bluuebunny/crossref_metadata_2025_split huggingface dataset:
The role of biology in planetary evolution: cyanobacterial primary production in low‐oxygen Proterozoic oceans
Authors: Hamilton Trinity L. , Bryant Donald A. , Macalady Jennifer L. 
Published: November 2015

SummaryUnderstanding the role of biology in planetary evolution remains an outstanding challenge to geobiologists. Progress towards unravelling this puzzle for Earth is hindered by the scarcity of well‐preserved rocks from the Archean (4.0 to 2.5 Gyr ago) and Proterozoic (2.5 to 0.5 Gyr ago) Eons. In addition, the microscopic life that dominated Earth's biota for most of its history left a poor fossil record, consisting primarily of lithified microbial mats, rare microbial body fossils and membrane‐derived hydrocarbon molecules that are still challenging to interpret. However, it is clear from the sulfur isotope record and other geochemical proxies that the production of oxygen or oxidizing power radically changed Earth's surface and atmosphere during the Proterozoic Eon, pushing it away from the more reducing conditions prevalent during the Archean. In addition to ancient rocks, our reconstruction of Earth's redox evolution is informed by our knowledge of biogeochemical cycles catalysed by extant biota. The emergence of oxygenic photosynthesis in ancient cyanobacteria represents one of the most impressive microbial innovations in Earth's history, and oxygenic photosynthesis is the largest source of O2 in the atmosphere today. Thus the study of microbial metabolisms and evolution provides an important link between extant biota and the clues from the geologic record. Here, we consider the physiology of cyanobacteria (the only microorganisms capable of oxygenic photosynthesis), their co‐occurrence with anoxygenic phototrophs in a variety of environments and their persistence in low‐oxygen environments, including in water columns as well as mats, throughout much of Earth's history. We examine insights gained from both the rock record and cyanobacteria presently living in early Earth analogue ecosystems and synthesize current knowledge of these ancient microbial mediators in planetary redox evolution. Our analysis supports the hypothesis that anoxygenic photosynthesis, including the activity of metabolically versatile cyanobacteria, played an important role in delaying the oxygenation of Earth's surface ocean during the Proterozoic Eon.
Regulation of oxidative response and extracellular polysaccharide synthesis by a diadenylate cyclase in Streptococcus mutans
Authors: Cheng Xingqun , Zheng Xin , Zhou Xuedong , Zeng Jumei , Ren Zhi , Xu Xin , Cheng Lei , Li Mingyun , Li Jiyao , Li Yuqing 
Published: November 2015

SummaryCyclic diadenosine monophosphate (c‐di‐AMP) has been implicated in the control of many important bacterial activities. However, the function of this molecule in Streptococcus mutans, the primary aetiological agent of human dental caries, is unknown. In this study, we identified and characterized a diadenylate cyclase, named CdaA, in S. mutans. Furthermore, we showed that in‐frame deletion of the cdaA gene in S. mutans causes decreased c‐di‐AMP levels, increased sensitivity to hydrogen peroxide and increased production of extracellular polysaccharides. Global gene expression profiling revealed that more than 200 genes were significantly upregulated or downregulated (> 2.0‐fold) in the cdaA mutant. Interestingly, genes with increased or decreased expression were clustered in cellular polysaccharide biosynthetic processes and oxidoreductase activity respectively. Notably, the expression of several genomic islands, such as GTF‐B/C, TnSmu, CRISPR1‐Cas and CRISPR2‐Cas, was found to be altered in the cdaA mutant, indicating a possible link between these genomic islands and c‐di‐AMP signalling. Collectively, the results reported here show that CdaA is an important global modulator in S. mutans and is required for optimal growth and environmental adaption. This report also paves the way to unveil further the roles of c‐di‐AMP signalling networks in the biology and pathogenicity of S. mutans.
The Theory of Value‐Based Payment Incentives and Their Application to Health Care
Authors: Conrad Douglas A. 
Published: November 2015

ObjectivesTo present the implications of agency theory in microeconomics, augmented by behavioral economics, for different methods of value‐based payment in health care; and to derive a set of future research questions and policy recommendations based on that conceptual analysis.Data SourcesOriginal literature of agency theory, and secondarily behavioral economics, combined with applied research and empirical evidence on the application of those principles to value‐based payment.Study DesignConceptual analysis and targeted review of theoretical research and empirical literature relevant to value‐based payment in health care.Principal FindingsAgency theory and secondarily behavioral economics have powerful implications for design of value‐based payment in health care. To achieve improved value—better patient experience, clinical quality, health outcomes, and lower costs of care—high‐powered incentives should directly target improved care processes, enhanced patient experience, and create achievable benchmarks for improved outcomes. Differing forms of value‐based payment (e.g., shared savings and risk, reference pricing, capitation, and bundled payment), coupled with adjunct incentives for quality and efficiency, can be tailored to different market conditions and organizational settings.ConclusionsPayment contracts that are “incentive compatible”—which directly encourage better care and reduced cost, mitigate gaming, and selectively induce clinically efficient providers to participate—will focus differentially on evidence‐based care processes, will right‐size and structure incentives to avoid crowd‐out of providers’ intrinsic motivation, and will align patient incentives with value. Future research should address the details of putting these and related principles into practice; further, by deploying these insights in payment design, policy makers will improve health care value for patients and purchasers.
The Changing Landscape of Accrual Accounting
Authors: BUSHMAN ROBERT M. , LERMAN ALINA , ZHANG X. FRANK 
Published: November 2015

ABSTRACTA fundamental property of accrual accounting is to smooth temporary timing fluctuations in operating cash flows, indicating an inherent negative correlation between accruals and cash flows. We show that the overall correlation between accruals and cash flows has dramatically declined in magnitude over the past half century and has largely disappeared in more recent years. The adjusted R 2 from regressing (changes in) accruals on (changes in) cash flows drops from about 70% (90%) in the 1960s to near zero (under 20%) in more recent years. In exploring potential reasons for the observed attenuation, we find that increases in non‐timing‐related accrual recognition, as proxied by one‐time and nonoperating items and the frequency of loss firm‐years, explain the majority of the overall decline. On the other hand, temporal changes in the matching between revenues and expenses, and the growth of intangible‐intensive industries play only a limited role in explaining the observed attenuation. Finally, the relative decline of the timing role of accruals does not appear to be associated with an increase in the asymmetrically timely loss recognition role.
Death from Hypothermia during a Training Course under “Extreme Conditions”: Related to Two Cases
Authors: Perich Pierre , Tuchtan Lucile , Bartoli Christophe , Léonetti Georges , Piercecchi‐Marti Marie‐Dominique 
Published: November 2015

AbstractDeath from hypothermia following exhaustion or from various complicated pathologies is no longer a frequent cause of death among combat troops. During a training course under “extreme conditions” in the French Alps, two young African officers died. Confronted with these two clinically confirmed cases of hypothermia, the unknown anatomopathological and biological specificities associated with death from hypothermia were highlighted. In these typical and clinically confirmed cases of death from subacute exhaustion hypothermia, none of the signs revealed by the autopsy were specific. Although some recent publications have addressed the utility of postmortem biochemical markers when establishing a diagnosis, with no anamnesis, with no knowledge or analysis of the circumstances of death, and without an in situ examination of the body, it appears difficult, if not impossible, to confirm that death was caused by hypothermia.
Comparative analysis of peptidoglycan recognition proteins in endoparasitoid wasp Microplitis mediator
Authors: Wang Rui‐Juan , Lin Zhe , Jiang Hong , Li Jiancheng , Saha Tusar T. , Lu Ziyun , Lu Zhiqiang , Zou Zhen 
Published: November 2015

AbstractPeptidoglycan recognition proteins (PGRPs) are a family of innate immune receptors that specifically recognize peptidoglycans (PGNs) on the surface of a number of pathogens. Here, we have identified and characterized six PGRPs from endoparasitoid wasp, Microplitis mediator (MmePGRPs). To understand the roles of PGRPs in parasitoid wasps, we analyzed their evolutionary relationship and orthology, expression profiles during different developmental stages, and transcriptional expression following infection with Gram‐positive and ‐negative bacteria and a fungus. MmePGRP‐S1 was significantly induced in response to pathogenic infection. This prompted us to evaluate the effects of RNA interference mediated gene specific knockdown of MmePGRP‐S1. The knockdown of MmePGRP‐S1 (iMmePGRP‐S1) dramatically affected wasps’ survival following challenge by Micrococcus luteus, indicating the involvement of this particular PGRP in immune responses against Gram‐positive bacteria. This action is likely to be mediated by the Toll pathway, but the mechanism remains to be determined. MmePGRP‐S1 does not play a significant role in anti‐fungal immunity as indicated by the survival rate of iMmePGRP‐S1 wasps. This study provides a comprehensive characterization of PGRPs in the economically important hymenopteran species M. mediator.
Differentiation of Wines Treated with Wood Chips Based on Their Phenolic Content, Volatile Composition, and Sensory Parameters
Authors: Kyraleou Maria , Kallithraka Stamatina , Chira Kleopatra , Tzanakouli Eleni , Ligas Ioannis , Kotseridis Yorgos 
Published: November 2015

AbstractThe effects of both wood chips addition and contact time on phenolic content, volatile composition, color parameters, and organoleptic character of red wine made by a native Greek variety (Agiorgitiko) were evaluated. For this purpose, chips from American, French, Slavonia oak, and Acacia were added in the wine after fermentation. A mixture consisting of 50% French and 50% Americal oak chips was also evaluated. In an attempt to categorize wine samples, various chemical parameters of wines and sensory parameters were studied after 1, 2, and 3 mo of contact time with chips. The results showed that regardless of the type of wood chips added in the wines, it was possible to differentiate the samples according to the contact time based on their phenolic composition and color parameters. In addition, wood‐extracted volatile compounds seem to be the critical parameter that could separate the samples according to the wood type. The wines that were in contact with Acacia and Slavonia chips could be separated from the rest mainly due to their distinct sensory characters.
Predictors and rate of adjuvant radiation therapy following radical prostatectomy: A report from the Prostate Cancer Registry
Authors: Daniels Christopher P , Millar Jeremy L , Spelman Tim , Sengupta Shomik , Evans Sue M 
Published: November 2015

AbstractIntroductionLong‐term data from three randomized trials have demonstrated that adjuvant radiation therapy (ART) reduces the rate of biochemical failure in high‐risk men following radical prostatectomy (RP). One of these trials has shown a survival advantage. We investigated the rate of ART in Victoria and the predictors for this treatment.MethodsWe analysed data from eligible patients who were notified to the Victorian Prostate Cancer Registry (PCR) by 37 Victorian hospitals between 1 August 2008 and 31 October 2011. We defined ART as radiation therapy (RT) delivered within 6 months of RP. Predictors of ART receipt were modelled using adjusted and unadjusted logistic regression.ResultsThere were 4626 eligible cases from which 2018 underwent RP with recorded date of surgery. Of these eligible prostatectomy cases, a total of 89 received ART. A subgroup of 833 men had an adverse pathologic feature, of whom 78 received ART. In a multivariate model, pathologic tumour stage pT3a (odds ratio (OR) 2.64; 95% confidence interval (CI) 1.4–5.00; P = 0.003), pT3b (OR 4.58; 95% CI 2.12–9.89; P = 0.000), a positive surgical margin (OR 8.91; 95% CI 4.61–17.2; P = 0.000) and pathologic Gleason grade >7 (OR 7.18; 95% CI 1.54–33.6; P = 0.012) predicted receipt of ART.ConclusionAdverse pathologic features and high pathologic Gleason score predict for receiving ART in Victorian men after RP, but overall, ART is not commonly prescribed. This finding is consistent with other published series and may reflect clinician scepticism regarding the benefit of ART over salvage RT and concern about toxicity and the risk of over treatment.
Audit of demand for after‐hours CT scanning services in RANZCR‐accredited training departments
Authors: Goergen Stacy K , Grimm Jane , Paul Eldho , Fabiny Robert , Lee Wai Kit , Blome Steven , Zhou Kim , Munro Philip L 
Published: November 2015

AbstractIntroductionThe aims of this study were to measure: (i) the growth in after‐hours emergency department – referred CT (ED–CT) performed in accredited training departments between 2011 and 2013; (ii) the growth in ED CT relative to growth in ED presentations at the same hospitals; and (iii) trainee workload resulting from after‐hours ED CT.MethodsEthics approval was obtained for all participating sites. Accredited training facilities in Australia and New Zealand with three or more trainees and serving one or more EDs were invited to participate (N = 32). Four nights were surveyed between August and December 2013. For data collection, the number of ED patients having one or more CT scans; ED CT scan total images; non‐contrast head CTs; and ED patients (total and categories 1 and 2) attending the ED in the preceding 24 h and first half of calendar year were collected for 2013 and corresponding days in 2012 and 2011. Trainee staffing levels were measured.ResultsEleven of 32 sites provided data for all four nights and 14 of 32 for one or more nights. A 15.7% increase in number of ED CTs between 1700 and 2200 h and 16.8% increase between 2201 and 0730 h occurred in the 2 years between 2011 and 2013 compared with a 6.9% increase in overall ED and 26% increase in categories 1 and 2 presentations over the same period. The number of CT images, however, increased 23%.ConclusionGrowth in demand by EDs for after‐hours CT services has implications for service provision and trainee workloads in Royal Australian and New Zealand College of Radiologists‐accredited training departments.
Novel CT and scintigraphic findings of bone metastasis from invasive lobular breast cancer
Authors: Al‐Ogaili Zeyad , Troedson Russell 
Published: November 2015

AbstractIntroductionThe aim of this study is to identify and describe the computed tomography and scintigraphic imaging patterns of osseous metastasis from invasive lobular breast cancer (ILC).Materials and methodsCT and skeletal scintigraphy (SS) studies of 23 patients with diagnosis of ILC and osseous metastasis on their initial presentation were reviewed.ResultsOsseous metastases in 14 patients (60.8%) appear as uniform small sclerotic lesions (USSL) on CT scan. The SS in these patients were interpreted as negative for metastasis (either normal or with some equivocal findings not typical for metastasis).ConclusionOsseous metastasis from ILC can have a characteristic imaging pattern on CT and SS. The pattern of USSL on CT scan with negative SS is highly suggestive of osseous metastasis from ILC.
Noradrenergic inputs from locus coeruleus to posterior ventral tegmental area are essential to support ethanol reinforcement
Authors: Shelkar Gajanan P. , Kumar Santosh , Singru Praful S. , Subhedar Nishikant K. , Kokare Dadasaheb M. 
Published: November 2015

AbstractAlthough dysregulation of the dopaminergic mesolimbic system is generally considered central to addiction, the involvement of other circuits is increasingly being appreciated. An interaction between locus coeruleus (LC) noradrenergic neurons and the posterior ventral tegmental area (pVTA) dopaminergic system, in the processing of drug‐triggered reward, has been suggested, but not demonstrated in behaving animals. Herein, we try to tease out the precise role of noradrenergic neurons in the LC–VTA circuit in mediating reward and reinforcement behavior associated with ethanol. In the standard two‐lever (active/inactive) operant paradigm, the rats were trained to self‐administer ethanol in pVTA and subjected to pharmacological intervention. Intra‐pVTA administration of phenylephrine (alpha‐1 adrenoceptor agonist) increased ethanol self‐administration, while prazosin and disulfiram (agents that reduce noradrenergic tone) produced opposite effects. While degeneration [N‐(2‐chloroethyl)‐N‐ethyl‐2‐bromobenzylamine hydrochloride, DSP‐4, intraperitoneal route] or silencing (lidocaine or muscimol, both via intra‐LC route) of the LC noradrenergic neurons decreased, phenylephrine via the intra‐LC route reinstated ethanol self‐administration. Furthermore, lidocaine reduced ethanol self‐administration, but the effect was fully attenuated by noradrenaline given directly in the pVTA. This suggests that the feedback signals from LC to pVTA are necessary to sustain the ethanol self‐infusion activity. Ethanol self‐administration significantly increased tyrosine hydroxylase immunoreactivity in pVTA and LC; the response was blocked by DSP‐4 pre‐treatment. While dopamine D1, but not D2, receptors were localized on noradrenergic LC neurons, pre‐treatment with SCH‐23390 (intra‐LC) dampened the lever press activity. We suggest that two‐way communications between VTA and LC regions is essential for ethanol‐triggered reinforcement behavior.
Excess risk of urinary tract cancers in patients receiving thiopurines for inflammatory bowel disease: a prospective observational cohort study
Authors: Bourrier A. , Carrat F. , Colombel J.‐F. , Bouvier A.‐M. , Abitbol V. , Marteau P. , Cosnes J. , Simon T. , Peyrin‐Biroulet L. , Beaugerie L. ,   the CESAME study group
Published: November 2015

SummaryBackgroundThe risk of urinary tract cancers, including kidney and bladder cancers, was increased in transplant recipients receiving thiopurines.AimTo assess the risk of urinary tract cancers in patients with inflammatory bowel disease (IBD) receiving thiopurines in the CESAME observational cohort.MethodsBetween May 2004 and June 2005, 19 486 patients with IBD, 30.1% of whom were receiving thiopurines, were enrolled. Median follow‐up was 35 months (IQR: 29–40).ResultsTen and six patients developed respectively kidney and bladder cancer. The incidence rates of urinary tract cancer were 0.48/1000 patient‐years in patients receiving thiopurines (95% CI: 0.21–0.95), 0.10/1000 patient‐years in patients who discontinued thiopurines (95% CI: 0.00–0.56) and 0.30/1000 patient‐years in patients never treated with thiopurines (95% CI: 0.12–0.62) at entry. The standardised incidence ratio of urinary tract cancer was 3.40 (95% CI: 1.47–6.71, P = 0.006) in patients receiving thiopurines, 0.64 (95% CI: 0.01–3.56, P = 0.92) in patients previously exposed to thiopurines and 1.17 (95% CI: 0.47–12.42, P = 0.78) in patients never treated with thiopurines. The multivariate‐adjusted hazard ratio (HR) of urinary tract cancer between patients receiving thiopurines and those not receiving thiopurines was 2.82 (95% CI: 1.04–7.68, P = 0.04). Other significant risk factors were male gender (HR: 3.98, 95% CI: 1.12–14.10, P = 0.03) and increasing age (HR after 65 years (ref <50): 13.26, 95% CI: 3.52–50.03, P = 0.0001).ConclusionPatients with IBD receiving thiopurines have an increased risk of urinary tract cancers. Clinically relevant excess risk is observed in older men.
Evidence of Different Propofol Pharmacokinetics under Short and Prolonged Infusion Times in Rabbits
Authors: Campos Sónia , Monteiro Joaquim , Valenzuela Belén , Gonçalinho Helena , de Pinho Paula Guedes , Fresco Paula , Félix Luis , Antunes Luís 
Published: November 2015

AbstractPropofol is an anaesthetic widely used in both human beings and animals. However, the characterization of propofol pharmacokinetics (PK) is not well understood when long‐term infusions are used. The main objective of this study was to explore the PK behaviour of propofol in a rabbit model during short and prolonged propofol infusions and to develop an internally validated PK model, for propofol dose individualization in the rabbit for future use. Population 1 (P1) was constituted by seven New Zealand rabbits and was used to characterize the PK profile of propofol at short infusions. Animals were anaesthetized with a bolus of 20 mg/kg, followed by an infusion rate of 50 mg/kg/hr of propofol at 1%, which was then maintained for 30 min. A second rabbit population (P2, n = 7) was sedated according to reflexes responses and Index of Consciousness values, for 20 consecutive hours using propofol 2% aiming at characterizing propofol behaviour at long‐term infusions. Clinical data and blood samples were collected at specific time‐points in both populations. Propofol plasma concentrations were determined by gas chromatography/ion trap mass spectrometry. The NONMEM VII software was used to evaluate the relationships between dose and plasma concentrations. A linear two‐compartment model with different central compartment volume and plasma clearance (separately modelled in the two populations) was the one that best described propofol concentrations. The time course of propofol plasma concentrations was well characterized by the PK model developed, which simultaneously accounts for propofol short‐ and long‐term infusions and can be used to optimize future PK studies in rabbits.
Glucagon‐Like Peptide‐1 Formulation – the Present and Future Development in Diabetes Treatment
Authors: Lee Chooi Yeng 
Published: November 2015

AbstractType 2 diabetes mellitus is a chronic metabolic disorder that has become the fourth leading cause of death in the developed countries. The disorder is characterized by pancreatic β‐cells dysfunction, which causes hyperglycaemia leading to several other complications. Treatment by far, which focuses on insulin administration and glycaemic control, has not been satisfactory. Glucagon‐like peptide‐1 (GLP1) is an endogenous peptide that stimulates post‐prandial insulin secretion. Despite being able to mimic the effect of insulin, GLP1 has not been the target drug in diabetes treatment due to the peptide's metabolic instability. After a decade‐long effort to improve the pharmacokinetics of GLP1, a number of GLP1 analogues are currently available on the market. The current Minireview does not discuss these drugs but presents strategies that were undertaken to address the weaknesses of the native GLP1, particularly drug delivery techniques used in developing GLP1 nanoparticles and modified GLP1 molecule. The article highlights how each of the selected preparations has improved the efficacy of GLP1, and more importantly, through an overview of these studies, it will provide an insight into strategies that may be adopted in the future in the development of a more effective oral GLP1 formulation.