bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of over‐expression of HIF‐1alpha in bone marrow‐derived mesenchymal stem cells on traumatic brain injury
Authors: Shi Xiaodong , Zhang Guodong , Sun Huijuan , Bai Yunan , Liu Yuguang , Zhang Wei , Xiao Hang
Published: March 2018

Mesenchymal stem cells (MSCs) have been shown to play therapeutic effect in traumatic brain injury (TBI). To augment the therapeutic effect, MSCs could be engineered to over‐express genes that are beneficial for treatment. In the present study, we over‐expressed hypoxia inducible factor (HIF)‐1alpha in bone marrow derived MSCs (BM‐MSCs) and sought to investigate whether HIF‐1alpha could enhance the therapeutic effect of MSCs in a mouse model of TBI. Balb/c mice were subjected to controlled cortical impact injury and MSCs were transplanted intravenously at 6 h after injury. The lesion volume and brain water content were measured and the neurological function was assessed by modified neurologic severity score tests. Double‐labeled immunofluorescence for BrdU and NeuU was performed to determine angiogenesis and neurogenesis. The expression of erythropoietin (EPO) and vascular endothelial growth factor (VEGF) was measured by quantitative RT‐PCR and western blotting. After TBI, mice received BM‐MSCs over‐expressing HIF‐1alpha showed significantly more functional recovery, reduced brain damage, increased angiogenesis and neurogenesis and increased expression of VEGF and EPO, compared with control mice or mice treated with non‐transduced BM‐MSCs. Over‐expression of HIF‐1alpha enhanced BM‐MSCs induced improvement of neurological recovery after TBI, by stimulating angiogenesis and neurogenesis.
Connectivity assessment in Mediterranean vineyards using improved stock unearthing method, LiDAR and soil erosion field surveys
Authors: Rodrigo Comino Jesús , Keesstra Saskia D. , Cerdà Artemi
Published: March 2018

The interaction between processes and landforms is accelerated in vineyards due to bare tilled soils that enhance splash, runoff, and erosion. Traditionally, in order to assess these processes, the stock unearthing method (SUM) is considered a useful methodology that uses the graft union of the vine plant as passive bio‐indicator of the topsoil level changes. However, SUM assumes that the topography between the rows is planar when development of a model of the current micro‐topography is performed. Thus, we consider that there is a need to develop a new methodology (ISUM: improved SUM) that, by adding new measurements in the inter‐row areas (at least 3), allows inclusion of the absent micro‐topographical information of SUM. In this way, the main aim of this research was to estimate the micro‐topographical changes and soil transport at three different slope positions (upper, middle and lower parts) in a 25‐years‐old vineyard in eastern Spain. LiDAR data were used to compare the connectivity processes at the catchment with the pedon scale. We obtained maps that showed topsoil level changes and detected soil depletion and accumulation signals. We estimated soil displacement rates of –1.6 Mg ha yr‐1 (depletion), +2.8 Mg ha yr‐1 and +13.3 Mg ha yr‐1 (accumulation) at upper, middle and lower slope positions, respectively. The total average soil erosion rates in the inter‐rows were –5.7 Mg ha‐1 yr‐1. In the row areas, deposition of +10.5 Mg ha yr‐1 was measured. Field erosion marks surveyed after each rainfall event gave insights to the connectivity at the inter‐row and the slope scale. It was found that at the row scale there were sinks of sediments underneath the vines and sources in the inter‐row parts, although they are the highest and lowest local topographical terrain, respectively. This is due to tillage erosion that redistributed the sediments. At the slope scale, the lower part of the slope collected sediments from the upper slope positions, which were transported along the middle part of the slope, as the measurement of ISUM and the field survey after intense rainfall events demonstrated. Connectivity of the flows along the whole slope were rare (twice), and along individual slope parts connectivity was found eight times, and 19 at the inter‐row scale after 8 years of field observations. Copyright © 2018 John Wiley & Sons, Ltd.
A novel, efficient, and ecologically relevant bioassay method using aquatic fungi and fungus-like organisms for fungicide ecological effect assessment
Authors: Nagai Takashi
Published: March 2018

Fungicides are used to control fungal plant pathogens, but they may also be highly toxic to aquatic fungi, which play an important role in natural aquatic ecosystems. However, a bioassay method using aquatic fungi has not been sufficiently developed. In the present study, a novel, efficient, and ecologically relevant bioassay method was developed for the ecological effect assessment of fungicides. Candidate test species were selected by considering the following 4 factors: 1) their ecological relevance (i.e., widely distributed and frequently observed) in freshwater habitats, 2) inclusion of a wide range of taxonomic groups, 3) availability from public culture collections, and 4) suitability for culture experiments using a microplate. The following 5 fungal species were selected: Rhizophydium brooksiaum (Chitridiomycota), Chytriomyces hyalinus (Chitridiomycota), Tetracladium setigerum (Ascomycota), Sporobolomyces roseus (Basidiomycota), and Aphanomyces stellatus (Oomycota, fungus-like organism). An efficient test method using the 5 species was developed based on a microplate assay using a 96-well white microplate and a test duration of 48 h. Fungal biomass was determined as adenosine 5′-triphosphate (ATP) luminescence, which is known to be proportional to live cell density and can be determined with a microplate reader. Test performance was evaluated by conducting bioassays of 3,5-dichlorophenol and malachite green as standard test substances. Fungal species were clearly more sensitive than other species to the fungicide malachite green. Environ Toxicol Chem 2018;37:1980–1989. © 2018 SETAC

Abstract
Comparative in vitro and in vivo effects of chlorpyrifos oxon in the outbred CD-1 mouse (Mus musculus) and great plains toad (Anaxyrus cognatus)
Authors: Anderson Tim , Liu Jing , McMurry Scott , Pope Carey
Published: March 2018

We compared biochemical, functional, and behavioral responses to the organophosphorus anticholinesterase chlorpyrifos oxon (CPO) in mice (Mus musculus, CD-1) and toads (Anaxyrus cognatus, Great Plains toad). Toads were substantially less sensitive to acute lethality of CPO based on the maximum tolerated (nonlethal) dose (toads, 77 mg/kg; mice, 5.9 mg/kg). Sublethal exposures led to classical signs of toxicity (increased involuntary movements, autonomic secretions) in mice but hypoactivity in toads. Motor performance in an inclined plane test was not affected by CPO in mice but was altered at the highest dosage in toads. Acetylcholinesterase (AChE), butyrylcholinesterase, monoacylglycerol lipase, and fatty acid amide hydrolase activities in brain were inhibited in mice but not in toads, and fatty acid amide hydrolase activity in the liver was inhibited in both species. Toad brain AChE was less sensitive to in vitro inhibition by CPO (50% inhibitory concentration [IC50; 20 min, 37 °C], 101 vs 7.8 nM; IC50 [20 min, 26 °C], 149 vs 6.2 nM), and studies of inhibitor kinetics indicated substantially lower anticholinesterase potency of CPO against the toad brain enzyme. Using an in vitro indirect inhibition assay, preincubation of CPO with toad brain homogenate was more effective than an equivalent mouse brain homogenate at reducing CPO potency. These data suggest that the relatively low sensitivity of toads to cholinergic toxicity is based on the low sensitivity of brain AChE, which in turn may be attributable to more effective target-site detoxification. Environ Toxicol Chem 2018;37:1898–1906. © 2018 SETAC
Nonlinear energy‐harvesting relaying with beamforming and hardware impairments in κ−μ shadowed fading environment
Authors: Hussain Ayaz , Kim Sang‐Hyo , Chang Seok‐Ho
Published: March 2018

In this paper, the energy harvesting in a decode‐and‐forward (DF) relaying system with beamforming and hardware impairments that is based on a realistic nonlinear model is studied under κ−μ shadowed fading environments. This study was undertaken in consideration of a source and a destination that are equipped with multiple antennas and communication that occurs through a single‐antenna energy‐constrained DF relay. At the relay node, a nonlinear energy harvester is assumed, which limits the level of the harvested power with a saturation threshold. Here, a power‐splitting‐based relaying protocol is considered, whereby new and exact analytical expressions are derived for the outage probability and throughput under κ−μ shadowed fading, accounting for hardware impairments at all nodes. The κ−μ shadowed fading model is capable of modeling the different kinds of empirical wireless channels that undergo either shadowing or fading and fading and shadowing simultaneously, including the particular cases of the κ−μ, Rician shadowed, Rician, Nakagami‐
, and Rayleigh fading channels. The authors analyze the system performance for different system parameters such as the power splitting ratio, number of antennas, hardware impairments, saturation threshold power, and fading and shadowing parameters. These results are then generalized and can easily be reduced for an ideal hardware and linear energy‐harvesting relaying, and for a number of particular cases including the Rayleigh/Rayleigh, Nakagami‐
/Nakagami‐
, Rician/Rician, Rician shadowed/Rician shadowed, and mixed κ−μ shadowed, κ−μ, Rician shadowed, Rician, Nakagami‐
, and Rayleigh fading channels. The results of this study are helpful in terms of the analysis of the performance of the energy‐harvesting DF relay network under a variety of environments for which the fading and the shadowing arise jointly and separately.
New insights about cadmium impacts on tomato: Plant acclimation, nutritional changes, fruit quality and yield
Authors: Carvalho Marcia E. A. , Piotto Fernando A. , Gaziola Salete A. , Jacomino Angelo P. , Jozefczak Marijke , Cuypers Ann , Azevedo Ricardo A.
Published: March 2018

Tomato is an important crop worldwide. Cadmium (Cd) concentrations in fruits depend on tomato genotype. This work aimed to study the relation among Cd accumulation, tolerance mechanisms, and fruit features in two tomato cultivars with contrasting tolerance to Cd stress. Tolerant (Yoshimatsu) and sensitive (Tropic Two Orders) plants were grown in control and contaminated soils (0.04 and 3.77 mg/kg Cd, respectively) from the seedling stage to fruit production. Both cultivars were able to acclimatize to Cd exposure, probably through mechanisms associated with reductions in the magnesium status. Cadmium concentrations varied according to the following descending order: roots = leaf blades > (peduncle + sepals) > stem = fruits. However, the tolerant cultivar accumulated more Cd than did the sensitive one. Although Cd reached the fruits from the first to the fourth bunches, peduncle and sepals may act as a barrier to Cd entrance in tomato pulp and peel. The Cd‐induced changes in the fruit mineral profile varied according to plant cultivar, organ, tomato tissue, and bunch position. Moreover, plant yield was not affected by the Cd stress, which was able to improve fruit size and weight in the tolerant cultivar. In conclusion, new insights about the Cd‐induced effects on tomato development and fruit attributes were provided by growing plants in soil, which is the media generally used to cultivate this crop, rather than hydroponics. It was shown that tomato cultivars with contrasting tolerance to Cd toxicity can reach sexual maturity and produce fruits with no yield losses, despite impacts on development from long‐term Cd exposure. This study also revealed the role of floral receptacle and its related structures in limiting, even partially, Cd translocation to the fruits. Furthermore, Yoshimatsu's capacity to produce bigger and heavier fruits, in plants under Cd exposure, may probably be associated with enhanced Cd accumulation.
A simple iteration algorithm to price perpetual Bermudan options under the lognormal jump‐diffusion‐ruin process
Authors: Chung San‐Lin , Wang Jr‐Yan
Published: March 2018

We propose an analytical‐form framework for pricing perpetual Bermudan options (PBOs) under the lognormal jump‐diffusion‐ruin model of Merton (1976). We first analytically derive the holding and early exercise values of PBOs. The optimal exercise boundary of the PBO, determined by equating the holding and early exercise values, is then solved using an iteration algorithm. We finally evaluate the PBO by taking the expectation of the option prices at the subsequent exercisable date and discounting it at the risk‐free rate. The numerical results indicate that our method is far more efficient than the competing methods in the literature for pricing PBOs.
Source analysis of quartz from the Upper Ordovician and Lower Silurian black shale and its effects on shale gas reservoir in the southern Sichuan Basin and its periphery, China
Authors: Han Chao , Han Mei , Jiang Zaixing , Han Zuozhen , Li Hao , Song Zhigang , Zhong Wenjian , Liu Kaixuan , Wang Chunhao
Published: March 2018

A major breakthrough in shale gas exploration and development has been made concerning the black shale of the Upper Ordovician and Lower Silurian. In recent years, significant progresses have been made regarding the exploration and development of shale gas in the black shale of the Upper Ordovician and Lower Silurian. Accordingly, we investigated the petrological and geochemical characteristics of the black shale from WF2‐LM5 graptolite biozones and performed a source analysis of quartz as well as evaluated its effect on shale gas reservoirs. The black shale mainly contains clay, carbonate, and quartz with the average TOC of 2.21%. Three quartz types, Q1, Q2, and Q3, were identified via petrological and cathodoluminescence (CL) analysis. Q1 of detrital origin as suggested by its typical morphology with monocrystal structure, large grain‐size, subrounded to angular outlines, and clear edges. This is further supported by the occurrence of medium luminescence under cathodoluminescence and medium intensity of P1 and P2 and high intensity P3 according to CL images. Q2 accounts for more than 90% of quartz and exhibits cryptocrystalline texture, an irregular shape, blurring edges, and low luminescence, and its CL images show low intensity P1, low intensity P2, and high intensity P3. Q3 have the morphologies of siliceous organisms, for example, sponge spicules, radiolaria, and foraminifera. Q2 and Q3 belong to authigenic quartz derived from siliceous organisms. Th/U and V/Cr indicate black shale from LM1–3 mainly deposited in the dysoxic‐anoxic environment while black shale from LM4–5 deposited in the oxic environment. Authigenic quartz‐rich shales from LM1–3 were speculated to be the best shale gas reservoirs characterized by high TOC content, high gas content, and with negligible amount of detrital quartz. Compared with shale from LM1–3, black shale from LM4–5 usually have relatively high detrital quartz content and low TOC content and gas content. Considering the abundant interparticle pore space, the detrital quartz‐rich shale interbedded within the black shale from LM4–5, could also become good shale gas reservoirs if sufficient gas supply is guaranteed.
Influence of white matter injury on gray matter reactive gliosis upon stab wound in the adult murine cerebral cortex
Authors: Mattugini Nicola , Merl‐Pham Juliane , Petrozziello Elisabetta , Schindler Lisa , Bernhagen Jürgen , Hauck Stefanie M. , Götz Magdalena
Published: March 2018

Traumatic brain injury frequently affects the cerebral cortex, yet little is known about the differential effects that occur if only the gray matter (GM) is damaged or if the injury also involves the white matter (WM). To tackle this important question and directly compare similarities and differences in reactive gliosis, we performed stab wound injury affecting GM and WM (GM+) and one restricted to the GM (GM−) in the adult murine cerebral cortex. First, we examined glial reactivity in the regions affected (WM and GM) and determined the influence of WM injury on reactive gliosis in the GM comparing the same area in the two injury paradigms. In the GM+ injury microglia proliferation is increased in the WM compared with GM, while proliferating astrocytes are more abundant in the GM than in the WM. Interestingly, WM lesion exerted a strong influence on the proliferation of the GM glial cells that was most pronounced at early stages, 3 days post lesion. While astrocyte proliferation was increased, NG2 glia proliferation was decreased in the GM+ compared with GM‐ lesion condition. Importantly, these differences were not observed when a lesion of the same size affected only the GM. Unbiased proteomic analyses further corroborate our findings in support of a profound difference in GM reactivity when WM is also injured and revealed MIF as a key regulator of NG2 glia proliferation.
Inhibition in the face of emotion: Characterization of the spatial‐temporal dynamics that facilitate automatic emotion regulation
Authors: Taylor Margot J. , Robertson Amanda , Keller Anne E. , Sato Julie , Urbain Charline , Pang Elizabeth W.
Published: March 2018

Emotion regulation mediates socio‐cognitive functions and is essential for interactions with others. The capacity to automatically inhibit responses to emotional stimuli is an important aspect of emotion regulation; the underlying neural mechanisms of this ability have been rarely investigated. Forty adults completed a Go/No‐go task during magnetoencephalographic (MEG) recordings, where they responded rapidly to either a blue or purple frame which contained angry or happy faces. Subjects responded to the target color in an inhibition (75% Go trials) and a vigilance condition (25% Go trials). As expected, inhibition processes showed early, sustained activation (200–450 ms) in the right inferior frontal gyrus (IFG). Emotion‐related inhibition processes showed greater activity with angry faces bilaterally in the orbital‐frontal gyri (OFG) starting at 225 ms and temporal poles from 250 ms, with right hemisphere dominance. The presence of happy faces elicited earlier activity in the right OFG. This study demonstrates that the timing of inhibition processes varies with the emotional context and that there is much greater activation in the presence of angry faces. It underscores the importance of the right IFG for inhibition processes, but the OFG in automatic emotion regulation.
Meta‐analytic evidence for altered mesolimbic responses to reward in schizophrenia
Authors: Chase Henry W. , Loriemi Polina , Wensing Tobias , Eickhoff Simon B. , Nickl‐Jockschat Thomas
Published: March 2018

Dysfunction of reward‐related neural circuitry in schizophrenia (SCZ) has been widely reported, and may provide insight into the motivational and cognitive disturbances that characterize the disorder. Although previous meta‐analyses of reward learning paradigms in SCZ have been performed, a meta‐analysis of whole‐brain coordinate maps in SCZ alone has not been conducted. In this study, we performed an activation likelihood estimate (ALE) meta‐analysis, and performed a follow‐up analysis of functional connectivity and functional decoding of identified regions. We report several salient findings that extend prior work in this area. First, an alteration in reward‐related activation was observed in the right ventral striatum, but this was not solely driven by hypoactivation in the SCZ group compared to healthy controls. Second, the region was characterized by functional connectivity primarily with the lateral prefrontal cortex and pre‐supplementary motor area (preSMA), as well as subcortical regions such as the thalamus which show structural deficits in SCZ. Finally, although the meta‐analysis showed no regions outside the ventral striatum to be significantly altered, regions with higher functional connectivity with the ventral striatum showed a greater number of subthreshold foci. Together, these findings confirm the alteration of ventral striatal function in SCZ, but suggest that a network‐based approach may assist future analysis of the functional underpinnings of the disorder.
Neural correlates of reduced depressive symptoms following cognitive training for chronic traumatic brain injury
Authors: Han Kihwan , Martinez David , Chapman Sandra B. , Krawczyk Daniel C.
Published: March 2018

Depression is the most frequent comorbid psychiatric condition among individuals with traumatic brain injury (TBI). Yet, little is known about changes in the brain associated with reduced depressive symptoms following rehabilitation for TBI. We identified whether cognitive training alleviates comorbid depressive symptoms in chronic TBI (>6 months post‐injury) as a secondary effect. Further, we elucidated neural correlates of alleviated depressive symptoms following cognitive training. A total of seventy‐nine individuals with chronic TBI (53 depressed and 26 non‐depressed individuals, measured using the Beck Depressive Inventory [BDI]), underwent either strategy‐ or information‐based cognitive training in a small group for 8 weeks. We measured psychological functioning scores, cortical thickness, and resting‐state functional connectivity (rsFC) for these individuals before training, immediately post‐training, and 3 months post‐training. After confirming that changes in BDI scores were independent of training group affiliation, we identified that the depressive‐symptoms group showed reductions in BDI scores over time relative to the non‐depressed TBI controls (p < .01). Within the depressive‐symptoms group, reduced BDI scores was associated with improvements in scores for post‐traumatic stress disorder, TBI symptom awareness, and functional status (p < .00625), increases in cortical thickness in four regions within the right prefrontal cortex (pvertex < .01, pcluster<.05), and decreases in rsFC with each of these four prefrontal regions (pvertex < .01, pcluster < .0125). Overall, these findings suggest that cognitive training can reduce depressive symptoms in TBI even when the training does not directly target psychiatric symptoms. Importantly, cortical thickness and brain connectivity may offer promising neuroimaging markers of training‐induced improvement in mental health status in TBI.
Missing data in trial‐based cost‐effectiveness analysis: An incomplete journey
Authors: Leurent Baptiste , Gomes Manuel , Carpenter James R.
Published: March 2018

Cost‐effectiveness analyses (CEA) conducted alongside randomised trials provide key evidence for informing healthcare decision making, but missing data pose substantive challenges. Recently, there have been a number of developments in methods and guidelines addressing missing data in trials. However, it is unclear whether these developments have permeated CEA practice. This paper critically reviews the extent of and methods used to address missing data in recently published trial‐based CEA.

Issues of the Health Technology Assessment journal from 2013 to 2015 were searched. Fifty‐two eligible studies were identified. Missing data were very common; the median proportion of trial participants with complete cost‐effectiveness data was 63% (interquartile range: 47%–81%). The most common approach for the primary analysis was to restrict analysis to those with complete data (43%), followed by multiple imputation (30%). Half of the studies conducted some sort of sensitivity analyses, but only 2 (4%) considered possible departures from the missing‐at‐random assumption.

Further improvements are needed to address missing data in cost‐effectiveness analyses conducted alongside randomised trials. These should focus on limiting the extent of missing data, choosing an appropriate method for the primary analysis that is valid under contextually plausible assumptions, and conducting sensitivity analyses to departures from the missing‐at‐random assumption.
Depressive symptoms, social anxiety, and perceived neck function in patients with head and neck cancer
Authors: Rhoten Bethany Andrews , Murphy Barbara A. , Dietrich Mary S. , Ridner Sheila Hedden
Published: March 2018

Background

This study examined the relationships of depressive symptoms and social anxiety with perceived neck function in patients treated for head and neck cancer.

Methods

Depressive symptoms, social anxiety, and perceived neck‐related function were measured at baseline, posttreatment, every 6 weeks thereafter for 1 year after the end of treatment, and at 15 and 18 months posttreatment. Group‐based trajectory modeling was used to generate clusters of patients with similar baseline and trajectories of perceived neck‐related function after head and neck cancer treatment.

Results

Participants included 83 subjects who had completed at least 1 follow‐up assessment. Three clusters of longitudinal patterns in neck disability were identified: none/mild, moderate, and severe. Significant associations were found between membership in the neck disability index trajectories and membership in the longitudinal patterns of depressive symptoms and social anxiety.

Conclusion

Impaired physical function and psychological distress are intertwined for patients with head and neck cancer long after completing treatment.
Head and neck cancer reirradiation with interstitial high‐dose‐rate brachytherapy
Authors: Hegde John V. , Demanes D. Jeffrey , Veruttipong Darlene , Chin Robert K. , Park Sang‐June , Kamrava Mitchell
Published: March 2018

Background

As high‐dose‐rate (HDR) brachytherapy can preferentially spare normal anatomic structures surrounding the radiation target, we report on our experience using this technique in head and neck cancer reirradiation.

Methods

Twenty patients received HDR brachytherapy reirradiation with curative or palliative intent from 2010‐2015. Clinical and toxicity outcomes were recorded. Actuarial outcomes were calculated using Kaplan‐Meier analysis.

Results

For curative treatment, actuarial 2‐year rates of local control and overall survival (OS) were 73% and 56%, respectively. Palliatively, a 6‐month local control rate of 65% was seen. Age >70 years was associated with poorer OS (P = .042). Prior salvage resection showed a trend toward improved local control and OS (P = .069 and P = .063, respectively). Thirty‐three percent had grade 3 to 4 late toxicities.

Conclusion

Curative‐intent HDR brachytherapy reirradiation can provide excellent local control and encouraging OS. Given the late toxicity rates, patient selection is essential, with particular utility for younger patients or those treated with salvage resection.
Argininosuccinate synthase 1 and periportal gene expression in sonic hedgehog hepatocellular adenomas
Authors: Nault Jean‐Charles , Couchy Gabrielle , Caruso Stefano , Meunier Léa , Caruana Laure , Letouzé Eric , Rebouissou Sandra , Paradis Valérie , Calderaro Julien , Zucman‐Rossi Jessica
Published: March 2018

Genetic alterations define different molecular subclasses of hepatocellular adenoma (HCA) linked with risk factors, histology and clinical behavior. Recently, Argininosuccinate Synthase 1 (ASS1), a major periportal protein, was proposed as a marker of HCA with a high risk of hemorrhage. We aimed to assess the significance of ASS1 expression through the scope of the HCA molecular classification. ASS1 expression was evaluated using RNAseq, quantitative reverse transcriptase polymerase chain reaction (RT‐PCR) and Immunohistochemistry. ASS1 and glioma‐associated oncogene 1 (GLI1) expression were analyzed in vitro after modulation of GLI1 expression. Using RNAseq in 27 HCA and five nontumor liver samples, ASS1 expression was highly correlated with GLI1 expression (P<0.0001, R=0.75). In the overall series of 408 HCA, ASS1 overexpression was significantly associated with sonic hedgehog HCA (shHCA) compared to other molecular subgroups (P<0.0001), suggesting that sonic hedgehog signaling controls ASS1 expression. GLI1 expression silencing by siRNA induced a downregulation of ASS1 in PLC/PFR5 and SNU878 cell lines. In 390 HCA, we showed that ASS1 expression belonged to the periportal expression program that was maintained in shHCA but down‐regulated in all the other HCA subtypes. In contrast, HCA with β‐catenin activation showed an activation of a perivenous program. Despite the significant association between GLI1 and ASS1 expression, ASS1 mRNA expression was not associated with specific clinical features. At the protein level using immunohistochemistry, prostaglandin D synthase (PTGDS) was strongly and specifically overexpressed in shHCA. Conclusion: ASS1 is associated with sonic hedgehog activation as part of a periportal program expressed in shHCA, a molecular subgroup defined by INHBE‐GLI1 gene fusion. (Hepatology 2018).
Sphingosine kinase 1 promotes liver fibrosis by preventing miR‐19b‐3p‐mediated inhibition of CCR2
Authors: Lan Tian , Li Changzheng , Yang Guizhi , Sun Yue , Zhuang Lihang , Ou Yitao , Li Hui , Wang Genshu , Kisseleva Tatiana , Brenner David , Guo Jiao
Published: March 2018

Chronic liver disease mediated by activation of hepatic stellate cells (HSCs) and Kupffer cells (KCs) leads to liver fibrosis. Here, we aimed to investigate the molecular mechanism and define the cell type involved in mediating the sphingosine kinase (SphK)1‐dependent effect on liver fibrosis. The levels of expression and activity of SphK1 were significantly increased in fibrotic livers compared with the normal livers in human. SphK1 was coexpressed with a range of HSC/KC markers including desmin, α‐smooth muscle actin (α‐SMA) and F4/80 in fibrotic liver. Deficiency of SphK1 (SphK1−/−) resulted in a marked amelioration of hepatic injury, including transaminase activities, histology, collagen deposition, α‐SMA and inflammation, in CCl4 or bile duct ligation (BDL)‐induced mice. Likewise, treatment with a specific inhibitor of SphK1, 5C, also significantly prevented liver injury and fibrosis in mice induced by CCl4 or BDL. In cellular levels, inhibition of SphK1 significantly blocked the activation and migration of HSCs and KCs. Moreover, SphK1 knockout in KCs reduced the secretion of CCL2, and SphK1 knockout in HSCs reduced C‐C motif chemokine receptor 2 ([CCR2] CCL2 receptor) expression in HSCs. CCL2 in SphK1−/− mice was lower whereas microRNA‐19b‐3p in SphK1−/− mice was higher compared with wild‐type (WT) mice. Furthermore, microRNA‐19b‐3p downregulated CCR2 in HSCs. The functional effect of SphK1 in HSCs on liver fibrosis was further strengthened by the results of animal experiments using a bone marrow transplantation (BMT) method. Conclusion: SphK1 has distinct roles in the activation of KCs and HSCs in liver fibrosis. Mechanistically, SphK1 in KCs mediates CCL2 secretion, and SphK1 in HSCs upregulates CCR2 by downregulation of miR‐19b‐3p. (Hepatology 2018).
Health system organizational reform in governing Iranian public hospitals: A content analysis to comprehend the barriers in Board of Trustees' hospitals
Authors: Jafari Mehdi , Habibirad Amin , Pourtaleb Arefeh , Salarianzadeh Mohammad Hossein
Published: March 2018

Background

Since the early 1990s, Iran has initiated structural and decentralization reforms in the hospital system. This policy led to the formation of a Board of Trustees (BOTs) for the governing of public educational hospitals and making important modifications in hospitals' financing. This study was conducted to identify the barriers in implementing this policy.

Methods

All the Iranian Medical Sciences Universities and hospitals involved in the policy implementation were included in this qualitative study. The data were analyzed by using content analysis.

Results

In total, 403 problems were divided into 9 classes including problems related to implementing regulation, financial problems in policy implementation, problems related to faculty members, ambiguity in executive regulation, problems related to the BOTs, authority level, hospital structure, the quality and quantity of hospital human resources, and fee for services.

Conclusion

It appears that “implementing regulation” and “financial problems” embrace over 50% of the barriers. Apparently, the new approach to hospitals' autonomy has not achieved the desired goals. Considering the contextual factor, the evidence and identification of the clear role of various stakeholders should be essential determinants. Partial implementation of this policy without paying attention to the other aspects would end in failure. The results showed insufficient budget to be the most influential factor that posed a dilemma in implementing the BOTs' policy. However, BOTs in Iranian health system need to strive toward a higher level of performance that will improve effectiveness and efficiency now more than ever.
The social context of compensation design: Social norms and the impact of equity incentives
Authors: Zolotoy Leon , O’Sullivan Don , Martin Geoffrey P.
Published: March 2018

Drawing on arguments from institutional theory, this study examines how social norms—specifically, local religious social norms—affect the motivational impact of equity‐based incentives. We test our model using longitudinal data on local religious norms, CEO equity incentives, and firm value. Consistent with our theoretical predictions, we find that local religious social norms attenuate the impact of CEO option incentives upon firm value. Furthermore, we find that the attenuating impact of local religious social norms increases with managerial discretion. These findings provide valuable insight for human resource professionals aiming to design compensation contracts for employees that are aligned with firm goals. Our findings also contribute to research on the motivational effect of equity incentives by demonstrating the importance of considering the social context in which executives are embedded.
How perceived riskiness influences the selection of women and men as senior leaders
Authors: van Esch Chantal , Hopkins Margaret M. , O'Neil Deborah A. , Bilimoria Diana
Published: March 2018

This study investigates the role of perceived riskiness in senior leadership selection decisions. Perceived riskiness is defined as the degree of uncertainty and the significance of the outcomes from the selection decision. Hypotheses that perceived riskiness is a mediator between a candidate's qualifications and selection as well as salary offer, and that gender moderates those relationships, were examined through structural equation modeling and logistic regression. A sample of 253 individuals with prior experience in hiring and promotion decisions responded to an online survey where they read a job description and candidate profile summary of one of the following: a highly qualified female, a highly qualified male, a moderately qualified female, or a moderately qualified male. The results demonstrated a complementary mediating effect of perceived riskiness between a candidate's qualifications and their selection, and between a candidate's qualifications and their salary offer. In addition, gender moderates the pathway from qualifications to perceived riskiness in that highly qualified women were perceived as less risky for senior leadership than highly qualified men, while moderately qualified women were seen as riskier for senior leadership than moderately qualified men. We offer recommendations for human resource professionals and hiring managers to recognize and mitigate the perceived riskiness of women in the selection process for senior leadership roles.
Effects of bovine lipid extract surfactant administration in preterm infants treated for respiratory distress syndrome
Authors: Stockley Elizabeth , Valotaire Ronald , Miller Michael , da Silva Orlando
Published: March 2018

Aim

To review the initial effectiveness of bovine lipid extract surfactant (BLES) for the treatment of respiratory distress syndrome in preterm infants.

Methods and results

A retrospective review of data collected from infants born <37‐week gestation with respiratory distress syndrome treated with BLES between February 1, 2015 and March 1, 2016. Data were analyzed to determine the timing of initial dose, the length of time to wean the fraction of inspired oxygen (FiO2) concentration to 0.21 following initial dose, and the number of repeated doses given during hospital admission. Infants were subgrouped by gestational age stratum, 230 to 276 weeks (group 1), 280 to 316 weeks (group 2), and 320 to 366 weeks (group 3). Ninety‐eight infants received the surfactant during the study period. After applying exclusion criteria, 77 infants were analyzed. Mean (SD) gestational age was 28 (4) weeks, and mean (SD) birth weight was 1250 (602) g. Initial dose of BLES was given at a median (interquartile range) time of 29 (19‐43) minutes in group 1, 150 (20‐615) minutes in group 2, and 990 (53‐2025) minutes in group 3. Median (interquartile range) length of time to wean the FiO2 concentration to 0.21 was 14 (5‐56) minutes, 10 (5‐53) minutes, and 10 (5‐38) minutes in groups 1, 2, and 3, respectively. Ten infants required repeated doses.

Conclusion

Given the rapid response of BLES in all the groups, careful monitoring of ventilator parameters is paramount to allow for rapid weaning and early extubation to avoid lung injury associated with mechanical ventilation.
Roughness scale dependence of the relationship between tracer longitudinal dispersion and Peclet number in variable‐aperture fractures
Authors: Dou Zhi , Zhou Zhifang , Wang Jinguo , Huang Yong
Published: March 2018

The relationship between the longitudinal dispersion (DL) and Peclet number (Pe) is crucial for predicting and simulating tracer through the variable‐aperture fracture. In this study, the roughness of the self‐affine fracture wall was decomposed into primary roughness (relatively large‐scale waviness) and secondary roughness (relatively small‐scale waviness) by a multiscaled wavelet analysis technique. Based on the complete dispersion mechanism (diffusion, macrodispersion, and Taylor dispersion) in the variable‐aperture fracture, three relationships (second‐order, power‐law, and linear relationships) between the DL and Pe were investigated at large and small scales, respectively. Our results showed that the primary roughness mostly controlled the Taylor dispersion mechanism, whereas the secondary roughness was a dominant factor for the macrodispersion mechanism. Increasing the Hurst exponent and removing the secondary roughness led to the decreasing range of Pe where macrodispersion mechanism dominated the solute transport. It was found that estimating the DL from the power‐law relationship based on Taylor dispersion theory resulted in considerable errors, even in the range of Pe where the Taylor dispersion mechanism dominated. The exponent of the power‐law relationship increased as the secondary roughness was removed. Analysing the linear relationship between the DL and Pe revealed that the longitudinal dispersivity αL increased linearly. However, this linear increase became weak as the Taylor dispersion mechanism dominated. In the range of Pe where the macrodispersion mechanism dominated, increasing the Hurst exponent caused the increase of αL and the secondary roughness played a significant role in enhancing the αL. As the Taylor dispersion mechanism dominated, the αL was insensitive to the influence of multiscale roughness in variable‐aperture fractures.
Characterization of tidally influenced seasonal nutrient flux to the Bay of Bengal and its implications on the coastal ecosystem
Authors: Debnath Palash , Mukherjee Abhijit , Das Kousik
Published: March 2018

Submarine groundwater discharge (SGD) introduces solute and nutrients to the global oceans, resulting in considerable nutrient cycling and dynamics in the coastal areas. We have conducted high‐resolution, spatio‐temporal, lunar tidal cycle patterns and variability of discharged solute/nutrient assessment to get an overview of seasonal nutrient flux to the Bay of Bengal in eastern parts of the Indian subcontinent. Whereas the premonsoon season SGD was found to be dominant in the marine influence (M‐SGD), the postmonsoon season was found to be predominated by the terrestrial component of SGD (T‐SGD), extending from coast to near offshore. The solute fluxes and redox transformation were found to be extensively influenced by tidal and diurnal cycles, overlapping on seasonal patterns. We have assessed the possible role of SGD‐associated solute/nutrient fluxes and their discharge mechanisms, and their associated temporal distributions have severe implications on the biological productivity of the Bay of Bengal. The estimated annual solute fluxes, using the average end‐member concentration of the SGD‐associated nutrients, were found to be 240 and 224 mM·m−2·day−1 for NO3− and Fetot, respectively. Together with huge freshwater flux from the Himalayan and Peninsular Indian rivers, the SGD has considerable influence on the bay water circulation, stratification, and solute cycling. Thus, the observation from this study implies that SGD‐associated nutrient flux to the Bay of Bengal may function as a nutrient sink, which might influence the long‐term solute/nutrient flux along the eastern coast of India.
Quantifying the impacts of climate change and land use/cover change on runoff in the lowerConnecticut River Basin
Authors: Wang Hui , Stephenson Scott R.
Published: March 2018

Climate change and land use and cover change (LUCC) have had great impacts on watershed hydrological processes. Although previous studies have focused on quantitative assessment of the impacts of climate change and human activities on decreasing run‐off change, few studies have examined regions that have significant increasing run‐off due to both climate variability and land cover change. We show that annual run‐off had a significant increasing trend from 1956 to 2014 in the U.S. lower Connecticut River Basin. Abrupt change point years of annual run‐off for four subbasins are detected by nonparametric Mann–Kendall–Sneyers test and reconfirmed by the double mass curve. We then divide the study period into 2 subperiods at the abrupt change point year in the early 1970s for each subbasin. The Choudhury–Yang equation based on Budyko hypothesis was used to calculate precipitation and potential evapotranspiration, and landscape elasticities of run‐off. The results show that the difference in mean annual run‐off between 2 subperiods for each subbasin ranged from 102 to 165.6 mm. Climate variations were the primary drivers of increasing run‐off in this region. Quantitative contributions of precipitation and potential evapotranspiration in all subbasins are 106.5% and −3.6% on average, respectively. However, LUCC contributed both positively and negatively to run‐off: −18.6%, −13.3%, and 10.1% and 9.9% for 4 subbasins. This may be attributed to historical LUCC occurring after the abrupt change point in each subbasin. Our results provide critical insight on the hydrological dynamics of north‐east tidal river systems to communities and policymakers engaged in water resources management in this region.
The biologically active zone in upland habitats at the Hanford Site, Washington, USA: Focus on plant rooting depth and biomobilization
Authors: Lovtang Sara , Delistraty Damon , Rochette Elizabeth
Published: March 2018

We challenge the suggestion by Sample et al. (2015) that a depth of 305 cm (10 ft) exceeds the depth of biological activity in soils at the Hanford Site, Washington, USA, or similar sites. Instead, we support the standard point of compliance, identified in the Model Toxics Control Act in the state of Washington, which specifies a depth of 457 cm (15 ft) for the protection of both human and ecological receptors at the Hanford Site. Our position is based on additional information considered in our expanded review of the literature, the influence of a changing environment over time, plant community dynamics at the Hanford Site, and inherent uncertainty in the Sample et al. (2015) analysis. Integr Environ Assess Manag 2018;14:442–446. © 2018 SETAC

Key Points

We support the implementation of the standard point of compliance in the Model Toxics Control Act (MTCA) regulation (457 cm [15 ft]), based on additional information considered in our expanded review of the literature. Bitterbrush, one of the deeper-rooted shrubs at Hanford, Washington, USA, do occur in the potential vegetation types on site. Using an ecological lens we explore the deep-rooted plants that are found at Hanford and the strengths and weaknesses of rooting studies done on site. The types of fill and barriers used at Hanford Site allow for plants, and deep-rooted plants have occurred on them.
The impact of proteinuria on maternal and perinatal outcomes among women with pre‐eclampsia
Authors: Guida Jose P. , Parpinelli Mary A. , Surita Fernanda G. , Costa Maria L.
Published: March 2018

Objective

To assess the impact of proteinuria on pregnancy outcomes among women with pre‐eclampsia.

Methods

The present retrospective cohort study included patients with pre‐eclampsia who delivered at a referral maternity hospital in Brazil between January 1, 2009, and December 31, 2013. Patients were stratified into three groups based on 24‐hour urinary protein excretion during pregnancy: mild (0.3–<2.0 g), severe (2.0–<5.0 g), and massive (≥5.0 g).

Results

There were 293 patients included in the study; 88, 129, and 76 had mild, severe, and massive proteinuria, respectively. Chronic hypertension was the most frequent pre‐existing condition among all women (86 [29.4%]). The mean pregnancy duration at the onset of maternal pre‐eclampsia was longest in the mild group compared and decreased with increasing proteinuria severity (P<0.001). Preterm delivery was recorded among 205 of 293 (70.0%) neonates; there were 66 (22.5%) neonates that were preterm and in the massive proteinuria group. The incidence of severe pre‐eclampsia was lowest in the mild proteinuria group (P=0.002) and tended to occur at 34 weeks. Cesarean delivery rates exceeded 80.0% in all groups. Most patients assessed at 40–60 days postpartum remained proteinuric (40/61[66%]).

Conclusions

Quantifying the severity of proteinuria could identify a subgroup of women with pre‐eclampsia at increased risk of adverse outcomes.
Cyclicality in losses on bank loans
Authors: Keijsers Bart , Diris Bart , Kole Erik
Published: March 2018

Based on unique data we show that macro variables, the default rate and loss given default of bank loans share common cyclical components. The innovation in our model is the distinction between loans with either severe or mild losses. The variation in the proportion of these two types drives the cyclic behavior of the loss given default and constitutes the links with the default rate and macro variables. These links vary according to loan and borrower characteristics. During downturns, the proportion of defaults with severe losses increases, but the distribution of losses conditional on their being mild or severe does not change. although loans are monitored more closely than bonds and are more senior, the cyclical variation in their losses resembles those for bonds, albeit around a lower average level. This variation leads to an increase in the capital reserves required for loan portfolios.