bluuebunny/crossref_metadata_2025 huggingface dataset:
Multiple large ownership structure, audit committee activity and audit fees
Authors: Adelopo Ismail , Jallow Kumba , Scott Peter
Published: September 2012

Purpose

The purpose of this study is to examine the impact of multiple large ownership structure (MLS) and audit committee activity (ACA) on audit pricing for a sample of UK listed companies.

Design/methodology/approach

One way analysis of variance (ANOVA) and cross sectional multiple regression analysis of a sample of UK listed companies showed statistically significant differences in the audit fees, firm size and audit committee activities of these firms when they are categorised based on the number of MLS.

Findings

The study finds a significant negative relationship between audit fees and number of MLS, but a surprising positive relationship with ACA. The findings confirm the beneficial effects of more active institutional investors’ monitoring, but also show that increasing monitoring by audit committees is associated with increase in audit fees.

Research limitations/implications

The results reported in this research are based on cross sectional data. It is likely that the result may be different if the issue is examined over a relatively longer period.

Practical implications

The study showed that monitoring intensity of the large shareholders can be captured through their number and not simply through their shareholding. It also confirms the suggestion in previous studies that audit committees’ members protect themselves from depletion in human capital, litigation and reputational risk by buying more audit related services from their auditors.

Originality/value

The study empirically examined the impact of multiple large ownership structure on audit pricing and thereby extends the practical and theoretical understanding on the monitoring roles of large shareholders as well as the audit committees.
FINRA's 2011 enforcement record, priorities, and trends
Authors: Heilizer Deborah G. , Rubin Brian L. , McCormick Andrew M.
Published: September 2012

Purpose

The paper's aim is to describe a recent increase in FINRA enforcement activity and to discuss how broker‐dealers and representatives may want to prepare themselves for FINRA's increasing willingness to sanction members in the wake of the recent financial crisis.

Design/methodology/approach

The paper analyzes FINRA's recent enforcement record, including trends over the past several years in disciplinary actions and fines. It also discusses FINRA's top enforcement issues in 2011; advertising, short selling, auction rate securities, and suitability; and recommends increased compliance efforts in light of FINRA's growing aggressiveness.

Findings

It is important that firms and representatives understand how the priorities of this self‐regulatory organization have changed since the financial crisis, fueling this recent growth in FINRA enforcement activity.

Originality/value

The paper offers practical guidance from experienced financial services lawyers.
CFTC proposes harmonization rules for mutual funds
Authors: Molesworth Rita , Tuchman Deborah A. , O'Donnell Dianne E. , Burwick Jonathan , Lippert James
Published: September 2012

Purpose

The paper aims to analyze amendments proposed by the US Commodity Futures Trading Commission to its disclosure, recordkeeping and reporting rules that are designed to resolve or minimize certain conflicts between CFTC rules and US Securities and Exchange Commission rules applicable to registered investment companies (Futures RICs) whose futures and swaps trading will subject their advisers to regulation as commodity pool operators as a result of the amendments to CFTC Rule 4.5.

Design/methodology/approach

The paper explains certain significant differences between the CFTC's rules applicable to commodity pool operators (CPOs) and the SEC's rules applicable to Futures RICs and their advisers in the areas of disclosure, reporting and recordkeeping and describes how the CFTC's proposed rules for Futures RICs are intended to resolve or minimize conflicts with SEC rules.

Findings

CFTC and SEC rules differ in several significant areas, including the required contents of the disclosure document by which the pool is offered; when the disclosure document has to be delivered; how disclosure documents are updated and reviewed; when periodic reports are required to be made and what they are required to contain; and whether required books and records may be maintained at a location other than the main business office. The proposed harmonization rules attempt to resolve these conflicts by exempting the CPOs of Futures RICs from certain CFTC requirements regarding delivery of disclosure documents and recordkeeping, permitting CFTC‐required disclosures to appear in the prospectuses of Futures RICs after the SEC‐required disclosures and requiring monthly account statements to be posted to the CPO's website rather than distributed to shareholders of Futures RICs. Other conflicts between CFTC and SEC rules applicable to Futures RICs were not addressed by the proposed harmonization rules.

Practical implications

The proposed harmonization rules attempt to adapt CFTC requirements to Futures RICs that have not been subject to CFTC regulation since 2003. Other conflicts between CFTC and SEC rules were not addressed. The CFTC has not adopted the final rules in this area.

Originality/value

The paper provides expert guidance by lawyers experienced in regulation of CPOs and RICs.
Relevance lost! A critical review of project management standardisation
Authors: Hällgren Markus , Nilsson Andreas , Blomquist Tomas , Söderholm Anders
Published: September 2012

Purpose

The purpose of this paper is to critically analyze the consequences of the diffusion of generic project management knowledge.

Design/methodology/approach

This paper is conceptual in its nature, using short examples of four different areas (education, research, certification and practice) to show the diffusion of project management knowledge throughout these areas.

Findings

In this paper the authors argue that relevance may be lost at two levels. The first loss occurs when the practice of project management is transferred, through generalisation and standardisation, into what is generally known as “Best Practice”. The second occurs when “Best Practice” is transferred back to where it is applied (education, research, certification and practice).

Research limitations/implications

The risk of losing relevance has consequences for what one bases one's assumptions of the nature of projects upon. If the assumptions are based on standardized knowledge, without critically assessing its correctness, the likelihood of producing less relevant research is higher.

Practical implications

With the risk of losing relevance the authors argue that anyone involved in the areas of education, research, certification and practice needs to be cautious of how they perceive and work with the standards. There is a risk that the knowledge becomes even less relevant and students and practitioners are therefore less prepared for reality.

Originality/value

This paper is part of the literature critiquing the standardization of project management knowledge but it is distinct in terms of how the diffusion processes are perceived and utilized in a project setting.
Critical success factors in projects
Authors: Müller Ralf , Jugdev Kam
Published: September 2012

Purpose

Few scholars have been cited as frequently as Pinto, Slevin, and Prescott for their contributions to project success and related critical success factors (CSF) in the 1980s. Studies since then built on their articles to broaden and refine our understanding of the topic. The purpose of this paper is to discuss the reasons for the impact of these seminal contributions and how the topic of project success continues to evolve.

Design/methodology/approach

The paper analyses the popularity of Pinto and his colleagues' contributions to project success and reviews the development of this field of research since then.

Findings

Project success remains a vibrant school of thought as do the earlier definitions, measurement scales and dimensions, and assessment techniques that Pinto and his colleagues developed. The authors view success more broadly and think of it strategically because they consider longer‐term business objectives. Some research is now based on managerial or organizational theories and reflects the multi‐dimensional and networked nature of project success.

Practical implications

Practically, the classic contributions in project success continue to be valid. The authors see diversity in how success is defined and measured. The CSFs vary by project types, life cycle phases, industries, nationalities, individuals, and organizations.

Originality/value

The paper relates earlier understandings of project success to subsequent research in the field and underscores the significant findings by Pinto, Slevin, and Prescott.
Optimism in foreign investors
Authors: Lasfer Meziane , Xiaowen Lin Sharon , Muradoglu Gulnur
Published: September 2012

Purpose

The purpose of this paper is to compare the short‐term trading behaviour of A shares owned by domestic investors and their dually‐traded B shares owned by foreign investors, after a period of significant price change.

Design/methodology/approach

Given that the fundamentals of A and B shares are the same, the paper tests the hypothesis that both types of stocks should behave homogeneously either by exhibiting a momentum behaviour or an over‐reaction pattern. The paper relates any deviations in post‐shock stock returns to the differences in the trading patterns of foreign relative to domestic investors.

Findings

While the prices of the A shares are relatively random after the event, those of the B shares carry on increasing significantly after both positive and negative shocks. This trend is more pronounced for large firms with high liquidity, in contrast to the efficient market hypothesis expectations, which suggests that any abnormal performance should be arbitraged away sooner in a frictionless (in this case liquid) market.

Originality/value

The paper relates these results to the high level of optimism of foreign investors, which is an under‐researched area in behaviour finance.
Overconfidence and debiasing in the financial industry
Authors: Kaustia Markku , Perttula Milla
Published: September 2012

Purpose

The purpose of this paper is to measure overconfidence amongst finance professionals in domain relevant knowledge, and test for the impact of different debiasing methods.

Design/methodology/approach

The approach used was survey field experiments with varying debiasing attempts.

Findings

The subjects were overconfident in terms of probability calibration, better‐than‐average beliefs, and unfounded confidence. Debiasing attempts yielded mixed results. Explicit written warnings reduced better‐than‐average‐type of overconfidence. There was a further strong effect from attending lectures on investor psychology covering relevant examples. In contrast, there was only limited success in reducing miscalibration in probability assessments.

Research limitations/implications

Different types of overconfidence are distinct and respond differentially to debiasing. Future research on debiasing professional judgment should concentrate on testing in‐depth/personally engaging methods.

Practical implications

It is important for bankers to acknowledge the dangers of overconfidence. Correct confidence interval calibration is needed in order to have a sense of the risks involved in different asset allocation policies and trading strategies. Bankers should also be able to help their clients avoid overconfidence.

Social implications

Debiasing overconfidence in the finance industry likely carries public benefits. The results imply that this task is not easy, but not impossible either. The authors think further investment in this endeavor is justified.

Originality/value

Documenting an important judgment bias among finance professionals and estimating the effects of debiasing.
Vertical distribution of Stomoxys spp. (Diptera: Muscidae) in a rainforest area of Gabon
Authors: Mavoungou Jacques François , Kohagne Tongué Lisette , Acapovi‐Yao Geneviève Lydie , Gilles Jérémie , Ketoh Koffivi Guillaume , Duvallet Gérard
Published: August 2012

The vertical distribution of Stomoxys spp. was studied in a rainforest area, Ipassa‐Makokou biosphere reserve located in the Ivindo National Park of Gabon. From April to June 2006, Vavoua traps were set out during 15 consecutive days per month at different heights above ground level corresponding to vertical layers of rainforest: 50 cm, 10, 20 and 30 m. Stomoxys calcitrans, S. transvittatus, S. omega, S. niger niger and S. niger bilineatus were more abundant at near ground level (50 cm), whereas abundance of S. xanthomelas was greatest in traps higher (20 and 30 m) in the canopy. Fly abundance was significantly different among vertical layers of the forest (H = 36.91; P < 0.001, ddl = 3), and among species to another (H = 41.11, P < 0.001). Vertical distribution of fly species corroborates feeding behaviour as the identification of blood meal origins showed heterogeneity of feeding hosts. High densities of flies were also observed at 10 m, and most S. inornatus were captured at that level. These results show that Stomoxyine flies in this rainforest are present in all vertical layers, from the ground level to the canopy. Their ubiquity, regarding both their habitats and their hosts, should be taken into account if a vector control strategy is planned in this touristic area.
The Effects of GM‐CSF and IL‐5 as Molecular Adjuvants on Immune Responses and Contraception Induced by mZP3 DNA Vaccination
Authors: Ma Xiaolin , Kadir Zibirnisa , Li Jinyao , Zhang Fuchun
Published: August 2012

Problem

Various approaches have been developed to improve the antibody response of zona pellucida glycoprotein‐3 (ZP3) vaccination. In this study, we investigated whether GM‐CSF and IL‐5 can be used as cytokine adjuvants to increase the humoral immune response generated by mouse ZP3 (mZP3) DNA vaccine.

Method of study

Mice in experimental group were injected by GM‐CSF 4 days before the co‐immunization of IL‐5 and mZP3 DNA vaccine. The contraception and the correlation with humoral and cellular immune responses were analyzed after immunization and mating. The effect of cytokine adjuvant on the maturation of DCs was evaluated.

Results

Co‐immunization of GM‐CSF and IL‐5 with mZP3 DNA vaccine induced the highest level of serum IgG and IL‐4 expression in CD4+ T cells. Importantly, this strategy reduced mice fertility without disrupting normal ovarian morphology. GM‐CSF enhanced the maturation of DCs evidenced by up‐regulating the expression of MHC‐II and CD86.

Conclusion

GM‐CSF and IL‐5 co‐administration enhanced humoral immune responses to mZP3, and this may be a potential strategy for development of immunocontraceptive vaccine.
Necrotizing enterocolitis after red blood cell transfusion in preterm infants with patent ductus arteriosus: a case series
Authors: Sellmer Anna , Tauris Lene Hjelle , Johansen Anders , Henriksen Tine Brink
Published: September 2012

Aim:  Both patent ductus arteriosus (PDA) and packed red blood cell (PRBC) transfusion are risk factors for necrotizing enterocolitis (NEC). The combination of PDA and PRBC transfusion may have a synergistic effect on the intestinal circulation.

Methods:  We present four cases of NEC in very low birth weight (VLBW) infants within 14 h after PRBC transfusion.

Results:  All infants were growing on full enteral feeding, and they all had a PDA.

Conclusion:  We are concerned that the simultaneous presence of a PDA and PRBC transfusion in VLBW infants may place the infant at even greater risk of NEC than each of these factors alone.
Inhibition of lymphatic metastasis in neuroblastoma by a novel neutralizing antibody to vascular endothelial growth factor‐D
Authors: Kashima Kenji , Watanabe Miho , Satoh Yasuko , Hata Junichi , Ishii Nobuya , Aoki Yuko
Published: September 2012

Lymphatic spread is an important clinical determinant in the prognosis of many human cancers. The lymphangiogenic factor vascular endothelial growth factor‐D (VEGF‐D) is implicated in the promotion of lymphatic metastasis through the development of lymphatic vessels in some human cancers. In this study, we developed an anti‐VEGF‐D monoclonal antibody, cVE199, and investigated its in vitro properties, in vivo effects against tumors and possible target indications to evaluate its potential as a therapeutic antibody. The cVE199 molecule was revealed to have a specific binding reactivity against human VEGF‐D, as well as a specific inhibitory activity against the binding of human VEGF‐D to VEGFR‐3. In addition, cVE199 was found to inhibit the biological activity of VEGF‐D against lymphatic cells in vitro. Because we determined that a neuroblastoma cell line, SK‐N‐DZ, abundantly expressed VEGF‐D, an in vivo efficacy study was performed using a xenograft model of SK‐N‐DZ. We found that cVE199 significantly decreased lymphatic metastasis of SK‐N‐DZ as well as lymphangiogenesis in primary lesions. Finally, we investigated VEGF‐D expression in human neuroblastoma, finding that the molecule was expressed in 11 of 29 human neuroblastoma specimens (37.9%). In conclusion, we found that a novel anti‐VEGF‐D monoclonal antibody, cVE199, with specific reactivity against human VEGF‐D, prevents lymphatic metastasis of neuroblastoma through the inhibition of lymphangiogenesis in an animal model. In addition, our results show that VEGF‐D is expressed in some cases of human neuroblastomas, which suggests that cVE199 is a potential anti‐metastasis therapeutic antibody in neuroblastoma treatment.
Skin autofluorescence and risk of micro‐ and macrovascular complications in patients with Type 2 diabetes mellitus—a multi‐centre study
Authors: Noordzij M. J. , Mulder D. J. , Oomen P. H. N. , Brouwer T. , Jager J. , Castro Cabezas M. , Lefrandt J. D. , Smit A. J.
Published: September 2012

Diabet. Med. 29, 1556–1561 (2012)

Aims  Skin autofluorescence is a non‐invasive marker of advanced glycation end product accumulation. In a previous study, skin autofluorescence correlated with and predicted micro‐ and macrovascular complications in Type 2 diabetes in a primary care setting. The present cross‐sectional study aims to confirm the association between skin autofluorescence and diabetic complications in patients with Type 2 diabetes in a multi‐centre secondary care setting.

Methods  We analysed 563 subjects with Type 2 diabetes mellitus from five Dutch hospitals.

Results  Median age was 64 years, median duration of diabetes 13 years and median HbA1c 58 mmol/mol (7.5%). Sixty‐one per cent of patients had microvascular complications (38% nephropathy, 36% retinopathy, 35% neuropathy) and 42% had macrovascular complications. Median UK Prospective Diabetes Study 10‐year risk for coronary events was 19%. Median skin autofluorescence was elevated compared with age‐matched healthy control subjects: 2.77 (interquartile range 2.39–3.28) vs. 2.46 (2.08–2.84) arbitrary units. Skin autofluorescence was particularly increased in patients with complications: no complications, median 2.56 (2.26–2.90); microvascular complications, 2.79 (2.38–3.29); macrovascular complications, 2.85 (2.41–3.41); both micro‐ and macrovascular complications, 2.96 (2.56–3.60) arbitrary units, P < 0.001. Logistic regression analysis showed that age, duration of diabetes, renal function, gender, atrial fibrillation and skin autofluorescence were independently associated with macrovascular complications. Multiple regression analysis identified age, smoking, renal function, macrovascular complications and the number of microvascular complications as the determinants of skin autofluorescence.

Conclusions  This study confirms that skin autofluorescence is increased in patients with Type 2 diabetes in a secondary care setting. Skin autofluorescence was associated with macrovascular complications in patients with diabetes and this association was independent of classical risk factors.
Red cell and platelet‐derived microparticles are increased in G6PD‐deficient subjects
Authors: Nantakomol Duangdao , Palasuwan Attakorn , Chaowanathikhom Mallika , Soogarun Suphan , Imwong Mallika
Published: September 2012

In response to oxidative stress and during apoptosis, cells often shed microparticles (MPs), submicron elements carrying phosphatidylserine and protein antigens. Glucose‐6‐phosphate dehydrogenase (G6PD)‐deficient cells are extremely sensitive to oxidative damage that may lead to the formation of MPs. To determine whether G6PD deficiency alters membrane phospholipid asymmetry and increases MPs production, we determined the concentrations and cellular origins of MPs in G6PD‐deficient individuals using flow cytometry. G6PD‐deficient individuals showed an increase in circulating MPs concentrations as compared with G6PD‐normal individuals [1051/μL (865–2532/μL) vs. 258/μL (235–575/μL), P < 0.01]. MPs concentrations were significantly increased with the severity of G6PD deficiency. Median MPs concentrations from individuals with severe G6PD deficiency, and individuals with moderate G6PD deficiency were 2567/μL (1216–2532/μL) and 984/μL (685–2107/μL), respectively (P < 0.01). Importantly, G6PD enzymatic activity was significantly correlated with MPs concentrations with r2 = 0.731. MPs found in G6PD deficiency individuals were largely derived from red blood cells (RBCs) (45%) and platelets (30%). Additionally, Atomic Force Microscopy was used to study the morphology and measures the diameter of MPs found in G6PD‐deficient individuals. The mean (SD) width and height of RMPs were 0. 41 (0.18) and 2.04 (0.14) μm, respectively. Together, these results indicate that MP concentration is significantly correlated with G6PD enzymatic activity and is increased in G6PD‐deficient as compared with G6PD‐normal individuals. Our data also provide an evidence for an alteration in cell membrane associated with a decreased in G6PD activity. However, the significance of MPs in G6PD deficiency needs further clarification.
Sensitivity of coral calcification to ocean acidification: a meta‐analysis
Authors: Chan Neil C. S. , Connolly Sean R.
Published: September 2012

To date, meta‐analyses of effects of acidification have focused on the overall strength of evidence for statistically significant responses; however, to anticipate likely consequences of ocean acidification, quantitative estimates of the magnitude of likely responses are also needed. Herein, we use random effects meta‐analysis to produce a systematically integrated measure of the distribution of magnitudes of the response of coral calcification to decreasing ΩArag. We also tested whether methodological and biological factors that have been hypothesized to drive variation in response magnitude explain a significant proportion of the among‐study variation. We found that the overall mean response of coral calcification is ~15% per unit decrease in ΩAragover the range 2 < ΩArag < 4. Among‐study variation is large (standard deviation of 8% per unit decrease in ΩArag). Neither differences in carbonate chemistry manipulation method, study duration, irradiance level, nor study species growth rate explained a significant proportion of the among‐study variation. However, studies employing buoyant weighting found significantly smaller decreases in calcification per unit ΩArag(~10%), compared with studies using the alkalinity anomaly technique (~25%). These differences may be due to the greater tendency for the former to integrate over light and dark calcification. If the existing body of experimental work is indeed representative of likely responses of corals in nature, our results imply that, under business as usual conditions, declines in coral calcification by end‐of‐century will be ~22%, on average, or ~15% if only studies integrating light and dark calcification are considered. These values are near the low end of published projections, but support the emerging view that variability due to local environmental conditions and species composition is likely to be substantial.
Amazon's vulnerability to climate change heightened by deforestation and man‐made dispersal barriers
Authors: Feeley Kenneth J. , Rehm Evan M.
Published: September 2012

Species migrations in response to climate change have already been observed in many taxonomic groups worldwide. However, it remains uncertain if species will be able to keep pace with future climate change. Keeping pace will be especially challenging for tropical lowland rainforests due to their high velocities of climate change combined with high rates of deforestation, which may eliminate potential climate analogs and/or increase the effective distances between analogs by blocking species movements. Here, we calculate the distances between current and future climate analogs under various climate change and deforestation scenarios. Under even the most sanguine of climate change models (IPSL_CM4, A1b emissions scenario), we find that the median distance between areas in the Amazon rainforest and their closest future (2050) climate analog as predicted based on just temperature changes alone is nearly 300 km. If we include precipitation, the median distance increases by over 50% to >475 km. Since deforestation is generally concentrated in the hottest and driest portions of the Amazon, we predict that the habitat loss will have little direct impact on distances between climate analogs. If, however, deforested areas also act as a barrier to species movements, nearly 30% or 55% of the Amazon will effectively have no climate analogs anywhere in tropical South America under projections of reduced or Business‐As‐Usual deforestation, respectively. These ‘disappearing climates’ will be concentrated primarily in the southeastern Amazon. Consequently, we predict that several Amazonian ecoregions will have no areas with future climate analogs, greatly increasing the vulnerability of any populations or species specialized on these conditions. These results highlight the importance of including multiple climatic factors and human land‐use in predicting the effects of climate change, as well as the daunting challenges that Amazonian diversity faces in the near future.
BRAF V600E and KRAS G12S mutations in peripheral nerve sheath tumours
Authors: Serrano César , Simonetti Sara , Hernández‐Losa Javier , Valverde Claudia , Carrato Cristina , Bagué Silvia , Orellana Ruth , Somoza Rosa , Moliné Teresa , Carles Joan , Huguet Pere , Romagosa Cleofé , Ramón y Cajal Santiago
Published: September 2012

Aims

Benign (BPNST) and malignant (MPNST) peripheral nerve sheath tumours occur either sporadically or are related to neurofibromatosis (NF). The mechanisms involved are well known in NF‐related tumours, but still remain unclear in sporadic cases. Somatic BRAF and KRAS mutations represent the most frequent genetic events in melanocytic neoplastic lesions. Because melanocytes and Schwann cells both derive from neural crest cells, we hypothesized that BRAF and KRAS mutations might influence BPNST and MPNST development.

Methods and results

BRAF exon 15 and KRAS exons 2 and 3 polymerase chain reaction (PCR) sequencing was performed in formalin‐fixed/paraffin‐embedded samples of 99 BPNST and MPNST, related and non‐related to NF types 1 and 2. Oncogenic BRAF V600E mutations were found in four of 40 schwannomas (including one acoustic neuroma) and one of 13 MPNST, not associated with NF. A KRAS G12S mutation was also evident in one sporadic schwannoma.

Conclusion

Our findings suggest that RAS pathway activation due to BRAF V600E and KRAS mutations is an important event in a subset of peripheral nerve sheath tumours not related to NF.
Characterization of neutralizing mouse‐human chimeric and shuffling antibodies against botulinum neurotoxin A
Authors: Mukamoto Masafumi , Maeda Hiroaki , Kohda Tomoko , Nozaki Chikateru , Takahashi Motohide , Kozaki Shunji
Published: September 2012

Mouse‐human chimeric monoclonal antibodies that could neutralize botulinum neurotoxins were developed and an attempt was made to establish mouse hybridoma cell clones that produced monoclonal antibodies that neutralized botulinum neurotoxin serotype A (BoNT/A). Four clones (2–4, 2–5, 9–4 and B1) were selected for chimerization on the basis of their neutralizing activity against BoNT/A and the cDNA of the variable regions of their heavy (VH) and light chains (VL) were fused with the upstream regions of the constant counterparts of human kappa light and gamma 1 heavy chain genes, respectively. CHO‐DG44 cells were transfected with these plasmids and mouse‐human chimeric antibodies (AC24, AC25, AC94 and ACB1) purified to examine their binding and neutralizing activities. Each chimeric antibody exhibited almost the same capability as each parent mouse mAb to bind and neutralize activities against BoNT/A. From the chimeric antibodies against BoNT/A, shuffling chimeric antibodies designed with replacement of their VH or VL domains were constructed. A shuffling antibody (AC2494) that derived its VH and VL domains from chimeric antibodies AC24 and AC94, respectively, showed much higher neutralizing activity than did other shuffling antibodies and parent counterparts. This result indicates that it is possible to build high‐potency neutralizing chimeric antibodies by selecting and shuffling VH and VL domains from a variety of repertoires. A shuffling chimeric antibody might be the best candidate for replacing horse antitoxin for inducing passive immunotherapy against botulism.
Sequence analysis of MHC class I α2 domain exon variants in one diploid and two haploid Atlantic salmon pedigrees
Authors: Grimholt U , Olsaker I , Lingaas F , Lie Ø
Published: September 2012

Genetic diversity in the second domain exon of Atlantic salmon (Salmo salar) major histocompatibility complex (Mhc) class I was investigated in two dams and nine of their haploid offspring by means of polymerase chain reaction (PCR) and DNA sequence analysis. A similar study was also performed on nine diploid offspring from one of these dams. The complex segregation patterns and sequence similarities between variants make definitive allele, haplotype and locus assignments difficult. There are, however, indications of six Mhc‐Sasa class I loci and a fairly well‐defined haplotype of four variants. One non‐polymorphic variant present in most specimens could be a salmon analogue to the human non‐classical loci.
Pain management and satisfaction in postsurgical patients
Authors: Tocher Jennifer , Rodgers Sheila , Smith Margaret AC , Watt Deborah , Dickson Lesley
Published: September 2012

Aims and objectives.  To examine the relationship between patient satisfaction and the incidence of severe and enduring pain through a health board wide hospital satisfaction questionnaire.

Background.  The incidence and management of acute postoperative pain and its relationship to patient satisfaction have been of great interest to clinicians over the last 20 years. Evidence suggests that despite many moves to address this problem with the advent of acute pain nurse specialists and dedicated pain teams, severe and enduring pain continues to be a problem. However, patients appear to report high satisfaction levels.

Design.  The study design was a postal questionnaire the results of which were analysed statistically.

Methods.  The postal questionnaire was sent to patients who had been discharged from acute hospitals in one health board in the previous two weeks. A total of three large acute hospitals were included. The data were analysed to produce descriptive statistics for all patients on the pain questions and then for patients with severe and enduring pain on the variables of age, gender, ethnic group, responses to pain questions and type of admission.

Results.  Twenty‐six percent of patients reported having pain all or most of the time. Patients suffering from severe and enduring pain were younger females.

Conclusion.  Acute postoperative pain continues to be a problem, although patients continue reporting moderate satisfaction levels.

Relevance to clinical practice.  Acute postoperative pain is an ongoing issue for postsurgical patients. It is crucial to understand and recognise issues that can adversely contribute to increased pain severity.
Transportin 1 colocalization with Fused in Sarcoma (FUS) inclusions is not characteristic for amyotrophic lateral sclerosis‐FUS confirming disrupted nuclear import of mutant FUS and distinguishing it from frontotemporal lobar degeneration with FUS inclusions
Authors: Troakes C. , Hortobágyi T. , Vance C. , Al‐Sarraj S. , Rogelj B. , Shaw C. E.
Published: August 2012

C. Troakes, T. Hortobágyi, C. Vance, S. Al‐Sarraj, B. Rogelj and C. E. Shaw (2013) Neuropathology and Applied Neurobiology39, 553–561

Transportin 1 colocalization with Fused in Sarcoma (FUS) inclusions is not characteristic for amyotrophic lateral sclerosis‐FUS confirming disrupted nuclear import of mutant FUS and distinguishing it from frontotemporal lobar degeneration with FUS inclusions

Aims: Transportin 1 (TNPO 1) is an abundant component of the Fused in Sarcoma (FUS)‐immunopositive inclusions seen in a subgroup of frontotemporal lobar degeneration (FTLD‐FUS). TNPO 1 has been shown to bind to the C‐terminal nuclear localizing signal (NLS) of FUS and mediate its nuclear import. Amyotrophic lateral sclerosis (ALS)‐linked C‐terminal mutants disrupt TNPO 1 binding to the NLS and impair nuclear import in cell culture. If this held true for human ALS then we predicted that FUS inclusions in patients with C‐terminal FUS mutations would not colocalize with TNPO 1. Methods: Expression of TNPO 1 and colocalization with FUS was studied in the frontal cortex of FTLD‐FUS (n = 3) and brain and spinal cord of ALS‐FUS (n = 3), ALS‐C9orf72 (n = 3), sporadic ALS (n = 7) and controls (n = 7). Expression levels and detergent solubility of TNPO 1 was measured by Western blot. Results: Aggregates of TNPO 1 were abundant and colocalized with FUS inclusions in the cortex of all FTLD‐FUS cases. In contrast, no TNPO 1‐positive aggregates or FUS colocalization was evident in two‐thirds, ALS‐FUS cases and was rare in one ALS‐FUS case. Nor were they present in C9orf72 or sporadic ALS. No increase in the levels of TNPO 1 was seen in Western blots of spinal cord tissues from all ALS cases compared with controls. Conclusions: These findings confirm that C‐terminal FUS mutations prevent TNPO 1 binding to the NLS, inhibiting nuclear import and promoting cytoplasmic aggregation. The presence of TNPO 1 in wild‐type FUS aggregates in FTLD‐FUS distinguishes the two pathologies and implicates different disease mechanisms.
In vitro and in planta nematicidal activity of Fumaria parviflora (Fumariaceae) against the southern root‐knot nematode Meloidogyne incognita
Authors: Naz I. , Palomares‐Rius J. E. , Saifullah  , Blok V. , Khan M. R. , Ali S. , Ali S.
Published: September 2012

Root and stem extracts of Fumaria parviflora showed strong nematicidal activity against Meloidogyne incognita in in vitro and in planta experiments. Phytochemical screening of F. parviflora revealed the presence of seven classes of bioactive compounds (alkaloids, flavonoids, glycosides, tannins, saponins, steroids and phenols). Quantitative determination of the plant extracts showed the highest percentages of alkaloids (0·9 ± 0·04) and saponins (1·3 ± 0·07) in the roots and total phenolic contents in the stem (16·75 ± 0·07 μg dry g−1). The n‐hexane, chloroform, ethyl acetate and methanol extracts of roots and stems at concentrations of 3·12, 6·24, 12·5, 25·0 and 50·0 mg mL−1, significantly inhibited hatching and increased mortality of second‐stage juveniles (J2s) compared with water controls. Percentage J2 mortality and hatch inhibition were directly related to exposure time. In pot trials with tomato cv. Rio Grande, root and stem extracts at concentrations of 1000, 2000 and 3000 ppm, applied as soil drenches, significantly reduced the number of galls, galling index, eggs masses, eggs and reproduction factor compared with the water control. Regardless of concentration, all the extracts significantly increased the host plant growth parameters studied. The n‐hexane extracts from the roots and stem were the most active, followed by the methanol ones, at all concentrations. The in vitro and in planta results suggest that extracts from the roots and stem of F. parviflora may be potential novel nematicides.
Downregulation of the lycopene ϵ‐cyclase gene increases carotenoid synthesis via the β‐branch‐specific pathway and enhances salt‐stress tolerance in sweetpotato transgenic calli
Authors: Kim Sun Ha , Kim Yun‐Hee , Ahn Young Ock , Ahn Mi‐Jeong , Jeong Jae Cheol , Lee Haeng‐Soon , Kwak Sang‐Soo
Published: September 2012

Lycopene ϵ‐cyclase (LCY‐ϵ) is involved in the first step of the α‐branch synthesis pathway of carotenoids from lycopene in plants. In this study, to enhance carotenoid synthesis via the β‐branch‐specific pathway [which yields β‐carotene and abscisic acid (ABA)] in sweetpotato, the expression of IbLCY‐ϵ was downregulated by RNAi (RNA interference) technology. The RNAi‐IbLCY‐ϵ vector was constructed using a partial cDNA of sweetpotato LCY‐ϵ isolated from the storage root and introduced into cultured sweetpotato cells by Agrobacterium‐mediated transformation. Both semi‐quantitative Reverse transcription polymerase chain reaction (RT‐PCR) of carotenoid biosynthesis genes and high‐performance liquid chromatography (HPLC) analysis of the metabolites in transgenic calli, in which the LCY‐ϵ gene was silenced, showed the activation of β‐branch carotenoids and its related genes. In the transgenic calli, the β‐carotene content was approximately 21‐fold higher than in control calli, whereas the lutein content of the transgenic calli was reduced to levels undetectable by HPLC. Similarly, expression of the RNAi‐IbLCY‐ϵ transgene resulted in a twofold increase in ABA content compared to control calli. The transgenic calli showed significant tolerance of 200 mM NaCl. Furthermore, both the β‐branch carotenoids content and the expression levels of various branch‐specific genes were higher under salt stress than in control calli. These results suggest that, in sweetpotato, downregulation of the ϵ‐cyclization of lycopene increases carotenoid synthesis via the β‐branch‐specific pathway and may positively regulate cellular defenses against salt‐mediated oxidative stress.
Improvement of Iranian nurses' competence through professional portfolio: A quasi‐experimental study
Authors: Bahreini Masoud , Moattari Marzieh , Shahamat Shohreh , Dobaradaran Sina , Ravanipour Mariam
Published: August 2012

The aim of the study was to determine the effect of a portfolio‐based professional development program on nurses' competence in a university hospital in Iran. A pre‐test/post‐test, controlled, quasi‐experimental design was used. From the university hospital's 18 general wards, four wards were randomly selected. Two wards were randomly allocated as the experimental group (35 subjects) and two wards as the control group (38 subjects). Nurses in the experimental group participated in a 12‐month portfolio‐based professional development program and nurses in the control group participated in the routine professional development programs of their wards. The data were collected by the Nurse Competence Scale and were analyzed using descriptive statistics and independent and paired t‐tests. After intervention, the average nurses' competence in the experimental group increased significantly (P < 0.001) but these changes in the control group were not significant (P = 0.08). This study shows that the professional portfolio is an effective tool for improving nurses' competence. The professional portfolios help nurses update their knowledge, skills, and competence towards their full role as nurses.
Correlated discharges in the primate prefrontal cortex before and after working memory training
Authors: Qi Xue‐Lian , Constantinidis Christos
Published: August 2012

The correlation of discharges between single neurons can provide information about the computations and network properties of neuronal populations during the performance of cognitive tasks. In recent years, dynamic modulation of neuronal correlations by attention has been revealed during the execution of behavioral tasks. Much less is known about the influence of learning and performing a task itself. We therefore sought to quantify the correlated firing of simultaneously recorded pairs of neurons in the prefrontal cortex of naïve monkeys that were only required to fixate, and to examine how this correlation was altered after they had learned to perform a working memory task. We found that the trial‐to‐trial correlation of discharge rates between pairs of neurons (noise correlation) differed across neurons depending on their responsiveness and selectivity for stimuli, even before training in a working memory task. After monkeys had learned to perform the task, correlated firing decreased overall, although the effects varied according to the functional properties of the neurons. The greatest decreases were observed on comparison of populations of neurons that exhibited elevated firing rates during the trial events and those that had more similar spatial and temporal tuning. Greater decreases in noise correlation were also observed for pairs comprising one fast spiking neuron (putative interneuron) and one regular spiking neuron (putative pyramidal neuron) than pairs comprising regular spiking neurons only. Our results demonstrate that learning and performance of a cognitive task alters the correlation structure of neuronal firing in the prefrontal cortex.
Optical spectroscopy techniques can accurately distinguish benign and malignant renal tumours
Authors: Couapel Jean‐Philippe , Senhadji Lotfi , Rioux‐Leclercq Nathalie , Verhoest Grégory , Lavastre Olivier , de Crevoisier Renaud , Bensalah Karim
Published: August 2012

What's known on the subject? and What does the study add?

There is little known about optical spectroscopy techniques ability to evaluate renal tumours.

This study shows for the first time the ability of Raman and optical reflectance spectroscopy to distinguish benign and malignant renal tumours in an ex vivo environment. We plan to develop this optical assistance in the operating room in the near future.

Objective

To evaluate the ability of Raman spectroscopy (RS) and optical reflectance spectroscopy (ORS) to distinguish benign and malignant renal tumours at surgery.

Materials and Methods

Between March and October 2011, RS and ORS spectra were prospectively acquired on surgical renal specimens removed for suspicion of renal cell carcinoma (RCC). Optical measurements were done immediately after surgery.

Optical signals were normalised to ensure comparison between spectra. Initial and final portions of each spectrum were removed to avoid artefacts.

A support vector machine (SVM) was built and tested using a leave‐one‐out cross‐validation.

Classification scores, including accuracy, sensitivity and specificity were calculated on the entire population and in patients with tumours of <4 cm.

Results

In all, 60 nephrectomies were performed for 53 malignant tumours (41 clear‐cell, eight papillary and four chromophobe carcinomas) and seven benign tumours (four oncocytomas, two angiomyolipomas and a haemorrhagic cyst). In all, >700 optical spectra were obtained and submitted to SVM classification.

The SVM could recognise benign and malignant renal tumours with an accuracy of 96% (RS) and 88% (ORS) in the whole population and with an accuracy of 93% (RS) and 95% (ORS) in the present subset of small renal tumours (<4 cm).

Histological subtype could be determined in 80% and 88% of the cases with RS and ORS, respectively.

The SVM was able to differentiate chromophobe carcinomas and benign lesions with an accuracy of 96% in RS and 98% in ORS.

Conclusion

Benign and malignant renal tumours can be accurately discriminated by a combination of RS and ORS. In vivo experiments are needed to further assess the value of optical spectroscopy techniques.
Proteaceae from severely phosphorus‐impoverished soils extensively replace phospholipids with galactolipids and sulfolipids during leaf development to achieve a high photosynthetic phosphorus‐use‐efficiency
Authors: Lambers Hans , Cawthray Gregory R. , Giavalisco Patrick , Kuo John , Laliberté Etienne , Pearse Stuart J. , Scheible Wolf‐Rüdiger , Stitt Mark , Teste François , Turner Benjamin L.
Published: September 2012

Proteaceae species in south‐western Australia occur on severely phosphorus (P)‐impoverished soils. They have very low leaf P concentrations, but relatively fast rates of photosynthesis, thus exhibiting extremely high photosynthetic phosphorus‐use‐efficiency (PPUE). Although the mechanisms underpinning their high PPUE remain unknown, one possibility is that these species may be able to replace phospholipids with nonphospholipids during leaf development, without compromising photosynthesis.

For six Proteaceae species, we measured soil and leaf P concentrations and rates of photosynthesis of both young expanding and mature leaves. We also assessed the investment in galactolipids, sulfolipids and phospholipids in young and mature leaves, and compared these results with those on Arabidopsis thaliana, grown under both P‐sufficient and P‐deficient conditions.

In all Proteaceae species, phospholipid levels strongly decreased during leaf development, whereas those of galactolipids and sulfolipids strongly increased. Photosynthetic rates increased from young to mature leaves. This shows that these species extensively replace phospholipids with nonphospholipids during leaf development, without compromising photosynthesis. A considerably less pronounced shift was observed in A. thaliana.

Our results clearly show that a low investment in phospholipids, relative to nonphospholipids, offers a partial explanation for a high photosynthetic rate per unit leaf P in Proteaceae adapted to P‐impoverished soils.
Peripheral administration of prokineticin 2 potently reduces food intake and body weight in mice via the brainstem
Authors: Beale KEL , Gardiner JV , Bewick GA , Hostomska K , Patel NA , Hussain SS , Jayasena CN , Ebling FJP , Jethwa PH , Prosser HM , Lattanzi R , Negri L , Ghatei MA , Bloom SR , Dhillo WS
Published: August 2012

Background and Purpose

Prokineticin 2 (PK2) has recently been shown to acutely reduce food intake in rodents. We aimed to determine the CNS sites and receptors that mediate the anorectic effects of peripherally administered PK2 and its chronic effects on glucose and energy homeostasis.

Experimental Approach

We investigated neuronal activation following i.p. administration of PK2 using c‐Fos‐like immunoreactivity (CFL‐IR). The anorectic effect of PK2 was examined in mice with targeted deletion of either prokineticin receptor 1 (PKR1) or prokineticin receptor 2 (PKR2), and in wild‐type mice following administration of the PKR1 antagonist, PC1. The effect of IP PK2 administration on glucose homeostasis was investigated. Finally, the effect of long‐term administration of PK2 on glucose and energy homeostasis in diet‐induced obese (DIO) mice was determined.

Key Results

I.p. PK2 administration significantly increased CFL‐IR in the dorsal motor vagal nucleus of the brainstem. The anorectic effect of PK2 was maintained in mice lacking the PKR2 but abolished in mice lacking PKR1 and in wild‐type mice pre‐treated with PC1. DIO mice treated chronically with PK2 had no changes in glucose levels but significantly reduced food intake and body weight compared to controls.

Conclusions and Implications

Together, our data suggest that the anorectic effects of peripherally administered PK2 are mediated via the brainstem and this effect requires PKR1 but not PKR2 signalling. Chronic administration of PK2 reduces food intake and body weight in a mouse model of human obesity, suggesting that PKR1‐selective agonists have potential to be novel therapeutics for the treatment of obesity.