bluuebunny/crossref_metadata_2025 huggingface dataset:
Understanding success: economics and human nature
Authors: Verity Julie
Published: July 2007

Purpose

The purpose of this article is to raise issues about how managers think strategically. Specifically, it concerns issues about the appeal of relatively simple, economic concepts at the expense of those that are more complex and involve an understanding of human nature.

Design/methodology/approach

Learning in the article is drawn from two sets of observations: the study of a successful company, conducted over a period of eight years since 1997, and teaching the case study to classes of business students, managers and executives.

Findings

Managers find relatively simple economic concepts, such as economies of scale, attractive in explaining why companies are successful, and are keen to hold to this reasoning even when there is evidence that challenges the basis of their thinking. The article suggests that this is true in the classroom and in practice. This way of thinking is compared with the reality in the case where competitive advantage arises from complex combinations of tangible and intangible resources, the source of which is the motivations and passions of leaders or deeply held philosophies and beliefs in the company's culture.

Practical implications

The article argues against the inclination of managers to focus too strongly on rational, economic concepts in their strategic thinking and practice. It gives examples of why this is dangerous. The article also postulates the length of time it might take a leader to fully appreciate the nature of a company's success and illustrates the fragility of sustainable competitive advantage if this knowledge is not transferred from leader to successor.

Originality/value

Sound strategic decisions are not made with rational thinking alone. A deep understanding of human nature, especially what motivates people, is at least as important and could be vital to prevent destroying competitive advantage.
Placing organizational learning in the context of strategic management
Authors: Trim Peter , Lee Yang‐Im
Published: July 2007

Purpose

The purpose of the paper is to place organizational learning within the context of strategic management and to explain why it is important that senior managers view training and staff development as being continuous. Practising managers will be able to appraise the way in which their organization undertakes training and staff development, and adapt the current level of thinking within the organization so that a more holistic approach to strategy formulation and implementation is adopted.

Design/methodology/approach

The work is based on a review of the literature and a number of case examples are referred to. A conceptual model is outlined and highlights how the organizational learning concept links training and managerial development programs with the development of organizational culture.

Findings

By placing training and staff development within an organizational learning context, it is possible to utilize international project groups and to develop new management practices. Practising managers will be able to use the conceptual model to devise, plan and execute a number of change‐oriented strategies.

Practical implications

The conceptual model can be used by human resource management specialists to devise continuing professional development programs that are tailored to individual requirements. The objective is to match the organization's requirements with the capability of the staff, and in so doing achieve internal fit.

Originality/value

The conceptual model outlines how organizational learning can be used to increase the organization's knowledge base and a link is made with the deployment of international project groups that can facilitate cross‐cultural decision‐making.
Driving cultural change through behavioral differentiation at Westinghouse
Authors: Bacon Terry R.
Published: July 2007

Purpose

This article describes the successful application of behavioral differentiation in transforming the culture of a large engineering‐oriented company as it strived to become more customer‐centric.

Design/methodology/approach

Customer satisfaction surveys and interviews indicated that the company was difficult to work with and not customer‐focused. Subsequent benchmarking included an employee engagement survey, Lore's Behavioral Differentiation Survey, and the Denison Cultural Survey.

Findings

The results, which showed significant disagreement between internal and customer perceptions of the issues, indicated that the company had six behavioral improvement areas to focus on: customer relationship management, communication, execution‐related behaviors, information sharing, customer success, and organizational alignment.

Research limitations/implications

The cultural change initiative is ongoing, and further research is needed to identify the strength, effectiveness, and durability of the behavioral changes.

Practical implications

However, early anecdotal evidence shows that the company is transforming not only its behavior toward customers but customer perceptions of the company and, more importantly, the company is winning new business as a result of its behavioral changes.

Originality/value

This article illustrates one of the first attempts by a large company to transform its culture by focusing on behavioral differentiation. In businesses that are becoming increasingly commoditized, behavior is usually the final frontier in competitive strategy. The article will be of interest to any firms seeking large‐scale transformation of how employees behave toward customers.
Is your sales force a barrier to more profitable pricing … or is it you?
Authors: Nagle Tom , Hogan John
Published: July 2007

Purpose

The article seeks to discuss how and why it is possible to motivate a sales force to follow the guidelines of a consistent pricing policy that promotes profitability and increases margin, and which is beneficial to both providers and consumers of products and services.

Design/methodology/approach

Theories and examples stemming from the authors' research and experience with the subject matter are stated. The sales incentive theory in particular is supported by a specific formula that determines the sales credit someone would earn for making a sale based on profit contribution rather than price.

Findings

While employing flexible pricing policies in competitive markets is enticing for suppliers, it can ultimately lead to price erosion and falling margins. A sound pricing policy lets customers know that the price they are paying is related to the value they receive, and keeps salespeople from dealing with long, complicated negotiation processes. While many managers worry that their sales force won't accept such a change, most salespeople will adopt it if the new policy is implemented well. The key is to recompense salespeople for driving profitability instead of just revenue and sales volume.

Originality/value

This article addresses an ongoing problem that many companies face as they try to win and maintain business using flexible pricing policies to cut customer‐specific deals. It discusses how and why it is possible to change this behavior using sales incentives that reward profitable sales rather than just sales volume.
How “winning” boards contribute to corporate growth
Authors: Coulson‐Thomas Colin
Published: July 2007

Purpose

This article summarizes findings relating to the conduct of directors and boards from a continuing investigation into why some companies are so much more effective than others at key activities such as business development, building relationships and creating and exploiting know‐how.

Design/methodology/approach

The research program ranks companies in terms of the outcomes they achieve in the areas examined and compares the most and least effective to isolate critical success factors and distinguish between successful/winning and unsuccessful/losing approaches.

Findings

The findings of the investigation suggest the performance of many companies depends primarily upon what their boards actually do and how their members behave rather than formal governance considerations such as a board's committee structure.

Practical implications

Effective boards adopt particular approaches and can behave very differently from their less successful peers, for example when communicating with various groups of stakeholders. Many boards would make a more significant contribution to the growth and development of their companies if they understood and adopted the approaches of more effective boards. A key element of good corporate governance is to achieve an appropriate balance between a number of critical factors, for example performance today and the capability to compete and win in the future.

Originality/value

In comparison with what could be achieved if more “winning approaches” were adopted many boards are failing to deliver and could do much better. Many appear to be rubber‐stamping rather than shaping things to come, picking over the past rather than creating the future.
Modeling fatty acid delivery from intestinal fatty acid binding protein to a membrane
Authors: Mihajlovic Maja , Lazaridis Themis
Published: July 2007

Intestinal fatty acid binding protein (IFABP) interacts with biological membranes and delivers fatty acid (FA) into them via a collisional mechanism. However, the membrane‐bound structure of the protein and the pathway of FA transfer are not precisely known. We used molecular dynamics (MD) simulations with an implicit membrane model to determine the optimal orientation of apo‐ and holo‐IFABP (bound with palmitate) on an anionic membrane. In this orientation, the helical portal region, delimited by the αII helix and the βC‐βD and βE‐βF turns, is oriented toward the membrane whereas the putative β‐strand portal, delimited by the βB‐βC, βF‐βG, βH‐βI turns and the N terminus, is exposed to solvent. Starting from the MD structure of holo‐IFABP in the optimal orientation relative to the membrane, we examined the release of palmitate via both pathways. Although the domains can widen enough to allow the passage of palmitate, fatty acid release through the helical portal region incurs smaller conformational changes and a lower energetic cost.
Total chemical synthesis and biophysical characterization of the minimal isoform of the KChIP2 potassium channel regulatory subunit
Authors: Rajagopal Sudarshan , Kent Stephen B.H.
Published: July 2007

The potassium channel accessory subunit KChIP2 associates with Kv4.2 channels in the cardiac myocyte and is involved in the regulation of the transient outward current (Ito) during the early phase of repolarization of the action potential. As a first step to biophysically probe the mechanism of KChIP2, we have chemically synthesized its minimal isoform, KChIP2d, using Boc chemistry solid phase peptide synthesis in conjunction with native chemical ligation. The synthetic KChIP2d protein is primarily alpha‐helical as predicted and becomes more structured upon binding calcium as assessed by 1H‐NMR and CD spectroscopy. Synthetic KChIP2d is in a monomer‐dimer equilibrium in solution, and there is evidence for two monomer binding sites on an N‐terminal peptide of Kv4.2. Planned future studies include the incorporation of fluorescent and spin labeled probes in KChIP2d to yield structural information in parallel with electrophysiologic studies to elucidate KChIP2d's mechanism of action.
Loopholes and missing links in protein modeling
Authors: Rossi Karen A. , Weigelt Carolyn A. , Nayeem Akbar , Krystek Stanley R.
Published: July 2007

This paper provides an unbiased comparison of four commercially available programs for loop sampling, Prime, Modeler, ICM, and Sybyl, each of which uses a different modeling protocol. The study assesses the quality of results and examines the relative strengths and weaknesses of each method. The set of loops to be modeled varied in length from 4–12 amino acids. The approaches used for loop modeling can be classified into two methodologies: ab initio loop generation (Modeler and Prime) and database searches (Sybyl and ICM). Comparison of the modeled loops to the native structures was used to determine the accuracy of each method. All of the protocols returned similar results for short loop lengths (four to six residues), but as loop length increased, the quality of the results varied among the programs. Prime generated loops with RMSDs <2.5 Å for loops up to 10 residues, while the other three methods met the 2.5 Å criteria at seven‐residue loops. Additionally, the ability of the software to utilize disulfide bonds and X‐ray crystal packing influenced the quality of the results. In the final analysis, the top‐ranking loop from each program was rarely the loop with the lowest RMSD with respect to the native template, revealing a weakness in all programs to correctly rank the modeled loops.
Probing the local conformational change of α1‐antitrypsin
Authors: Baek Je‐Hyun , Im Hana , Kang Un‐Beom , Seong Ki Moon , Lee Cheolju , Kim Joon , Yu Myeong‐Hee
Published: July 2007

The native form of serpins (serine protease inhibitors) is a metastable conformation, which converts into a more stable form upon complex formation with a target protease. It has been suggested that movement of helix‐F (hF) and the following loop connecting to strand 3 of β‐sheet A (thFs3A) is critical for such conformational change. Despite many speculations inferred from analysis of the serpin structure itself, direct experimental evidence for the mobilization of hF/thFs3A during the inhibition process is lacking. To probe the mechanistic role of hF and thFs3A during protease inhibition, a disulfide bond was engineered in α1‐antitrypsin, which would lock the displacement of thFs3A from β‐sheet A. We measured the inhibitory activity of each disulfide‐locked mutant and its heat stability against loop–sheet polymerization. Presence of a disulfide between thFs3A and s5A but not between thFs3A and s3A caused loss of the inhibitory activity, suggesting that displacement of hF/thFs3A from strand 5A but not from strand 3A is required during the inhibition process. While showing little influence on the inhibitory activity, the disulfide between thFs3A and s3A retarded loop–sheet polymerization significantly. This successful protein engineering of α1‐antitrypsin is expected to be of value in clinical applications. Based on our current studies, we propose that the reactive‐site loop of a serpin glides through between s5A and thFs3A for the full insertion into β‐sheet A while a substantial portion of the interactions between hF and s3A is kept intact.
Destabilization of human glycine N‐methyltransferase by H176N mutation
Authors: Luka Zigmund , Pakhomova Svetlana , Luka Yury , Newcomer Marcia E. , Wagner Conrad
Published: July 2007

In the presence of moderate (2–4 M) urea concentrations the tetrameric enzyme, glycine N‐methyltransferase (GNMT), dissociates into compact monomers. Higher concentrations of urea (7–8 M) promote complete denaturation of the enzyme. We report here that the H176N mutation in this enzyme, found in humans with hypermethioninaemia, significantly decreases stability of the tetramer, although H176 is located far from the intersubunit contact areas. Dissociation of the tetramer to compact monomers and unfolding of compact monomers of the mutant protein were detected by circular dichroism, quenching of fluorescence emission, size‐exclusion chromatography, and enzyme activity. The values of apparent free energy of dissociation of tetramer and of unfolding of compact monomers for the H176N mutant (27.7 and 4.2 kcal/mol, respectively) are lower than those of wild‐type protein (37.5 and 6.2 kcal/mol). A 2.7 Å resolution structure of the mutant protein revealed no significant difference in the conformation of the protein near the mutated residue.
Production of selenomethionyl‐derivatized proteins in baculovirus‐infected insect cells
Authors: Cronin Ciarán N. , Lim Kheng B. , Rogers Joe
Published: July 2007

A protocol is described for the production of both intracellularly expressed and secreted selenomethionyl‐derivatized recombinant proteins in baculovirus‐infected insect cells. The method results in the production of recombinant soluble proteins with an SeMet occupancy of ∼75% and with a recovery of ∼20% that of native protein expression. The method is independent of the percentage methionine content of the protein and is reliable and consistent. Similar results are obtained using either Spodoptera frugiperda Sf9 or Trichoplusia ni High Five insect cells as the expression host, and when cultures are grown in either shake flasks or in Wave BioReactors.
Constraining specificity in the N‐domain of tissue inhibitor of metalloproteinases‐1; gelatinase‐selective inhibitors
Authors: Hamze Asmaa B. , Wei Shuo , Bahudhanapati Harinath , Kota Smitha , Acharya K. Ravi , Brew Keith
Published: July 2007

The tissue inhibitors of metalloproteinases (TIMPs) are endogenous inhibitors of the matrix metalloproteinases (MMPs). Since unregulated MMP activities are linked to arthritis, cancer, and atherosclerosis, TIMP variants that are selective inhibitors of disease‐related MMPs have potential therapeutic value. The structures of TIMP/MMP complexes reveal that most interactions with the MMP involve the N‐terminal pentapeptide of TIMP and the C–D β‐strand connector which occupy the primed and unprimed regions of the active site. The loop between β‐strands A and B forms a secondary interaction site for some MMPs, ranging from multiple contacts in the TIMP‐2/membrane type‐1 (MT1)‐MMP complex to none in the TIMP‐1/MMP‐1 complex. TIMP‐1 and its inhibitory domain, N‐TIMP‐1, are weak inhibitors of MT1‐MMP; inhibition is not improved by grafting the longer AB loop from TIMP‐2 into N‐TIMP‐1, but this change impairs binding to MMP‐3 and MMP‐7. Mutational studies with N‐TIMP‐1 suggest that its weak inhibition of MT1‐MMP, as compared to other N‐TIMPs, arises from multiple (>3) sequence differences in the interaction site. Substitutions for Thr2 of N‐TIMP‐1 strongly influence MMP selectivity; Arg and Gly, that generally reduce MMP affinity, have less effect on binding to MMP‐9. When the Arg mutation is added to the N‐TIMP‐1(AB2) mutant, it produces a gelatinase‐specific inhibitor with Ki values of 2.8 and 0.4 nM for MMP‐2 and ‐9, respectively. Interestingly, the Gly mutant has a Ki of 2.1 nM for MMP‐9 and >40 μM for MMP‐2, indicating that engineered TIMPs can discriminate between MMPs in the same subfamily.
Apo‐nitrophorin 4 at atomic resolution
Authors: Amoia Angela M. , Montfort William R.
Published: July 2007

The nitrophorins from Rhodnius prolixus, the kissing bug, are heme‐containing proteins used for the transport of nitric oxide to aide the insect in obtaining a blood meal. The Rhodnius nitrophorins display an eight‐stranded antiparallel beta‐barrel motif, typical of lipocalins, with a histidine‐linked heme in the open end of the barrel. Heme is stabilized in the ferric state and highly distorted, displaying a ruffled conformation that may be of importance in the setting of the reduction potential. To help in understanding the means by which the protein matrix, an inherently soft material, is able to distort the heme from its low‐energy planar conformation, we have determined the crystal structure of apo‐nitrophorin 4–1.1 Å resolution. Removal of the heme from nitrophorin 4 has very little effect on its structure: The heme binding cavity remains open and the loops near the cavity entrance respond to lower pH in the same manner as the intact protein. We conclude that the general stability of the lipocalin fold and apparent rigidity of the beta‐barrel provide the means for distorting the heme cofactor.
What difference does training make? A randomized trial with waiting‐list control of general practitioners seeking advanced training in drug misuse
Authors: Strang John , Hunt Claire , Gerada Clare , Marsden John
Published: July 2007

Aim  To measure changes in knowledge, attitudes and clinical practice of general practitioners (GPs) enrolled to receive training in the management of drug misusers.

Design  Two‐group randomized trial with training (T) and waiting‐list (WL) control comparison conditions.

Setting and participants  A total of 112 GPs working in primary care practices in England.

Interventions  A 6‐month, part‐time, mixed‐methods training course provided by the Royal College of General Practitioners. GPs randomized to the WL control received no special training or guidance during the study period.

Outcome measures and analysis  Knowledge, therapeutic attitudes (commitment, role security, situational constraints and prescribing confidence) and clinical practice behaviour change (numbers of drug misusers seen, treated). Intention‐to‐treat/train (ITT) analysis, supplemented by treatment/training received (TR) analysis.

Findings  Training applicants had positive attitudes towards and were already involved in the care of drug misusers. Improvements in attitudes and behaviour were greatest among the T group, although only ‘role security’ and ‘situational constraint’ reached statistical significance (ITT). A subgroup in the WL group circumvented their allocation and received training, prompting supplementary analysis by TR. Overall, GPs who received training showed markedly greater improvements in knowledge, attitudinal and prescribing confidence measures and remained more actively involved in treating drug misusers than GPs who remained in the WL control group (TR analysis).

Conclusions  GPs seeking special training for the care of drug misusers are both positively disposed to this patient population and clinically active. Benefits unambiguously attributable to the course were modest. While a TR effect was observed, strict adherence to ITT analysis failed to identify significant benefits observed with the training provided. Randomisation and waiting‐list controls design are insufficient as a research method for training evaluation studies if ITT analysis is used exclusively.
Lenalidomide‐induced myelosuppression is associated with renal dysfunction: adverse events evaluation of treatment‐naïve patients undergoing front‐line lenalidomide and dexamethasone therapy
Authors: Niesvizky Ruben , Naib Tara , Christos Paul J. , Jayabalan David , Furst Jessica R. , Jalbrzikowski Jessica , Zafar Faiza , Mark Tomer , Lent Richard , Pearse Roger N. , Ely Scott , Leonard John P. , Mazumdar Madhu , Chen‐Kiang Selina , Coleman Morton
Published: August 2007

Data on 72 patients receiving lenalidomide/dexamethasone for multiple myeloma (MM) was used to determine the factors that are associated with lenalidomide‐induced myelosuppression. Eight of 14 patients with grade ≥3 myelosuppression had baseline creatinine clearance (CrCl) ≤0·67 ml/s. Kaplan–Meier analysis by log‐rank test demonstrated a significant association (P < 0·0001) between renal insufficiency and time to myelosuppression (hazard ratio = 8·4; 95% confidence interval 2·9–24·7, P = 0·0001). Therefore, CrCl is inversely associated with significant myelosuppression. Caution should be exercised when lenalidomide therapy is commenced and CrCl should be incorporated as a determinant of the initial dosing of lenalidomide in MM patients.
Detection of phospho‐STAT5 in mast cells: a reliable phenotypic marker of systemic mast cell disease that reflects constitutive tyrosine kinase activation
Authors: Zuluaga Toro Tania , Hsieh Fred H. , Bodo Juraj , Dong Henry Y. , Hsi Eric D.
Published: July 2007

Systemic mastocytosis (SM) is characterized by the abnormal proliferation and accumulation of mast cells (MCs). Constitutive activation of kit, a receptor tyrosine kinase (TK), has been associated with all types of SM. Signal transducers and activators of transcription (STATs), such as STAT5, mediate downstream kit signalling. We hypothesized that nuclear phospho‐STAT5 (pSTAT5) in MCs might reflect TK activation and would be a marker of abnormal MCs in SM. Expression of tryptase, CD25, CD2 and pSTAT5 was evaluated by immunohistochemistry (IHC) on archival cases of SM and cutaneous mastocytosis (CM). pSTAT5 was detected in 23/23 of SM and 1/9 of CM MC nuclei. 23/23 SM had CD25 + MCs. Control tissue MCs were negative for pSTAT5. Nuclear pSTAT5 in MCs from SM reflects abnormal TK activation. We propose nuclear pSTAT5 positivity in MCs as an additional minor phenotypic criterion for diagnosis of SM in future World Health Organization classification schemes.
AKAP12, a gene with tumour suppressor properties, is a target of promoter DNA methylation in childhood myeloid malignancies
Authors: Flotho Christian , Paulun Annika , Batz Christiane , Niemeyer Charlotte M.
Published: August 2007

A‐kinase anchor protein 12 (AKAP12) is a scaffold protein that participates in mitotic regulation and other signalling processes and probably exerts tumour suppressor function. We hypothesized that epigenetic repression of the AKAP12 gene might occur in malignant myeloid disorders. This study demonstrated that the 5′ CpG island of AKAP12 was unmethylated in normal haematopoietic progenitors and granulocytes but exhibited profound methylation in Kasumi‐1 and SKNO‐1 leukaemic myeloblasts. Correspondingly, AKAP12 was expressed in normal progenitors but transcriptionally silent in leukaemic blasts. Re‐expression of AKAP12 in Kasumi‐1 and SKNO‐1 cells was accomplished by treatment with MS275 alone or in combination with zebularine, indicating epigenetic mechanisms of gene repression. AKAP12 hypermethylation was found in one case of refractory anaemia with excess blasts (RAEB) and two cases of acute myeloid leukaemia (AML) in a panel of 21 blood or bone marrow samples from children with malignant myeloid disorders including refractory cytopenia, RAEB, juvenile myelomonocytic leukaemia and AML. While AKAP12 function has not been previously linked to leukaemogenesis, our results raise the possibility that epigenetic silencing of AKAP12 is involved in myeloid malignancies.
Frequent occurrence of B‐cell lymphomas in angioimmunoblastic T‐cell lymphoma and proliferation of Epstein–Barr virus‐infected cells in early cases
Authors: Willenbrock Klaus , Bräuninger Andreas , Hansmann Martin‐Leo
Published: August 2007

Secondary lymphomas occurring in the setting of angioimmunoblastic T‐cell lymphoma (AILT) are considered to be rare. Their occurrence has been attributed to Epstein–Barr virus (EBV)‐associated lymphoproliferations. A previous study detected a dysregulated hypermutation process in B‐cells of AILT. The present study aimed at estimating the frequency of B‐cell lymphomas in AILT. By studying the expression of EBV and activation‐induced cytidine deaminase (AID) as an indicator of hypermutating cells, we assessed whether B‐cell lymphoproliferations in AILT were strictly associated with EBV and whether hypermutation might contribute to lymphomagenesis. Among 161 cases of AILT, diagnosed between 1996 and 2005 at the lymph node registry, Frankfurt, Germany, 19 cases were detected that also had B‐cell non‐Hodgkin lymphoma (NHL) and two cases had classical Hodgkin lymphoma (HL). EBV was detected in tumour cells of 7/18 NHL and both HL, suggesting that factors other than EBV contribute to lymphomagenesis. AID was expressed in AILT in large cells disseminated in the tissue, implying that the process of somatic hypermutation is ongoing in AILT, although the GC architecture is disrupted. This might be relevant in the development of secondary lymphomas.
Storage of small bale silage and haylage – influence of storage period on fermentation variables and microbial composition
Authors: Müller C. E. , Pauly T. M. , Udén P.
Published: August 2007

An experiment investigating changes in fermentation variables and microbial composition during storage of small‐bale silage and haylage was performed. Haylage was defined as silage with a dry‐matter (DM) content exceeding 500 g kg−1. Grass was wilted to three different DM contents, and baled into silage (350 g DM kg−1), haylage with a low DM content (550 g kg−1) and haylage with high DM content (700 g kg−1) in small rectangular‐shaped bales (0·80 m × 0·48 m × 0·36 m) that were individually wrapped. Bales were stored for short (2 months) or long (14 months) periods before opening and sampling. Silage had higher concentrations of fermentation products and a lower pH than either of the two haylage types. In general, long‐term storage influenced all fermentation variables except concentrations of butyric acid and succinic acid, and yeast counts were higher after 14 months than 2 months of storage. However, silage changed in more fermentation variables during storage than the two haylage types. Although differences between short‐ and long‐term stored silage were found, linear correlations between short‐ and long‐term stored bales were present for all chemical variables. Pearson's correlation coefficients were highest for lactic acid, followed by pH.
Seasonal changes in herbage mass and nutritive value of a range of grazed legume swards under Mediterranean and cool temperate conditions
Authors: Sölter U. , Hopkins A. , Sitzia M. , Goby J. P. , Greef J. M.
Published: August 2007

Seasonal changes in herbage mass and herbage quality of legume‐based swards under grazing by sheep or cattle were investigated at four locations in climatically different zones of Europe: Sardinia (Italy), southern France, northern Germany and south‐west England (UK). At each location standard treatments were applied to legumes typical of species widely used in each locality:Medicago polymorphain Italy,Medicago sativain France, andTrifolium repensin Germany and in UK. At each site comparisons were made of two other legumes:Trifolium subterraneumandHedysarum coronariumin Italy,Onobrychis sativaandTrifolium incarnatumin France,Trifolium pratenseandLotus corniculatusin Germany, andTrifolium ambiguumandL. corniculatusin UK. Legumes were sown in mixture with locally appropriate companion grasses, and measurements were made over two or three grazing periods. In ItalyM. polymorphaswards gave the greatest herbage mass in grazing period 1 butH. coronariumwas more persistent. At the French site all legumes established poorly with no significant herbage mass differences between treatments. At both the UK and German sitesL. corniculatusmaintained a high proportion of legume in the sward;T. repensshowed poor persistence under continuous sheep grazing in UK but persisted under cattle grazing in Germany, whileT. ambiguumwas slow to establish in the UK, andT. pratenseproved to be of comparable herbage mass to the standardT. repens‐based sward in the last year of the experiment. The concentration of crude protein andin vitrodigestibility of organic matter in the dry matter of herbage showed greater within‐season variation than between treatments at each site. It is concluded that, in addition to currently used species, legume‐based swards containingH. coronarium, O. sativaandL. corniculatusall have potential to contribute to forage production for low‐input grazing and their use merits further consideration in systems of livestock production in Europe.
Characterization of human invariant natural killer T subsets in health and disease using a novel invariant natural killer T cell‐clonotypic monoclonal antibody, 6B11
Authors: Montoya Carlos J. , Pollard David , Martinson Jeffrey , Kumari Kumud , Wasserfall Clive , Mulder Candice B. , Rugeles Maria T. , Atkinson Mark A. , Landay Alan L. , Wilson S. Brian
Published: July 2007

Identification of human CD1d‐restricted T‐cell receptor (TCR)‐invariant natural killer T (iNKT) cells has been dependent on utilizing combinations of monoclonal antibodies or CD1d tetramers, which do not allow for the most specific analysis of this T‐cell subpopulation. A novel monoclonal antibody (clone 6B11), specific for the invariant CDR3 loop of human canonical Vα24Jα18 TCR α chain, was developed and used to specifically characterize iNKT cells. In healthy individuals studied for up to 1 year, a wide but stable frequency of circulating iNKT cells (range: 0·01–0·92%) was observed, with no differences in frequency by gender. Four stable iNKT cell subsets were characterized in peripheral blood based on the expression of CD4 and CD8, with CD8+ iNKT cells being a phenotypic and functionally different subset from CD4+ and double negative iNKT cells; in particular, LAG‐3 was preferentially expressed on CD8+ iNKT cells. In addition, a strong negative linear correlation between the frequency of total iNKT cells and percentage of the CD4+ subset was observed. In terms of their potential association with disease, patients at risk for type 1 diabetes had significantly expanded frequencies of double negative iNKT cells when compared to matched controls and first‐degree relatives. Moreover, peripheral blood CD4+ iNKT cells were the highest producers of interleukin‐4, while the production of interferon‐γ and tumour necrosis factor‐α was similar amongst all iNKT cell subsets. These differences in iNKT cell subsets suggest that in humans the relative ratio of iNKT cell subsets may influence susceptibility vs. resistance to immune‐mediated diseases.
Role stress and job satisfaction for nurse specialists
Authors: Chen Yao‐Mei , Chen Sue‐Hui , Tsai Chiu‐Yueh , Lo Liang‐Yueh
Published: August 2007

Title.  Role stress and job satisfaction for nurse specialists

Aim.  This paper is a report of a study to illustrate the unique relationship between role stress and job satisfaction and provide recommendations for advanced nursing practice in Taiwan.

Background.  International literature has shown that work role‐related stress experienced by staff nurses predicts role strain, which in turn influences job satisfaction and intention to leave the job. In this study, the direct relationship between role stress and job satisfaction of nurse specialists was examined after controlling for personality trait and personal characteristics.

Method.  In 2004 a convenience sample of 129 nurse specialists from five acute care teaching hospitals in Taiwan participated. They completed a questionnaire (response rate 81%) focusing on personal characteristics, the Five Factor Model of personality traits, role stress (i.e. ambiguity, conflict, overload, incompetence) and job satisfaction (i.e. professionalism, interaction, demand/reward, control/recognition). Data were analysed using hierarchical regression models.

Results.  After controlling for personality traits and personal characteristics, role stress variables predicted 24·8% of the variance in job satisfaction. Role ambiguity (P < 0·001) and role overload (P < 0·01) were the best predictors, but role conflict was not statistically significant. Role stress explained statistically significant proportions of the variance for each component of job satisfaction: professionalism (10·6%), interaction (16·7%), demand/reward (27·1%) and control/recognition (18·5%). Role ambiguity predicted all four satisfaction components, role overload predicted demand/reward and role incompetence predicted interaction.

Conclusion.  Organizational restructuring and administrative support are recommended to address the issues raised. Appropriate training, sufficient communications and supportive legislation are required. Future research should be conducted to evaluate the impact of these interventions.
An innovative approach to integrated medicines management
Authors: Scullin Claire , Scott Michael G. , Hogg Anita , McElnay James C.
Published: July 2007

Rationale, aims and objectives  To determine whether an increased input by clinical pharmacists at each stage of the patient’s hospital journey, from admission through discharge, resulted in an enhanced level of patient care as measured by a number of clinical and economic outcomes.

Methods  This project was designed to address medicines management issues in patients deemed at risk of drug‐related problems. During the project, these latter patients at the time of admission were randomly assigned to an integrated medicines management (IMM) service group (n = 371) or regular hospital care group (n = 391). The IMM service involved comprehensive pharmaceutical care provided by a pharmacy team throughout each of three stages: patient admission, inpatient monitoring and counselling, and patient discharge.

Results  Patients who received the IMM service benefited from a reduced length of hospital stay [by 2 days (P = 0.003; independent samples t‐test loge)]. IMM patients also had a decreased rate of readmission over a 12‐month follow‐up period (40.8% vs. 49.3%; p = 0.027; Fisher’s exact test) and an increased time to readmission [20 days longer (P = 0.0356; log rank test)]. A numbers‐needed‐to‐treat calculation indicated that for approximately every 12 patients receiving the IMM service, one readmission to hospital, within 12 months of discharge, would be prevented. The new service was welcomed by cognate health care professionals.

Conclusion  The IMM service proved very effective and can be used as a template to support the implementation of comprehensive pharmaceutical care as a routine service across Northern Ireland and beyond.
Effectiveness of a lifestyle modification programme in weight maintenance in obese subjects after cessation of treatment with Orlistat
Authors: Woo Jean , Sea Mandy M. M. , Tong Peter , Ko Gary T. C. , Lee Zoe , Chan Juliana , Chow Francis C. C.
Published: July 2007

Objective  To examine the efficacy of a lifestyle modification programme in weight maintenance for obese subjects after cessation of treatment with Orlistat.

Methods  Fifty‐five subjects with and without diabetes mellitus were randomized to a lifestyle modification programme or to usual care at the end of 6 months’ treatment with Orlistat. The intervention programme was nutritionist led, consisting of components of dietary management, physical activity, peer group support and discussion using techniques of self‐monitoring, stimulus control and cognitive restructuring. Anthropometric indices, body composition, basal metabolic rate, blood pressure, fasting glucose, glycosylated haemoglobin, lipid profile, 24‐hour urinary albumin excretion, dietary intake, physical activity level, and quality of life were assessed before and after the intervention period.

Results  Subjects in the intervention group maintained their weight loss and favourable anthropometric, metabolic, dietary intake, physical activity and quality of life profiles, while most parameters deteriorated in the usual care group, being more marked in subjects with diabetes. The magnitude of weight gain was comparable to that lost during Orlistat treatment.

Conclusion  A specially designed nutritionist‐led lifestyle modification programme for obese subjects is effective in weight maintenance after treatment with Orlistat, in the absence of which the benefits of drug treatment were lost. The magnitude of the effect of lifestyle modification is comparable to that observed with Orlistat.
In vivo and In vitro Control of Leishmania mexicana due to Garlic‐induced NO Production
Authors: Gamboa‐León M. R. , Aranda‐González I. , Mut‐Martín M. , García‐Miss M. R. , Dumonteil E.
Published: July 2007

Leishmania mexicana is the main causal agent of cutaneous leishmaniasis in the Yucatán peninsula in Mexico. Control of this disease is associated with a Th1‐type immune response and garlic extract has been reported as a Th1 immunomodulator in BALB/c mice infected with Leishmania major. In this study, we investigated the effect of garlic extracts on L. mexicana infection in vivo and in vitro. Garlic extract reduced footpad lesions in L. mexicana‐infected BALB/c mice by inducing IFN‐γ production from T cells. In vitro, garlic extract reduced macrophage infection through induction of nitric oxide (NO) production. Garlic extract may thus act on both T cells and macrophages to stimulate IFN‐γ production and NO synthesis for parasite killing. A 10‐ to 14‐kDa fraction was identified as responsible for the in vitro effect of the whole extract and may lead to the identification of novel immunomodulating drugs and therapeutic alternatives for the treatment of leishmaniasis.
Omalizumab (Xolair) in children with seasonal allergic rhinitis: Leukotriene release as a potential in vitro parameter to monitor therapeutic effects
Authors: Kopp Matthias Volkmar , Stenglein Stefan , Kamin Wolfgang , Friedrichs Frank , Von Berg Andrea , Zielen Stefan , Hamelmann Eckard , Wahn Ulrich , Kuehr Joachim
Published: August 2007

To investigate the effect of omalizumab, a humanized monoclonal antibody, in addition to specific immunotherapy (SIT) on in vitro sulfidoleukotriene release (SLT) (A) before, (B) directly after, and (C) 1 yr after treatment with omalizumab. Children and adolescents (6.3–17.6 yr) with sensitization to birch and grass pollens and suffering from seasonal allergic rhinitis were included in a Phase III, placebo‐controlled, multicenter clinical study. Within the four‐arm study, patients were randomly chosen to receive SIT for either birch or grass pollen and either subcutaneous omalizumab or placebo for 24 wk during the pollen season. Thereafter, omalizumab or placebo treatment ended, but SIT therapy continued. Blood samples were collected from 92 (A, B) and 78 children (C), respectively. Leukocytes were isolated and stimulated with grass and birch pollen allergens. In the supernatants, SLT (LTC4, LTD4, LTE4) were measured using ELISA [cellular allergen stimulation test, DPC‐Biermann, Germany]. At the end of treatment the combination of omalizumab + SIT‐grass [median SLT‐release: 2125 (before) and 416 ng/ml (after omalizumab treatment); p < 0.001] as well as omalizumab + SIT‐birch [1404 and 207 ng/ml; p < 0.001] resulted in significantly lower SLT release after stimulation with the corresponding allergen compared to placebo + SIT‐grass [2231 and 2490 ng/ml] or placebo + SIT‐birch [1324 and 2489 ng/ml]. One year after omalizumab or placebo treatment, there was no significant difference in SLT release between the 4 groups (omalizumab + SIT‐grass: 2855; SIT‐grass + placebo: 2543; omalizumab + SIT‐birch: 2417; SIT‐birch + placebo: 2573 ng/ml). These results strongly suggest that the observed effects of decreased SLT release after omalizumab treatment were attributable to the treatment with omalizumab, rather than to SIT therapy.
Diet, wheeze, and atopy in school children in Menorca, Spain
Authors: Chatzi Leda , Torrent Matias , Romieu Isabelle , Garcia‐Esteban Raquel , Ferrer Carlos , Vioque Jesus , Kogevinas Manolis , Sunyer Jordi
Published: August 2007

Epidemiological studies have shown inverse associations of asthma symptoms with fish, vegetable, and fruit intake. We evaluated the association between several dietary factors with wheeze and atopy among children in Menorca, a Spanish Mediterranean island. A cross‐sectional analysis was performed on 460 children at age 6.5 yr. Parents completed a questionnaire on the child's respiratory and allergic symptoms, and a 96‐item food frequency questionnaire. Children underwent skin prick tests with six common aeroallergens. The average daily intake was relatively high for fruits (177 g) and fish (54 g), and moderate for vegetables (59 g). A high consumption (>40 g/day) of fruity vegetables (tomatoes, eggplants, cucumber, green beans, zucchini) was found to have beneficial effect on current wheeze [odds ratio (OR), 0.38; 95% confidence interval (CI), 0.15–0.95, p < 0.05], and atopic wheeze with a significant decreasing trend when intake was increased (OR, 0.19; 95% CI, 0.04–0.95, p for trend = 0.04). No other fruits or vegetables were significantly associated with wheeze or atopy prevalence. An inverse association was found between a fish intake ≥60 g/day and atopy (OR, 0.43; 95% CI, 0.21–0.90, p < 0.05). The associations remained significant after adjustment for energy intake and maternal diet during pregnancy. Our results support a potential protective effect of fruity vegetables and fish intake during childhood on wheeze and atopy respectively.
Production of homozygous α‐1,3‐galactosyltransferase knockout pigs by breeding and somatic cell nuclear transfer
Authors: Nottle Mark B. , Beebe Luke F. S. , Harrison Sharon J. , McIlfatrick Stephen M. , Ashman Rodney J. , O’Connell Phillip J. , Salvaris Evelyn J. , Fisicaro Nella , Pommey Sandra , Cowan Peter J. , D’Apice Anthony J. F.
Published: July 2007

Abstract:  We report here our experience regarding the production of double or homozygous Gal knockout (Gal KO) pigs by breeding and somatic cell nuclear transfer (SCNT). Large White × Landrace female heterozygous Gal KO founders produced using SCNT were mated with Hampshire or Duroc males to produce a F1 generation. F1 heterozygous pigs were then bred to half‐sibs to produce a F2 generation which contained Gal KO pigs. To determine the viability of mating Gal KO pigs with each other, one female F2 Gal KO pig was bred to a half‐sib and subsequently a full‐sib Gal KO. F1 and F2 heterozygous females were also mated to F2 Gal KO males. All three types of matings produced Gal KO pigs. To produce Gal KO pigs by SCNT, heterozygous F1s were bred together and F2 fetuses were harvested to establish primary cultures of Gal KO fetal fibroblasts. Gal KO embryos were transferred to five recipients, one of which became pregnant and had a litter of four piglets. Together our results demonstrate that Gal KO pigs can be produced by breeding with each other and by SCNT using Gal KO fetal fibroblasts.
Rapid loss of intraportally transplanted islets: an overview of pathophysiology and preventive strategies
Authors: Van Der Windt Dirk J. , Bottino Rita , Casu Anna , Campanile Nathalie , Cooper David K.C.
Published: July 2007

Abstract:  Islets isolated from multiple pancreas donors are often necessary to achieve euglycemia in type 1 diabetic patients treated by islet allotransplantation. This increases the burden on the limited pool of donor organs. After infusion into the portal vein, a substantial percentage of islets are lost in the immediate post‐transplant period through an inflammatory response termed the instant blood‐mediated inflammatory reaction (IBMIR). IBMIR is equally, if not more of a problem after islet xenotransplantation, e.g., using pig islets in non‐human primates. Coagulation, platelet aggregation, complement activation, and neutrophil and monocyte infiltration play roles in this reaction. IBMIR is potentially triggered by islet surface molecules, such as tissue factor and collagen residues that are normally not in direct contact with the blood. Also, stress during the islet isolation process results in the expression and production of several inflammatory mediators by the islets themselves. The potential mechanisms involved in this rapid graft loss and treatment options to reduce this loss are reviewed. Preventive strategies for IBMIR can include systemic treatment of the recipient, pre‐conditioning of the isolated islets, or, in the case of xenotransplantation, genetic modification of the organ‐source pig. Pre‐conditioning of islets in culture by exposure to anti‐inflammatory agents or by genetic modification harbors fewer risks of systemic complications in the recipient. The future of clinical islet transplantation will, at least in part, depend on the success of efforts made to reduce rapid graft loss, and thus allow islet transplantation to become a more efficient therapy by the use of single donors.