bluuebunny/crossref_metadata_2025 huggingface dataset:
Structural Characteristics of the Basement beneath Qiangtang Basin in Qinghai‐Tibet Plateau: Results of Interaction Interpretation from Seismic Reflection/Refraction Data
Authors: Qiusheng LI , Rui GAO , Shaoying FENG , Zhanwu LU , Hesheng HOU , Ye GUAN , Pengwu LI , Haiyan WANG , Zhuo YE , Xiaosong XIONG , Jinkai LIU , Rizheng HE
Published: April 2013

The studies on configuration, character/property of the basement of Qiangtang basin is helpful for evaluating petroleum and nature gas resources as well as understanding the basin evolvement. Recently a moderate to high‐grade metamorphic gneiss rock was found underlying beneath very low metamorphic Ordovician strata in Mayer Kangri to the north of the central uplift. That fact actually proved existence of the crystalline basement just the distribution and structures of pre‐Paleozoic crystalline basement still remain puzzle. In recent years a number of active sources deep seismic profiling, to aim at lithospheric structure of northern Tibet and petroleum resources of the Qiangtang basin, had been conducted that make it possible to image the structure of the basement of the Qiangtang. Near vertical reflection profiles, included those acquired previously and those during 2004 to 2008, have been utilized in this study. By through the interaction process and interpretation between the reflection profiles and the wide‐angle profile, a model with the detailed structure and velocity distribution from surface to the depth of 20 km of Qiangtang basin has been imaged. Based on the results and discussions of this study, the preliminary conclusions are as follows: (1) The velocity structure section (∼20 km) that is interactively constrained by the refraction and reflection seismic data reveals that the sedimentary stratum gently lie until 10 km in the south Qiangtang basin. (2) The basement consists of fold basement (the upper) and crystalline basement (the lower). The fold basement buried at the average depth of 6 km with a velocity of 5.2–5.8 km/s. The shallowest appear at range of the central uplift. The crystalline basement is underlying beneath the fold basement at the average depth of 10 km with a velocity of 5.9–6.0 km/s except near Bangong‐Nujiang suture. (3) The high‐velocity body at the depth range of 3–6 km of the central uplift is considered as a fragment of the crystalline basement that perhaps was raised by Thermal or deformation. (4) The lower‐consolidated fold basement show more affinity of Yangtze block but the crystalline basement seems more approximate to Lhasa terrene in geophysical nature. We have attempted to improve the resolution and reliability by interaction of the active seismic data and prove it effective to image complex basement structure. It will be a potential to process the piggy‐back acquisition data and has wide prospects.
Study on the Tectonic Setting for the Ophiolites in Xigaze, Tibet
Authors: Peisheng BAO , Li SU , Jun WANG , Qingguo ZHAI
Published: April 2013

The Xigaze ophiolite is located in the middle section of the Yarlung Zangbo River ophiolite belt and includes a well‐preserved sequence section of seven ophiolite blocks. The relatively complete ophiolitic sequence sections are represented by Jiding, Dejixiang, Baigang, and Dazhuqu ophiolites and consist of three–four units. The complete ophiolite sequence in order from the bottom to top consists of mantle peridotite, cumulates, sheeted sill dike swarms, and basic lavas±radiolarian chert. These cumulates are absent in the remaining blocks of Dejixiang and Luqu. The age of radiolaria in the radiolarian chert is Late Jurassic–Cretaceous. The basalt and ultramafic rock of the ophiolite also are overlaid by Tertiary Liuqu conglomerate, which contains numerous pebble components of ophiolite, indicating that the Tethys Ocean began to close at the end of Cretaceous Period. The isotopic data of gabbro, diabase, and albite granite in the Xigaze ophiolite are approximately 126–139 Ma, which indicates that the ophiolite formed in the Early Cretaceous. The K‐Ar age of amphibole in garnet amphibolite in the ophiolite mélange is 81 Ma, indicating that tectonic ophiolite emplacement occurred at the end of Late Cretaceous. Research in petrology, petrological chemistry, mineralogy, and geochemistry of volcanic rocks and dikes of the Xigaze ophiolite indicate the following characteristics: (1) They are mainly composed of basalt, basaltic andesite, dolerite, and diabase and are characterized by high TiO2 (0.7–1.47%), low MgO (mostly less than 8%), and low SiO2 (mostly less than 53%). (2) The volcanic rocks and dikes of the Xigaze ophiolite show light rare earth element (LREE)‐depleted rare earth element (REE) patterns. (3) The spider diagrams of the volcanic rocks and dikes of the Xigaze ophiolite exhibit LILE depletion relative to high‐field‐strength element (HFSE) patterns with left oblique features. (4) No protogenetic olivine and clinoenstatite was detected. (5) Some dikes show low TiO2 and high MgO, in which a few of Cr‐enriched spinels and a very few pseudomorphs of olivine, orthopyroxene can be seen. They show more distinctive affinity as boninitic rock and canbe classified to boninite series rock. The previously mentioned features of the volcanic rocks and dikes in the Xigaze ophiolite implies that these ophiolites formed in a mid‐ocean ridge (MOR) in the earlier stage and than forearc extension of subduction initiation occurred once at the later stage of the evolution of the Xigaze ophiolite. The forearc extention caused further melting of the residue‐depleted mantle, resulting in the formation of melts with lower TiO2 and higher MgO. These melts formed as dikes and intruded into the oceanic crust formed in the earlier stage, resulting in a close association of mid‐ocean ridge basalt and the boninite rock of the Xigaze ophiolite.
Petrology, Geochemistry and Tectonic Significance of the Metamorphic Peridotites from Longmuco–Shuanghu Ophiolitic Melange Belt, Tibet
Authors: Yanwang WU , Cai LI , Chaoming XIE , Ming WANG , Peiyuan HU
Published: April 2013

Taoxinghu metamorphic peridotite is a firstly reported mantle sequence of ophiolite since Longmuco‐Shuanghu‐Lancangjiang suture zone (LSLSZ) was proposed, and it is also an important discovered for ophiolite studying in central Qiangtang. Based on detailed analyses of whole–rock geochemistry of Taoxinghu metamorphic peridotites and contrast to metamorphic peridotites in typical ophiolites worldwide, the paper investigates their petrogenesis and geological implication. The petrologic results show that the protolith of Taoxinghu metamorphic perdotites have the mineral assemblage and texture characteristic of mantle peridotite. Most metamorphic peridotites hav near global abyssal peridotites major elements contents, while the few is similar to SSZ‐type peridotites. They exhibit typically U‐shaped REE patterns, characterized by slight enrichment of LREE and HREE relative to MREE and a low fractionated LREE to HREE segment. Trace elements contents are low and all samples are strong enrichment in Cs, U, Pb, weak enrichment in Ba and depletion in Th, but negative Nb anomalies are only observed in few samples. That suggests Taoxinghu metamorphic peridotites have depletion mantle and suprasubduction affinities. A two‐stage evolution history is considered: Taoxinghu metamorphic peridotites originated as the residue from melting at a ridge with 7%‐20% degree of fraction melting and were subsequently modified by interaction with mafic melt and aqueous fluid within mantle wedge on subducted zone. Combined with previous studies, we preliminarily propose Taoxinghu metamorphic peridotites may be the Products of initial rifting of palo–Tethys, forming at middle Ordivician‐upper Cambrian, and they may be the direct evidences for spreading of palo–Tethys.
Zircon Dating and Geological Implications of Granitic Gneiss in the Metamorphic Zone of Gaoligong Mountains in Western Yunnan, China
Authors: Xiaohong TAN , Bo ZHAO , Xikang LI , Zhangbao XU , Zhen ZHANG
Published: April 2013

The general classification of intermediate‐acid intrusive rocks in the metamorphic zone of Gaoligong Mountains as one of the metamorphic terranes of Proterozoic Gaoligong Mountains is problematic regarding the intrusion stage and age, as well as the subsequent metamorphism and deformation. In this study, we investigated granitic gneiss in the metamorphic zone of Gaoligong Mountains based on the 1:50,000 regional geological survey of Qushi Street (2011–2013) and SHRIMP U‐Pb zircon geochronology. Results showed that the SHRIMP U‐Pb zircon dating of granitic gneiss ranged from 163.5±5.7 Ma to 74.0±2.0 Ma. Thus, the granitic gneiss was grouped into orthometamorphic rocks (metamorphic intrusions). The dating data of granite rocks associated with intense metamorphism and deformation were divided into three groups, 163.5±5.7 to 162.3±3.1 Ma, 132.2–101.0 Ma and 99.4±3.5–74.0±2.0 Ma, which respectively represented three independent geologic events including an important magma intrusion with superimposed metamorphic effects in the late Middle Jurassic, regional dynamic metamorphism and superimposed reformation of fluid action in the early Cretaceous, and dynamic metamorphism dominated by ductile shear and metamorphism starting from the late Cretaceous.
Jurassic Black Shales Facies from Qiangtang Basin (Northern Tibet): Rare Earth and Trace Elements for Paleoceanographic Implications
Authors: Lan CHEN , Haisheng YI , Louis Loung‐Yie TSAI , Guiwen XU , Xuejuan DA , Andrew Tien‐Shun LIN
Published: April 2013

The Biluo Co and Amdo 114 station, northern Tibet, cropping out the Early Toarcian and Middle‐Late Tithonian (Jurassic) organic‐rich black shales, have been a focus to petroleum geologists in discussing their oil‐producing potential. This paper first reports the trace elements and rare earth elements to discuss the paleoenvironments, redox conditions and sedimentary mechanisms of those black shales. Both sections exhibit variation in trace element abundances with concentrations <0.1 ppm to 760 ppm, mostly enriched in V, Cr, Ni, Cu, Zn, Mo, Ba and U. Element ratios of Ni/Co, V/Cr, U/Th and V/(V+Ni) plus U were used to identify redox conditions. The shale‐normalized rare earth element (REE) patterns are characterized by the flat‐shale type with instable Ce anomalies and very weekly positive Eu anomalies. Positive Ceanom values are significant with values varying between −0.064 and 0.029 in Biluo Co, which may be interpreted as release of REE and input of riverine terrestrial matter with rich Ce (resulting in pH change) during the anoxic conditions. In the middle parts of Amdo 114 station, distinct negative Ceanom values are observed (−0.238 to −0.111) and associated surface water warming were interpreted as being related to a major sea level rise. In contrast, the formation of the black shales in the lower and upper part of the studied succession took place during a cooler (Ceanom values >−0.10), lower surface water productivity, and lower sea‐level stage. Thus, we emphasize the role of different factors that control the formation of local and regional black shales. The most important factors are sea‐level fluctuations and increasing productivity.
Sedimentary Evolution of the Qinghai–Tibet Plateau in Cenozoic and its Response to the Uplift of the Plateau
Authors: Kexin ZHANG , Guocan WANG , Yadong XU , Mansheng LUO , Junliang JI , Guoqiao XIAO , An WANG , Bowen SONG , Yinpin LIANG , Shangsong JIANG , Kai CAO , Fenning CHEN , Ruiming CHEN , Yongfeng YANG
Published: April 2013

We have studied the evolution of the tectonic lithofacies paleogeography of Paleocene–Eocene, Oligocene, Miocene, and Pliocene of the Qinghai–Tibet Plateau by compiling data regarding the type, tectonic setting, and lithostratigraphic sequence of 98 remnant basins in the plateau area. Our results can be summarized as follows. (1) The Paleocene to Eocene is characterized by uplift and erosion in the Songpan–Garzê and Gangdisê belts, depression (lakes and pluvial plains) in eastern Tarim, Qaidam, Qiangtang, and Hoh Xil, and the Neo‐Tethys Sea in the western and southern Qinghai–Tibet Plateau. (2) The Oligocene is characterized by uplift in the Gangdisê–Himalaya and Karakorum regions (marked by the absence of sedimentation), fluvial transport (originating eastward and flowing westward) in the Brahmaputra region (marked by the deposition of Dazhuka conglomerate), uplift and erosion in western Kunlun and Songpan‐Garzê, and depression (lakes) in the Tarim, Qaidam, Qiangtang, and Hoh Xil. The Oligocene is further characterized by depressional littoral and neritic basins in southwestern Tarim, with marine facies deposition ceasing at the end of the Oligocene. (3) For the Miocene, a widespread regional unconformity (ca. 23 Ma) in and adjacent to the plateau indicates comprehensive uplift of the plateau. This period is characterized by depressions (lakes) in the Tarim, Qaidam, Xining–Nanzhou, Qiangtang, and Hoh Xil. Lacustrine facies deposition expanded to peak in and adjacent to the plateau ca. 18–13 Ma, and north–south fault basins formed in southern Tibet ca. 13–10 Ma. All of these features indicate that the plateau uplifted to its peak and began to collapse. (4) Uplift and erosion occurred during the Pliocene in most parts of the plateau, except in the Hoh Xil–Qiangtang, Tarim, and Qaidam. The continuous uplift and intensive taphrogeny in the plateau divided the original large basin into small basins, deposition of lacustrine facies decreased considerably, and boulderstone accumulated, indicating a response to the overall uplift of the plateau. Here, we discuss the evolution of tectonic lithofacies paleogeography in Cenozoic and its response to the tectonic uplift of the Qinghai‐Tibet Plateau in relation to the above characteristics. We have recognized five major uplift events, which occurred during 58–53 Ma, 45–30 Ma, 25–20 Ma, 13–7 Ma, and since 5 Ma. The results presented here indicate that the paleogeomorphic configurations of the Qinghai–Tibet Plateau turned over during the late Miocene, with high elevations in the east during the pre‐Miocene switching to high contours in the west at the end of Miocene.
Magnetostratigraphy and Anisotropy of Magnetic Susceptibility of the Lulehe Formation in the Northeastern Qaidam Basin
Authors: Xue KE , Junliang JI , Kexin ZHANG , Xiaohu KOU , Bowen SONG , Chaowen WANG
Published: April 2013

The timing of onset of deposition of the Lulehe Formation is a significant factor in understanding the genesis of the Qaidam basin and the evolution of the Tibetan Plateau. Here, we describe a detailed magnetostratigraphic and magnetic fabric study of the middle and lower parts of the Lulehe Formation. A total of 234 samples were collected from 117 sites throughout a thickness of almost 460 m of fluvial and lacustrine deposits at the Xitieshan section in the northeastern Qaidam basin. Out of these sites, 94 sites yielded well‐defined characteristic remanent magnetization components by stepwise thermal demagnetization and were used to establish the magnetostratigraphy of the studied section. Based on correlation with the geomagnetic polarity timescale, the studied section spans the period from 53.8 Ma to 50.7 Ma. Our results show a three‐fold decrease in sedimentation rates as well as marked change in facies from braided river to delta and shore–shallow lake around 52.6 Ma, which suggests tectonic uplift of the northeastern Qaidam basin margin ridge was rapid at the onset of formation of the Qaidam basin and subsequently weakened after 52.6 Ma. The anisotropy of magnetic susceptibility results indicate that tectonic compression stress had reached the northeastern Tibetan Plateau by the early stages of Indo–Eurasian plate collision and that the direction of stress in the study area was NE–SW. Furthermore, a weakening of tectonic compression stress around 52.6 Ma is consistent with sedimentary records. The age of initial deposition of the Qaidam basin (around 53.8 Ma) was almost synchronous with that of the Qiangtang, Hoh Xil, Xining, and Lanzhou basins, which implies that stress was transferred rapidly through the Tibetan Plateau during or immediately after the onset of Indo–Eurasian collision.
Distance transform: a tool for the study of animal colour patterns
Authors: Taylor Christopher H. , Gilbert Francis , Reader Tom
Published: April 2013

The information in animal colour patterns plays a key role in many ecological interactions; quantification would help us to study them, but this is problematic. Comparing patterns using human judgement is subjective and inconsistent. Traditional shape analysis is unsuitable as patterns do not usually contain conserved landmarks. Alternative statistical approaches also have weaknesses, particularly as they are generally based on summary measures that discard most or all of the spatial information in a pattern.

We present a method for quantifying the similarity of a pair of patterns based on the distance transform of a binary image. The method compares the whole pattern, pixel by pixel, while being robust to small spatial variations among images.

We demonstrate the utility of the distance transform method using three ecological examples. We generate a measure of mimetic accuracy between hoverflies (Diptera: Syrphidae) and wasps (Hymenoptera) based on abdominal pattern and show that this correlates strongly with the perception of a model predator (humans). We calculate similarity values within a group of mimetic butterflies and compare this with proposed pairings of Müllerian comimics. Finally, we characterise variation in clypeal badges of a paper wasp (Polistes dominula) and compare this with previous measures of variation.

While our results generally support the findings of existing studies that have used simpler ad hoc methods for measuring differences between patterns, our method is able to detect more subtle variation and hence reveal previously overlooked trends.
A Novel Oxygenated Machine Perfusion System for Preservation of the Liver
Authors: Dirkes Marcel C. , Post Ivo C.J.H. , Heger Michal , van Gulik Thomas M.
Published: April 2013

Machine perfusion (MP) is a potential method to increase the donor pool for organ transplantation. However, MP systems for liver grafts remain difficult to use because of organ‐specific demands. Our aim was to test a novel, portable MP system for hypothermic preservation of the liver. A portable, pressure‐regulated, oxygenated MP system designed for kidney preservation was adapted to perfuse liver grafts via the portal vein (PV). Three porcine livers underwent 20 h of hypothermic perfusion using Belzer MP solution. The MP system was assessed for perfusate flow, temperature, venous pressure, and pO2/pCO2 during the preservation period. Biochemical and histological parameters were analyzed to determine postpreservation organ damage. Perfusate flow through the PV increased over time from 157 ± 25 mL/min at start to 177 ± 25 mL/min after 20 h. PV pressure remained stable at 13 ± 1 mm Hg. Perfusate temperature increased from 9.7 ± 0.6°C at the start to 11.0 ± 0.0°C after 20 h. Aspartate aminotransferase and lactate dehydrogenase increased from 281 ± 158 and 308 ± 171 U/L after 1 h to 524 ± 163 and 537 ± 168 U/L after 20 h, respectively. Blood gas analysis showed a stable pO2 of 338 ± 20 mm Hg before perfusion of the liver and 125 ± 14 mm Hg after 1 h perfusion. The pCO2 increased from 15 ± 5 mm Hg after 1 h to 53 ± 4 mm Hg after 20 h. No histological changes were found after 20 h of MP. This study demonstrated the feasibility of a portable MP system for preservation of the liver and showed that continuous perfusion via the PV can be maintained with an oxygen‐driven pump system without notable preservation damage of the organ.
Experiments with Lithic Tools: Understanding Starch Residues from Crop Harvesting
Authors: Yang X. , Ma Z. , Li Q. , Perry L. , Huan X. , Wan Z. , Li M. , Zheng J.
Published: April 2013

Stone knives were used widely in Neolithic East Asia, presumably in the harvesting of grain crops, but their function has not been clearly understood due to the lack of study of residues from these tools. To address this issue, starch grain analysis was employed to study the residues on the surface of ancient stone knives and large amounts of starches were recovered. The sources of these starches, however, were not well understood, because harvesting of crops involves the cutting of stems rather than direct contact with starchy seeds. To determine whether harvesting could deposit these types of residues, we designed a simulation experiment using stone flakes to harvest ears of wheat, rice and foxtail millet, then analysed the residues on both the flakes and in the plant tissues. A large number of starch grains were found in the stems, including both typical morphotypes from seeds and newly described types that occur only in stems, which can be used as indicators of harvesting. Our study demonstrates that starch grains from residues on the surfaces of archaeological stone knives can indicate not only that the tools were used to harvest ears, but also the type of crops harvested.
Equine leptospirosis in tropical Northern Queensland
Authors: Wangdi C , Picard J , Tan R , Condon F , Dowling B , Gummow B
Published: April 2013

Objective

Determine leptospiral serodiversity, serodominant serovars and prevalence in the horse population of Northern Queensland (NQ), Australia, with special focus on the Atherton Tableland and Townsville–Burdekin regions.

Design

Cross‐sectional survey.

Methods

Serum samples from 429 horses originating from 172 horse‐owning properties in NQ were collected at regional horse shows and veterinary clinics. Samples were analysed using a microscopic agglutination test. Owners were interviewed on potential risk factors associated with leptospirosis.

Results

Of the 172 properties that submitted samples, horses from 60 properties (35%, 95% confidence interval (CI) 31–39%) in NQ showed evidence of exposure to one or more serovars of Leptospira at a serum dilution of 1 : 100. The proportion of seropositive properties in the Atherton Tableland and Townsville–Burdekin regions was 25% (95% CI 17–33%) and 36% (95% CI 30–43%), respectively. In total, 81 horses had titres to a single serovar and the remained had titres to two or more serovars. Although 20 serovars representing 17 serogroups were detected, serovar Arborea was serodominant and detected in horses from 29 properties. Geldings were more at risk (odds ratio 3.3) of being seropositive to serovar Arborea. The detection of serovar Arborea‐seropositive horses was strongly associated (P < 0.05) with the average annual rainfall each property received and the presence of pigs and sugarcane fields in the vicinity.

Conclusion

Serological evidence of leptospirosis in horses in NQ indicates that prevalence is high and horses have been exposed to a wide range of serovars.
In vitro susceptibilities of feline and canine Escherichia coli and Pseudomonas spp. isolates to ticarcillin and ticarcillin–clavulanic acid
Authors: Bennett AB , Martin PA , Gottlieb SA , Govendir M
Published: April 2013

Objectives

To investigate in vitro susceptibilities of canine and feline Escherichia coli and canine Pseudomonas spp. isolates to ticarcillin and ticarcillin–clavulanic acid (T/C).

Design

In vitro susceptibility testing of bacterial isolates collected from infections.

Methods

We tested 148 (83 canine and 65 feline) E. coli and 61 canine Pseudomonas spp. isolates for susceptibility to T/C using both disc diffusion and Epsilometer tests (E‐tests). Additionally, susceptibilities of 96 E. coli and 23 canine Pseudomonas spp. isolates were tested via disc diffusion to ticarcillin alone.

Results

Of the E. coli isolates obtained from canine and feline urine, 92% by disc diffusion and 91% by E‐tests were susceptible to T/C. Of the canine Pseudomonas isolates, 90% by disc diffusion and 82% by E‐tests were susceptible to T/C. Of the Pseudomonas spp. isolates from the canine ear canal or tympanic bullae, 12% of isolates tested via disc diffusion and 23% via E‐tests were found to be resistant to T/C. The 50% minimum inhibitory concentration of T/C for all feline E. coli isolates was significantly lower than that for all canine E. coli isolates (P = 0.0031). The addition of clavulanic acid significantly increased the efficacy of ticarcillin against E. coli (P< 0.0001), but had negligible effect against canine Pseudomonas spp. isolates.

Conclusion

Ticarcillin‐clavulanic acid has reasonable in vitro efficacy against canine and feline E. coli, and canine Pseudomonas spp. isolates. However, decisions to use this drug therapeutically must be made on prudent considerations to minimise selection for bacterial resistance.
Junior doctor‐led ‘near‐peer’ prescribing education for medical students
Authors: Gibson Kyle R. , Qureshi Zeshan U. , Ross Michael T. , Maxwell Simon R.
Published: April 2013

Aims

Prescribing errors are common and inadequate preparation of prescribers appears to contribute. A junior doctor‐led prescribing tutorial programme has been developed for Edinburgh final year medical students to increase exposure to common prescribing tasks. The aim of this study was to assess the impact of these tutorials on students and tutors.

Methods

One hundred and ninety‐six tutorials were delivered to 183 students during 2010–2011. Each student completed a questionnaire after tutorial attendance which explored their previous prescribing experiences and the perceived benefits of tutorial attendance. Tutors completed a questionnaire which evaluated their teaching experiences and the impact on their prescribing practice. Student tutorial attendance was compared with end‐of‐year examination performance using linear regression analysis.

Results

The students reported increased confidence in their prescribing knowledge and skills after attending tutorials. Students who attended more tutorials also tended to perform better in end‐of‐year examinations (Drug prescribing: r = 0.16, P = 0.015; Fluid prescribing: r = 0.18, P = 0.007). Tutors considered that participation enhanced their own prescribing knowledge and skills. Although they were occasionally unable to address student uncertainties, 80% of tutors reported frequently correcting misconceptions and deficits in student knowledge. Ninety‐five percent of students expressed a preference for prescribing training delivered by junior doctors over more senior doctors.

Conclusions

A ‘near‐peer’ junior doctor‐led approach to delivering prescribing training to medical students was highly valued by both students and tutors. Although junior doctors have relatively less clinical experience of prescribing, we believe that this can be addressed by training and academic supervision and is outweighed by the benefits of these tutorials.
Incidence and risk of hypertension with a novel multi‐targeted kinase inhibitor axitinib in cancer patients: a systematic review and meta‐analysis
Authors: Qi Wei‐Xiang , He Ai‐Na , Shen Zan , Yao Yang
Published: April 2013

Aims

To investigate the overall incidence and risk of hypertension in cancer patients who receive axitinib and compare the differences in incidences between axitinib and the other four approved vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKIs).

Methods

Several databases were searched, including Pubmed, Embase and Cochrane databases. Eligible studies were phase II and III prospective clinical trials of patients with cancer assigned axitinib at a starting dose of 5 mg orally twice daily with data on hypertension available. Overall incidence rates, relative risk (RR), and 95% confidence intervals (CI) were calculated employing fixed or random effects models depending on the heterogeneity of the included trials.

Results

A total of 1908 patients from 10 clinical trials were included. The overall incidences of all grade and high grade hypertension in cancer patients were 40.1% (95% CI 30.9, 50.2%) and 13.1% (95% CI 6.7, 24%). The use of axitinib was associated with significantly increased risk of all grade (RR 3.00, 95% CI 1.29, 6.97, P = 0.011) and high grade hypertension (RR1.71, 95% CI 1.21, 2.43, P = 0.003). The risk of axitinib associated all grade and high grade hypertension in renal cell carcinoma (RCC) was significantly higher than that in non‐RCC. Additionally, the risk of hypertension with axitinib was substantially higher than other approved VEGFR‐TKIs, while the risk of all grade hypertension with axitinib was similar to pazopanib (RR 1.05; 95% CI 0.95‐, 1.17, P = 0.34).

Conclusions

While sharing a similar spectrum of target receptors with other VEGFR‐TKIs, axitinib is associated with an unexpectedly high risk of developing hypertension. Close monitoring and appropriate management for hypertension are recommended during the treatment.
Not‐in‐trial simulation I: Bridging cardiovascular risk from clinical trials to real‐life conditions
Authors: Chain Anne S. Y. , Dieleman Jeanne P. , van Noord Charlotte , Hofman Albert , Stricker Bruno H. Ch. , Danhof Meindert , Sturkenboom Miriam C. J. M. , Della Pasqua Oscar
Published: April 2013

Aims

The assessment of heart rate‐corrected QT (QTc) interval prolongation relies on the evidence of drug effects in healthy subjects. This study demonstrates the relevance of pharmacokinetic–pharmacodynamic (PKPD) relationships to characterize drug‐induced QTc interval prolongation and explore the discrepancies between clinical trials and real‐life conditions.

Methods

d,l‐Sotalol data from healthy subjects and from the Rotterdam Study cohort were used to assess treatment response in a phase I setting and in a real‐life conditions, respectively. Using modelling and simulation, drug effects at therapeutic doses were predicted in both populations.

Results

Inclusion criteria were shown to restrict the representativeness of the trial population in comparison to real‐life conditions. A significant part of the typical patient population was excluded from trials due to weight and baseline QTc interval criteria. Relative risk was significantly different between sotalol users with and without heart failure, hypertension, diabetes and myocardial infarction (P < 0.01). Although drug effects do cause an increase in the relative risk of QTc interval prolongation, the presence of diabetes represented an increase from 4.0 [95% confidence interval (CI) 2.7–5.8] to 6.5 (95% CI 1.6–27.1), whilst for myocardial infarction it increased from 3.4 (95% CI 2.3–5.13) to 15.5 (95% CI 4.9–49.3).

Conclusions

Our findings show that drug effects on QTc interval do not explain the observed QTc values in the population. The prevalence of high QTc values in the real‐life population can be assigned to co‐morbidities and concomitant medications. These findings substantiate the need to account for these factors when evaluating the cardiovascular risk of medicinal products.
Chronic lymphocytic leukaemia – the role of the microenvironment pathogenesis and therapy
Authors: Ramsay Alan D. , Rodriguez‐Justo Manuel
Published: April 2013

Chronic lymphocytic leukaemia/small lymphocytic lymphoma (CLL) is one of the more common forms of B cell malignancy. Although the condition has a variable clinical course, the trend is towards eventual relapse and the disease is considered incurable. Whilst the majority of the circulating CD5‐positive neoplastic B cells are arrested in the G0 phase of the cell cycle, those in the bone marrow and lymphoid tissues proliferate at a rate of 0·1–1% of the entire clone per day. This proliferation is supported by the tissue microenvironment, which has been shown to induce upregulation of anti‐apoptotic proteins and enhance the survival of the neoplastic cells. Microenvironmental factors are also thought to be important in tumour relapse and resistance to therapy. This review outlines the main signalling pathways involved in these tumour cell‐stromal interactions, and includes potential therapeutic strategies based on the manipulation of key components within the CLL microenvironment.
Use of a biosimilar granulocyte colony‐stimulating factor for peripheral blood stem cell mobilization: an analysis of mobilization and engraftment
Authors: Publicover Amy , Richardson Deborah S. , Davies Andrew , Hill Kate S. , Hurlock Carol , Hutchins David , Jenner Matthew W. , Johnson Peter W. , Lamb Jane , Launders Harriet , McKeag Nikki , Newman Joan , Orchard Kim H.
Published: April 2013

Peripheral blood haematopoietic progenitor cell mobilization has become a standard procedure prior to autologous stem cell transplantation. Biosimilar granulocyte colony‐stimulating factors (GCSF) have recently been awarded European Union (EU) licences for stem cell mobilization but data for their use in this context remain limited. The biosimilar GCSF, Ratiograstim® (Ratiopharm, Ulm, Germany) was granted an EU licence in September 2008 and incorporated into clinical practice in the Wessex Blood and Marrow Transplantation Programme in December 2008. Data were retrospectively collected for 154 consecutive patients undergoing peripheral blood stem cell harvest between January 2009 and December 2011 using the biosimilar GCSF. 131 consecutive patients from the preceding 3 years, who had received Neupogen®, were used as a control. We analysed both parameters relevant to stem cell collection and engraftment data, where patients proceeded to transplantation. We found no statistically significant difference between the two groups when comparing CD34 predictors, total number of CD34+ stem cells collected, number of days required for collection, or for time to engraftment. This is, to our knowledge, the largest direct comparison of a biosimilar GCSF with originator GCSF for stem cell mobilization. The use of biosimilar GCSF can produce a significant cost saving, allowing investment in other areas of stem cell transplantation.
CD43 expression is associated with inferior survival in the non‐germinal centre B‐cell subgroup of diffuse large B‐cell lymphoma
Authors: Mitrovic Zdravko , Iqbal Javeed , Fu Kai , Smith Lynette M. , Bast Martin , Greiner Timothy C. , Aoun Patricia , Armitage James O. , Vose Julie M. , Weisenburger Dennis D. , Chan Wing C.
Published: April 2013

We evaluated the prognostic significance of CD43 (SPN), a membrane glycoprotein, in 140 patients with diffuse large B‐cell lymphoma (DLBCL) by tissue microarray (TMA) immunostaining, and gene expression profiling (GEP) in 43 patients. CD43 protein was expressed in 19% of the cases and was strongly related to the non‐germinal centre B‐cell (non‐GCB) subgroup by both TMA and GEP. Patients with CD43(+) DLBCL had an inferior 3‐year overall survival (OS) compared to those with CD43(‐) DLBCL (50% vs. 76%, P = 0·01). Within the non‐GCB subgroup, patients with CD43(+) DLBCL had a particularly poor 3‐year OS (32% vs. 71%, P < 0·001). Gene set enrichment analysis within the activated B‐cell subgroup revealed significant enrichment in the stromal‐1 signature in CD43(−) cases. We conclude that CD43 is an adverse prognostic marker in DLBCL, and is preferentially expressed in the non‐GCB subgroup. The dismal outcome of CD43(+) cases in the non‐GCB subgroup may be explained, at least in part, by a less favourable microenvironment.
A Misinterpreted Case of Aorta Prosthesis Endocarditis: Remember The Phenomenon of Microbubbles
Authors: Lerche Christian Johann , Haugan Ketil Jørgen , Reimers Jesper Irving , Ihlemann Nikolaj
Published: April 2013

A 17‐year‐old male with a history of newly implanted mechanical valve at the aortic position, presented with fever, rigors, and painful cutaneous abscesses on his lower extremities and was suspected for infective endocarditis. Transthoracic echocardiography (TTE) showed a vegetation‐like structure following the movement of the mechanical heart valve (MHV), which eventually proved to be a product of degassing microbubbles (MB).
Angiogenin outperforms VEGF, EPCs and CECs in predicting Dukes' and AJCC stage in colorectal cancer
Authors: Ramcharan Sean K. , Lip Gregory Y. H. , Stonelake Paul S. , Blann Andrew D.
Published: April 2013

Background

Circulating endothelial cells (CECs), endothelial progenitor cells (EPCs), Willebrand factor (vWf), soluble E‐selectin, vascular endothelial growth factor (VEGF) and angiogenin are of interest in cancer vascular biology. However, few studies have looked at more than one in combination. We set out to determine which would be best in predicting the Dukes' and American Joint Committee on Cancer (AJCC) scores in colorectal cancer patients.

Methods

We recruited 154 patients with colorectal cancer, 29 healthy controls and 26 patients with benign bowel disease. CD34+/CD45−/CD146+ CECs and CD34+/CD45−/CD309[KDR]+ EPCs were measured by flow cytometry, plasma markers by ELISA.

Results

All research indices were raised in colorectal cancer (P < 0·05) compared to control groups. Although CECs (P < 0·05), EPCs (P < 0·01) and angiogenin (P < 0·01) increased stepwise across the four Dukes' stages and four AJCC stages, only angiogenin remained significant in multiple regression analysis (P = 0·003 for Dukes, P = 0·01 for AJCC). Angiogenin levels were higher in Dukes' stages C and D compared to stage A, and AJCC stages 4–6 and 7–10 compared to stage 1 (all P < 0·05). Adding a second research marker to angiogenin did not markedly improve this relationship.

Conclusion

Although we found disturbances in endotheliod cells and plasma markers of the endothelium and growth factors, only angiogenin levels were independently associated with progression of the Dukes' stage and AJCC stage, with the association with Duke's stage being stronger. We suggest that angiogenin is a potential biomarker in risk stratification for colorectal cancer, and may aid clinical decision making.
Novel RUNX2 frameshift mutations in Chinese patients with cleidocranial dysplasia
Authors: Huang Yanyu , Song Yaling , Zhang Chenzheng , Chen Guoxin , Wang Shihua , Bian Zhuan
Published: April 2013

Cleidocranial dysplasia (CCD) is a skeletal disorder caused by heterozygous mutations in the runt‐related transcription factor 2 (RUNX2) gene. We evaluated the phenotypes of eight Chinese patients with CCD from three unrelated families followed by analysis of the RUNX2 genes. Three different RUNX2 frameshift mutations were identified. Two of the mutations are novel (c.887insC and c.592delA) and one (c.90insC) has been described previously. Surprisingly, the patient with the most severely truncated RUNX2 protein (c.90insC) had the mildest phenotype. The RUNX2 mutations identified were assessed for their effect on the subcellular localization of the mutant RUNX2 proteins because of previously reported inconsistent findings. All three mutant proteins showed at least partially impaired nuclear localization compared with wild‐type RUNX2, which was localized exclusively in the nucleus. Our findings support the notion that haploinsufficiency of RUNX2 may be mainly responsible for CCD. However, because the correlation between the severity of the phenotype and the degree of mutational impairment of RUNX2 is not consistent, other factors, such as nonsense‐mediated mRNA decay and negative dominant effects, may also play a role. In addition, we show that despite the presence of the best characterized nuclear localization signal, nuclear translocation of truncated RUNX2 can be inhibited, possibly as a result of precipitation in the cytoplasm.
Seeking a Sex‐Specific Coolidge Effect in a Simultaneous Hermaphrodite
Authors: Werminghausen Johanna , Lange Rolanda , Anthes Nils
Published: April 2013

In polygamous mating systems, a capability to discriminate against familiar mates may be beneficial to both sexes. Polyandrous females, for instance, may enhance the odds of finding sires with optimal genetic compatibility or high genetic quality by mating with multiple different males; polygynous males, in addition, may more efficiently invest their limited ejaculates across multiple (rather than single) females. The Coolidge effect facilitates this kind of mate discrimination, as sexual motivation declines across consecutive copulations with a familiar partner but resurrects with a novel mate. In simultaneous hermaphrodites, we expect the Coolidge effect to show sex role‐dependent patterns and vary with previous sex‐specific mating activity. Using the promiscuous hermaphroditic sea slug Chelidonura sandrana, we investigated (1) whether sexual motivation indeed declines when repeatedly exposed to familiar partners, (2) whether the Coolidge effect occurs in a sex‐specific manner and (3) whether ejaculation is strategic with respect to partner familiarity. We found neither mating latency, nor penis intromission duration, mating propensity or the frequency of sex role alternations to vary significantly with treatments. Furthermore, slugs did not donate larger ejaculates to novel than to familiar partners. Partner novelty thus elicited no detectable response in sexual motivation or mating effort in C. sandrana. We suggest that the sea slugs' promiscuous mating system in often large mating aggregations makes mate discrimination based on novelty obsolete in comparison with more relevant criteria such as partner body size or mating history.
From Policy to Implementation—How Family Relationship Centres Became a Reality
Authors: Pidgeon Sue
Published: April 2013

This article deals with the process undertaken by the Australian Government to develop and implement Family Relationship Centres (FRCs) as part of a major package of reforms to the Australian family law system. The article outlines consultation undertaken in developing the reforms and explains the role of the FRCs. The article details the practical steps taken to roll‐out the new FRCs. The services were to be outsourced to community‐based service providers but there were many issues for the Government to address, including: how an FRC should operate; where they should be located; how to allocate the funding; and how to manage the roll‐out of so many services. Other aspects of the implementation covered in the article include: addressing accessibility and quality control issues; training FRC staff; establishing a national telephone advice line and website; and informing the public about the new services. The article also refers to steps taken to support the introduction of compulsory dispute resolution; and research and evaluation undertaken to measure the impact of the reforms.

Keypoints for the Family Court Community

Family Relationship Centres (FRCs) were a new type of service and their development and implementation raised a range of issues to be dealt with by the Australian Government.

Determining where and when FRCs would be rolled out, selecting community‐based service providers, addressing accessibility and quality control issues, training FRC staff and raising public awareness of the new services were all part of the implementation process.

As brand new services, FRCs were able to be innovative and to develop new processes (and adapt old ones) to suit their role as an alternative to the courts and as a doorway to the wider family law system.
Child Protection in Family Relationship Centres: Innovations in Western Australia
Authors: Hannan Jennifer
Published: April 2013

Family Relationship Centres (FRCs) established in Australia in 2006 are seeing parents from increasingly complex backgrounds including families where child protection matters may be of serious concern. These matters have required practitioners to shift their thinking about what responsibility they have for hearing the voices of children and their role in child protection. Many of the safety issues that present at FRC's fall below the statutory threshold for child protection intervention and this paper argues that FRC's are well placed to act as a referral and assessment point for families who might not otherwise be assessed or referred to services. This paper outlines a model of child inclusive practice (CIP) used in Anglicare WA's FRC's which is child inclusive but does not proceed to family dispute resolution. Where a risk factor such as family violence, mental health issues, or drug and alcohol issues is identified on intake with parents, children are routinely seen for an interview in order to obtain information about their needs and wellbeing. Literature indicates that many victims minimise violence and the risks associated with it; many parents maintain child contact with perpetrators for fear of retaliation; and many children protect their parents by not disclosing violence or other issues, because they do not want to “add fuel to the fire” or “be disloyal” to a parent. Case studies are provided to underline the importance of safety assessment.

Keypoints for the Family Court Community

High numbers of complex child protection matters that present at Family Law services

Importance of undertaking a safety assessment with children as well as parents where indicated

Importance of referral to support services even if cases do not reach child protection threshold
Thioredoxin h regulates calcium dependent protein kinases in plasma membranes
Authors: Ueoka‐Nakanishi Hanayo , Sazuka Takashi , Nakanishi Yoichi , Maeshima Masayoshi , Mori Hitoshi , Hisabori Toru
Published: April 2013

Thioredoxin (Trx) is a key player in redox homeostasis in various cells, modulating the functions of target proteins by catalyzing a thiol–disulfide exchange reaction. Target proteins of cytosolic Trx‐h of higher plants were studied, particularly in the plasma membrane, because plant plasma membranes include various functionally important protein molecules such as transporters and signal receptors. Plasma membrane proteins from Arabidopsis thaliana cell cultures were screened using a resin Trx‐h1 mutant‐immobilized, and a total of 48 candidate proteins obtained. These included two calcium‐sensing proteins: a phosphoinositide‐specific phospholipase 2 (AtPLC2) and a calcium‐dependent protein kinase 21 (AtCPK21). A redox‐dependent change in AtCPK21 kinase activity was demonstrated in vitro. Oxidation of AtCPK21 resulted in a decrease in kinase activity to 19% of that of untreated AtCPK21, but Trx‐h1 effectively restored the activity to 90%. An intramolecular disulfide bond (Cys97–Cys108) that is responsible for this redox modulation was then identified. In addition, endogenous AtCPK21 was shown to be oxidized in vivo when the culture cells were treated with H2O2. These results suggest that redox regulation of AtCPK21 by Trx‐h in response to external stimuli is important for appropriate cellular responses. The relationship between the redox regulation system and Ca2+ signaling pathways is discussed.

Structured digital abstract

CPK21 physically interacts with TRXH1 by two hybrid (View interaction)

TRXH1 physically interacts with AT1G56075, CPK21, PRX2B, HIR3, RAA4B, TC132, RAD2C, AT3G03270, AT3G53990, METK4, AT3G17020, AT1G20760, MPCP3, SKS2, AT5G23890, DTC, AT1G56070, TBB3, ACT8, TI110, DHSB1, TBA3, AOX1A, PLCD2, CLAH1, CLAH2, RSSA1, APX1, RAB1C, ACT7, ARF1, NRL1, ADT1, TBB7, RAD2A, G3PC1, TBB4, MD37E, DHSA1, TC159, AT4G22710, GPX6, RABC1, VATA, GPX2 and RAA2A by affinity chromatography technology (View interaction)
Kienböck's disease associated with radiocephalic fistula formation in a patient with end‐stage renal disease
Authors: Kang Gun Woo , Lee Da Young , Lee Young‐Hwan , Ahn Ki Sung , Kim Shin‐Kun , Lee In Hee
Published: April 2013

Kienböck's disease, which consists of osteonecrosis and collapse of the lunate bone, causes chronic pain and dysfunction of the wrist. Patients on hemodialysis are occasionally present with wrist pain, but Kienböck's disease is rarely reported in dialysis patients. This case study describes Kienböck's disease in a patient with end‐stage renal disease on hemodialysis. A 39‐year‐old male with a 1‐year history of hemodialysis presented with left wrist pain that increased progressively over 6 months. The patient had no history of trauma or any other risk factors known to be associated with Kienböck's disease. Physical examination of the wrist at the site of the arteriovenous fistula showed swelling and tenderness with decreased range of motion. Radiographic examination showed articular collapse and fracture of the body of lunate consistent with stage IIIb Kienböck's disease. An intercarpal arthrodesis with autogenous bone graft was performed.