional differentiation is particularly relevant in the spatial context of the European Commission's Water Framework Directive. Nine pharmaceuticals are identified as having a risk quotient greater than 1. Four of these, the antibacterials piperacillin, tazobactam, flucloxacillin, and ciprofloxacin, had high hospital contributions and had not been highlighted previously in rankings based on community prescriptions. Some drugs with a risk quotient &lt; 0.1 are used almost exclusively in hospitals and could be more concentrated near effluents carrying hospital wastewater, where they may be of local concern. Although treating hospital effluents separately is a policy option, specifically including hospital consumption is important. Continually increasing the availability of ecotoxicological data and trends in consumption further contributes to a substantially different prioritization than in previous rankings. This leads the authors to conclude that regular review of risk is necessary. Environ Toxicol Chem 2016;35:1043–1050. © 2015 SETAC
Concentrations of levonorgestrel and ethinylestradiol in wastewater effluents: Is the progestin also cause for concern?
Authors: King Olivia C. , van de Merwe Jason P. , McDonald James A. , Leusch Frederic D.L. 
Published: November 2015

Abstract

Synthetic hormones have been widely reported in treated sewage effluents, and consequently receiving aquatic environments. Ethinylestradiol (EE2) is a potent synthetic estrogen commonly used in conjunction with levonorgestrel in oral contraceptive pills. Both EE2 and levonorgestrel have been identified in the aquatic environment, but although there is a significant amount of literature on EE2, there is much less information on levonorgestrel. Using Australian prescription data as well as excretion and predicted wastewater removal rates, the concentrations of EE2 and levonorgestrel in Australian wastewater were calculated at 0.1 ng/L to 0.5 ng/L and 0.2 ng/L to 0.6 ng/L, respectively. Both compounds were analyzed in treated wastewater and surface water grab samples from 3 Southeast Queensland, Australia sites. The predicted no-effect concentration (PNEC) for EE2 of 0.1 ng/L was exceeded at most sites, with EE2 concentrations up to 2 ng/L in treated effluent, albeit quickly diluted to 0.1 ng/L to 0.2 ng/L in the receiving environment. A provisional PNEC for levonorgestrel of 0.1 ng/L derived in the present study was slightly lower than predicted effluent concentrations of 0.2 ng/L to 0.6 ng/L, indicating a potential risk of endocrine-related effects in exposed aquatic species. The detection limit for levonorgestrel in the present study was 2.5 ng/L, and all samples were below detection limit. The present study's results suggest that improvements in analytical capabilities for levonorgestrel are warranted to more accurately quantify the risk of this compound in the receiving environment. Environ Toxicol Chem 2016;35:1378–1385. © 2015 SETAC
Courage, Context, and Contemporary Health Care
Authors: Berger Jeffrey T. 
Published: November 2015

AbstractA commentary on “Must We Be Courageous?,” by Ann Hamric, John Arras, and Margaret Mohrmann, and on “Patient‐Satisfaction Surveys on a Scale of 0 to 10: Improving Health Care, or Leading It Astray?,” by Alexandra Junewicz and Stuart J. Youngner , bothin the May‐June 2015 issue.
Engineering the Brain: Ethical Issues and the Introduction of Neural Devices
Authors: Klein Eran , Brown Tim , Sample Matthew , Truitt Anjali R. , Goering Sara 
Published: November 2015

AbstractNeural engineering technologies such as implanted deep brain stimulators and brain‐computer interfaces represent exciting and potentially transformative tools for improving human health and well‐being. Yet their current use and future prospects raise a variety of ethical and philosophical concerns. Devices that alter brain function invite us to think deeply about a range of ethical concerns—identity, normality, authority, responsibility, privacy, and justice. If a device is stimulating my brain while I decide upon an action, am I still the author of the action? Does a device make the interiority of my experience accessible to others? Will the device change the way I think of myself and others think of me? Such fundamental questions arise even when a device is designed for only a relatively circumscribed purpose, such as restoring functioning via a smart prosthetic.We are part of a National Science Foundation‐funded Engineering Research Center tasked with investigating philosophical and social implications of neural engineering research and technologies. Neural devices already in clinical use, such as deep brain stimulators for Parkinson's disease or essential tremor, have spurred healthy debate about such implications. Devices currently under development—such as the BrainGate System of implanted brain sensors coupled to robotics in persons with paralysis, exoskeletons for augmented movement, transcranial do‐it‐yourself stimulators, closed‐loop brain stimulating systems, or even brain‐to‐brain interfacing—promise to extend and deepen these debates. At our center, brain‐computer interfaces are the principal focus of work. Even acknowledging that the clinical translation of neural devices and seamless integration by end users may still largely reside in the future, the potential these devices hold calls for careful early analysis. The launching of the Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative in April 2013 provides further impetus for this work.
Neural Technologies: The Ethics of Intimate Access to the Mind
Authors: Green Ronald M. 
Published: November 2015

AbstractScience fiction is fast becoming reality as scientists and engineers seek to develop new ways of directly accessing and controlling our brains through brain‐computer and even brain‐to‐brain interfaces. If such research is to receive continuing public approval and support—and not invite opposition—it must anticipate the special ethical challenges it creates. By pointing to some of the acute concerns raised by neural engineering technologies—around issues of identity, normality, authority, responsibility, privacy, and justice—Eran Klein and colleagues model and stimulate the kind of reflection that will be needed as new brain technologies are developed.And yet, as I read their informative discussion, I find myself asking even more questions. One concerns the ethical novelty of these technologies. For example, in terms of questions of identity, normality, responsibility, and authority, how different is deep brain stimulation from the potent psychiatric drugs that have been administered for decades? How different in terms of issues of liability associated with malfunction or misuse are brain‐computer interfaces from other complex devices now routinely in use? Neither ethics nor law will have to rethink things from scratch as new neural devices and capabilities are introduced: the groundwork for answering some of these questions has already been laid in a variety of fields from bioethics, to health and product liability law. Nevertheless, I conclude that there are new questions here. It is not simply the fact that neural technologies pose questions of identity, privacy, and the like but that they do so with a degree of intensity that creates qualitatively new challenges.
Pannexin-1 and P2X7-Receptor Are Required for Apoptotic Osteocytes in Fatigued Bone to Trigger RANKL Production in Neighboring Bystander Osteocytes
Authors: Cheung Wing Yee , Fritton J Christopher , Morgan Stacy Ann , Seref-Ferlengez Zeynep , Basta-Pljakic Jelena , Thi Mia M , Suadicani Sylvia O , Spray David C , Majeska Robert J , Schaffler Mitchell B 
Published: November 2015

ABSTRACT

Osteocyte apoptosis is required to induce intracortical bone remodeling after microdamage in animal models, but how apoptotic osteocytes signal neighboring “bystander” cells to initiate the remodeling process is unknown. Apoptosis has been shown to open pannexin-1 (Panx1) channels to release adenosine diphosphate (ATP) as a “find-me” signal for phagocytic cells. To address whether apoptotic osteocytes use this signaling mechanism, we adapted the rat ulnar fatigue-loading model to reproducibly introduce microdamage into mouse cortical bone and measured subsequent changes in osteocyte apoptosis, receptor activator of NF-κB ligand (RANKL) expression and osteoclastic bone resorption in wild-type (WT; C57Bl/6) mice and in mice genetically deficient in Panx1 (Panx1KO). Mouse ulnar loading produced linear microcracks comparable in number and location to the rat model. WT mice showed increased osteocyte apoptosis and RANKL expression at microdamage sites at 3 days after loading and increased intracortical remodeling and endocortical tunneling at day 14. With fatigue, Panx1KO mice exhibited levels of microdamage and osteocyte apoptosis identical to WT mice. However, they did not upregulate RANKL in bystander osteocytes or initiate resorption. Panx1 interacts with P2X7R in ATP release; thus, we examined P2X7R-deficient mice and WT mice treated with P2X7R antagonist Brilliant Blue G (BBG) to test the possible role of ATP as a find-me signal. P2X7RKO mice failed to upregulate RANKL in osteocytes or induce resorption despite normally elevated osteocyte apoptosis after fatigue loading. Similarly, treatment of fatigued C57Bl/6 mice with BBG mimicked behavior of both Panx1KO and P2X7RKO mice; BBG had no effect on osteocyte apoptosis in fatigued bone but completely prevented increases in bystander osteocyte RANKL expression and attenuated activation of resorption by more than 50%. These results indicate that activation of Panx1 and P2X7R are required for apoptotic osteocytes in fatigued bone to trigger RANKL production in neighboring bystander osteocytes and implicate ATP as an essential signal mediating this process. © 2016 American Society for Bone and Mineral Research.
Sclerostin Enhances Adipocyte Differentiation in 3T3‐L1 Cells
Authors: Ukita Mayumi , Yamaguchi Taihiko , Ohata Noboru , Tamura Masato 
Published: November 2015

ABSTRACTSclerostin, a secreted protein encoded by the Sost gene, is produced by osteocytes and is inhibited by osteoblast differentiation and bone formation. Recently, a functional association between bone and fat tissue has been suggested, and a correlation between circulating sclerostin levels and lipid metabolism has been reported in humans. However, the effects of sclerostin on adipogenesis remain unexplored. In the present study, we examined the role of sclerostin in regulating adipocyte differentiation using 3T3‐L1 preadipocytes. In these cells, sclerostin enhanced adipocyte‐specific gene expression and the accumulation of lipid deposits. Sclerostin also upregulated CCAAT/enhancer binding protein β expression but not cell proliferation and caspase‐3/7 activities. Sclerostin also attenuated canonical Wnt3a‐inhibited adipocyte differentiation. Recently, the transcriptional modulator TAZ has been involved in the canonical Wnt signaling pathway. Sclerostin reduced TAZ‐responsive transcriptional activity and TAZ‐responsive gene expression. Transfection of 3T3‐L1 cells with TAZ siRNA increased the lipid deposits and adipogenic gene expression. These results show that sclerostin upregulates adipocyte differentiation in 3T3‐L1 cells, suggesting a possible role for the osteocyte‐derived sclerostin as a regulator of fat metabolism and as a reciprocal regulator of bone and adipose tissues metabolism. J. Cell. Biochem. 117: 1419–1428, 2016. © 2015 Wiley Periodicals, Inc.
Impact of Aid and Public Spending—A Macro–micro Framework
Authors: Levin Jorgen , Lofgren Hans , Dessus Sebastien 
Published: November 2015

AbstractIn this study, we have used Tanzania as a case to illustrate how a simulation model can be used to evaluate the impact of aid and the trade‐offs between public spending categories and their impact on income poverty and other social development targets. Our results suggest the following. First, under plausible growth, fiscal and foreign assistance assumptions, in line with observed patterns, the enormous difficulty of achieving most millennium development goals (MDGs) by 2015 is evident. Second, there existed trade‐offs between the various MDGs, in particular between achievements for poverty and other social development targets. © 2015 UNU‐WIDER. Journal of International Development published by John Wiley & Sons, Ltd.
The selective expression of carbonic anhydrase genes ofAspergillus nidulansin response to changes in mineral nutrition andCO2concentration
Authors: Xiao Leilei , Lian Bin , Dong Cuiling , Liu Fanghua 
Published: November 2015

AbstractCarbonic anhydrase (CA) plays an important role in the formation and evolution of life. However, to our knowledge, there has been no report onCAisoenzyme function differentiation in fungi. Two differentCAgene sequences inAspergillus nidulanswith clear genetic background provide us a favorable basis for studying function differentiation ofCAisoenzymes. Heterologously expressedCA1 was used to test its weathering ability on silicate minerals and real‐time quantitativePCRwas used to detect expression of theCA1 andCA2 genes at differentCO2concentrations and in the presence of different potassium sources. The northern blot method was applied to confirm the result ofCA1 gene expression. Heterologously expressedCA1 significantly promoted dissolution of biotite and wollastonite, andCA1 gene expression increased significantly in response to soluble K‐deficiency. The northern blot test further showed thatCA1 participated in K‐feldspar weathering. In addition, the results showed thatCA2 was primary involved in adapting toCO2concentration change. Taken together,A. nidulanscan choose differentCAto meet their survival needs, which imply that some environmental microbes have evolved differentCAs to adapt to changes inCO2concentration and acquire mineral nutrition so that they can better adapt to environmental changes. Inversely, their adaption may impact mineral weathering and/orCO2concentration, and even global change.
The ‘cause’ of my cancer, beliefs about cause among breast cancer patients and survivors who do and do not seek IO care
Authors: Andersen M. Robyn , Afdem Kelsey , Hager Shelly , Gaul Marcia , Sweet Erin , Standish Leanna J. 
Published: November 2015

AbstractObjectiveWe sought to describe survivors' beliefs about the cause of their breast cancer and to test the hypothesis that beliefs about cancer's cause are associated with treatment preferences in accordance with the common sense model of self‐regulation of health and illness.MethodsBreast cancer survivors (n = 552) participating in an observational study of cancer outcomes responded to an open‐ended question about the cause of their cancer. Of these, 245 women had sought treatment from complementary and alternative integrative oncology (IO) clinics, and 307 women did not.ResultsWomen frequently described theories for their cancer's cause including genetics and family history (31%), stress and coping (31%), toxins and chemicals (27%), a variety of lifestyle and epidemiological risk factors, and randomness (17%). Self‐reported beliefs about cancer's cause differed among women in association with their use of IO. IO users were somewhat more likely to describe stress and poor coping as causes of their cancer and less likely to describe random chance as a cause of cancer (p < 0.05).ConclusionsBeliefs about the cause of cancer change over time and may predict decisions to use specific treatment including complementary and alternative medicine and IO. Copyright © 2015 John Wiley & Sons, Ltd.
Analysis of stable isotope ratios in blood of tracked wandering albatrosses fails to distinguish a δ13C gradient within their winter foraging areas in the southwest Atlantic Ocean
Authors: Ceia Filipe R. , Ramos Jaime A. , Phillips Richard A. , Cherel Yves , Jones Daniel C. , Vieira Rui P. , Xavier José C. 
Published: November 2015

RationaleThe main limitation of isotopic tracking for inferring distribution is the lack of detailed reference maps of the isotopic landscape (i.e. isoscapes) in the marine environment. Here, we attempt to map the marine δ13C isoscape for the southwestern sector of the Atlantic Ocean, and assess any temporal variation using the wandering albatross as a model species.MethodsTracking data and blood and diet samples were collected monthly from wandering albatrosses rearing chicks at Bird Island, South Georgia, during the austral winter between May and October 2009. The δ13C and δ15N values were measured by mass spectrometry in plasma and blood cells, and related to highly accurate data on individual movements and feeding activity obtained using three types of device: GPS, activity (immersion) loggers and stomach temperature probes.ResultsThe tracked birds foraged in waters to the north or northwest of South Georgia, including the Patagonian shelf‐break, as far as 2000 km from the colony. The foraging region encompassed the two main fronts in the Southern Ocean (Polar and Subantarctic fronts). The δ13C values varied by only 2.1 ‰ in plasma and 2.5 ‰ in blood cells, and no relationships were found between the δ13C values in plasma and the mean latitude or longitude of landings or feeding events of each individual.ConclusionsThe failure to distinguish a major biogeographic gradient in δ13C values suggest that these values in the south Atlantic Ocean are fairly homogeneous. There was no substantial variation among months in either the δ13C or the δ15N values of plasma or blood cells of tracked birds. As birds did not show a significant change in diet composition or foraging areas during the study period, these results provide no evidence for major temporal variation in stable isotope ratios in consumer tissues, or in the regional marine isoscape in the austral winter of 2009. Copyright © 2015 John Wiley & Sons, Ltd.
A tutorial on Bayesian bivariate meta‐analysis of mixed binary‐continuous outcomes with missing treatment effects
Authors: Gajic‐Veljanoski Olga , Cheung Angela M. , Bayoumi Ahmed M. , Tomlinson George 
Published: November 2015

Bivariate random‐effects meta‐analysis (BVMA) is a method of data synthesis that accounts for treatment effects measured on two outcomes. BVMA gives more precise estimates of the population mean and predicted values than two univariate random‐effects meta‐analyses (UVMAs). BVMA also addresses bias from incomplete reporting of outcomes.A few tutorials have covered technical details of BVMA of categorical or continuous outcomes. Limited guidance is available on how to analyze datasets that include trials with mixed continuous‐binary outcomes where treatment effects on one outcome or the other are not reported. Given the advantages of Bayesian BVMA for handling missing outcomes, we present a tutorial for Bayesian BVMA of incompletely reported treatment effects on mixed bivariate outcomes. This step‐by‐step approach can serve as a model for our intended audience, the methodologist familiar with Bayesian meta‐analysis, looking for practical advice on fitting bivariate models. To facilitate application of the proposed methods, we include our WinBUGS code.As an example, we use aggregate‐level data from published trials to demonstrate the estimation of the effects of vitamin K and bisphosphonates on two correlated bone outcomes, fracture, and bone mineral density. We present datasets where reporting of the pairs of treatment effects on both outcomes was ‘partially’ complete (i.e., pairs completely reported in some trials), and we outline steps for modeling the incompletely reported data. To assess what is gained from the additional work required by BVMA, we compare the resulting estimates to those from separate UVMAs. We discuss methodological findings and make four recommendations. Copyright © 2015 John Wiley & Sons, Ltd.
CVTree3 Web Server for Whole-Genome-Based and Alignment-Free Prokaryotic Phylogeny and Taxonomy
Authors: Zuo Guanghong , Hao Bailin 
Published: November 2015

Abstract
A faithful phylogeny and an objective taxonomy for prokaryotes should agree with each other and ultimately follow the genome data. With the number of sequenced genomes reaching tens of thousands, both tree inference and detailed comparison with taxonomy are great challenges. We now provide one solution in the latest Release 3.0 of the alignment-free and whole-genome-based web server CVTree3. The server resides in a cluster of 64 cores and is equipped with an interactive, collapsible, and expandable tree display. It is capable of comparing the tree branching order with prokaryotic classification at all taxonomic ranks from domains down to species and strains. CVTree3 allows for inquiry by taxon names and trial on lineage modifications. In addition, it reports a summary of monophyletic and non-monophyletic taxa at all ranks as well as produces print-quality subtree figures. After giving an overview of retrospective verification of the CVTree approach, the power of the new server is described for the mega-classification of prokaryotes and determination of taxonomic placement of some newly-sequenced genomes. A few discrepancies between CVTree and 16S rRNA analyses are also summarized with regard to possible taxonomic revisions. CVTree3 is freely accessible to all users at http://tlife.fudan.edu.cn/cvtree3/ without login requirements.
In situ vaccination: Cancer immunotherapy both personalized and off‐the‐shelf
Authors: Hammerich Linda , Binder Adam , Brody Joshua D. 
Published: November 2015

As cancer immunotherapy continues to benefit from novel approaches which cut immune ‘brake pedals’ (e.g. anti‐PD1 and anti‐CTLA4 antibodies) and push immune cell gas pedals (e.g. IL2, and IFNα) there will be increasing need to develop immune ‘steering wheels’ such as vaccines to guide the immune system specifically toward tumor associated antigens. Two primary hurdles in cancer vaccines have been: identification of universal antigens to be used in ‘off‐the‐shelf’ vaccines for common cancers, and 2) logistical hurdles of ex vivo production of individualized whole tumor cell vaccines. Here we summarize approaches using ‘in situ vaccination’ in which intratumoral administration of off‐the‐shelf immunomodulators have been developed to specifically induce (or amplify) T cell responses to each patient's individual tumor. Clinical studies have confirmed the induction of systemic immune and clinical responses to such approaches and preclinical models have suggested ways to further potentiate the translation of in situ vaccine trials for our patients.