bluuebunny/crossref_metadata_2025 huggingface dataset:
Management incentives to recognise intangible assets
Authors: Russell Mark
Published: July 2015

The paper examines whether the introduction of the international financial reporting standards (IFRS) in Australia changed management incentives to recognise intangible assets. We examine post‐IFRS changes in managerial opportunism and economic benefits associated with the recognition of intangible assets. We find evidence after IFRS of significant change in intangible asset recognition concurrent with share issues. We also find that the association between economic benefits and intangible assets changed following IFRS. Evidence is provided that the economic benefits associated with goodwill were enhanced by IFRS, whereas IIA and E&E asset information became less useful to financial report users.
Prevalence of infraocclusion of primary molars determined using a new 2D image analysis methodology
Authors: Odeh R , Mihailidis S , Townsend G , Lähdesmäki R , Hughes T , Brook A
Published: July 2015

Background

The reported prevalence of infraocclusion varies widely, reflecting differences in definitions and measurement/scoring approaches. This study aimed to quantify the prevalence and extent of infraocclusion in singletons and twins during the late mixed dentition stage of dental development using a new diagnostic imaging method and objective criteria. The study also aimed to determine any associations between infraocclusion and gender, arch type, arch side and tooth type.

Methods

Two samples were analysed, 1454 panoramic radiographs of singletons and 270 dental models of twins. Both samples ranged in age from 8 to 11 years. Adobe Photoshop CS5 was used to measure the extent of infraocclusion. Repeatability tests showed systematic and random errors were small.

Results

The prevalence in the maxilla was low (<1%), whereas the prevalence in the mandible was 22% in the singleton sample and 32% in the twin sample. The primary mandibular first molar was affected more often than the second molar. There was no significant difference in the expression between genders or sides.

Conclusions

A new technique for measuring infraocclusion has been developed with high intra‐ and interoperator reproducibility. This method should enhance early diagnosis of tooth developmental abnormalities and treatment planning during the late mixed dentition stage of development.
Thyme travels: 15N isoscapes of Thymus vulgaris L. invasion in lightly grazed pastoral communities
Authors: Nielsen J. A. , Frew R. D. , Whigham P. A. , Callaway R. M. , Dickinson K. J. M.
Published: July 2015

Alterations to ecosystem nitrogen (N) cycling by introduced plant species may increase the invasibility of habitat providing a positive feedback for the introduced species to become invasive. Spatial patterns of foliar and soil δ15N ratios reflect variation in rates and process of N‐cycling across invaded landscapes and provide insight into N‐source uptake and utilization strategies of invasive plant species. To evaluate invasion‐associated changes in soil and foliar δ15N at different scales: regional (among different sites), local (between north‐ and south‐facing aspect at the same site), and microsite (within populations in the same community), we measured foliar and soil δ15 N, animal faeces cover (as a proxy for grazing intensity) and N2‐fixing species cover from inside to outside Thymus vulgaris L. (thyme)‐invaded lightly grazed pastoral communities in Central Otago, southern South Island, New Zealand. Mean thyme foliar δ15N were near‐zero across the invaded landscape, and did not change across the advancing edge of invasion or with aspect. There was no evidence that associations with N2‐fixing species provide a potential N source. Soil δ15N was lower inside of thyme compared to at the edge or outside of thyme and was varied between aspects at some sites. Animal faeces cover as a proxy for grazing intensity explained only 23% of this observed variation of soil δ15N. Thyme invasion may result in lowered soil δ15N reflecting alterations to N dynamics. Associated invasion‐related impacts of animal grazing may also impact soil δ15N. Further studies are required to distinguish the underlying mechanism responsible for the observed patterns of foliar and soil δ15N values across thyme‐invaded Central Otago landscapes.
HE4, CA125, the Risk of Malignancy Algorithm and the Risk of Malignancy Index and complex pelvic masses ‐ a prospective comparison in the pre‐operative evaluation of pelvic masses in an Australian population
Authors: Richards Anthony , Herbst Unine , Manalang Jane , Pather Selvan , Saidi Samir , Tejada‐Berges Trevor , Tan Kris , Williams Paul , Carter Jonathan
Published: July 2015

Background

Human epididymis protein 4 (HE4) has been proposed as a novel biomarker for the diagnosis of epithelial ovarian cancer. Using HE4 and CA125, the risk of malignancy algorithm (ROMA) has been shown to be effective in the stratification of epithelial ovarian cancer risk.

Aims

To determine the effectiveness of HE4 and ROMA in the diagnosis of malignancy of women presenting with a complex pelvic mass in an Australian population and to compare it with CA125 and the risk of malignancy index (RMI).

Materials and Methods

Prospective recruitment of women was conducted between October 2012 and March 2014 (n = 50). CA125 and HE4 serum concentrations were collected and stored for subsequent analysis. Sensitivities, specificities, positive predictive values (PPV) and negative predictive values (NPV) were calculated for HE4, CA125, ROMA and the RMI. Receiver operating characteristic (ROC) area under the curves (AUC) were also calculated for comparison.

Results

There was a higher HE4 level in women with ovarian cancer compared with women with benign pathology (P = 0.008), and this observation was seen in benign versus stage 1 ovarian cancer women (P = 0.025). HE4 had a better specificity than CA125 for the diagnosis of ovarian cancer in all women (P = 0.022), and this effect was also observed in premenopausal women (P = 0.012). Furthermore, the ROC‐AUC for HE4 was superior than CA125 in all women (P = 0.0451). The ROMA algorithm was not inferior to the RMI calculation in this population.

Conclusions

In an Australian population, HE4 and ROMA are useful in the diagnosis of epithelial ovarian cancer.
Outcomes of high‐risk obstetric transfers in New South Wales and the Australian Capital Territory: The High‐Risk Obstetric Transfer Study
Authors: Goh Amy , Browning Carmo Kathryn , Morris Jonathan , Berry Andrew , Wall Margaret , Abdel‐Latif Mohamed
Published: July 2015

Background

In New South Wales and the Australian Capital Territory, in utero transfers to manage maternal or neonatal risks are highly challenging owing to geography and centralisation of tertiary perinatal care.

Aims

The study aims to document the outcomes of high‐risk obstetric transfers.

Materials and Methods

A prospective observational study was conducted from 2010 to 2011 documenting urgent requests for obstetric transfers to tertiary centres across NSW/ACT for pregnancies 20 weeks’ gestation or greater. Outcomes of transfers were allocated apriori to ‘delivered at the receiving hospital’, ‘failed/delayed transfer’ or ‘discharged/transferred undelivered’. Our hypothesis is that each outcome has a specific group of associated clinical factors.

Results

Of the 249 transfer requests included in the study, 40% delivered at the receiving hospital, 7% were failed/delayed transfers, and 45% were discharged/transferred undelivered. Cases delivering at the receiving hospital were significantly associated with older mothers, twin pregnancies, pregnancy induced hypertension (PIH) or premature rupture of membranes (PROM) with/without threatened preterm labour (TPL) as the indications for transfer and having three indications for transfer. Cases that were discharged/transferred undelivered were significantly associated with singleton pregnancies, TPL and/or antepartum haemorrhage (APH) as the indication for transfer and having one indication for transfer. There were no significantly associated factors for failed/delayed transfers.

Conclusions

The study confirms the hypothesis that particular transfer outcomes are associated with different factors. The findings also show that less than half of urgent obstetric transfers result in delivery at the receiving hospital, suggesting that there exists significant opportunities for further research into predicting preterm delivery, thereby improving the care of women with high‐risk pregnancies.
T helper 2 response in allergic bronchopulmonary aspergillosis is not driven by specific Aspergillus antigens
Authors: Jolink H. , de Boer R. , Willems L. N. A. , van Dissel J. T. , Falkenburg J. H. F. , Heemskerk M. H. M.
Published: July 2015

Allergic bronchopulmonary aspergillosis (ABPA) is characterized by an allergic immunological response to Aspergillus fumigatus. In this study, we investigated whether certain Aspergillus antigens are more allergenic than others, as was postulated previously. We stimulated peripheral blood mononuclear cells from patients with ABPA with the classically described A. fumigatus allergens Aspf1, Aspf2, Aspf3, and Aspf4, as well as two other Aspergillus antigens, Crf1 and Catalase1. Activated CD4+ T cells displayed a T helper 2 phenotype with the production of IL‐4 in response to stimulation with several of these different antigens. Immune responses were not limited to the classically described A. fumigatus allergens. In healthy individuals, we demonstrated a similar recognition profile to the different antigens, but in contrast the activated CD4+ T cells exerted a T helper 1 phenotype and mainly produced IFN‐γ after stimulation with A. fumigatus antigens. In conclusion, irrespective of the A. fumigatus antigen, the T‐cell immune response in patients with ABPA is skewed to a T helper 2 cytokine secretion profile.
Parotidectomy: surgery in evolution
Authors: Eviston Timothy J. , Yabe Takako E. , Gupta Ruta , Ebrahimi Ardalan , Clark Jonathan R.
Published: July 2015

Background

Approximately 15 years ago, Bron and O'Brien described a large Australian series of 248 patients focusing on facial nerve function post parotidectomy performed by a single surgeon over an 8‐year period. The primary aim of this study was to assess changes in pathology, surgical approach and outcomes following parotidectomy in a comparable single surgeon series from the same institution.

Methods

Details of patients undergoing parotidectomy by, or under the supervision of, the senior author (JRC) between February 2006 and December 2013 were retrospectively reviewed. Operative reports and post‐operative complications were recorded using standardized templates. Comparison with the Bron and O'Brien outcomes is presented.

Results

A total of 405 consecutive parotidectomies were performed for both benign and malignant disease in 401 patients. Univariable predictors of facial nerve weakness (temporary or permanent) on logistic regression were neck dissection (odds ratio 2.1, 95% confidence interval (CI) 1.23–3.67, P = 0.007) and operation type, with focused tumour dissection having 0.07 times the odds (95% CI 0.01–0.52, P = 0.010) and a limited parotidectomy approach having 0.5 times the odds (95% CI 0.26–0.91, P = 0.024) of facial palsy compared with a complete superficial parotidectomy.

Conclusion

A number of changes in the management of parotid pathology in Australia have occurred in the last two decades, including improvements in the characterization of malignant parotid tumours, a continuing evolution towards less aggressive surgery, a more selective approach to elective neck dissection and an increasing appreciation of the techniques that can be used to minimize the aesthetic complications of parotid surgery.
Role of upfront surgery for recurrent gastrointestinal stromal tumours
Authors: Tan Grace Hwei Ching , Wong Jolene Si Min , Quek Richard , Goh Brian Kim Poh , Kwok Li Lian , Pan Summer , Soo Khee Chee , Teo Melissa Ching Ching
Published: July 2015

Background

Gastrointestinal stromal tumours (GISTs), despite complete surgical cytoreduction, are associated with recurrence rates of up to 50% at 2 years. At recurrence, tyrosine kinase inhibitor (TKI) therapy is recommended, conferring a survival of up to 55 months. Several studies have shown that patients with TKI‐responsive recurrent GIST benefit from surgery. However, no studies have compared upfront surgery versus TKI alone.

Methods

Data were retrospectively collected from patients with recurrent GIST treated at Singapore General Hospital and National Cancer Centre Singapore over a 12‐year period. Our primary end points were disease‐free and overall survival (OS).

Results

A total of 186 patients underwent curative surgery for GIST between January 2000 and June 2012. Fifty‐six (30%) patients experienced recurrence, of which 30 (54%) had resectable recurrent disease. Twenty‐four patients underwent upfront surgery for their recurrence while the remaining six patients opted for non‐surgical management. The median OS for all patients with recurrent GIST was 5.3 years (95% confidence interval (CI) 3.2–8.4). It was not reached for patients who underwent curative surgery for their recurrence, and was 3.9 years (95% CI 2.4–7.0) for patients who had palliative TKI and conservative management. There were significant differences in OS and disease‐specific survival between patients who underwent curative surgery for recurrence compared with those who had not.

Conclusion

Our study shows that upfront surgery is a reasonable treatment strategy for selected patients with recurrent GIST.
Assessment of the management outcomes of body packers
Authors: Alfa‐Wali Maryam , Atinga Angela , Tanham Matthew , Iqbal Qamar , Meng Aw‐Yong , Mohsen Yasser
Published: July 2015

Background

The constant need for rapid financial gain drives the international illegal drug industry, which encourages healthy individuals to smuggle drugs through internal concealment. The aim of this study was to evaluate our practice of the management of body packers using a hospital‐based protocol in order to validate it.

Methods

Electronic hospital data were retrospectively reviewed between 2000 and 2013 of all patients that were admitted to Hillingdon Hospital with a history of internal drug concealment. Demographic as well as clinical data including investigations and management were collected.

Results

One hundred and twenty patients were admitted over the study period to our surgical unit. This included 86 male and 34 female patients with a mean age of 38 (range 19–64) years. Three per cent (n = 4) underwent surgery for either cocaine toxicity or obstruction. The rest of the patients were managed conservatively with bowel cleansing preparations to encourage the natural passage of drug packages.

Conclusion

Conservative treatment is safe and effective for drug body packers. We therefore recommend conservative management to be the mainstay for body packers with surgery only being indicated on clinical grounds.
Basic data underlying clinical decision‐making and outcomes in emergency department thoracotomy: tabular review
Authors: Dayama Anand , Sugano Dordaneh , Spielman Daniel , Stone Melvin E. , Kaban Jody , Mahmoud Ahmed , McNelis John
Published: July 2015

Background

Emergency department thoracotomy (EDT) is a formidable and dramatic last attempt by the trauma surgeon to save the life of a patient in extremis. The aim of this report is to provide a benchmark for comparison with past results by reviewing all available published data since the American College of Surgeons Committee on Trauma review article in 2001, which reviewed literature from 1966 to 1999 regarding indications for and outcomes of EDT.

Methods

A comprehensive literature search in MEDLINE Library databases was performed for EDT. Data were extracted by three independent reviewers.

Results

We identified 37 papers with a total of 3466 patients. A total of 85.2% (1720 of the 2018) had penetrating trauma, 58.3% (372 of the 638) had cardiac injuries, 43.0% (251 of the 584) had thoracic injuries and 26.2% (143 of the 546) had abdominal injuries. The overall rate survival in this review was 8% (267 of the 3466, range 0–33.3%). Of 25 papers reporting cases of EDT for penetrating traumas, their survival rate was 9.8% (169 of the 1719, range 0–45.5); similarly, of 14 papers assessing EDT for blunt injuries, the survival rate was 5.2% (24 of the 460, range 0–12.2). Of 15 papers reporting neurological outcomes 84.6% (143 of the 169, range 50–100%) of patients returned to baseline. The survival outcome of EDT in US experience versus non‐US experiences was 6.3% (164 of the 2612, range 0–14.9) versus 11.9% (89 of the 745, range 0–33.3) respectively.

Conclusion

The authors intend this review to serve as a practical and prompt literature search tool for all surgeons who encounter resuscitative thoracotomy in their practice.
Revisiting Key Sedimentary Archives Yields Evidence Of A Rapid Onset Of Mining In The Mid‐13th Century At The Great Copper Mountain, Falun, Sweden
Authors: Bindler R. , Rydberg J.
Published: July 2015

Mining in Falun, Sweden, was first mentioned in a deed from ad 1288, but previous studies of peat and lake sediments inferred that mining began during the fifth to eighth centuries. In order to reassess these findings, we performed new geochemical analyses on new samples from three key sites: Tisksjöbergets myr, a buried mire alongside the mine; Tisken, a small lake in Falun; and Runn, the main recipient for waters draining through Falun. At Tisksjöbergets myr, the peat contains up to 6% copper, giving it the characteristics of a cupriferous bog. Hence, this record is not useful for tracing early mining. The sediments of Tisken—upon which many of the old interpretations have relied—contain numerous cut wood fragments, and two of those gave young and reversed radiocarbon dates (19th and 16th centuries for 192 and 187 cm, respectively). This indicates that the sediment was derived from infilling and, thus, has little value as a historical record. Runn's sediment—the only reliable record—provides clear evidence of a rapid onset of large‐scale mining from c. ad 1245, with abrupt increases in ore‐related elements—for example, a 34‐fold increase in copper—this increase is consistent with the mid‐13th century burial of the mire at Tisksjöberget.
Pre‐Industrial Iron Smelting and Silver Extraction in North‐Eastern Greece: an Archaeometallurgical Approach
Authors: Nerantzis N.
Published: July 2015

In contrast to Western Europe's well‐documented contribution to global industrialization, Eastern Europe has not received adequate attention. This paper addresses this asymmetry by defining a secure socio‐technical framework for the development of metallurgical technology in one of the most important mineralized zones in Eastern Europe, namely the uplands of north‐eastern Greece. The interplay of technological innovation, geography and social process has made this region central in European political history from the Classical and Roman periods up to recent times. Metal procurement has been crucial particularly between the 15th and 19th centuries ad, when armed conflicts escalated across the Balkans and the high inflation throughout Europe increased the demand for raw materials from the East. Field data from north‐eastern Greece and instrumental analysis corroborate the concept of iron extraction during this period from complex ores that were potentially used for their precious metals contents as well. Chemical analysis of slag points to iron bloomery processes, while analysis of respective residues (speiss) reveals significant concentrations of silver and thus testifies to the extraction of precious metals. This study addresses concerns that preoccupy political and technological minds today, and provides a context for understanding the effects of changing attitudes to the environment, social development, consumption and natural resources.
A Compositional and Microstructural Study of Eighth‐Century BC Bronzes from Moita Da Ladra (Tagus Estuary): How Did the Spread of the Phoenician Metallurgy Take Place in Western Iberia?
Authors: Valério P. , Soares A. M. M. , Monteiro M. , Pereira A. , Araújo M. F. , Silva R. J. C.
Published: July 2015

Metals from a votive deposit at Moita da Ladra (Tagus Estuary) dating to the eighth century bc were studied by micro‐EDXRF, optical microscopy and Vickers testing to investigate the adoption of Phoenician innovations by indigenous communities. Artefacts are made of bronze alloys with suitable tin contents (11.6 ± 2.3 wt%) and very low iron impurities (<0.05 wt%), and were often manufactured using the long post‐casting sequence. Comparisons with indigenous and Phoenician metallurgies from western Iberia revealed a conservative technology suggesting that the spread of Phoenician innovations was very slow. In this region, the adoption of a diversified copper‐based metallurgy and reduction furnaces only seems to occur during the Post‐Orientalizing Period, c. sixth to fourth centuries bc.
Ultrastructure and distribution of chromatophores in the skin of the leopard gecko (Eublepharis macularius)
Authors: Szydłowski Paweł , Madej Jan P. , Mazurkiewicz‐Kania Marta
Published: July 2015

The aim of this study was to describe the ultrastructure and arrangement of pigment cells in the leopard gecko (Eublepharis macularius) skin to explain how wild‐type coloration is formed. The study also attempted to explain, on a morphological level, how skin colour changes occur. Samples of leopard gecko skin were collected from wild‐type coloration adult specimens. The morphology of pigmented cells was determined using light microscopy on haematoxylin and eosin (H&E) stained sections and in transmission electron microscopy. These studies indicate that skin of E. macularis contains xanthophores and melanophores but lacks iridophores and that this is probably related to nocturnal activity. The number and distribution of xanthophores and melanophores determines the skin colour and pigmentation pattern. The colour changes depend on the arrangement of characteristic protrusions of melanophores and the degree of filling them with melanosomes.
Effect of different diets on digestive enzyme activities, in vitro digestibility, and midgut gland structure in juvenile crayfish, Cherax quadricarinatus
Authors: Sacristán Hernán Javier , Fernández‐Gimenez Analía Verónica , Chaulet Anouk , Franco Tadic Luis Marcelo , Fenucci Jorge , López Greco Laura Susana
Published: July 2015

This study investigated the effects of food quality on digestive enzyme activities, in vitro protein digestibility and histological traits of the midgut gland in juvenile crayfish Cherax quadricarinatus. Animals of a wide weight range were fed different diets: two commercial diets with high or low lipid content (high lipid and low lipid, respectively) and were compared with a reference diet (RF) previously formulated for this species. Proteinase, lipase and amylase activities were significantly influenced by diet and weight. Specific trypsin activity was significantly higher for crayfish fed with the HL diet. Trypsin activity depended on diet and weight. Protein digestibility showed that HL was the most digestible diet and RF the least. The weight of the animals did not affect protein digestibility. Structural disorganization, hypertrophy of B‐cells and presence of large vacuoles in R‐cells were mainly observed in juveniles fed with HL, indicative of malnutrition. Thus, our data suggest that the HL diet would not be the most appropriate for C. quadricarinatus, while RF diet would be more convenient for culture of this species.
Exposure–response for biomarkers of anticoagulant effects by the oral direct thrombin inhibitor AZD0837 in patients with atrial fibrillation
Authors: Lip Gregory Y. H. , Rasmussen Lars H. , Olsson S. Bertil , Jensen Eva , Hamrén Bengt , Eriksson Ulf G. , Wåhlander Karin
Published: July 2015

Aims

AZD0837 is a novel oral anticoagulant investigated in clinical studies for stroke prevention in patients with atrial fibrillation (AF). It is bioconverted to its active form, AR‐H067637, a potent, specific and reversible thrombin inhibitor. The effects on coagulation biomarkers were correlated with the pharmacokinetic (PK) exposure of AR‐H067637 to guide selection of the effective dose regimen for a confirmatory efficacy study in AF patients.

Methods

Blood samples were obtained from 601 AF patients randomized to one of four doses of AZD0837 (blinded treatment) or dose‐adjusted vitamin K antagonists (VKA, open treatment) for 3–9 months. A pharmacodynamic model was developed to describe the time course of the AR‐H067637 exposure dependent effects and the effect of VKA on fibrin D‐dimer. The thrombin generation measured ex vivo in venous plasma was also investigated.

Results

The PK exposure of AR‐H067637 was stable with an interindividual variability of 33% and no or minor influence of patient demographics or comedications. For AZD0837, D‐dimer levels decreased with more rapid onset than for VKA. The decrease in D‐dimer levels correlated with steady‐state plasma concentrations (Css) of AR‐H067637, with a maximum decrease of baseline D‐dimer levels estimated to approximately 60% for both AZD0837 and VKA therapy. The effect on thrombin generation correlated closely with the plasma concentration of AR‐H067637.

Conclusions

The effects on thrombin generation and fibrin D‐dimer levels correlated with the plasma concentration of its active form and provided comparable effects to well‐controlled VKA therapy at an exposure at least corresponding to the 300 mg once daily dose of AZD0837.
Cato Guldberg and Peter Waage, the history of the Law of Mass Action, and its relevance to clinical pharmacology
Authors: Ferner Robin E. , Aronson Jeffrey K.
Published: July 2015

We have traced the historical link between the Law of Mass Action and clinical pharmacology. The Law evolved from the work of the French chemist Claude Louis Berthollet, was first formulated by Cato Guldberg and Peter Waage in 1864 and later clarified by the Dutch chemist Jacobus van ‘t Hoff in 1877. It has profoundly influenced our qualitative and quantitative understanding of a number of physiological and pharmacological phenomena. According to the Law of Mass Action, the velocity of a chemical reaction depends on the concentrations of the reactants. At equilibrium the concentrations of the chemicals involved bear a constant relation to each other, described by the equilibrium constant, K. The Law of Mass Action is relevant to various physiological and pharmacological concepts, including concentration–effect curves, dose–response curves, and ligand–receptor binding curves, all of which are important in describing the pharmacological actions of medications, the Langmuir adsorption isotherm, which describes the binding of medications to proteins, activation curves for transmembrane ion transport, enzyme inhibition and the Henderson–Hasselbalch equation, which describes the relation between pH, as a measure of acidity and the concentrations of the contributory acids and bases. Guldberg and Waage recognized the importance of dynamic equilibrium, while others failed to do so. Their ideas, over 150 years old, are embedded in and still relevant to clinical pharmacology. Here we explain the ideas and in a subsequent paper show how they are relevant to understanding adverse drug reactions.
Histamine‐2 Receptor Antagonists and Semen Quality
Authors: Banihani Saleem A.
Published: July 2015

Histamine‐2 receptor antagonists are a class of drugs used to treat the acid‐related gastrointestinal diseases such as ulcer and gastro‐oesophageal reflux disease. Although such drugs, especially ranitidine and famotidine, are still widely used, their effects on semen quality, and hence on male infertility, is still unclear. This MiniReview systematically addresses and summarizes the effect of histamine‐2 receptor antagonists (cimetidine, ranitidine, nizatidine and famotidine) on semen quality, particularly, on sperm function. Cimetidine appears to have adverse effects on semen quality. While the effects of ranitidine and nizatidine on semen quality are still controversial, famotidine does not appear to change semen quality. Therefore, additional studies will be required to clarify whether histamine‐2 receptor‐independent effects of these drugs play a role in semen quality as well as further clinical studies including direct comparison of the histamine‐2 receptor antagonists.
The Role of Urotensin Receptors in the Paracetamol‐Induced Hepatotoxicity Model in Mice: Ameliorative Potential of Urotensin II Antagonist
Authors: Palabiyik Saziye S. , Karakus Emre , Akpinar Erol , Halici Zekai , Bayir Yasin , Yayla Muhammed , Kose Duygu
Published: July 2015

We aimed to evaluate the possible protective effect of a UTR antagonist and to determine the effect of the antagonist on ALT and AST levels in serum, the mRNA expression level of UTR, tumour necrosis factor‐alpha (TNF‐α) and IL‐1β and SOD activity, GSH and MDA levels in liver tissues, which are important mediators or markers for the hepatotoxicity animal model in mice. Animals fasted overnight and were divided into seven equal groups (n = 12). The first group was the healthy group (administered 0.1% DMSO intraperitoneally). Group 2 received only paracetamol (PARA) (administered orally at a dosage of 300 mg/kg). Groups 3 and 4 were treated with only AGO (AC7954, UTR agonist) 15 and 30 mg/kg intraperitoneally, respectively. Groups 5 and 6 were treated with only ANTA (SB657510, UTR antagonist) 30 and 60 mg/kg intraperitoneally, respectively. Group 7 was treated with AGO 30 mg/kg and ANTA 60 mg/kg intraperitoneally. One hour after the pre‐treatment drugs were administered, groups 3 through 7 were given PARA. After the experimental period, the mice were killed 6 and 24 hr after PARA was administered. Antagonist administration significantly decreased the ALT and AST levels, while agonist administration did not. In addition, SOD activity and GSH levels increased, and the MDA level decreased with the pre‐treatment of two antagonist doses. The increased UTR gene expression through PARA was significantly lower in both doses of the antagonist groups at 24 hr when compared with the agonist and PARA groups. This study showed that UTR antagonists have hepatoprotective and anti‐inflammatory effects on high‐dose PARA‐induced hepatotoxicity in mice.
Predictors of prostate cancer specific mortality after radical prostatectomy: 10 year oncologic outcomes from the Victorian Radical Prostatectomy Registry
Authors: Bolton Damien M. , Papa Nathan , Ta Anthony D. , Millar Jeremy , Davidson Adee‐Jonathan , Pedersen John , Syme Rodney , Patel Manish I. , Giles Graham G.
Published: July 2015

Purpose

To identify the ability of multiple variables to predict prostate cancer specific mortality (PCSM) in a whole of population series of all radical prostatectomies (RP) performed in Victoria, Australia.

Materials & Methods

A total of 2154 open RPs were performed in Victoria between July 1995 and December 2000. Subjects without follow up data, Gleason grade, pathological stage were excluded as were those who had pT4 disease or received neoadjuvant treatment. 1967 cases (91.3% of total) met the inclusion criteria for this study. Tumour characteristics were collated via a central registry. We used competing hazards regression models to investigate associations.

Results

At median follow up of 10.3 years pT stage of RP (P < 0.001) and high Gleason score of the RP specimen (P < 0.001 for ≥8 [Subhazard ratio (SHR) 11.19] and 4 + 3 = 7 [SHR 7.10]) compared with Gleason score 6 disease were strong predictors of progression to PCSM. Gleason score 3 + 4 = 7 was not at this time a significant predictor of PCSM (P = 0.08, SHR 1.84). Predictors of PCSM, independent of stage and grade, included rural residency (P = 0.003), primary surgeon contributing less than 40 cases (low‐volume) to the VRPR (P = 0.025) and the involvement of a trainee surgeon in the operation (P = 0.031).

Conclusion

The significant prediction of PCSM by pT cancer stage, Gleason score and primary Gleason pattern at RP in this whole of population study suggests a need to avoid understaging/grading in the process of cancer diagnosis and active surveillance protocols. Multi‐modality therapy is likely to have a greater impact on PCSM in higher stage and Gleason grade disease. Identification of increased PCSM with rural residency and with involvement of a trainee urologist, and reduction in PCSM with higher surgeon volume all suggest potential for improved PC outcomes to be achieved with changes to surgical training and service delivery.
The effectiveness of BCG and interferon against non‐muscle invasive bladder cancer: a New Zealand perspective
Authors: O'Regan Toni , Tatton Michael , Lyon Maryanne , Masters Jonathan
Published: July 2015

Objective

To ascertain whether the current practice at Auckland City Hospital of adding interferon to BCG in patients with high risk or recurrent non‐muscle invasive bladder cancer (NMIBC) unable or unwilling to undergo radical cystectomy is effective.

Subjects and Method

This study examined all institutional cases where BCG alone had not been effective or tolerated as primary treatment for NMIBC and the next guideline agreed step of radical cystectomy was unable to be performed. We identified all patients unwilling or unable to undergo radical cystectomy due to patient co‐morbidities or preference for whom ongoing treatment and care was required and included 45 in the data analysis. Current practice at Auckland City Hospital is adding interferon α‐2b to BCG for this population group and all patients that were given this therapy with at least three years of follow up data from diagnosis were included into the study. Patients were either on maintenance BCG or single dosing. Several secondary outcomes were also assessed concurrently to the primary objective.

Results

This observational study showed that adding interferon to BCG proved to be an effective therapy for both treatment and salvage therapy in this patient group with 56% of the patients disease (and recurrence) free at the time of audit. 8/45 patients died whilst undergoing treatment with two of these as a direct result of bladder cancer due to disease progression.

Conclusion

This therapy has improved outcomes at our institution and has a place as a treatment of choice in this difficult to manage patient group.
Eicosapentaenoic acid prevents TCDD‐induced oxidative stress and inflammatory response by modulating MAP kinases and redox‐sensitive transcription factors
Authors: Palanisamy Kalaiselvi , Krishnaswamy Rajashree , Paramasivan Poornima , Chih‐Yang Huang , Vishwanadha Vijaya Padma
Published: July 2015

Background and Purpose

Oxidative stress and subsequent activation of inflammatory responses is a widely accepted consequence of exposure to environmental toxins. TCDD (2,3,7,8‐tetrachlorodibenzo‐p‐dioxin), a well‐known environmental toxin, exerts its toxicity through many signalling mechanisms, with liver being the principal organ affected. However, an effective antidote to TCDD‐induced toxicity is unknown. The present study evaluated the effect of eicosapentaenoic acid (EPA), an n3 fatty acid, on TCDD‐induced toxicity.

Experimental Approach

In cultures of HepG2 cells, the EPA/AA ratio was determined using gas chromatography, oxidative stress and inflammatory responses through reactive oxygen species (ROS) levels, antioxidant status, [Ca2+]i, nuclear migration of two redox‐sensitive transcription factors, NF‐κB p65 and Nrf‐2, expression of MAP kinase (p‐Erk, p‐p38), NF‐κB p65, COX‐2 and Nrf‐2. Cellular changes in ΔΨm, acidic vesicular organelle formation, cell cycle analysis and scanning electron microscopy analysis were performed.

Key Results

EPA offered significant cytoprotection by increasing EPA/AA ratios in cell membranes, inhibiting ROS generation, enhancing antioxidant status and modulating nuclear translocation of redox‐sensitive transcription factors (NF‐κB p65 and Nrf‐2) and expression of NF‐κB p65, COX‐2 and Nrf‐2. Furthermore, TCDD‐induced upstream events of MAPK phosphorylation, the increase in [Ca2+]i levels and cell surface changes in microvilli were significantly inhibited by EPA. EPA treatment maintained ΔΨm and prevented formation of acidic vesicular organelles.

Conclusion and Implications

The present study demonstrates for the first time some underlying molecular mechanisms of cytoprotection exerted by EPA against TCDD‐induced oxidative stress and inflammatory responses.
Activating mitochondrial function and haemoglobin expression with EH‐201, an inducer of erythropoietin in neuronal cells, reverses memory impairment
Authors: Horng Lin‐Yea , Hsu Pei‐Lun , Chen Li‐Wen , Tseng Wang‐Zou , Hsu Kai‐Tin , Wu Chia‐Ling , Wu Rong‐Tsun
Published: July 2015

Background and Purpose

Memory impairment can be progressive in neurodegenerative diseases, and physiological ageing or brain injury, mitochondrial dysfunction and oxidative stress are critical components of these issues. An early clinical study has demonstrated cognitive improvement during erythropoietin treatment in patients with chronic renal failure. As erythropoietin cannot freely cross the blood–brain barrier, we tested EH‐201 (2,3,5,4′‐tetrahydroxystilbene‐2‐O‐β‐d‐glucoside, also known as TSG), a low MW inducer of erythropoietin, for its therapeutic effects on memory impairment in models of neurodegenerative diseases, physiological ageing or brain injury.

Experimental Approach

The effects of EH‐201 were investigated in astrocytes and PC12 neuronal‐like cells. In vivo, we used sleep‐deprived (SD) mice as a stress model, amyloid‐β (Aβ)‐injected mice as a physiological ageing model and kainic acid (KA)‐injected mice as a brain damage model to assess the therapeutic effects of EH‐201.

Key Results

EH‐201 induced expression of erythropoietin, PPAR‐γ coactivator 1α (PGC‐1α) and haemoglobin in astrocytes and PC12 neuronal‐like cells. In vivo, EH‐201 treatment restored memory impairment, as assessed by the passive avoidance test, in SD, Aβ and KA mouse models. In the hippocampus of mice given EH‐201 in their diet, levels of erythropoietin, PGC‐1α and haemoglobin were increased

Conclusions and Implications

The induction of endogenous erythropoietin in neuronal cells by inducers such as EH‐201 might be a therapeutic strategy for memory impairment in neurodegenerative disease, physiological ageing or traumatic brain injury.
Geological structure and kinematics of normal faults in the Otway Basin, Australia, based on quantitative analysis of 3‐D seismic reflection data
Authors: Ziesch Jennifer , Aruffo Chiara M. , Tanner David C. , Beilecke Thies , Dance Tess , Henk Andreas , Weber Bastian , Tenthorey Eric , Lippmann Andrea , Krawczyk Charlotte M.
Published: July 2015

The Otway Basin in the south of Victoria, Australia underwent three phases of deformation during breakup of the southern Australian margin. We assess the geometry and kinematics of faulting in the basin by analysing a 3‐D reflection seismic volume. Eight stratigraphic horizons and 24 SW‐dipping normal faults as well as subordinate antithetic faults were interpreted. This resulted in a high‐resolution geological 3‐D model (ca. 8 km × 7 km × 4 km depth) that we present as a supplementary 3‐D PDF (Data S1). We identified hard‐ and soft‐linking fault connections over the entire area, such as antithetic faults and relay ramps, respectively. Most major faults were continuously active from Early to Late Cretaceous, with two faults in the northern part of the study area active until at least the Oligocene. Allan maps of faults show tectonic activity continuously waned over this time period. Isopach maps of stratigraphic volumes quantify the amount of syn‐sedimentary movement that is characteristic of passive margins, such as the Otway Basin. We show that the faults possess strong corrugations (with amplitudes above the seismic resolution), which we illustrated by novel techniques, such as cylindricity and curvature. We argue that the corrugations are produced by sutures between sub‐vertical fault segments and this morphology was maintained during fault growth. Thus, they can be used to indicate the kinematics vector of the fault movement. This evidences, together with left‐stepping relay ramps, that 40% of the faults had a small component (up to 25°) of dextral oblique slip as well as normal (dip‐slip) movement.
Interdisciplinarity to reconstruct historical introductions: solving the status of cryptogenic crayfish
Authors: Clavero Miguel , Nores Carlos , Kubersky‐Piredda Susanne , Centeno‐Cuadros Alejandro
Published: July 2015

Anciently introduced species can be confounded with native species because introduction pre‐dates the first species inventories or because of the loss of the collective memory of the introductions. The term ‘cryptogenic species’ denotes species of unknown or unclear status (nativeversusnon‐native) in a given territory, and disciplinary approaches are often insufficient for solving their true status. Here, we follow an integrative, multidisciplinary approach to solve the status of a cryptogenic species, proposing that building on evidence from multiple disciplines can produce robust and clarifying insights. We undertook an exhaustive review of information on a putatively native crayfish (Austropotamobius italicus) inSpain. The reviewed information included taxonomy, genetics and phylogeography, history, archaeology, linguistics, biogeography, ecology, symbiotic organisms and even gastronomy and pharmacy. The knowledge produced by different scientific disciplines converges to indicate thatA. italicusis a non‐native species inSpain. Historical documents even identify the first introduction event: crayfish were shipped fromItaly toSpain in 1588 as a diplomatic gift fromFrancescoIde'Medici toKingPhilipIIofSpain. Previous discussions on the status ofA. italicusfocussed on inconclusive and often confusing genetic results and excluded the rich and clarifying evidence available from other approaches and disciplines. Interdisciplinarity is an often‐invoked but rarely implemented practice in an academic environment that increasingly promotes narrow‐focussed specialization. Our review shows that the integration of disciplines can surpass disciplinary approaches in solving scientific controversies. Our results have straightforward implications for strategies to conserve biological diversity inSpain andEurope, urging a debate on the appropriateness of devoting conservation efforts to non‐native species.
Changes in Patterns of Species Co‐occurrence across Two Tropical Cloud Forests Differing in Soil Nutrients and Air Temperature
Authors: Long Wenxing , Xiong Menghui , Zang Runguo , Schamp Brandon S. , Yang Xiaobo , Ding Yi , Huang Yunfeng , Xiang Yangzhou
Published: July 2015

Patterns of co‐occurrence of species are increasingly used to examine the contribution of biotic interactions to community assembly. We assessed patterns of co‐occurrence at four scales, in two types of tropical cloud forests in Hainan Island, China (tropical montane evergreen forests, TMEF and tropical dwarf forests, TDF) that varied significantly in soil nutrients and temperature. We tested if the patterns of co‐occurrence changed when we sorted species into classes by abundance and diameter at breast height (dbh). Co‐occurrence differed by forest type and with plot size, with significant species aggregation observed across larger plots in TDF and patterns of species segregation observed in smaller plots in TMEF. Analyses of differential abundance and dbh classes also showed that smaller plots in TMEF tend to have negative co‐occurrence patterns, but larger plots in TDF tend to show patterns of aggregation, suggesting competitive and facilitative interactions. This underscores the scale‐dependence of the processes contributing to community assembly. Furthermore, it is consistent with predictions of the stress gradient hypothesis that facilitation will be most important in biological systems subject to abiotic stress, while competition will be more important in less abiotically stressful habitats. Our results clearly demonstrate that these two types of tropical cloud forest exhibit different co‐occurrence patterns, and that these patterns are scale‐dependent, though independent of plant abundance and size class.
Impact of KRAS mutation on response and outcome of patients with stage III non‐squamous non‐small cell lung cancer
Authors: Yagishita Shigehiro , Horinouchi Hidehito , Sunami Kuniko S. , Kanda Shintaro , Fujiwara Yutaka , Nokihara Hiroshi , Yamamoto Noboru , Sumi Minako , Shiraishi Kouya , Kohno Takashi , Furuta Koh , Tsuta Koji , Tamura Tomohide , Ohe Yuichiro
Published: July 2015

The frequency and clinical profile of patients with stage III non‐small cell lung cancer harboring KRAS mutations have not yet been well documented. Here, we analyzed hotspot KRAS mutations using high‐resolution melting analyses in tumor specimens from patients who received chemoradiotherapy between January 2001 and December 2010 at the National Cancer Center Hospital. The associations between the presence of KRAS mutations and the response rate, relapse‐free survival, first relapse sites, survival post‐progression and overall survival were investigated. A total of 274 non‐squamous non‐small cell lung cancer patients received chemoradiotherapy at our hospital. After excluding 121 patients for whom tumor specimens were not available and 34 patients with EGFR mutations, the remaining 119 patients were included in the analysis. KRAS mutations were found at a frequency of 13%. Patients with KRAS mutations had a shorter median relapse‐free survival (6.1 vs 10.9 months) and a lower response rate (63% vs 81%). As for the first relapse site, patients with KRAS mutations had fewer local relapses (8% vs 23%) and more brain metastases (46% vs 12%). After disease progression, patients with KRAS mutations had a significantly shorter median survival post‐progression (2.5 vs 7.3 months, P = 0.028) and median overall survival (15.1 vs 29.1 months, P = 0.022). Our results suggested that KRAS mutation could be associated with a reduced efficacy of chemoradiotherapy and a shortened survival time.
Histidine‐rich calcium binding protein promotes growth of hepatocellular carcinoma in vitro and in vivo
Authors: Liu Jingmei , Han Ping , Li Mengke , Yan Wei , Liu Jiqiao , He Jiayi , Gong Jin , Wang Yunwu , Tian Dean
Published: July 2015

We have recently shown that the histidine‐rich calcium binding protein (HRC) promotes the invasion and metastasis of hepatocellular carcinoma (HCC). In the current study, we evaluated whether HRC may also affect the growth of HCC. We found that ectopic expression of HRC obviously enhanced proliferation and colony formation, while suppression of HRC exhibited inhibitory effects. Furthermore, we demonstrated that HRC promoted tumor growth in nude mice. These effects may result from the ability of HRC to upregulate cyclinD1 and cyclin‐dependent kinase 2 (CDK2) expressions and promote G1/S transition. Further study showed that MEK/ERK signaling pathway was involved in HRC‐induced cell proliferation. Interestingly, overexpression or depletion of HRC revealed its regulation on endoplasmic reticulum stress (ERS) and apoptosis, which was partially dependent on PERK/ATF4/CHOP signaling pathway. In addition, blocking ERS using 4‐phenylbutyric acid (4‐PBA) not only downregulated the expression of PERK, ATF4 and CHOP, but also significantly decreased apoptosis induced by HRC silence, whereas ERS inducer thapsigargin (TG) exerted the opposite effects. Our study thus demonstrates a role of HRC in promoting HCC growth, besides its role in inducing HCC metastasis, and highlights HRC as a promising intervention target for HCC.