bluuebunny/crossref_metadata_2025 huggingface dataset:
Predicting drug‐induced arrhythmias by multiscale modeling
Authors: Sahli Costabal Francisco , Yao Jiang , Kuhl Ellen
Published: February 2018

Drugs often have undesired side effects. In the heart, they can induce lethal arrhythmias such as torsades de pointes. The risk evaluation of a new compound is costly and can take a long time, which often hinders the development of new drugs. Here, we establish a high‐resolution, multiscale computational model to quickly assess the cardiac toxicity of new and existing drugs. The input of the model is the drug‐specific current block from single cell electrophysiology; the output is the spatio‐temporal activation profile and the associated electrocardiogram. We demonstrate the potential of our model for a low‐risk drug, ranolazine, and a high‐risk drug, quinidine: For ranolazine, our model predicts a prolonged QT interval of 19.4% compared with baseline and a regular sinus rhythm at 60.15 beats per minute. For quinidine, our model predicts a prolonged QT interval of 78.4% and a spontaneous development of torsades de pointes both in the activation profile and in the electrocardiogram. Our model reveals the mechanisms by which electrophysiological abnormalities propagate across the spatio‐temporal scales, from specific channel blockage, via altered single cell action potentials and prolonged QT intervals, to the spontaneous emergence of ventricular tachycardia in the form of torsades de pointes. Our model could have important implications for researchers, regulatory agencies, and pharmaceutical companies on rationalizing safe drug development and reducing the time‐to‐market of new drugs.
Stakeholder Engagement for Corporate Sustainability: A Comparative Analysis of B2C and B2B Companies
Authors: Johnson Matthew , Redlbacher Friederike , Schaltegger Stefan
Published: February 2018

Stakeholder engagement is vital for corporate sustainability for various reasons from securing legitimacy to spurring innovation. While stakeholder engagement is well established in academic discourse, recent studies have examined the effects of customer segments on this engagement for corporate sustainability. Initial empirical analyses indicated that business‐to‐consumer companies are more frequently scrutinized on their sustainability activities than business‐to‐business companies, and subsequently they are more likely to report on sustainability activities. Nevertheless, further approaches of stakeholder engagement, including stakeholder engagement tools, environmental management standards, and various activities, have not been investigated thus far. This paper compares various approaches of stakeholder engagement according to customer segment based on a 2012 empirical study of large German companies. The results show that customer segment has no major significant influence on stakeholder engagement, but rather value‐oriented aspects of firms, including family‐run operations and sustainability values in a company's business, make a difference to these activities. Copyright © 2018 John Wiley & Sons, Ltd and ERP Environment
Stable isotopes document the winter foraging ecology of king penguins and highlight connectivity between subantarctic and Antarctic ecosystems
Authors: Cherel Yves , Parenteau Charline , Bustamante Paco , Bost Charles‐André
Published: February 2018

The poorly known winter foraging ecology of the king penguin, a major Southern Ocean consumer, was investigated at the subantarctic Crozet Islands where the largest global population breeds. Blood δ13C and δ15N values were used as proxies of the birds’ foraging habitat and diet, respectively, and circulating prolactin levels helped in determining the birds’ reproductive status. Plasma prolactin concentrations showed that king penguin adults of unknown breeding status (n = 52) that were present at the colony in winter were in fact breeders and failed breeders, but were not non ‐breeders. Circulating prolactin was neither related to δ13C nor δ15N values, thus suggesting that both breeders and failed breeders used the same foraging habitats and fed on the same prey. Plasma and blood cell isotopic values depicted four new relevant biological features on the feeding strategies of king penguins during the critical winter period: (1) 42% of the birds foraged in the distant Antarctic Zone, but 58% fed primarily in subantarctic waters (δ13C), (2) they preyed upon myctophids in both zones (δ15N), (3) individuals were consistent in their foraging strategies over the winter months (δ13C and δ15N), and (4) a higher proportion of females (77%–80%) than males (27%–31%) favored feeding in distant Antarctic waters (δ13C). This study highlights trophic connectivity between subantarctic and Antarctic ecosystems and hence the key role of energy export from Antarctic waters to sustain breeding populations of subantarctic predators, including during the Austral winter.
Response of phreatophytes to short‐term groundwater pumping in a semiarid region: Field experiments and numerical simulations
Authors: Yin Lihe , Zhou Yangxiao , Xu Dandan , Zhang Jun , Wang Xiaoyong , Ma Hongyun , Dong Jiaqiu
Published: February 2018

Balancing the water demand between human usage and ecosystems remains a challenge in water‐limited regions where one of the main groundwater uses is short‐term pumping. A 23‐day pumping test was performed in a semiarid site of north‐west China to test the hypothesis that native phreatophytes can tolerate short‐term pumping. The monitoring indicated that sap flow velocity of groundwater‐dependent willow trees began to decrease on Day 4 after pumping and almost fully recovered on Day 9 after the cessation of pumping. Numerical simulations using HYDRUS‐1D were conducted for the period of 1954–2013 to assess the response of phreatophytes to groundwater withdrawal under various climatic conditions. The modelling results reveal that phreatophytes can recover from the stress induced by groundwater pumping because they can adapt to short periods of water stress using physiological and morphological traits and the degree of water stress depends on the amount and/or frequency of rainfall during and after pumping. Therefore, pulsed pumping, under particular climatic conditions, could be used to reduce negative impacts of groundwater extraction on phreatophytes, while still providing groundwater for socio‐economic activities in semiarid zones.
Predicting new‐onset HF in patients undergoing coronary or peripheral angiography: results from the Catheter Sampled Blood Archive in Cardiovascular Diseases (CASABLANCA) study
Authors: Ibrahim Nasrien E. , Lyass Asya , Gaggin Hanna K. , Liu Yuyin , van Kimmenade Roland R.J. , Motiwala Shweta R. , Kelly Noreen P. , Gandhi Parul U. , Simon Mandy L. , Belcher Arianna M. , Harisiades Jamie E. , Massaro Joseph M. , D'Agostino Ralph B. , Januzzi James L.
Published: February 2018

Aims

Methods to identify patients at risk for incident HF would be welcome as such patients might benefit from earlier interventions.

Methods and results

From a registry of 1251 patients referred for coronary and/or peripheral angiography, we sought to identify independent predictors of incident HF during follow‐up and develop a clinical and biomarker strategy to predict this outcome. There were 991 patients free of prevalent HF at baseline. Cox proportional hazard models were developed to predict adjudicated diagnosis of incident HF. Model discrimination and reclassification were evaluated. At follow‐up, 177 (18%) developed new‐onset HF. Independent predictors of new‐onset HF included five clinical variables (age, male sex, heart rate, history of atrial fibrillation/flutter, and history of hypertension) and two biomarkers (amino‐terminal pro‐B type natriuretic peptide and ST2). The c‐statistic for the model without biomarkers was 0.69; including biomarkers increased the c‐statistic to 0.76 (P < 0.001). A score was developed from the model. Patients in the highest score quintile had shortest time to incident HF compared with lower quintiles (log‐rank P < 0.001). Following 100 bootstrap iterations, internal validation was confirmed with Harrell's c‐statistic of 0.77. Use of angiotensin‐converting enzyme inhibitors, angiotensin receptor blockers, and beta‐blockers at enrollment was associated with substantial attenuation of predictive value of the risk score.

Conclusions

Patients undergoing coronary/peripheral angiographic procedures are a population at high risk for incident HF. We describe an accurate clinical and biomarker strategy for predicting incident HF and possibly intervening in such patients (NCT00842868).
Stereoselective Construction of Spiro‐Indolenine Frameworks through a Prins/Friedel–Crafts Cyclization Cascade Reaction
Authors: Chandrashekhar Rapelli , Vemulapalli Sahithya Phani Babu , Sridhar Balasubramanian , Subba Reddy Basireddy Venkata
Published: February 2018

A strategy has been developed for the synthesis of dispiro‐3H‐indoles by employing a 3‐({[2‐(1H‐indol‐3‐yl)ethyl]amino}methyl)but‐3‐en‐1‐ol derivative and various aldehydes in a sequential Prins/Friedel–Crafts cyclization in the presence of readily accessible trifluoroacetic acid (TFA) under mild conditions over a short period of time. This method proceeded smoothly with a wide range of aldehydes and provided the products in good yields with a broad pattern of substituents.
Local condiments from fermented tropical legume seeds modulate activities of critical enzymes relevant to cardiovascular diseases and endothelial function
Authors: Ademiluyi Adedayo O.
Published: February 2018

Investigation into modulatory effects of local condiments produced from fermented legume (African locust bean and soybean) seeds on activities of enzymes relevant to endothelial function and cardiovascular disease (arginase, phosphodiesterase‐5, acetylcholinesterase, and, ecto 5′‐nucleotidase) in vitro was the focus of this study. The condiments were prepared according to traditional methods of fermentation. Thereafter, modulatory effects of aqueous extracts from the condiments on activities of the enzymes were subsequently carried out. Results showed the extracts significantly inhibited activities of arginase, phosphodiesterase‐5 and acetylcholinesterase, while the activity of ecto 5′‐nucleotidase was stimulated at sample concentrations tested. Thus, the observed enzyme modulatory properties exhibited by the condiments could be novel mechanisms to support their use as functional foods and nutraceuticals for the management of cardiovascular disease and associated endothelial dysfunction.
Assessment of banana fruit handling practices and associated fungal pathogens in Jimma town market, southwest Ethiopia
Authors: Kuyu Chala G. , Tola Yetenayet B.
Published: February 2018

Banana fruits are highly perishable and affected by different microbial contaminates because ripe bananas are very perishable. One of the most important factors causing great economical loss of banana fruits is postharvest fungal diseases caused by lack of proper handling along postharvest chains. In line with this, the study was carried out to assess banana fruits handling practices and identify the major causal agents of postharvest fungal disease of banana fruits in Jimma town of bishishe market. Assessment was carried out using purposive sampling to select the study area, followed by simple random sampling to collect information on handling practices through observation and interview using pretested questioners. The survey result revealed that losses of banana fruits due to spoilage and physical injury were common problems for all fruit vendors. Practices such as lack of sanitation, temperature management, and improper packaging and transportation problems were identified among the common causes for observed losses. A total of 48 fruits were purposively selected from open market, wholesales and retailers and fruit damage, disease incidence, disease severity and identification of diseases causing fungal pathogen were conducted under laboratory. The highest fruit damage (56.2%) was recorded in sample taken from retailers’ shop, and the associated disease incidence and severity were 54.2% and 34%, respectively. Morphological identification of pure culture revealed that anthracnose caused by Colletotrichum musae and crown rot caused by fusarium spp. are the most important disease causing agents and result in large percentage of fruit loss in Jimma town of bishishe market.
Differential local tissue permissiveness influences the final fate of GPR17‐expressing oligodendrocyte precursors in two distinct models of demyelination
Authors: Coppolino Giusy T. , Marangon Davide , Negri Camilla , Menichetti Gianluca , Fumagalli Marta , Gelosa Paolo , Dimou Leda , Furlan Roberto , Lecca Davide , Abbracchio Maria P.
Published: February 2018

Promoting remyelination is recognized as a novel strategy to foster repair in neurodegenerative demyelinating diseases, such as multiple sclerosis. In this respect, the receptor GPR17, recently emerged as a new target for remyelination, is expressed by early oligodendrocyte precursors (OPCs) and after a certain differentiation stage it has to be downregulated to allow progression to mature myelinating oligodendrocytes. Here, we took advantage of the first inducible GPR17 reporter mouse line (GPR17‐iCreERT2xCAG‐eGFP mice) allowing to follow the final fate of GPR17+ cells by tamoxifen‐induced GFP‐labeling to unveil the destiny of these cells in two demyelination models: experimental autoimmune encephalomyelitis (EAE), characterized by marked immune cell activation and inflammation, and cuprizone induced demyelination, where myelin dysfunction is achieved by a toxic insult. In both models, demyelination induced a strong increase of fluorescent GFP+ cells at damaged areas. However, only in the cuprizone model reacting GFP+ cells terminally differentiated to mature oligodendrocytes, thus contributing to remyelination. In EAE, GFP+ cells were blocked at immature stages and never became myelinating oligodendrocytes. We suggest these strikingly distinct fates be due to different permissiveness of the local CNS environment. Based on previously reported GPR17 activation by emergency signals (e.g., Stromal Derived Factor‐1), we propose that a marked inflammatory milieu, such as that reproduced in EAE, induces GPR17 overactivation resulting in impaired downregulation, untimely and prolonged permanence in OPCs, leading, in turn, to differentiation blockade. Combined treatments with remyelinating agents and anti‐inflammatory drugs may represent new potential adequate strategies to halt neurodegeneration and foster recovery.
Ageing and healthcare expenditures: Exploring the role of individual health status
Authors: Carreras Marc , Ibern Pere , Inoriza José María
Published: February 2018

In 1999, Zweifel, Felder, and Meiers questioned conventional wisdom on ageing and healthcare expenditure (HCE). According to these authors, the positive association between age and HCE is due to an increasing age‐specific mortality and the high cost of dying. After a weighty academic debate, a new consensus was reached on the importance of proximity to death when analysing HCE. Nevertheless, the influence of individual health status remains unknown.

The objective of our study is to analyse the influence individual health status has on HCE, when compared to proximity to death and demographic effects and considering a comprehensive view of healthcare services and costs.

We examined data concerning different HCE components of N = 61,473 persons aged 30 to 95 years old. Using 2‐part models, we analysed the probability of use and positive HCE.

Regardless of the specific group of healthcare services, HCE at the end of life depends mainly on the individual health status. Proximity to death approximates individual morbidity when it is excluded from the model. The inclusion of morbidity generally improves the goodness of fit. These results provide implications for the analysis of ageing population and its impact on HCE that should be taken into account.
The gift of time? School starting age and mental health
Authors: Dee Thomas S. , Sievertsen Hans Henrik
Published: February 2018

Using linked Danish survey and register data, we estimate the causal effect of age at kindergarten entry on mental health. Danish children are supposed to enter kindergarten in the calendar year in which they turn 6 years. In a "fuzzy" regression‐discontinuity design based on this rule and exact dates of birth, we find that a 1‐year delay in kindergarten entry dramatically reduces inattention/hyperactivity at age 7 (effect size = –0.73), a measure of self‐regulation with strong negative links to student achievement. The effect is primarily identified for girls but persists at age 11.
Improved oxygenation dramatically alters metabolism and gene expression in cultured primary mouse hepatocytes
Authors: Gilglioni Eduardo H. , Chang Jung‐Chin , Duijst Suzanne , Go Simei , Adam Aziza A. A. , Hoekstra Ruurdtje , Verhoeven Arthur J. , Ishii‐Iwamoto Emy L. , Oude Elferink Ronald P.J.
Published: February 2018

Primary hepatocyte culture is an important in vitro system for the study of liver functions. In vivo, hepatocytes have high oxidative metabolism. However, oxygen supply by means of diffusion in in vitro static cultures is much less than that by blood circulation in vivo. Therefore, we investigated whether hypoxia contributes to dedifferentiation and deregulated metabolism in cultured hepatocytes. To this end, murine hepatocytes were cultured under static or shaken (60 revolutions per minute) conditions in a collagen sandwich. The effect of hypoxia on hepatocyte cultures was examined by metabolites in media and cells, hypoxia‐inducible factors (HIF)‐1/2α western blotting, and real‐time quantitative polymerase chain reaction for HIF target genes and key genes of glucose and lipid metabolism. Hepatocytes in shaken cultures showed lower glycolytic activity and triglyceride accumulation than static cultures, compatible with improved oxygen delivery and mitochondrial energy metabolism. Consistently, static cultures displayed significant HIF‐2α expression, which was undetectable in freshly isolated hepatocytes and shaken cultures. Transcript levels of HIF target genes (glyceraldehyde 3‐phosphate dehydrogenase [Gapdh], glucose transporter 1 [Glut1], pyruvate dehydrogenase kinase 1 [Pdk1], and lactate dehydrogenase A [Ldha]) and key genes of lipid metabolism, such as carnitine palmitoyltransferase 1 (Cpt1), apolipoprotein B (Apob), and acetyl‐coenzyme A carboxylase 1 (Acc1), were significantly lower in shaken compared to static cultures. Moreover, expression of hepatocyte nuclear factor 4α (Hnf4α) and farnesoid X receptor (Fxr) were better preserved in shaken cultures as a result of improved oxygen delivery. We further revealed that HIF‐2 signaling was involved in hypoxia‐induced down‐regulation of Fxr. Conclusion: Primary murine hepatocytes in static culture suffer from hypoxia. Improving oxygenation by simple shaking prevents major changes in expression of metabolic enzymes and aberrant triglyceride accumulation; in addition, it better maintains the differentiation state of the cells. The shaken culture is, therefore, an advisable strategy for the use of primary hepatocytes as an in vitro model. (Hepatology Communications 2018;2:299‐312)
Hormonal factors and pancreatic cancer risk in women: The Malmö Diet and Cancer Study
Authors: Andersson Gustav , Borgquist Signe , Jirström Karin
Published: February 2018

The incidence of pancreatic cancer is leveling between sexes. Smoking, high age and heredity are established risk factors, but evidence regarding the influence of hormonal factors is unclear. In this study, we investigated the associations of reproductive factors, use of oral contraceptives (OC) and hormone replacement therapy (HRT) with pancreatic cancer risk in the Malmö Diet and Cancer Study, a prospective, population‐based cohort encompassing 17,035 women. Up until 31 December 2015, 110 women were identified with incident pancreatic cancer through the Swedish Cancer Registry. Higher age at menarche was significantly associated with pancreatic cancer risk (age‐adjusted [hazard ratio] HR = 1.17; 95% confidence interval [CI] 1.04–1.32, and fully adjusted HR = 1.17; 95% CI 1.04–1.32). Ever use of OC was not significantly associated with pancreatic cancer risk but ever use of HRT was significantly associated with a decreased risk of pancreatic cancer (age‐adjusted HR = 0.47, 95% CI 0.23–0.97, and fully adjusted HR = 0.48, 95% CI 0.23–1.00), in particular use of estrogen‐only regimen (age‐adjusted HR = 0.21; 95% CI 0.05–0.87 and fully adjusted HR = 0.22; 95% CI 0.05–0.90). Age at menopause or first childbirth, parity and breastfeeding history were not significantly associated with pancreatic cancer risk. Collectively, these findings suggest a protective role of female hormones against pancreatic cancer. Further studies are needed, and potential modifying genetic factors and indirect hazardous effects of smoking should also be considered.
Report on Strategy Theme ‘ON‐FARM’
Authors: Lee Bonghoon , Ahmed Kadhim Mohsin
Published: February 2018

The International Commission on Irrigation and Drainage (ICID) organized four strategy themes in order to realize various missions of ICID: ON‐FARM, SCHEMES, BASIN and KNOWLEDGE. The Working Groups (WGs) under the theme ON‐FARM deal with the application of water at the farm level and the best way to use it to increase the productivity and impacts of application of irrigation water, including its quality at the farm level.

After presenting a review of the recent activities of three WGs under the strategy theme ON‐FARM, this report suggests the way forward and recommendations to contribute to addressing ICID's mission as follows: to foster sufficient capacity to the extent that ICID can cope with her mission in the future, it is necessary to foster young professionals (YPs) and to develop their capacity through designating a proper training centre from National Committees (NCs) with the cooperation of donor agency, e.g. UNESCO. In addition, it is important that ICID provide and develop an open international platform to involve all relevant stakeholders of water and agriculture, including the private sector. Copyright © 2018 John Wiley & Sons, Ltd.
THE IMAGINED COMMUNITY OF ACCESS AND EQUITY
Authors: Everingham Christine
Published: February 2018

Access and Equity programs are framed within the discourse of citizenship and organised around the notion of individual rights. This marks a shift in orientation away from the individual liberation strategies of the 1960s and 1970s, which utilised the notion of ‘community’ as the major site of struggle. Nevertheless, Access and Equity programs must engage with the multiple and contradictory meanings that were infused into the notion of community during these earlier struggles. They must also engage with the ‘communities’ that were politically constituted during this era and utilise the community‐based services that are now a fundamental part of the welfare system. It is argued that governments are able to utilise this legacy to resolve the contradictions inherent in Access and Equity programs, in particular the tension between ‘sameness’ and ‘difference’, universal citizenship and substantive equality. As this tension become more acute with government stringency measures, the limitations of reform strategies based on the notion of citizenship become more apparent.
HEALTH RISK ANALYSIS AND SOCIOMEDICAL TECHNOLOGIES OF THE SELF: PRIVATE HEALTH INSURANCE GETS INTO HEALTH PROMOTION
Authors: Cheek Julianne , Willis Eileen
Published: February 2018

In October 1994 the then Australian Federal Minister for Health, Dr. Carmen Lawrence, announced that Medicare, the Australian universal national healthcare fund was considering introducing Healthtrac a computerised health promotion program. The change of government in 1995 put paid to this plan, however, lifestyle based health promotion programs, including computerised programs, are an increasing trend in contemporary health care. Research from the United States indicates a growing interest by private insurers and Health Maintenance Organisations (HMOs) in funding and encouraging members, particularly older members and retirees, to engage in healthy lifestyle programs, some of which provide written reports, periodic up‐dates and checks to members as well as summary advice to employers and insurers.

In this article we argue that while many of these programs are well researched programs that take cognisance of the contradictions surrounding scientific research related to lifestyle behaviours, disease and disability, they take a narrow approach to health promotion. Further, in the hands of private insurers and HMOs these programs have the potential to become sociomedical techniques (Stone 1989) of dominance, arising out of risk analysis that informs and refines techniques of governance of the self (Burchell 1993; Rose 1993). Consistent with Stevensen and Burke (1991) we see health promotion not as a new social movement, but as a political strategy of the state and capitalism to deal with among other things, escalating health care budgets. Given this, health promotion strategies that overly focus on risk analysis for the individual citizen reinforce techniques of self‐governance by linking lifestyle behaviour to immorality as well as potentially creating a culture of anxiety ‐ surely a public health problem in itself.
SOURCES OF INFORMATION ABOUT HIV/AIDS AND PERCEIVED RISK OF INFECTION AMONG HETEROSEXUAL YOUNG ADULTS: 1989 AND 1994
Authors: Timmins Perri , Gallois Cynthia , McCamish Malcolm , Terry Deborah
Published: February 2018

This paper reports a study of sources of information about HIV/AIDS and trust of the sources among heterosexuals in 1989 (113 females and 91 males) and 1994 (185 females and 66 males). We also examined whether perceived personal risk of HIV infection was predicted by sources of information about HIV/AIDS, trust of the sources, how informed about AIDS people believed they were, and perceived risk of infection to others, as well as whether there was a relationship between perceived personal risk and safe sex behaviour. Participants received most of their information about AIDS/HIV from magazines, newspapers, and television, but placed most trust on sources such as doctors and HIV/AIDS organisations. Perceived personal risk was influenced most by perceived risk to friends and to people with the same sexual practices. In the 1994 sample, perceived personal risk was correlated with the amount of condom use among participants with sexual experience. These results indicate ther has been relative stability across a five‐year period. They also point to the continuing discrepancy among young heterosexuals between the most‐used and most‐trusted sources of information, as well as to the importance of peer influence on perceptions of personal risk of HIV infection.
SUPPRESSING THE VOICES OF THE SURVIVORS: SEXUAL EXPLOITATION BY HEALTH PRACTITIONERS
Authors: Easteal Patricia
Published: February 2018

It has been speculated that the effects of sexual assault on victims are exacerbated by non‐disclosure. It is therefore important to explore the reasons why survivors do not disclose or make formal reports. This paper looks at some of the factors that have stopped many survivors of sexual assault or exploitation by health professionals from reporting sexual assault. A sense of shame is the principal deterrent; this is coupled with other factors derived from the nature of the relationship ‐ the inequality and trust inherent between the patient and practitioner and, in counselling contexts, possibly the added power inequity in transference.

For those who do report, their experiences with complaints units, Medical Review Boards and the courts may prove to be less than satisfactory. The article looks in depth at an example of the latter, illustrating how interpretations of consent in sexual assault legislation can be particularly problematic with health practitioner perpetrators. The courts and boards may fail to understand the consent issue and delay in reporting from the point of view of survivors. Consequently, their voices will continue to be suppressed.
RURAL DISADVANTAGE IN THE DISTRIBUTION OF SOUTH AUSTRALIAN HOME AND COMMUNITY CARE FUNDING
Authors: Barber James G.
Published: February 2018

In this paper, the level of HACC funding under the South Australian Dementia Support and Respite Projects and the Community Support Scheme was compared across Domiciliary Care and Human Services and Health regions. Results revealed that metropolitan regions generally received more than their per capita share of HACC funding despite the greater cost of community services in rural areas and the relative paucity of supplementary or alternative rural services. The need for greater planning in the distribution of HACC funds, including moving towards formula funding is identified.
REGULATING WORKERS COMPENSATION: THE MEDICO LEGAL EVALUATION OF INJURED WORKERS IN VICTORIA
Authors: Gribich Carol , McGartland Michael , Polgar Steve
Published: February 2018

Sociological research on occupational injury has been dominated by perspectives from the social organisation of work and the labour process. What is missing from this literature is an explanation of the actual experiences at the individual worker within the processes of legitimation of occupational injury. This study explores the experiences of injured workers as they move through the medico‐legal process. Medical reports and clients perspectives were used to expose the positions of doctors, insurance companies, lawyers and workers compensation bureaucrats as they form a complex intersection of power and interest in the regulation of injured workers. In particular, the conflicting roles of doctors as both gatekeepers and service providers were highlighted in the maintenance of stigmatised damaged workers.
Epiproteome profiling of cadmium‐transformed human bronchial epithelial cells by quantitative histone post‐translational modification–enzyme‐linked immunosorbent assay
Authors: Liang Zhan‐Ling , Wu Dan‐Dan , Yao Yue , Yu Fei‐Yuan , Yang Lei , Tan Heng Wee , Hylkema Machteld N. , Rots Marianne G. , Xu Yan‐Ming , Lau Andy T. Y.
Published: February 2018

Cadmium (Cd), a carcinogenic toxic metal, is pervasively distributed in the soil, water and air. Chronic exposure to Cd has been correlated to lung disease development including cancers. Although many studies have been conducted to investigate the proteome response of cells challenged with Cd, the epiproteomic responses (i.e., global histone post‐translational modifications [PTMs]), particularly in human lung cells, are largely unexplored. Here, we provide an epiproteome profiling of human bronchial epithelial cells (BEAS‐2B) chronically treated with cadmium chloride (CdCl2), with the aim of identifying global epiproteomic signatures in response to Cd epigenotoxicity. Total histone proteins from Cd‐treated and untreated BEAS‐2B cells were isolated and subject to quantitative histone PTM–enzyme‐linked immunosorbent assay using 18 histone PTM antibodies. Our results unveiled that chronic Cd treatment led to the marked downregulation of H3K4me2 and H3K36me3 and upregulation of H3K9acS10ph, H4K5ac, H4K8ac and H4K12ac PTM marks. Cd‐treated cells exhibit transformed cell properties as evidenced by enhanced cell migration and the ability of anchorage‐independent growth on soft agar. Notably, treatment of Cd‐transformed cells with C646, a potent histone acetyltransferase inhibitor, suppressed the expression of mesenchymal marker genes and cell migration ability of these cells. Taken together, our studies provide for the first time the global epiproteomic interrogation of chronic Cd‐exposed human lung cells. The identified aberrant histone PTM alterations associated with Cd‐induced epigenotoxicity likely account for the epithelial−mesenchymal transition and neoplastic survival of these cells.
Biomimetic peptide display from a polymeric nanoparticle surface for targeting and antitumor activity to human triple‐negative breast cancer cells
Authors: Bressler Eric M. , Kim Jayoung , Shmueli Ron B. , Mirando Adam C. , Bazzazi Hojjat , Lee Esak , Popel Aleksander S. , Pandey Niranjan B. , Green Jordan J.
Published: February 2018

While poly(lactic‐co‐glycolic acid)‐block‐polyethylene glycol (PLGA‐PEG) nanoparticles (NPs) can encapsulate drug cargos and prolong circulation times, they show nonspecific accumulation in off‐target tissues. Targeted delivery of drugs to tumor tissue and tumor vasculature is a promising approach for treating solid tumors while enhancing specificity and reducing systemic toxicity. AXT050, a collagen‐IV derived peptide with both antitumor and antiangiogenic properties, is shown to bind to tumor‐associated integrins with high affinity, which leads to targeted accumulation in tumor tissue. AXT050 conjugated to PLGA‐PEG NPs at precisely controlled surface density functions both as a targeting agent to human tumor cells and demonstrates potential for simultaneous antitumorigenic and antiangiogenic activity. These targeted NPs cause inhibition of adhesion and proliferation in vitro when added to human triple‐negative breast cancer cells and microvascular endothelial cells through binding to integrin αVβ3. Furthermore, we find an in vivo biphasic relationship between tumor targeting and surface coating density of NPs coated with AXT050. NPs with an intermediate level of 10% peptide surface coating show approximately twofold greater accumulation in tumors and lower accumulation in the liver compared to nontargeted PLGA‐PEG NPs in a murine biodistribution model. Display of biomimetic peptides from NP surfaces to both target and inhibit cancer cells has the potential to enhance the activity of cancer nanomedicines. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1753–1764, 2018.
Negative influence of pKa on activation energy barrier: A case study for double proton transfer reaction in inorganic acid dimers
Authors: Parida Rakesh , Giri Santanab
Published: February 2018

Strength of acid can be determined by means of pKa value. Attempts have been made to find a relationship between pKa and activation energy barrier for a double proton transfer (DPT) reaction in inorganic acid dimers. Negative influence of pKa is observed on activation energy (Ea) which is contrary to the general convention of pKa. Four different levels of theories with two different basis sets have been used to calculate the activation energy barrier of the DPT reaction in inorganic acid dimers. A model based on first and second order polynomial has been created to find the relationship between activation energy for DPT reaction. © 2018 Wiley Periodicals, Inc.
Generalization of equivalence relations from photos to objects by preschool children
Authors: Ayres‐Pereira Vanessa , Canovas Daniela S. , Varella André A. B. , de Souza Deisy G.
Published: February 2018

Generalized equivalence classes are stimulus classes that consist of equivalent stimuli and other physically similar class‐member stimuli. The present study evaluated whether preschool children would form equivalence classes among photos of abstract objects (2D) and show equivalence generalization to the corresponding objects (3D), printed photos (2D stimuli), and to black‐and‐white drawn pictures (2D stimuli). Six typically developing children were taught arbitrary relations to establish three 3‐member equivalence classes with 2D stimuli presented on a computer screen. AB‐AC baseline relations (for half of the participants) and AB‐BC relations (for the other half) were taught using a multiple‐probe design to assess taught and tested relations. After class formation, three types of generalization probes were conducted: generalization to 3D stimuli, generalization between 2D (printed photos) and 3D stimuli, and generalization to drawn pictures (2D). All of the participants formed the equivalence classes. Two participants met the criterion for all three generalization probe types. Two participants presented mixed results across tests, and two participants did not exhibit equivalence generalization. The results demonstrated equivalence generalization from 2D to 3D stimuli in preschool children, although the variability across participants suggests that such generalization cannot be assumed a priori.
Synthesis, Structure, and Some Transformations of Novel 1,5‐methanonaphtho[1,2‐g][1,3,5]oxadiazocine Derivatives
Authors: Kulakov Ivan V. , Ogurtsova Diana N. , Seilkhanov Tulegen M. , Gatilov Yuriy V. , Fisyuk Alexander S.
Published: February 2018

Biginelli reaction of thiourea, 2‐hydroxy‐1‐naphthaldehyde, and acetoacetic ester (or benzoyl acetone) under solvent‐free conditions and MW irradiation gave novel 3‐thioxo‐2,3,4,5‐tetrahydro‐1H‐1,5‐methanonaphtho[1,2‐g][1,3,5]oxadiazocine derivatives. Subsequent reaction of the obtained compounds with α‐chloroacetamide led to 5‐methyl‐5H,13H‐5,13‐methanonaphtho[1,2‐g] thiazolo[2,3‐d][1,3,5]oxadiazocin‐1(2H)‐ones, which were converted to the Z‐isomers of 2‐arylylidene‐5H,13H‐5,13‐methanonaphtho[1,2‐g]thiazolo[2,3‐d][1,3,5]oxadiazocin‐1(2H)‐one derivatives by reaction with arylaldehydes. The structures of the products were characterized by 1H NMR, 13C NMR spectra, and X‐ray analysis.
A Green, Organometallic Catalyzed Synthesis of a Series of Novel Functionalized 4‐Aroyl‐4H‐benzo[g]chromenes through One‐pot, Three Component Reaction
Authors: Khalafy Jabbar , Ilkhanizadeh Siamand , Ranjbar Masoumeh
Published: February 2018

A new series of 4‐aroyl‐4H‐benzo[g]chromene derivatives have been synthesized through an efficient, straightforward, and environmentally acceptable one‐pot, three component reaction of malononitrile, different arylglyoxals, and 2‐hydroxy‐1,4‐naphtoquinone (lawsone) in short reaction times and high to excellent yields. The zinc complex of amino acid L‐proline, that is, Zn[L‐proline]2 has been prepared and used as highly active, recyclable, noncorrosive, and water soluble Lewis acid catalyst for this transformation.
Multicenter reproducibility study of diffusion MRI and fiber tractography of the lumbosacral nerves
Authors: Haakma Wieke , Hendrikse Jeroen , Uhrenholt Lars , Leemans Alexander , Warner Thorup Boel Lene , Pedersen Michael , Froeling Martijn
Published: February 2018

Background

Diffusion tensor imaging (DTI) has been applied in the lumbar and sacral nerves in vivo, but information about the reproducibility of this method is needed before DTI can be used reliably in clinical practice across centers.

Purpose

In this multicenter study the reproducibility of DTI of the lumbosacral nerves in healthy volunteers was investigated.

Study Type

Prospective control series.

Subjects

Twenty healthy subjects.

Field Strength/Sequence

3T MRI. 3D turbo spin echo, and 3.0 mm isotropic DTI scan.

Assessment

The DTI scan was performed three times (twice in the same session, intrascan reproducibility, and once after an hour, interscan reproducibility). At site 2, 1 week later, the protocol was repeated (interweek reproducibility). Fiber tractography (FT) of the lumbar and sacral nerves (L3–S2) was performed to obtain values for fractional anisotropy, mean, axial, and radial diffusivity.

Statistical Tests

Reproducibility was determined using the intraclass correlation coefficient (ICC), and power calculations were performed.

Results

FT was successful and reproducible in all datasets. ICCs for all diffusion parameters were high for intrascan (ranging from 0.70–0.85), intermediate for interscan (ranging from 0.61–0.73), and interweek reliability (ranging from 0.58–0.62). There were small but significant differences between the interweek diffusivity values (P < 0.0005). Depending on the effect size, nerve location, and parameter of interest, power calculations showed that sample sizes between 10 and 232 subjects are needed for cross‐sectional studies.

Data Conclusion

We found that DTI and FT of the lumbosacral nerves have intermediate to high reproducibility within and between scans. Based on these results, 10–58 subjects are needed to find a 10% change in parameters in cross‐sectional studies of the lumbar and sacral nerves. The small significant differences of the interweek comparison suggest that results from longitudinal studies need to be interpreted carefully, since small differences may also be caused by factors other than disease progression or therapeutic effects.

Level of Evidence: 1

Technical Efficacy: Stage 2

J. Magn. Reson. Imaging 2018;48:951–963.
Diagnostic performance of the Sofia® influenza A+B fluorescent immunoassay in adult outpatients in Northern Taiwan
Authors: Yang Jeng‐How , Huang Po‐Yen , Shie Shian‐Sen , Yang Shuan , Tsao Kuo‐Chien , Wu Tsu‐Lan , Wu Ting‐Shu , Huang Ching‐Tai
Published: February 2018

To evaluate the diagnostic performance of the Sofia influenza A+B fluorescent immunoassay (Sofia FIA), we performed a prospective study at the Chang Gung Memorial Hospital in Taiwan from January 2012 to December 2013. Patients who presented at out‐patient clinics or the emergency department with influenza‐like illness were included. Upper respiratory tract specimens were collected from oropharynx or nasopharynx. Performance of the Sofia FIA was compared to that of the Formosa One Sure Flu A/B Rapid Test. A Real‐time reverse transcriptase‐polymerase chain reaction assay (RT‐PCR) and/or virus culture were used as reference standards. Of the 109 enrolled patients, the sensitivity, specificity, positive, and negative predictive values of the Sofia FIA to detect influenza A virus were 82%, 89%, 77%, and 89%, respectively. These parameters were 100% when the samples were from nasopharynx. The positive predictive value for influenza B virus detection was 29%. The sensitivity of the Sofia FIA for detection of influenza A virus was 93% between days 2 and 4 after onset of symptoms. For specimens with low viral loads (RT‐PCR cycle threshold between 30 and 34.9), the sensitivity of The Sofia FIA was 83% (10/12). The Sofia FIA performed effectively in detecting influenza A virus infection. With nasopharyngeal samples, the performance was comparable to RT‐PCR. Although influenza viral load typically decreases with time, the Sofia FIA was sensitive enough to identify influenza infecting patients presenting after several days of illness. However, a high false positive rate limits the assay's usefulness to identify influenza B virus infection.
Implications of employing detailed urban canopy parameters for mesoscale climate modelling: a comparison between WUDAPT and GIS databases over Vienna, Austria
Authors: Hammerberg Kris , Brousse Oscar , Martilli Alberto , Mahdavi Ardeshir
Published: February 2018

One of the major obstacles to using numerical weather prediction models for guidance on mitigating urbanization's impact on local and regional climate is the lack of detailed and model ready morphological data at urban scale. The World Urban Database and Access Portal Tool (WUDAPT) is a recent project developed to extract climate relevant information on urban areas, in the form of local climate zones (LCZs), out of remote sensing imagery. This description of the urban landscape has been tested and used for parameterization of different urban canopy models (UCM) for mesoscale studies. As detailed information is usually bounded within cities' centres, crowdsourced and remote sensing data offer the possibility to move beyond the old barriers of urban climate investigations by studying the full range of variation from the urban core to the periphery and its related impacts on local climate. Thus, for this study we sought to compare the relative impact of using the WUDAPT methodology versus a simplified definition of the urban morphology extracted out of detailed GIS information to initialize a regional weather model and compare the output against official and crowdsourced weather station networks. A case study over Vienna, Austria was conducted using the weather research forecasting (WRF) model, coupled with the building effect parameterization and building energy models (BEP–BEM) in five distinct seasonal periods. Results demonstrated that using detailed GIS data to derive morphological descriptions of LCZs for mesoscale studies provided only a marginal overall improvement over using the default WUDAPT parameters based on the ranges proposed by Stewart and Oke (2012). The findings also highlighted the importance of developing techniques that are better at capturing the morphological heterogeneity across the entire urban landscape and thus improve our understandings of UCM performance over urban areas.
Evidence and mechanism by which upper partial fibulectomy improves knee biomechanics and decreases knee pain of osteoarthritis
Authors: ZeYu Huang Yong Nie , Xu Bin , Shen Bin , Kraus Virginia B. , Pei FuXing
Published: February 2018

To investigate the change in short‐term clinical outcomes and biomechanical properties of the knee in response to upper partial fibulectomy and to probe into the biomechanical mechanism underlying the clinical benefits of upper partial fibulectomy for medial compartment knee osteoarthritis (KOA). A total of 29 patients with medial compartment KOA underwent upper partial fibulectomy. Visual analog scale (VAS) pain, the hospital for special surgery knee score (HSS), hip‐knee‐ankle (HKA) angle (measured in the frontal plane), and flexion/extension range of motion of the knee were assessed before and up to 6 months after surgery. Patients and 20 healthy controls were evaluated by 3D gait analysis and dynamic lower limb musculoskeletal analysis. Both VAS pain and HSS score were significantly improved (p < 0.001) one day after surgery and steadily improved during the subsequent 6 months. HKA angle improved (p = 0.025) immediately and remained stable by 3 months after surgery. The decreased overall peak KAM (decreased by 11.1%) and increased HKA angle (increased by 1.80 degrees from a more varus to more neutral alignment) of affected and operated side by 6 months after surgery were observed. Muscle activity of biceps femoris caput longum of affected and operated side increased immediately and was equivalent to healthy controls by 6 months after surgery (p = 0.007). This pilot study provides biomechanical evidence of benefit from partial upper fibulectomy and indicates a plausible rationale for the improvement in clinical symptoms. Long‐term clinical outcomes and precise biomechanical mechanism of partial upper fibulectomy should be further investigated. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:2099–2108, 2018.