bluuebunny/crossref_metadata_2025 huggingface dataset:
Alkaline phosphatase activity in United Kingdom cheeses made from bovine pasteurised milk
Authors: Cassidy Sharon , Daly Carole , Early John , Rowe Michael T
Published: January 2014

The aim of this study was to assess the alkaline phosphatase activity of representative cheeses made from pasteurised milk in the United Kingdom. The results generated will contribute to similar data from other EU Member States to assess the efficacy of setting a legal standard of a maximum of 10 mU/g for such cheeses. The study indicated that UK cheeses had a probability of 97.68% of meeting such a standard. This is however probably an underestimate as one cheese was sprayed with honey which may harbour yeasts, some species of which produce the alkaline phosphatase enzyme, which may have skewed the statistical analysis.
Non‐invasive prenatal testing for trisomy 21: a cross‐sectional survey of service users' views and likely uptake
Authors: Lewis C , Hill M , Silcock C , Daley R , Chitty LS
Published: January 2014

Objective

To assess the views and likely uptake of non‐invasive prenatal testing (NIPT) for trisomy 21 among potential service users in the UK.

Design

Cross‐sectional survey.

Setting

Four antenatal clinics in England and two websites.

Sample

A total of 1131 women and partners.

Methods

Questionnaire conducted with women (and partners) recruited through antenatal clinics, a random sample of members of the website Mumsnet, and viewers of the website and Facebook page of the support group Antenatal Results and Choices (ARC).

Main outcome measures

Factors impacting decision‐making towards prenatal testing; views on NIPT, including service delivery and likely uptake; hypothetical scenarios, focused on current screening, invasive testing, and NIPT offered to women with a high‐risk screening result.

Results

The vast majority (95.7%; 1071/1119; 95% CI 94.4–96.8%) thought NIPT was a positive development in prenatal care, with 88.2% (972/1103; 95% CI 86.1–90%) indicating that they would use the test, including respondents who would currently decline trisomy 21 screening (P < 0.001). Of the respondents who would have NIPT, 30.7% (299/973; 95% CI = 27.8–33.7%) said that they were ‘likely’ to terminate an affected pregnancy (including those who would currently decline screening or invasive testing), and 36.5% (355/973; 95% CI 33.5–39.6%) were ‘not likely’ to terminate an affected pregnancy. Respondents overwhelmingly indicated that safety for the baby was the most important attribute of NIPT (70.1%; 712/1015; 95% CI 67.2–73%).

Conclusion

Respondents were overwhelmingly positive towards the introduction of NIPT. Uptake is likely to be high, and includes women who currently decline screening as well as those who will use the test for information only. Pre‐test counselling to ensure that women understand the implications of the test result is essential.
Knowledge of café and restaurant managers to provide a safe meal to food allergic consumers
Authors: Wham Carol A. , Sharma Kanchan M.
Published: January 2014

Aim

To identify knowledge of café and restaurant managers to provide safe meals to food allergic consumers.

Methods

A structured self‐administered knowledge questionnaire was completed by managers of 124 food establishments in Wellington, New Zealand.

Results

Three quarters (76%) of managers agreed to participate. Overall, 13% of respondents provided correct responses for all knowledge items. Most (93%) were very confident/confident to provide a safe meal to food allergic consumers and 64% very confident/confident to manage an allergen emergency. A quarter reported past training in food allergy management. Those with past training were more likely to have plans in place to provide a safe meal (14.8% vs. 3.4%; χ2 =2.918, P < 0.05), manage an emergency (37.8% vs 21.8%; χ2 = 2.158, P < 0.05) and to have a training program for staff (42.9% vs 8.8%; χ2 = 15.419, P < 0.001). Restaurant managers were more likely to have an emergency plan than café managers (33.3% vs 14.9%; χ2 = 3.974, P < 0.01). Two‐thirds (65%) of managers kept written recipes with ingredient details. Recipes were more likely kept if member of an industry association versus non‐member (81.6% vs 60.4%; χ2 = 4.332, P < 0.01). Seventy‐seven per cent were interested in future training. Interest was greater among industry association members (98.0% vs 83.7%; χ2 = 4.317, P < 0.02) and owners compared to managers (81.3% vs 71.7%; χ2 = 5.901, P < 0.02).

Conclusions

Food allergy knowledge of food establishment managers may compromise the safety of food allergic customers. Positive benefits of voluntary manager training are evident. For robust consumer protection, it is suggested that training be incorporated into the registration requirements for food establishments.
Magnetic resonance imaging in adults with epilepsy: A pictorial essay
Authors: van Heerden Jolandi , Desmond Patricia M. , Tress Brian M. , Kwan Patrick , O'Brien Terence J. , Lui Elaine H.
Published: January 2014

This pictorial essay highlights the role of the radiologist as a member of the adult epilepsy multidisciplinary team, and gives an overview of MRI‐evident epileptogenic lesions.
Diagnostic dilemma of paraneoplastic arthritis: case series
Authors: Kisacik Bunyamin , Onat Ahmet M. , Kasifoglu Timucin , Pehlivan Yavuz , Pamuk Omer N. , Dalkilic Ediz , Donmez Salim , Bilge Sule Y. , Yilmaz Sedat , Erdem Hakan , Mercan Ridvan , Ozturk Mehmet A. , Bes Cemal , Soy Mehmet , Erten Sukran , Cobankara Veli , Senel Soner , Oner Fatma A. , Direskeneli Haner , Yilmaz Sema , Yazici Ayten , Emmungil Hakan , Aksu Kenan , Kul Seval , Cetin Gozde Y. , Sayarlioglu Mehmet
Published: January 2014

Objectives

Paraneoplastic arthritis (PA) may mimic rheumatic diseases. While presenting the demographic and laboratory features of the patients diagnosed with PA, this study also aims to provide possible appropriate tools to differentiate the PA cases from early rheumatoid arthritis (ERA).

Methods

Sixty‐five patients with PA (male/female: 43/22) from 15 different rheumatology clinics and 50 consecutive patients with ERA (male/female: 13/37) fulfilling the 2010 American College of Rheumatology (ACR) criteria for the diagnosis if the RA from Gaziantep Rheumatology Early Arthritis Trial (GREAT) as controls who were diagnosed at least 12 months before, were enrolled into study.

Results

Mean ages of the patients with PA and ERA were 50.2 ± 15.3, and 42.7 ± 12.3, respectively, and the mean ages of the patients with PA were significantly higher than the ERA. Unlike the ERA patients, in our case series PA was predominantly observed among males. Oligoarthritis was significantly higher in solid tumors in contrast to ERA (P = 0.001). Polyarthritis and symmetric arthritis were significantly higher in the ERA group in contrast to all malignancies (P = 0.001). Rheumatoid factor (RF) and anticyclic citrullinated peptide antibody (anti‐CCP) positivity were significantly higher in the ERA group (each P = 0.001). Lactic dehydrogenase levels of hematologic malignancies were significantly higher than other groups (each, P = 0.001).

Conclusions

ERA patients had more symmetric joint involvement than PA; laboratory markers could be also an alternative where there is high RF and anti‐CCP positivity with antibody levels among the ERA patients. Finally, the demographic features can be used as differentiating factors; ERA was seen predominantly among females aged 40–59 years which refers to young adults.
The use of epidural analgesia for intrapartum pain relief in publicly funded healthcare
Authors: RÄISÄNEN SARI , KOKKI MERJA , KOKKI HANNU , GISSLER MIKA , KRAMER MICHAEL R. , HEINONEN SEPPO
Published: January 2014

Background

Epidural analgesia is the most effective way to relieve pain during birth. In a population‐based case–control study, we evaluated whether socioeconomic status (SES) affects the use of epidural analgesia for intrapartum pain relief in publicly funded health care.

Methods

Data gathered from the Finnish Medical Birth Register included all singleton births (n = 521,179) in 2000–2010. The likelihood of receiving epidural analgesia according to vaginal birth order, socio‐demographic factors and delivery characteristics was determined by using logistic regression analysis.

Results

Overall, 66.6% of women with first vaginal births and 22.4% of women with second or subsequent vaginal births had epidural analgesia. The use of epidural analgesia was associated with several factors, such as post‐term pregnancy, gestational diabetes, maternal diabetes mellitus, single marital status, smoking, depression and fear of childbirth, induction, high birth weight and giving birth by vacuum extraction regardless of vaginal birth order. Epidural use did not vary substantially by SES in first vaginal births, but a minor difference was found in second or subsequent vaginal births. The prevalence of epidural analgesia was 3% [adjusted odds ratio (aOR) 0.97, 95% confidence interval (CI) 0.93–1.00] and 13% (aOR 0.87, 95% CI 0.83–0.90) lower among lower white‐collar workers and blue‐collar workers, respectively, compared with upper white‐collar workers.

Conclusions

In Finland, the use of epidural analgesia for intrapartum pain relief reflected clinical indications and did not substantially vary by SES regardless of vaginal birth order. This could be considered as an important indicator measuring health equality.
A systematic review of controlled interventions to reduce overweight and obesity in people with schizophrenia
Authors: Hjorth P. , Davidsen A. S. , Kilian R. , Skrubbeltrang C.
Published: January 2014

Objective

Overweight and obesity are generally found among patients with schizophrenia. This may lead to serious implications for health and wellbeing. The aim was to review controlled intervention studies on reducing overweight/obesity and/or reducing physical illness in patients with schizophrenia.

Method

A systematic literature search was carried out in the bibliographic databases PubMed (MEDLINE), Embase (Ovid), PsycInfo (Ovid) and Cinahl (Ebsco). We included all randomised and non‐randomised clinically controlled studies that compared a non‐pharmacological intervention, aimed at weight reduction and/or reducing physical illness, with standard care for patients with schizophrenia.

Results

All 1713 references were evaluated for inclusion in the review. Twenty‐three met the inclusion criteria and were categorised into four subgroups according to tested interventions: diet, exercise and cognitive behavioural therapy, or mixed combinations of the three. In this review, interventions showed efficacy in reducing weight and improving physical health parameters confirming that physical health improvement was possible in patients with schizophrenia.

Conclusion

The included studies indicate that the interventions reduced weight and improved physical health parameters in patients with schizophrenia.
Digging into the Creative City: A Feminist Critique
Authors: McLean Heather
Published: January 2014

This paper contributes a critical and intersectional feminist analysis and methodological approach to debates about creative city policies and practices. Through a narrative description of community‐engaged arts interventions based on action research with the Toronto Free Gallery, an artist‐run centre and activist space, I demonstrate how feminist arts activism uncovers the multiple exclusions that creative city policies and practices entrench. In some ways, community‐engaged arts interventions can be complicit in exclusionary gentrification dynamics, particularly the production of spaces of white privilege and heteronormativity. But neoliberal imperatives are not always over determining. Feminist artists and activists are also finding ways to performatively and playfully push back at this highly regulated, gendered, and raced regime.
A new frontier in haematology – combining pharmacokinetic with pharmacodynamic factors to improve choice and dose of drug
Authors: Arpon David Rey , Gandhi Maher K. , Martin Jennifer H.
Published: January 2014

The issue of tailored dosing adjusted according to a range of patient‐specific factors other than bodyweight or body surface area is of large and increasing clinical and financial concern. Even if it is known that dosing alterations are likely to be required for parameters such as body composition, gender and pharmacogenetics, the amount of dosing change is unknown. Thus, pharmacokinetically guided dosing is making a resurgence, particularly in areas of medicine where there are cost constraints or safety issues, such as in haematology medications. However, the evidence to support the behaviour is minimal, particularly when long‐term outcomes are considered. In haematology, there are particular issues around efficacy, toxicity and overall cost. Newer targeted agents, such as the monoclonal antibody rituximab and the tyrosine kinase inhibitor imatinib, whilst clearly being highly effective, are dosed on a milligram per square metre (rituximab) or fixed dose basis (imatinib), regardless of body composition, tumour aspects or comorbidity. This review questions this practice and raises important clinical issues; specifically, the clinical potential for combined pharmacokinetically and pharmacodynamically guided dosing of new targeted agents in haematological malignancies. This pharmacokinetically and pharmacodynamically guided dosing is an emerging area of clinical pharmacology, driven predominantly by toxicity, efficacy and cost issues, but also because reasonable outcomes are being noted with more appropriately dosed older medications adjusted for patient‐specific factors. Clinical trials to investigate the optimization of rituximab dose scheduling are required.
European Medicines Agency initiatives and perspectives on pharmacogenomics
Authors: Ehmann Falk , Caneva Laura , Papaluca Marisa
Published: January 2014

Pharmacogenomics, the study of variations of DNA and RNA characteristics as related to drug response, has become an integral part of drug development and pharmacovigilance, as reflected by the incorporation of pharmacogenomic data in EU product information. In this short review article, we describe recent European Medicines Agency initiatives intended to support further the implementation of pharmacogenomics in drug development and surveillance so that patients and the public can benefit from advances in genomic science and technology.
Urinary coproporphyrin I/(I + III) ratio as a surrogate for MRP2 or other transporter activities involved in methotrexate clearance
Authors: Benz‐de Bretagne Isabelle , Zahr Noël , Le Gouge Amélie , Hulot Jean‐Sébastien , Houillier Caroline , Hoang‐Xuan Khe , Gyan Emmanuel , Lissandre Séverine , Choquet Sylvain , Le Guellec Chantal
Published: January 2014

Aims

The urinary coproporphyrin I/(I + III) ratio may be a surrogate for MRP2 activity. We conducted a prospective study in patients receiving methotrexate (MTX) to examine the relationship between this ratio and the pharmacokinetics of a MRP2 substrate.

Methods

Three urine samples were collected from 81 patients for UCP I/(I + III) ratio determination: one before (P1), one at the end of MTX infusion (P2), and one on the day of hospital discharge (P3). Three polymorphisms of ABCC2 were analysed and their relationships with basal UCP I/(I + III) ratio values assessed. All associated drugs were recorded and a drug interaction score (DIS) was assigned. Population pharmacokinetic analysis was conducted to assess whether MTX clearance (MTXCL) was associated with the basal UCP I/(I + III) ratio, its variation during MTX infusion, the DIS or other common covariates.

Results

The basal UCP I/(I + III) ratio was not associated with ABCC2 polymorphisms and did not differ according to the DIS. Significant changes in the ratio were observed over time, with an increase between P1 and P2 and a decrease at P3 (P < 0.001). No association was found between basal UCP I/(I + III) ratio and MTXCL. The final model indicates that MTXCL was dependent on the change in the ratio between P1 and P3, DIS and creatinine clearance.

Conclusion

The basal UCP I/(I + III) ratio is not predictive of MTXCL. However, it is sensitive to the presence of MTX, so it is plausible that it reflects a function modified in response to the drug.
The TRPM4 channel inhibitor 9‐phenanthrol
Authors: Guinamard R , Hof T , Del Negro C A
Published: January 2014

The phenanthrene‐derivative 9‐phenanthrol is a recently identified inhibitor of the transient receptor potential melastatin (TRPM) 4 channel, a Ca2+‐activated non‐selective cation channel whose mechanism of action remains to be determined. Subsequent studies performed on other ion channels confirm the specificity of the drug for TRPM4. In addition, 9‐phenanthrol modulates a variety of physiological processes through TRPM4 current inhibition and thus exerts beneficial effects in several pathological conditions. 9‐Phenanthrol modulates smooth muscle contraction in bladder and cerebral arteries, affects spontaneous activity in neurons and in the heart, and reduces lipopolysaccharide‐induced cell death. Among promising potential applications, 9‐phenanthrol exerts cardioprotective effects against ischaemia‐reperfusion injuries and reduces ischaemic stroke injuries. In addition to reviewing the biophysical effects of 9‐phenanthrol, here we present information about its appropriate use in physiological studies and possible clinical applications.
Cenozoic deformation in the Otway Basin, southern Australian margin: implications for the origin and nature of post‐breakup compression at rifted margins
Authors: Holford Simon P. , Tuitt Adrian K. , Hillis Richard R. , Green Paul F. , Stoker Martyn S. , Duddy Ian R. , Sandiford Mike , Tassone David R.
Published: January 2014

There is growing recognition that pulses of compressive tectonic structuring punctuate the post‐breakup subsidence histories of many ‘passive’ rifted continental margins. To obtain new insights into the nature and origin of compression at passive margins, we have conducted a comprehensive analysis of the post‐breakup (<43 Ma) deformation history of the offshore Otway Basin, southern Australian margin, using a regional seismic database tied to multiple wells. Through mapping of a number of regional intra‐Cenozoic unconformities we have determined growth chronologies for a number of major anticlinal structures, most of which are ˜NE–SW‐trending folds that developed during mild inversion of syn‐rift normal faults or through buckling of the post‐rift succession. These chronologies are supplemented by onshore structural evidence and by thermochronological data from key wells. Whilst our analysis confirms the occurrence of a well‐documented pulse of late Miocene–early Pliocene compression, post‐breakup deformation is not restricted to this time interval. We highlight the growth of a number of structures during the mid‐late Eocene and the Oligocene‐early Miocene, with evidence for considerable temporal and spatial migration of strain within the basin. Our results indicate a long‐lived ˜NW–SE maximum horizontal stress orientation since the mid‐late Eocene, consistent with contemporary stress observations but at variance with previous suggestions that this stress orientation was initiated in the late Miocene by increased coupling of the Australian‐Pacific plate boundary. We attribute the observed record of deformation to a compressional intraplate stress field, coupled to the progressive evolution of the boundaries of the Indo‐Australian Plate, ensuring that this margin has been subject to ongoing compressional forcing since mid‐Eocene breakup. Our results indicate that compressional deformation at passive margins may be more common than is generally assumed, and that passive margin basins with evidence for protracted post‐breakup deformation histories can provide useful natural laboratories for obtaining improved understanding of the evolution of intraplate stress fields over geological timescales.
Passive‐margin salt basins: hyperextension, evaporite deposition, and salt tectonics
Authors: Rowan M. G.
Published: January 2014

Passive‐margin salt basins are classified as prerift, syn‐stretching, syn‐thinning, and syn‐exhumation. Prerift salt, such as the Triassic Keuper in the Western Pyrenees, undergoes thick‐skinned extension, first decoupled and then coupled, along with its substrate and cover. The base salt develops significant relief, is attenuated on the largest faults, and ends up distributed across the entire margin. Syn‐stretching salt, such as along the Iberian and Newfoundland margins, is deposited during early rifting and is thus concentrated in proximal areas with variable thickness and extent, with decoupled and coupled thick‐skinned deformation dominant. Syn‐thinning salt, such as in the northern Red Sea, is also deposited during extension, with the base salt unconformably above proximal stretching faults but offset by distal thinning faults. Both thick‐skinned and gravity‐driven thin‐skinned deformation occur, with the latter strongly influenced by the ramp‐flat geometry of the base salt. Syn‐exhumation salt, such as in the Gulf of Mexico and South Atlantic salt basins, is deposited as part of the sag basin with broad distribution and a generally unfaulted base. Conjugate syn‐exhumation salt basins are originally contiguous, form partly over exhumed mantle on magma‐poor margin segments, and are commonly flanked by magma‐rich segments with volcanic highs (seaward‐dipping reflectors) that isolate the salt basin from marine water. Salt tectonics is characterized by gravitational failure of the salt and overburden, with proximal extension and distal contraction, and the development of allochthonous salt that includes frontal nappes that advance over newly formed oceanic crust.
Diachronous sub‐volcanic intrusion along deep‐water margins: insights from the Irish Rockall Basin
Authors: Magee C. , Jackson C. A.‐L. , Schofield N.
Published: January 2014

The movement of magma in sedimentary basins often occurs through an extensive and interconnected complex of sills. Field‐, modelling‐, and seismic reflection‐based studies indicate that the emplacement of shallow‐level sills is commonly accommodated by the formation of forced folds, which may be expressed at the free surface and onlapped by younger strata. If the age of these onlapping strata can be constrained, important insights can be gained into the timing of magma emplacement and associated regional, tectono‐magmatic events. Previous studies have focused on isolated intrusions that are overlain by an individual forced fold formed during a single tectono‐magmatic event. However, the structure and evolution of ‘compound’ folds developed above stacked, interconnected sills, and what they may reveal about polyphase intrusive events has not been investigated. In this study, we use 3D seismic reflection data from the Irish Rockall Basin, offshore western Ireland, to constrain the structural style and emplacement history of a sill complex that contains 82 seismically resolved intrusions. Individual forced folds, <41 km2 in plan view and with mean fold amplitudes of 111 m, are developed above single intrusions. However, where sills are stacked, broader (100–244 km2), larger amplitude (mean of 296 m) compound folds occur following the coalescence of individual folds. Stratigraphic onlap and truncation observed within the folds throughout the Palaeocene‐to‐Middle Eocene succession, indicates that emplacement and forced folding initiated at the end Maastrichtian and lasted for ca. 15 Ma, before ceasing near the end of the Ypresian. We demonstrate (i) intrusion‐induced forced folds evolve dynamically and can form broad areas of sustained local uplift, and (ii) that the formation of sill complexes within the upper crust may occur over prolonged time periods. This study also highlights the importance of seismic reflection data to understanding the structural style and age relationships between igneous systems.
Insights into the development of major rift‐related unconformities from geologically constrained subsidence modelling: Halten Terrace, offshore mid Norway
Authors: Bell R. E. , Jackson C. A‐L. , Elliott G. M. , Gawthorpe R. L. , Sharp Ian R , Michelsen Lisa
Published: January 2014

Due to the effects of sediment compaction, thermal subsidence and ‘post‐rift’ fault reactivation, the present‐day geometry of buried, ancient rift basins may not accurately reflect the geometry of the basin at any stage of its syn‐rift evolution. An understanding of the geometry of a rift basin through time is crucial for resolving the dynamics of continental rifting and in assessing the hydrocarbon prospectivity of such basins. In this study, we have restored the Late Jurassic–Early Cretaceous geometry of the southern Halten Terrace, offshore mid Norway, using a combination of well log‐ and core‐derived, sedimentological and stratigraphic data, seismic‐stratigraphic observations and reverse subsidence modelling. This integrated geological and geophysical approach has allowed the large number of input parameters involved in flexural backstripping and post‐rift thermal subsidence modelling to be constrained. We have thus been able to determine the regional structure of the basin at the end of the Late Jurassic–Early Cretaceous rift phase and the associated amount of crustal stretching. Our basin geometry reconstructions reveal that, during the latest syn‐rift period in the Late Jurassic–Early Cretaceous, the Halten Terrace was characterized by a series of isolated depocentres, located between footwall islands, which were not connected into a single depocentre until the Late Cretaceous (Coniacian). We show that two major unconformities, which are now vertically offset by ca. 2 km and located ca. 60 km apart, formed at similar subaerial elevations in the Late Jurassic–Early Cretaceous and were subsequently vertically offset by thermally induced tilting of the basin margin. Cretaceous sediments were deposited in a single, relatively unconfined basin in water depths of 1–1.5 km. The β profile that best restores palaeobathymetry to match our geological constraints is the same as that derived from summing visible post‐Late Triassic heave on faults plus 25–60% additional extension to account for sub‐seismic deformation. This indicates that, at least in the southern part of the Halten Terrace, the amount of upper‐crustal stretching during the Late Jurassic–Early Cretaceous rift phase is comparable to the total amount of lithospheric stretching, supporting a uniform pure‐shear stretching model.
Deep‐water continental margins: geological and economic frontiers
Authors: Alves T. M. , Bell R. E. , Jackson C. A.‐L. , Minshull T. A.
Published: January 2014

Deep‐water margins have been the focus of considerable research during the past decade. They comprise vast, underexplored regions, in which only recently have improvements in seismic imaging and drilling technology allowed the discovery of significant hydrocarbon accumulations. This volume comprises of a series of manuscripts based on studies from continental margins bordering India, East Africa, Australia, China, Norway, the United Kingdom, Iberia, Newfoundland, the southern US, West Africa and Brazil, thus offering a global perspective on the evolution and economic significance of deep‐water margins. The articles in this volume examine: (i) the quantification of extension and hyperextension in distal parts of continental margins, and their relationship with regional subsidence, (ii) the importance of magmatism in the structural and thermal evolution of rifted continental margins, (iii) the processes driving and the significance of regional exhumation during and after syn‐rift stretching, (iv) the tectonic setting of salt basins and (v) depositional patterns along deep‐water margins. To complement this work, we present a personal view of some of the specific questions that need to be addressed in the next few years of deep‐water continental margin research.
Phase I study of combination chemotherapy using sorafenib and transcatheter arterial infusion with cisplatin for advanced hepatocellular carcinoma
Authors: Hagihara Atsushi , Ikeda Masafumi , Ueno Hideki , Morizane Chigusa , Kondo Shunsuke , Nakachi Kohei , Mitsunaga Shuichi , Shimizu Satoshi , Kojima Yasushi , Suzuki Eiichiro , Katayama Kazuhiro , Imanaka Kazuho , Tamai Chie , Inaba Yoshitaka , Sato Yozo , Kato Mina , Okusaka Takuji
Published: January 2014

The aims of this study were to evaluate the frequency of dose‐limiting toxicities and to find the recommended dose of combination chemotherapy with sorafenib and transcatheter arterial infusion (TAI) using cisplatin for patients with advanced hepatocellular carcinoma (HCC), for whom surgical resection, local ablation therapy, or transcatheter arterial chemoembolization were not indicated. Patients received 800 mg sorafenib daily. Cisplatin was given at one of three dosages (level 1, 35 mg/m2/cycle; level 2, 50 mg/m2/cycle; and level 3, 65 mg/m2/cycle) from feeding arteries to the HCC. The treatment was repeated every 4–6 weeks up to a maximum of six cycles, until there were signs of tumor progression or unacceptable toxicity. The dose‐limiting toxicities experienced by the 20 enrolled patients were grade 4 increased aspartate aminotransferase at level 1, grade 3 gastrointestinal hemorrhaging at level 1, and grade 3 hypertension at level 3. The common drug‐related adverse events that were of severity grade 3 or 4 included the elevation of aspartate aminotransferase (30%), alanine aminotransferase (20%), amylase (30%), and lipase (30%). Partial response was seen in four patients (20%), and 13 patients (65%) had stable disease. The median overall survival and progression‐free survival were 9.1 and 3.3 months, respectively. The combination of sorafenib at 800 mg/day with TAI of cisplatin at 65 mg/m2/cycle was determined to be the recommended regimen. A randomized phase II trial of sorafenib alone versus sorafenib plus TAI of cisplatin is currently underway. This study was registered at UMIN as trial number UMIN000001496.
TMEPAI/PMEPA1 enhances tumorigenic activities in lung cancer cells
Authors: Vo Nguyen Thanh Thao , Watanabe Yukihide , Shiba Aya , Noguchi Masayuki , Itoh Susumu , Kato Mitsuyasu
Published: January 2014

TMEPAI/PMEPA1 is a transmembrane protein that was originally identified as a prostatic RNA, the synthesis of which is induced by testosterone or its derivatives. We have recently identified TMEPAI as a direct target gene of transforming growth factor‐β (TGF‐β)/Smad signaling that participates in negative feedback control of the duration and intensity of TGF‐β/Smad signaling. TMEPAI is constitutively and highly expressed in many types of cancer and is associated with poor prognosis. Here, we report that TMEPAI is highly expressed in the lung adenocarcinoma cell lines Calu3, NCI‐H23, and RERF‐LC‐KJ. Expression of TMEPAI in these cancer cells was significantly suppressed by a TGF‐β receptor kinase antagonist, SB208, and by TGF‐β neutralizing antibodies. These results suggest that constitutive expression of TMEPAI in these cancer cells depends on autocrine TGF‐β stimulation. Knockdown of TMEPAI in Calu3 and NCI‐H23 cells enhanced levels of Smad2 phosphorylation and significantly suppressed cell proliferation in the presence of TGF‐β, indicating that highly expressed TMEPAI suppresses levels of Smad phosphorylation in these cancer cells and reduces the growth inhibitory effects of TGF‐β/Smad signaling. Furthermore, knockdown of TMEPAI in Calu3 and NCI‐H23 cells suppressed sphere formation in vitro and tumor formation in s.c. tissues and in lungs after tail vein injection in NOD‐SCID mice in vivo. Together, these experiments indicate that TMEPAI promotes tumorigenic activities in lung cancer cells.
Inherent Noise‐Aware Insect Swarm Simulation
Authors: Wang Xinjie , Jin Xiaogang , Deng Zhigang , Zhou Linling
Published: January 2014

Collective behaviour of winged insects is a wondrous and familiar phenomenon in the real world. In this paper, we introduce a highly efficient field‐based approach to simulate various insect swarms. Its core idea is to construct a smooth yet noise‐aware governing velocity field that can be further decomposed into two sub‐fields: (i) a divergence‐free curl‐noise field to model noise‐induced movements of individual insects in a swarm, and (ii) an enhanced global velocity field to control navigational paths in a complex environment along which all the insects in a swarm fly. Through simulation experiments and comparisons with existing crowd simulation approaches, we demonstrate that our approach is effective to simulate various insect swarm behaviours including aggregation, positive phototaxis, sedation, mass‐migrating, and so on. Besides its high efficiency, our approach is very friendly to parallel implementation on GPUs (e.g. the speedup achieved through GPU acceleration is higher than 50 if the number of simulated insects is more than 10 000 on an off‐the‐shelf computer). Our approach is the first multi‐agent modelling system that introduces curl‐noise into agents' velocity field and uses its non‐scattering nature to maintain non‐colliding movements in 3D crowd simulation.
The range and prevalence of clinical signs and conformation associated with lameness in working draught donkeys in Pakistan
Authors: Reix (nèe Broster) C. E. , Burn C. C. , Pritchard J. C. , Barr A. R. S. , Whay H. R.
Published: January 2014

Reasons for performing the study

Lameness is prevalent in working donkeys and has major welfare implications; however, a detailed study of the associated clinical signs is lacking.

Objectives

To describe the range and prevalence of clinical signs and conformation associated with lameness in working draught donkeys.

Study design

Prospective, cross‐sectional, observational study.

Methods

Data were collected from 102 working draught donkeys in Pakistan. A lameness assessment adapted for working donkeys was used to record clinical signs of lameness, gait, limb conformation and pain responses in the feet, limbs and spine using observation, palpation and manipulation. Lameness at the walk was scored from 0 to 10 (sound to nonweightbearing).

Results

Every donkey examined had gait abnormalities, with 5% having a nonweightbearing limb. Lameness was significantly more severe with older age, lower body condition score and forward‐at‐the‐knee conformation. More severe lameness was also associated with pain responses in the hoof walls, palpation of limb joints and spinal flexion. Joint, tendon and foot pathology was highly prevalent, as well as pain responses to joint flexion and spinal manipulation. Conformational abnormalities showed lateral asymmetries.

Conclusions

Over 98% of the world's 42.2 million donkeys are in low‐income countries, most being used for work. The high prevalence of lameness, pain and multiple limb and spinal abnormalities in working donkeys is of great welfare concern and highlights the complexity of addressing this problem. This standardised lameness assessment can be used when implementing and monitoring interventions to reduce lameness prevalence in working donkeys.
Neural skyline filter for accelerating skyline search algorithms
Authors: Chen Yi‐Chung , Lee Chiang
Published: January 2014

The skyline search problem has been identified as one of the key problems in database research. None of the developed skyline search algorithms include the use of a filter to facilitate the search process. This paper proposes a novel modification involving the use of skyline filters to reduce the search space of a skyline problem by removing data points that cannot provide a viable skyline result. Three filters based on the concept of neural networks are proposed in this paper. The result is a reduction in execution time achieved through the reduction of the input tuples. The proposed filters may be used in conjunction with any existing skyline search algorithm. This is the first study to apply neural network technology to the skyline problem. Comprehensive simulation results demonstrate the effectiveness of the proposed skyline filtering system.
Differences between lutropin‐mediated and choriogonadotropin‐mediated receptor activation
Authors: Grzesik Paul , Teichmann Anke , Furkert Jens , Rutz Claudia , Wiesner Burkhard , Kleinau Gunnar , Schülein Ralf , Gromoll Jörg , Krause Gerd
Published: January 2014

The human lutropin/choriogonadotropin receptor (hLHR) for the gonadotropic hormones human luteinizing hormone (hLH; lutropin) and human choriogonadotropin (hCG) is crucial for normal sexual development and fertility. We aimed to unravel differences between the two hLHR hormones in molecular activation mechanisms at hLHR. We utilized a specific hLHR variant that lacks exon 10 (hLHR‐delExon10), which maintains full cAMP signaling by hCG, but decreases hLH‐induced receptor signaling, resulting in a pathogenic phenotype. Exon 10 encodes 27 amino acids within the hinge region, which is an extracellular segment that is important for signaling and hormone interaction. Initially, we assumed that the lack of exon 10 might disturb intermolecular trans‐activation of hLH, a mechanism that has been reported for hCG at hLHR. Coexpression of signaling‐deficient hLHR and binding‐deficient hLHR can be used to examine the mechanisms of receptor signaling, in particular intermolecular cooperation and intramolecular cis‐activation. Therefore, hLHR‐delExon10 was combined with the hLHR Lys605→Glu mutant, in which signaling is abolished, and the hLHR mutant Cys131→Arg, in which binding is deficient. We found that hCG signaling was partially rescued, indicating trans‐activation. However, the hLH signal could not be restored via forced trans‐activation with any construct. Fluorescence cross‐correlation spectroscopy detected oligomerization in all combinations, indicating that these functional differences cannot be explained by monomerization of hLHR‐delExon10. Thus, our data demonstrate not only that the different behavior of hLH at hLHR‐delExon10 is unlikely to be related to modified intermolecular receptor activation, but also that hLH may exclusively stimulate the targeted hLHR by cis‐activation, whereas hCG is also capable of inducing trans‐activation.

Structured digital abstract

hLHR and hLHR colocalize by confocal microscopy (View interaction)

hLHR and hLHR physically interact by fluorescence correlation spectroscopy (View interaction)
What Does the Corporate Bond Market Know?
Authors: Bittlingmayer George , Moser Shane M.
Published: January 2014

Do related markets reflect new information simultaneously? For high‐yield bonds, a large abnormal price decline in a corporation's most liquid bond over a month is followed by an average abnormal stock price decline of −1.42%. This effect is larger for stocks that have increased in value and for volatile stocks. It is also larger for bonds with high coupons and shorter maturities. These results support the view that high‐yield corporate bonds have an informational edge when news is negative and stock returns are noisy, and add to the growing literature on the substantial lags in price discovery between related markets.
Underwriter Compensation Structure: Can It Really Bond Underwriters?
Authors: Garner Jacqueline L. , Marshall Beverly B.
Published: January 2014

Underwriter compensation can be structured as all cash or a combination of cash and warrants. Using a sample of small initial public offerings (IPOs), we find that underwriter compensation contracts that include warrants in exchange for cash can serve as certification for IPO firms by substituting for reputation capital. When underwriters accept warrants when they could have received more cash compensation, the IPOs avoid the well documented long‐run underperformance. However, when underwriters receive warrants after maximizing cash compensation, the IPO experiences higher underpricing and poorer long‐run performance. The findings are consistent with a motivation by the underwriters to circumvent regulatory constraints.
Equity‐Based Incentives, Risk Aversion, and Merger‐Related Risk‐Taking Behavior
Authors: Benson Bradley W. , Park Jung Chul , Davidson Wallace N.
Published: January 2014

We find that post‐merger equity risk is negatively related to the sensitivity of CEO wealth to stock return volatility (vega), but is concentrated in CEOs with high proportions of options and options that are more in‐the‐money. The probability of industrial diversification also increases in vega. Additional tests show that the decline in post‐merger equity risk results in a significant decrease in shareholder wealth. This decrease is concentrated among firms with CEOs having the highest delta and the highest delta and vega. Our results suggest that the increased convexity provided by option‐based compensation does not necessarily increase risk‐taking behavior by CEOs.
Does Operational and Financial Hedging Reduce Exposure? Evidence from the U.S. Airline Industry
Authors: Treanor Stephen D. , Simkins Betty J. , Rogers Daniel A. , Carter David A.
Published: January 2014

We examine the effects of both financial and operational hedging on jet fuel exposure in the U.S. airline industry. Specifically, we investigate two operational hedging strategies: the extent to which airlines operate different aircraft types and the degree to which airlines operate fuel‐efficient fleets. We find that both financial and operational hedging are important tools in reducing airline exposure to jet fuel price risk. However, operational hedging strategies appear to be more economically important, which suggests that hedging with derivatives is more likely to be used to “fine‐tune” risk exposure, whereas operational choices have a higher order effect on risk exposure.
Individual and socially learned preferences for biserrula (Biserrula pelecinus L.) in sheep
Authors: Thomas D. T. , Milton J. T. B. , Revell C. K. , Ewing M. A. , Lindsay D. R.
Published: January 2014

This study examined how sheep develop a learned aversion to the annual legume biserrula (Biserrula pelecinus L.). Merino sheep were grazed on paddocks sown with either (i) biserrula, (ii) biserrula + ryegrass (Lolium rigidum Gaud.), (iii) crimson clover (Trifolium incarnatum L.), (iv) crimson clover + ryegrass or (v) ryegrass, for 4 weeks. Relative preference (Chesson–Manly selection index) was determined by offering randomly ordered monoculture plots of the three forage species. The groups of sheep were then combined into a single group and grazed a paddock containing a monoculture sward of each plant type for 5 d. Relative preference of sheep was tested again after the completion of the combined grazing. The experiment was repeated at three stages of plant phenology: vegetative, reproductive and senesced. Relative preference for biserrula was lower in sheep that had grazed the paddock sown with only biserrula compared with sheep that grazed a combination of biserrula + ryegrass, at both the vegetative (α; −0·11 vs. 0·32) and reproductive (α; 0·18 vs. 0·63) stages. At each stage of phenology, when groups were combined and grazed together, preference for biserrula became uniform. This supported the hypothesis that sheep develop an aversion to biserrula when they graze a pasture containing biserrula. However, we concluded that the familiarity of sheep with biserrula did not result in low relative preference; rather, the aversion was more likely a response to the high proportion of this plant in their diet. Social facilitation may have enabled sheep to overcome rapidly the food aversion.
BRECHT'S POEMS IN ENGLISH: THE OLD AND THE NEW
Authors: Kuhn Tom
Published: January 2014

Brecht can look easy to translate. His very clearly directed gestures of communication make his verse accessible and translatable. But he is an extraordinarily prolific and varied poet. When we look a little closer, some of the very same things that seemed on the face of it easy make it hard to capture the spirit of his verse: the laconic, slightly elevated register, for example, the subtle distortions of the vernacular and the many intercultural and intertextual references. There have been few attempts at translation so far (partly for reasons of copyright), but it is possible to identify three phases: Brecht's own contemporaries, the translations collected by the pioneering John Willett (with Ralph Manheim and Michael Hamburger) in the 1970s, and now a new generation. While paying tribute to the earlier translators, it is easy to find fault with what there is so far in print. The time is ripe for a new set of translations, both more faithful (above all to the structure of Brecht's own collections), and at the same time more daring in its solutions. A new AHRC‐funded project offers an opportunity to launch new translations, and at the same time to reflect on the processes of ‘Englishing’ Brecht, past and present.

Brecht zu übersetzen kann einfach erscheinen. Seine äußerst eindeutig gerichteten Gesten der Kommunikation machen seine Lyrik zugänglich und übersetzbar. Er ist aber auch ein außergewöhnlich produktiver und vielseitiger Dichter. Außerdem erschweren es bei genauerem Hinsehen eben jene Merkmale, die oberflächlich betrachtet einfach erschienen, den Nerv der Lyrik adäquat zu treffen. Darunter fallen zum Beispiel das lakonische, leicht gehobene Register, die subtilen Verzerrungen der Umgangssprache, und die vielen interkulturellen und intertextuellen Referenzen und Anspielungen. Bisher gab es nur wenige Übersetzungsversuche (teilweise aus Urheberrechtsgründen), aber drei Phasen sind identifizierbar: Brechts Zeitgenossen, die gesammelten Übersetzungen des Vorreiters John Willett (zusammen mit Ralph Manheim und Michael Hamburger) aus den 1970ern, und nun eine neue Generation von Übersetzern. Obwohl den frühen Übersetzern Tribut gezollt wird, ist es zur gleichen Zeit recht einfach, die vorhandenen Veröffentlichungen zu beanstanden. Die Zeit für eine neue Sammlung von Übersetzungen ist gekommen, welche sowohl werkgetreuer (besonders in Bezug auf die Struktur von Brechts eigenen Sammlungen) als auch zur gleichen Zeit kühner in ihren Lösungen ist. Ein neues, vom AHRC finanziertes Projekt bietet die Möglichkeit, neue Übersetzungen zu etablieren, und gleichzeitig die Prozesse der ‘Verenglischung’ von Brecht, damals und heute, zu reflektieren.
Landscape diversity slows the spread of an invasive forest pest species
Authors: Rigot Thibaud , van Halder Inge , Jactel Hervé
Published: January 2014

According to the associational resistance hypothesis, diverse habitats provide better resistance to biological invasions than monocultures. Host‐plant abundance has been shown to affect the range expansion of invasive pests, but the effect of landscape diversity (i.e. density of host/non‐host patches and diversity of forest habitat patches) on invasions remains largely untested. We used boundary displacement models and boosted regression tree analyses to investigate the effects of landscape diversity on the invasion of Corsica by the maritime pine bast scale Matsucoccus feytaudi over an 18‐yr period. Taking the passive wind dispersal of the scale into account, we showed that open habitats and connectivity between host patches accelerated spread by up to 13%, whereas landscapes with high tree diversity and a high density of non‐host trees decreased scale spread by up to 14%. We suggest a new mechanism for such associational resistance to pest invasion at the landscape level, which we term ‘the pitfall effect’.