bluuebunny/crossref_metadata_2025_split huggingface dataset:
Building on the Canadian approach to resolve the stalemate on the trade and environment agenda in the World Trade Organization
Authors: Dagne Teshager 
Published: July 2009

PurposeThe purpose of this paper is to analyze the competing views on the link between trade and environment in the World Trade Organization (WTO), and come up with a proposal that better clarifies the scope of legality of environmentally motivated unilateral trade measures in the multilateral trading system.Design/methodology/approachThe paper adopts a doctrinal approach to legal research in providing an exegesis on the various efforts towards the integration of trade and environment in the WTO framework.FindingsEmploying the theory of transnational social justice as its analytical tool, the paper suggests that a state contemplating the use of environmentally motivated unilateral trade measures first extend positive measures to the communities in other states that are affected by the purported measure. Accordingly, it argues that unilateral trade measures are allowed in the system only as a last resort and only if their application runs congruent to the values and objectives recognized by the system.Originality/valueIt is hoped that the discussion and proposition in this paper will contribute to the discourse on the clarification of the status of environmentally motivated unilateral trade measures in the WTO.
Cost‐effectiveness analysis on screening for colorectal neoplasm and management of colorectal cancer in Asia
Authors: TSOI K. K. F. , NG S. S. M. , LEUNG M. C. M. , SUNG J. J. Y. 
Published: July 2009

Aliment Pharmacol Ther 28, 353–363SummaryBackground  Faecal occult blood testing (FOBT), flexible sigmoidoscopy (FS) and colonoscopy are recommended for subjects above 50 years of age for screening for colorectal cancer (CRC).Aim  To evaluate the cost‐effectiveness of FOBT, FS and colonoscopy on the basis of disease prevalence, compliance rate and cost of screening procedures in Asian countries.Methods  A hypothetical population of 100 000 persons aged 50 undergoes either FOBT annually, FS every 5 years or colonoscopy every 10 years until the age of 80 years. Patients with positive FOBT or polyp in FS are offered colonoscopy. Surveillance colonoscopy is repeated every 3 years. The treatment cost of CRC, including surgery and chemotherapy, was evaluated. A Markov model was used to compare the cost‐effectiveness of different screening strategies.Results  Assuming a compliance rate of 90%, colonoscopy, FS and FOBT can reduce CRC incidence by 54.1%, 37.1% and 29.3% respectively. The incremental cost‐effectiveness ratio (ICER) for FOBT (US$6222 per life‐year saved) is lower than FS (US$8044 per life‐year saved) and colonoscopy (US$7211 per life‐year saved). When the compliance rate drops to 50% and 30%, FOBT still has the lowest ICER.Conclusion  FOBT is cost‐effective compared to FS or colonoscopy for CRC screening in average‐risk individuals aged from 50 to 80 years.
Anatomy of the seaward steps and seaward termination of the Brent clastic wedge
Authors: Mjøs Rune 
Published: July 2009

ABSTRACTThe northward and seaward outbuilding of the Middle Jurassic Brent delta in the Northern North Sea, comprising from the base and upwards Rannoch, Etive and Lower–Middle Ness Formations, displays a stacking pattern of coastal facies tracts described as ‘steps and rises’. Each ‘step and rise’ is formed in response to stratigraphic base‐level (A/S ratio) changes and defines high‐frequency cycles within the Brent Group. During a decreasing A/S ratio regime shoreface progradation dominated and formed the wave–storm‐dominated Rannoch facies tract with a rather flat shoreface trajectory curve resembling a step. A succeeding change to an increasing A/S ratio regime led to a transgression and stratigraphic rise (step‐up) due to aggradation of tidal bay and lagoonal–barrier complexes (Etive facies tract) on top of the previous deposited shoreface. This pattern was formed both due to sediment volume partitioning comprising spatial displacement of depocentres through time and facies differentiation involving changes in coastal geomorphology and dominant deposited facies tract. In the northern areas, where the Brent seaward stepping and the entire Brent clastic wedge terminates seaward, a vertical stack of Etive and Rannoch facies tracts occurs. The Rannoch facies tract has the northernmost extension and the termination of the Brent clastic wedge comprises a vertical stack of shoreface and shelf deposits. The aggradational nature of the tidal bay–barrier sandstone complex of the Etive facies tract explains the seaward thinning from 30 to 40 m to zero sandstone thickness within a short distance (a few kilometres). Facies tract mapping, architectural relationships and mass balance considerations do not indicate that the Etive facies tract was formed due to ‘forced regression’ or ‘lowstand’ developments. Instead, the basal surface of the Etive facies tract was probably formed by transgressive erosion. The embayments created by the transgression were filled by aggradational tidal bay and barrier complex deposition of the Etive facies tract.The seaward stepping, lower Brent Group, shows similarities to outcrop analogues of the Cretaceous, Mesa Verde Group in the Western Interior Seaway and the Palaeogene, Battfjellet Formation on Spitsbergen, supporting a model with facies differentiation within high‐frequency cycles, and that the large‐scale stratigraphic development is controlled by the stacking of these cycles.
Acute megakaryoblastic leukaemia (AMKL) and transient myeloproliferative disorder (TMD) in Down syndrome: a multi‐step model of myeloid leukaemogenesis
Authors: Roy Anindita , Roberts Irene , Norton Alice , Vyas Paresh 
Published: July 2009

SummaryChildren with Down syndrome (DS) have a marked increase in susceptibility to Acute Megakaryoblastic Leukaemia (DS‐AMKL) and the closely linked neonatal preleukaemic syndrome, Transient Myeloproliferative Disorder (DS‐TMD). The distinct stages of DS‐TMD and DS‐AMKL provide an excellent tractable model to study leukaemogenesis. This review focuses on recent studies describing clinical, haematological and biological features of DS‐AMKL and DS‐TMD. The findings from these studies suggest that mutations in the key haemopoietic regulator GATA1 (GATA binding protein 1) in DS‐AMKL and DS‐TMD may be useful in diagnosis and assessing minimal residual disease. These findings raise the possibility of population‐based screening strategies for DS‐TMD and the development of treatment to eliminate the preleukaemic TMD clone to prevent DS‐AMKL. Advances in our understanding of perturbed haemopoiesis in DS, the role of GATA1 and of cooperating mutations are also discussed. These findings have implications for leukaemia biology more broadly given the frequency of acquired trisomy in other human leukaemias.
Detection of gene copy number aberrations in mantle cell lymphoma by a single quantitative multiplex PCR assay: clinicopathological relevance and prognosis value
Authors: Jardin Fabrice , Picquenot Jean‐Michel , Parmentier Françoise , Ruminy Philippe , Cornic Marie , Penther Dominique , Bertrand Philippe , Lanic Hélène , Cassuto Ophélie , Humbrecht Catherine , Lemasle Emilie , Wautier Agathe , Bastard Christian , Tilly Hervé 
Published: July 2009

SummaryThe t(11;14)(q13;q32) is the hallmark of mantle cell lymphoma (MCL). Additional genetic alterations occur in the majority of cases. This study aimed to design a polymerase chain reaction (PCR) assay to determine the incidence and relevance of recurrent gene copy number aberrations in this disease. Forty‐two MCL cases with frozen‐ or paraffin‐embedded (FFPE) tissues were selected. Three different quantitative Multiplex PCR of Short Fluorescent Fragments (QMPSF) assays were designed to simultaneously analyse eight genes (CDKN2A, RB1, ATM, CDK2, TP53, MYC, CDKN1B, MDM2), to analyse the 9p21 locus (CDKN2A/CDKN2B) and FFPE tissues. Gains of MYC, CDK2, CDKN1B, and MDM2 were observed in 10% of cases. Losses of RB1, CDKN2A, ATM or TP53 were observed in 38%, 31%, 24% and 10% of cases, respectively. Analysis of the 9p21 locus indicated that, in most cases, tumours displayed a complete inactivation of p14ARF/p15INK4B/p16INK4A. CDKN2A and MYC aberrations were associated with a high MCL international prognostic index (MIPI). CDK2/MDM2 gains and CDKN2A/TP53 losses correlated with an unfavourable outcome. PCR experiments with frozen and FFPE‐tissues indicated that our approach is valid in a routine diagnostic setting, providing a powerful tool that could be used for patient stratification in combination with MIPI in future clinical trials.
Von Willebrand factor protects the Ca2+‐dependent structure of the factor VIII light chain
Authors: Takeyama Masahiro , Nogami Keiji , Okuda Masahiro , Shima Midori 
Published: July 2009

SummaryWe have recently reported that cation‐exchange iminodiacetate resin completely inactivated factor VIII (FVIII) by direct deprivation of metal ions, predominantly Ca2+, from its molecules, and that von Willebrand factor (VWF) protected FVIII antigen from resin‐induced degradation. The present study was further developed to investigate this mechanism. Western blotting analysis and enzyme‐linked immunosorbent assay showed that the antigenic structure of the FVIII light chain, especially the C2 domain, was completely impaired by the resin, whilst that of the heavy chain was little affected. However, the complex formation with VWF protected the C2 domain from the resin‐induced degradation. The resin‐treated C2 domain failed to interact with VWF and phospholipid. Furthermore, the addition of Ca2+ competitively blocked the resin‐induced impairment of the C2 domain structure. These results demonstrate that VWF protects the Ca2+‐dependent conformational structure of the FVIII light chain, especially the C2 domain, and may indicate that the C2 domain contains the Ca2+‐binding site(s).
NKG2D‐mediated immunity underlying paroxysmal nocturnal haemoglobinuria and related bone marrow failure syndromes
Authors: Hanaoka Nobuyoshi , Nakakuma Hideki , Horikawa Kentaro , Nagakura Shoichi , Tsuzuki Yasuchika , Shimanuki Masaya , Kojima Kensuke , Yonemura Yuji , Kawaguchi Tatsuya 
Published: July 2009

SummaryIt is considered that a similar immune mechanism acts in the pathogenesis of bone marrow (BM) failure in paroxysmal nocturnal haemoglobinuria (PNH) and its related disorders, such as aplastic anaemia (AA) and myelodysplastic syndromes (MDS). However, the molecular events in immune‐mediated marrow injury have not been elucidated. We recently reported an abnormal expression of stress‐inducible NKG2D (natural‐killer group 2, member D) ligands, such as ULBP (UL16‐binding protein) and MICA/B (major histocompatibility complex class I chain‐related molecules A/B), on granulocytes in some PNH patients and the granulocyte killing by autologous lymphocytes in vitro. The present study found that the expression of NKG2D ligands was common to both granulocytes and BM cells of patients with PNH, AA, and MDS, indicating their exposure to some incitement to induce the ligands. The haematopoietic colony formation in vitro by the patients’ marrow cells significantly improved when their BM cells were pretreated with antibodies against NKG2D receptor, suggesting that the antibodies rescued haematopoietic cells expressing NKG2D ligands from damage by autologous lymphocytes with NKG2D. Clinical courses of patients with PNH and AA showed a close association of the expression of NKG2D ligands with BM failure and a favourable response to immunosuppressive therapy. We therefore propose that NKG2D‐mediated immunity may underlie the BM failure in PNH and its‐related marrow diseases.
Vascular density in childhood acute lymphoblastic leukaemia correlates to biological factors and outcome
Authors: Norén‐Nyström Ulrika , Heyman Mats , Frisk Per , Golovleva Irina , Sundström Christer , Porwit Anna , Roos Göran , Bergh Anders , Forestier Erik 
Published: July 2009

SummaryThe issue of angiogenesis and its clinical relevance in childhood acute lymphoblastic leukaemia (ALL) is controversial. In the present study, microvessel density (MVD), analysed in 185 diagnostic bone marrow biopsies, was higher in T‐cell ALL compared to B‐cell precursor (BCP)‐ALL (P = 0·013). In the BCP group, cases with t(12;21) were characterized by a low MVD while patients with high‐hyperdiploid leukaemia (HeH, 51–61 chromosomes) showed a high MVD compared to other BCP patients (P = 0·001 and 0·002 respectively). There was a correlation between MVD and white blood cell (WBC) count in high‐risk BCP patients (P = 0·021). In addition, BCP patients with a high marrow reticulin fibre density and high MVD had an unfavourable outcome compared to the other BCP patients (P = 0·002). The fraction of vessels in which lumina were filled with blasts (blast congested vessel fraction) correlated strongly with WBC count (P < 0·001). These findings indicate that the angiogenic process interacts with other stroma‐factors, such as reticulin fibre density, in its effect on outcome, and is coupled to both the ALL genotype and phenotype. One possible implication is that different subtypes of childhood ALL may respond differently to anti‐angiogenic drugs as a supplement in first‐line treatment.
The Ascent to Competence conceptual framework: an outcome of a study of belongingness
Authors: Levett‐Jones Tracy , Lathlean Judith 
Published: July 2009

Aim.  This paper presents qualitative findings from a study that explored nursing students’ experience of belongingness when undertaking clinical placements. The aim is to locate the professional and practical implications of the research within an Ascent to Competence conceptual framework.Background.  The need to belong exerts a powerful influence on cognitive processes, emotional patterns, behavioural responses, health and well‐being and failure to satisfy this need can have devastating consequences. The literature suggests that diminished belongingness may impede students’ motivation for learning and influence the degree to which they are willing to conform rather than adopt a questioning approach to clinical practice.Design.  A mixed methods, cross national, multi‐site case study approach was adopted with third‐year preregistration nursing students from three universities (two in Australia and one in England) participating; 362 in the quantitative phase and 18 in the qualitative phase.Findings.  Qualitative findings demonstrated that, although the primary purpose of clinical education is to facilitate students’ progress towards the attainment of competence, the realisation of this goal is impacted by a wide range of individual, interpersonal, contextual and organisational factors which can be conceptualised hierarchically. By this structuring it is possible to see how belongingness is a crucial precursor to students’ learning and success.Conclusion.  The framework demonstrates that students progress to a stage where attainment of competence is possible only after their previous needs for safety and security, belongingness, healthy self‐concept and learning have been met.Relevance to clinical practice.  The future of the nursing profession depends upon the development of confident, competent professionals with a healthy self‐concept and a commitment to patient‐centred care and self‐directed learning. This paper demonstrates that the realisation of this goal is strongly influenced by the extent to which students’ clinical placement experiences promote and enhance their sense of belonging.
The structure of contraceptive education and instruction within nurse led family planning clinics: a grounded theory study
Authors: Hayter Mark 
Published: July 2009

Aims.  This study aimed to explore and analyse how nurses instruct women in contraceptive use during consultations in family planning clinics to produce a grounded theory of contraceptive education.Background.  Nurses play a key role in instructing women how to use contraception in family planning clinic consultations. These one‐to‐one situations are encounters where women are taught how to use contraceptive methods effectively. However, very little is known about the nature of these consultations.Design.  A qualitative study using a grounded theory approach was used.Results.  Three linked ‘core categories’ emerged from the data analysis. Firstly, women are educated about their body and how it responds to contraception: ‘reproductive education’. This core category is closely linked to ‘surveillance’ where women are taught to monitor their reproductive health and to ‘contraceptive regimen’ where women are instructed in techniques to successfully use a contraceptive method. Together these three core categories present a grounded theory of ‘contraceptive education’.Conclusions.  Nursing practice in this important area of women’s health care is complex and requires skilled practitioners. This study presents unique empirical data into how nurses conduct one‐to‐one consultations with women – providing a novel insight into how contraception is explained in clinical situations. Key issues for practice from the data were the lack of a balance when discussing side effects, the rigidity of some instructions and the lack of recognition of risk from sexually transmitted infection.Relevance to clinical practice.  Nurses working in sexual health need to ensure that women understand the often complex instructions they provide and that rigid instruction be occasionally amended to enable some flexibility. The manner in which side‐effects are discussed should also be balanced. Nurses need to address the risk of sexually transmitted infections more substantially in contraceptive discussions.
Impact of Platelets and Fresh Frozen Plasma in Contrast to Red Cell Concentrate on Unstimulated and Stimulated Cytokine Release in an In Vitro Model of Transfusion
Authors: Schneider S. O. , Rensing H. , Gräber S. , Kreuer S. , Kleinschmidt S. , Kreimeier S. , Müller P. , Mathes A. M. , Biedler A. E. 
Published: July 2009

AbstractTransfusion of blood may contribute to immunomodulation. Leuco‐depleted standard blood products are supposed to result in less immunomodulation compared with whole blood. To determine the influence of leuco‐depleted blood products on the cytokine response, red blood cell concentrates (RBC), fresh frozen plasma (FFP) and platelet concentrates (PC) were investigated in an in vitro model of blood transfusion. Leuco‐depleted standard blood bank RBC, FFP and PC were mixed in vitro with AB0 compatible venous blood from healthy volunteers in ratios of 3:1, 1:1 and 1:3. Specimens were incubated in presence or absence of lipopolysaccharide, 1 μg/ml. After 24 h of incubation cytokine release of tumour necrosis factor (TNF)‐α and interleukin‐10 (IL‐10) was measured in cell culture supernatants by means of enzyme‐linked immunsorbent assay. Addition of RBC, FFP and PC to venous blood from healthy volunteers led to a significant and dose‐dependent increase in spontaneous TNF‐α and IL‐10 release. After endotoxin stimulation, RBC, FFP and PC significantly suppressed the TNF‐α response, while the stimulated release of IL‐10 tended to increase, reaching significance only after high doses of FFP. Addition of leuco‐depleted blood products changed the spontaneous and stimulated cytokine response in an in vitro model of transfusion. These data may suggest a possible contribution of transfused FFP and PC to immunomodulation after transfusion similar to RBC.
Phytoene synthase activity controls the biosynthesis of carotenoids and the supply of their metabolic precursors in dark‐grown Arabidopsis seedlings
Authors: Rodríguez‐Villalón Antía , Gas Elisabet , Rodríguez‐Concepción Manuel 
Published: July 2009

SummaryCarotenoids are plastidial isoprenoids essential for plant life. In Arabidopsis thaliana carotenoid biosynthesis is strongly upregulated when seedlings that germinate in the dark (etiolated) emerge from the soil and light derepresses photomorphogenesis, causing etioplasts to become chloroplasts. We found that carotenoid biosynthesis is also induced when deetiolation is derepressed in the absence of actual light, eventually resulting in improved greening (chlorophyll accumulation) upon illumination. The increased production of carotenoids in the dark correlates with an upregulated activity of phytoene synthase (PSY; the first committed enzyme of carotenogenesis) and the induction of PSY gene expression in cotyledons (where carotenoids accumulate in dark‐grown seedlings). The metabolic precursors for carotenoid synthesis under these conditions are mostly supplied by the plastidial methylerythritol 4‐phosphate (MEP) pathway. Accumulation of flux‐controlling MEP pathway enzymes, such as deoxyxylulose 5‐phosphate synthase (DXS), is post‐transcriptionally increased when deetiolation is derepressed in the dark. Unlike the situation observed in light‐grown plants, however, the sole overexpression of DXS in dark‐grown seedlings does not increase carotenoid accumulation. By contrast, induced expression of a PSY‐encoding transgene results in increased carotenoid levels and a concomitant post‐transcriptional accumulation of DXS. These data provide evidence for a feedback mechanism by which PSY controls metabolic flux to the carotenoid pathway in plants.
An AP2‐type transcription factor, WRINKLED1, of Arabidopsis thaliana binds to the AW‐box sequence conserved among proximal upstream regions of genes involved in fatty acid synthesis
Authors: Maeo Kenichiro , Tokuda Tsuyoshi , Ayame Atsuko , Mitsui Naoko , Kawai Tsutae , Tsukagoshi Hironaka , Ishiguro Sumie , Nakamura Kenzo 
Published: July 2009

SummaryAlthough an APETALA2 (AP2)‐type transcription factor, WRINKLED1 (WRI1), has been shown to be required for accumulation of triacylglycerols (TAGs) in Arabidopsis seeds, its direct target genes have not been established. Overexpression of WRI1 up‐regulated a set of genes involved in fatty acid (FA) synthesis in plastids, including genes for a subunit of pyruvate kinase (Pl‐PKβ1), acetyl‐CoA carboxylase (BCCP2), acyl carrier protein (ACP1), and ketoacyl‐acyl carrier protein synthase (KAS1), while expression of these genes is reduced in mutants with reduced WRI1 expression. Transient expression of LUC reporter genes with the proximal sequences upstream from the ATG codon of Pl‐PKβ1, BCCP2, and KAS1 in protoplasts was activated by co‐expression of WRI1, and recombinant WRI1 bound to these upstream sequences in vitro. The seven WRI1 binding sites shared a sequence [CnTnG](n)7[CG], where n is any nucleotide designated as the AW‐box, and mutations in AW‐boxes near the transcription start site and in the 5′‐untranslated region of Pl‐PKβ1 abolished activation by WRI1 in protoplasts and expression during seed maturation. Although expression of genes for the synthesis of TAGs and packaging into oil bodies in the endoplasmic reticulum in developing seeds required WRI1, their expression was not up‐regulated by WRI1 overexpression. Thus, WRI1 promotes the flow of carbon to oil during seed maturation by directly activating genes involved in FA synthesis and controlling genes for assembly and storage of TAG.