bluuebunny/crossref_metadata_2025 huggingface dataset:
Safety and efficacy of a CXCR2 antagonist in patients with severe asthma and sputum neutrophils: a randomized, placebo‐controlled clinical trial
Authors: Nair P. , Gaga M. , Zervas E. , Alagha K. , Hargreave F. E. , O'Byrne P. M. , Stryszak P. , Gann L. , Sadeh J. , Chanez P. ,   on behalf of the study investigators
Published: June 2012

Background

Increased numbers of neutrophils are reported in the airways of patients with severe asthma. It is not clear if they contribute to the lack of control and severity. There are currently no strategies to investigate this by decreasing neutrophil numbers in the airways.

Objective

To investigate the safety and efficacy of SCH527123, a selective CXCR2 receptor antagonist, in patients with severe asthma and increased number of neutrophils in sputum.

Methods

In a randomized, double‐blind, parallel study, patients with severe asthma and sputum total cell count < 10 × 106/g and neutrophils > 40% were randomized to SCH527123, 30 mg daily PO (n = 22) or placebo (n = 12) for 4 weeks. Primary end‐points were safety and change in sputum and blood neutrophil counts. Secondary end‐points were change in asthma control questionnaire (ACQ) score, minor and major exacerbations, spirometry and sputum neutrophil activation markers.

Results

The SCH 527123 caused a mean reduction of 36.3% in sputum neutrophil percentage compared to a 6.7% increase in the placebo arm (P = 0.03). The mean absolute neutrophil count in blood was reduced by 14% at the end of 4 weeks, but recovered by the 5th week. There were no differences in the overall rates of adverse events among the groups. There were fewer mild exacerbations (1.3 vs. 2.25, P = 0.05) and a trend towards improvement in the ACQ score (mean difference between groups of 0.42 points, P = 0.053). No statistically significant changes were observed in forced expiratory volume in 1 s (FEV
1), sputum myeloperoxidase, IL8 or elastase.

Conclusions

The SCH527123 is safe and reduces sputum neutrophils in patients with severe asthma.

Clinical Relevance

This new treatment provides an opportunity to investigate the role of neutrophils in severe asthma with potential clinical benefits. Larger studies of longer duration are needed to evaluate the impact on other outcomes of asthma including exacerbations.
Oral contraceptive plus antiandrogen therapy and cardiometabolic risk in polycystic ovary syndrome
Authors: Harmanci Ayla , Cinar Nese , Bayraktar Miyase , Yildiz Bulent Okan
Published: June 2012

Objective

Oral contraceptives alone or in combination with antiandrogens are commonly used in the treatment for polycystic ovary syndrome (PCOS). We aimed to determine the effects of ethinyl estradiol/drospirenone (EE‐DRSP) plus spironolactone therapy on inflammation and cardiometabolic risk in PCOS.

Design

Prospective cohort study.

Patients

Twenty‐three lean, normal glucose‐tolerant patients with PCOS and 23 age‐ and body mass index (BMI)‐matched healthy control women.

Measurements

Androgens, high‐sensitivity C‐reactive protein (hsCRP), homocysteine, lipids, fasting insulin, and glucose levels during a standard 75‐g, 2‐h oral glucose tolerance test were measured. Patients with PCOS were evaluated before and after receiving EE‐DRSP (3 mg/30 μg) plus spironolactone (100 mg/day) for 6 months. Healthy controls were evaluated at baseline only.

Results

hsCRP, homocysteine, lipids, insulin and glucose levels were similar between patient and control groups at baseline. EE‐DRSP plus spironolactone increased hsCRP and homocysteine levels in patients with PCOS (0·50 ± 0·28 vs 1·5 ± 1·3 mg/l, P < 0·05 and 13·1 ± 5·2 vs 17·6 ± 5·3 μm, P < 0·05, respectively). BMI, waist‐to‐hip ratio, LDL, HDL cholesterol and triglycerides, and glucose tolerance did not change. Modified Ferriman–Gallwey hirsutism scores, testosterone levels and free androgen index improved (9·1 ± 4·2 vs 6·2 ± 3·4, P = 0·001; 80·6 ± 31·1 47·8 ± 20·3 ng/dl, P < 0·05; and 10·5 ± 7·4 vs 1·1 ± 0·8, P < 0·001, respectively).

Conclusions

EE‐DRSP plus spironolactone therapy in 6 months improves androgen excess in lean PCOS women without any adverse effects on adiposity, glucose tolerance status or lipid profile. However, this combination increases hsCRP and homocysteine levels.
Initial adhesion of Bacillus subtilis on soil minerals as related to their surface properties
Authors: Hong Z. , Rong X. , Cai P. , Dai K. , Liang W. , Chen W. , Huang Q.
Published: June 2012

The initial adhesion of micro‐organisms on solid surfaces strongly affects their transport and fate in soil and aquatic environments. Experiments on Bacillus subtilis with various soil minerals (including kaolinite, montmorillonite, goethite, birnessite, quartz and mica) were conducted to determine the role of surface properties in adhesion and to test the validity of the extended Derjaguin, Landau, Verwey and Overbeek (DLVO) theory for bacterial adhesion. Adhesion of B. subtilis on all six minerals conformed to the Langmuir equation. Adhesion capacity and affinity showed a significant correlation with the specific external surface area (SESA) of the minerals and the calculated electrostatic energy barrier, respectively, but no significant correlation was observed between hydrophobicity and the adhesion parameters. These results demonstrate that adhesion capacity and affinity are primarily controlled by the SESA of the minerals and the surface electrical properties, respectively. The dependence of the adhesion capacity on SESA may be explained by the cell–mineral interaction model. Adhesion could be well predicted by the extended DLVO theory. The initial adhesion of bacteria with soil minerals can be evaluated by using independently measured surface properties of these components based on the extended DLVO theory combined with the Langmuir equation.
Migratory benthic fishes may induce regime shifts in a tropical floodplain pond
Authors: MORMUL ROGER P. , THOMAZ SIDINEI M. , AGOSTINHO ANGELO A. , BONECKER CLAUDIA C. , MAZZEO NESTOR
Published: June 2012

1. Alternative states are a widely recorded phenomenon in shallow lakes, which may shift between turbid‐ and clear‐water conditions. Here, we investigate whether such shifts in a tropical floodplain pond may be related to the effect of the flood pulse regime on the community structures of fish and macrophytes.

2. Using a long‐term data set, we demonstrate how benthic fish migration together with colonisation by submerged plants affected the transition from a turbid to a macrophyte‐dominated state in a floodplain pond without top‐down control.

3. In our study, the turbid state occurred mostly during low water phases and was largely characterised by high values for the biomass of benthic fish, chlorophyll‐a and total phosphorous.

4. During the period of rising water levels, the migration of benthic fish out of the pond occurs simultaneously with the establishment of submerged plants, while water turbidity decreases along with phytoplankton and nutrient concentrations, inducing a clear‐water phase. However, when submerged plants are absent and fish migration is low, a transient state is generated.

5. We suggest that, in contrast to temperate ponds and shallow lakes, where the main driving mechanisms establishing alternative states are related to cascading effects via the food chain, in tropical ponds and shallow lakes it is resuspension of sediments by benthic fish that plays the most significant role in establishing alternative states. However, the effect of the flood pulse regime plays an important role in the temporal dynamics of fish community structure by controlling benthic fish migration.
The role of mitochondria in leaf nitrogen metabolism
Authors: SZAL BOŻENA , PODGÓRSKA ANNA
Published: June 2012

For optimal plant growth and development, cellular nitrogen (N) metabolism must be closely coordinated with other metabolic pathways, and mitochondria are thought to play a central role in this process. Recent studies using genetically modified plants have provided insight into the role of mitochondria in N metabolism. Mitochondrial metabolism is linked with N assimilation by amino acid, carbon (C) and redox metabolism. Mitochondria are not only an important source of C skeletons for N incorporation, they also produce other necessary metabolites and energy used in N remobilization processes. Nitric oxide of mitochondrial origin regulates respiration and influences primary N metabolism. Here, we discuss the changes in mitochondrial metabolism during ammonium or nitrate nutrition and under low N conditions. We also describe the involvement of mitochondria in the redistribution of N during senescence. The aim of this review was to demonstrate the role of mitochondria as an integration point of N cellular metabolism.
Increased human tumor necrosis factor‐α levels induce procoagulant change in porcine endothelial cells in vitro
Authors: Lee Kyoung Geun , Lee Haneulnari , Ha Jeong Mi , Lee Young Kyung , Kang Hee Jung , Park Chung‐Gyu , Kim Sang Joon
Published: June 2012

Lee KG, Lee H, Ha JM, Lee YK, Kang HJ, Park C‐G, Kim SJ. Increased human tumor necrosis factor‐α levels induce procoagulant change in porcine endothelial cells in vitro. Xenotransplantation 2012; 19: 186–195. © 2012 John Wiley & Sons A/S.

Abstract:  Background:  Intravascular thrombosis and systemic coagulation abnormalities are major hurdles to successful xenotransplantation and are signs of acute humoral rejection. Increased expression of tissue factor (TF) is associated with the development of microvascular thrombosis in xenografts. To develop an effective strategy to prevent accelerated coagulation in xenografts, we investigated the mechanism by which porcine endothelial cells (PECs) become procoagulant after contact with human blood.

Methods:  The changes in TF mRNA levels and activity in PECs after incubation with 20% human serum or human bioactive molecules, including C5a, tumor necrosis factor‐α (TNFα) and interleukin (IL)‐1α, were evaluated using real‐time PCR and the factor Xa chromogenic assay, respectively. The procoagulant changes in PECs by these agonists were evaluated by measuring the coagulation time of human citrated plasma suspended with PECs pretreated with each agonist. TF expression and coagulation times were also assessed in PECs transfected with short interfering RNA (siRNA) designed to knock down porcine TF. We also examined the production of proinflammatory cytokines in human whole‐blood or plasma after contact with PECs, which were screened using the cytometric bead array system. TNFα levels were measured using ELISA in whole‐blood after contact with PECs, with or without the addition of xenoreactive antibodies or C1 esterase inhibitor.

Results:  Porcine TF mRNA and activity in PECs were up‐regulated in response to human TNFα and IL‐1α but were not affected by C5a or 20% human serum. Up‐regulation of TF expression by human TNFα or IL‐1α shortened PEC‐induced coagulation time, while siRNA‐mediated knockdown of TF expression prolonged coagulation time. The incubation of PECs with human whole‐blood led to a significant increase in human TNFα levels in the blood, which was promoted by the addition of xenoreactive antibodies and prevented by C1 esterase inhibitor.

Conclusions:  Human TNFα level increases in human blood after contact with PECs, which is attributed to xenoreactive antibody binding and subsequent complement activation. Human TNFα induces procoagulant changes in PECs with increased TF expression. This study suggests that human TNFα may be one of the mediators linking complement activation with procoagulant changes in the xenoendothelium.
Complete absence of the αGal xenoantigen and isoglobotrihexosylceramide in α1,3galactosyltransferase knock‐out pigs
Authors: Puga Yung Gisella L. , Li Yunsen , Borsig Lubor , Millard Anne‐Laure , Karpova Maria B. , Zhou Dapeng , Seebach Jörg D.
Published: June 2012

Puga Yung GL, Li Y, Borsig L, Millard A‐L, Karpova MB, Zhou D, Seebach JD. Complete absence of the αGal xenoantigen and isoglobotrihexosylceramide in α1,3galactosyltransferase knock‐out pigs. Xenotransplantation 2012; 19: 196–206. © 2012 John Wiley & Sons A/S.

Abstract:  Background:  Anti‐Galα1,3Galβ‐R natural antibodies are responsible for hyperacute rejection in pig‐to‐primate xenotransplantation. Although the generation of pigs lacking the α1,3galactosyltransferase (GalT) has overcome hyperacute rejection, antibody‐mediated rejection is still a problem. It is possible that other enzymes synthesize antigens similar to Galα1,3Gal epitopes that are recognized by xenoreactive antibodies. The glycosphingolipid isoglobotrihexosylceramide (iGb3) represents such a candidate expressing an alternative Galα1,3Gal epitope. The present work determined whether the terminal Galα1,3Gal disaccharide is completely absent in Immerge pigs lacking the GalT using several different highly sensitive methods.

Methods:  The expression of Galα1,3Gal was evaluated using a panel of antibodies and lectins by flow cytometry and fluorescent microscopy; GalT activity was detected by an enzymatic assay; and ion trap mass spectroscopy of neutral cellular membranes extracted from aortic endothelial was used for the detection of sugar structures. Finally, the presence of iGb3 synthase mRNA was tested by RT‐PCR in pig thymus, spleen, lymph node, kidney, lung, and liver tissue samples.

Results:  Aortic endothelial cells derived from GalT knockout pigs expressed neither Galα1,3Gal nor iGb3 on their surface, and GalT enzymatic activity was also absent. Lectin staining showed an increase in the blood group H‐type sugar structures present in GalT knockout cells as compared to wild‐type pig aortic endothelial cells (PAEC). Mass spectroscopic analysis did not reveal Galα1,3Gal in membranes of GalT knockout PAEC; iGb3 was also totally absent, whereas a fucosylated form of iGb3 was detected at low levels in both pig aortic endothelial cell extracts. Isoglobotrihexosylceramide 3 synthase mRNA was expressed in all pig tissues tested whether derived from wild‐type or GalT knockout animals.

Conclusions:  These results confirm unequivocally the absence of terminal Galα1,3Gal disaccharides in GalT knockout endothelial cells. Future work will have to focus on other mechanisms responsible for xenograft rejection, in particular non‐Galα1,3Gal antibodies and cellular responses.
Nutrient digestibility and evaluation of protein and carbohydrate fractionation of citrus by‐products
Authors: Lashkari S. , Taghizadeh A.
Published: June 2012

The protein and carbohydrate fractionation and nutrient digestibility of citrus by‐products were determined. Ruminal, intestinal and total tract CP disappearance values were measured by a modified three‐step (MTSP) method and in vitro CP disappearance method (IVCP). Test feeds were orange pulp (OP), lime pulp (LP), lemon pulp (LEP), grapefruit pulp (GP), sweet lemon pulp (SLP), bitter lemon pulp (BLP), bergamot orange pulp (BP) and tangerine pulp (TP). The rumen undegradable protein (RUP) fractions of the feedstuffs were obtained by ruminal incubation in three cannulated wethers and incubation in protease solution (protease type xiv, Streptomyces griseus). The data were analysed using completely randomized design. There were significant differences between the tested feeds in protein fractions and acid detergent insoluble nitrogen (ADIN; C fraction) was highest in GP (14.56%) (p < 0.001). For carbohydrate fraction, the highest C fraction was also observed in GP (2.67%) and in relation to the other citrus pulps (p < 0.001). Ruminal CP disappearance was highest in OP (71.89%) (p < 0.001). The level of post‐ruminal CP disappearance, measured by MTSP, was highest for BP (34.94%) (p < 0.001). The highest in vitro dry matter digestibility (IVDMD) was found for TP (80.44%) followed by that estimated for BP (78.38%) (p < 0.001). The estimated metabolizable energy (MJ/kg DM) varied from 9.77 for LP to 12.91 for BP. Tangerine pulp had the highest true rumen digestibility (TRD) (p < 0.001). According to the results, it could be concluded that citrus by‐products have high nutritive value and also, the in vitro techniques can be easily used to determine of the nutritive value of citrus by‐products.
SREB2/GPR85, a schizophrenia risk factor, negatively regulates hippocampal adult neurogenesis and neurogenesis‐dependent learning and memory
Authors: Chen Qian , Kogan Jeffrey H. , Gross Adam K. , Zhou Yuan , Walton Noah M. , Shin Rick , Heusner Carrie L. , Miyake Shinichi , Tajinda Katsunori , Tamura Kouichi , Matsumoto Mitsuyuki
Published: June 2012

SREB2/GPR85, a member of the super‐conserved receptor expressed in brain (SREB) family, is the most conserved G‐protein‐coupled receptor in vertebrate evolution. Previous human and mouse genetic studies have indicated a possible link between SREB2 and schizophrenia. SREB2 is robustly expressed in the hippocampal formation, especially in the dentate gyrus, a structure with an established involvement in psychiatric disorders and cognition. However, the function of SREB2 in the hippocampus remains elusive. Here we show that SREB2 regulates hippocampal adult neurogenesis, which impacts on cognitive function. Bromodeoxyuridine incorporation and immunohistochemistry were conducted in SREB2 transgenic (Tg, over‐expression) and knockout (KO, null‐mutant) mice to quantitatively assay adult neurogenesis and newborn neuron dendritic morphology. Cognitive responses associated with adult neurogenesis alteration were evaluated in SREB2 mutant mice. In SREB2 Tg mice, both new cell proliferation and new neuron survival were decreased in the dentate gyrus, whereas an enhancement of new neuron survival occurred in SREB2 KO mouse dentate gyrus. Doublecortin staining revealed dendritic morphology deficits of newly generated neurons in SREB2 Tg mice. In a spatial pattern separation task, SREB2 Tg mice displayed a decreased ability to discriminate spatial relationships, whereas SREB2 KO mice had enhanced abilities in this task. Additionally, SREB2 Tg and KO mice had reciprocal phenotypes in a Y‐maze working memory task. Our results indicate that SREB2 is a negative regulator of adult neurogenesis and consequential cognitive functions. Inhibition of SREB2 function may be a novel approach to enhance hippocampal adult neurogenesis and cognitive abilities to ameliorate core symptoms of psychiatric patients.
The image of the special education teacher as reflected in drawings made by teachers in training in Israel
Authors: Regev Dafna , Ronen Tamie
Published: June 2012

This study, by Dr Dafna Regev of the University of Haifa and Professor Tamie Ronen of Tel Aviv University, examines the perceived image of the special education teacher as portrayed in the drawings of Jewish and Arab student teachers in Israel. Of the 187 female participants in this study, 82 were from the Jewish sector and 105 from the Arab sector; they were all at varying stages in their training. The drawings were analysed by three art therapists, and differences found between Jewish and Arab perspectives and between perspectives across the training programme are discussed. This article raises questions about the relationship between attitudes and behaviours and the perspectives of future special education teachers.
Dyslexics in time machines and alternate realities: thought experiments on the existence of dyslexics, ‘dyslexia’ and ‘Lexism’
Authors: Collinson Craig
Published: June 2012

This article explores the possibility that ‘dyslexics’ can be thought of as being ‘othered’ and defined by the social norms and educational practices surrounding literacy; which can be termed ‘Lexism’. As such the author, Craig Collinson, a postgraduate academic support officer at Edge Hill University, presents ‘Lexism’ as a new concept that allows us to reconsider how dyslexics can be said to exist. In a persuasive and original article, Craig argues that dyslexics can be defined by the existence of Lexism rather than the more problematic concept of ‘dyslexia’. He seeks to achieve these ends through a series of thought experiments which suggest a different way of looking at what defines someone as dyslexic in order to suggest that when we talk of the inclusion or exclusion of dyslexic pupils we should be aware of the influence Lexism may have upon us.
GREATER LONDON: SPECIAL REPORT
Authors: Crainer Stuart
Published: June 2012

London is the commercial heart of the UK and the financial centre of Europe. But what are the realities of business life for the 2012 Olympic city?
HEART OF THE CITY
Authors: Goldberg Beverly
Published: June 2012

As loudly lauded as it is vigorously questioned, the City of London is a critical financial hub. Beverly Goldberg ventures into the heart of the City.
THE ART OF EXPLORATION
Authors: Gibson‐Smith Chris
Published: June 2012

What is the role of business in society and in creating wealth?Chris Gibson‐Smith, chairman of the London Stock Exchange and British Land, offers a unique perspective.
THE RIGHT SIDE OF THE ROAD
Authors: Moore Celia
Published: June 2012

Recently appointed as a Fellow of the Edmond J. Safra Center for Ethics at Harvard University, Celia Moore is an Assistant Professor of Organisational Behaviour at London Business School. Her research focuses on the unexpected causes and consequences of corruption and unethical behaviour among individuals, groups and organisations.
TOXIC TAPE
Authors: Eccles Tony , Goddard Jules
Published: June 2012

There is a clamour for more and more regulation of the financial services industry so as to avoid another economic meltdown. The goal is admirable, perhaps, but Tony Eccles and Jules Goddard say that too much regulating can create problems of its own — worse problems
AGILITY IS KING
Authors: Richardson Mike
Published: June 2012

We used to say that “cash is king”. Not any more, argues Mike Richardson. Agility is king and cash is just a way of keeping score.
THE SPACEY PROGRAMME
Authors: Crainer Stuart
Published: June 2012

The American actor and director, Kevin Spacey, has revitalised London's Old Vic theatre. But what are the business lessons?
POSITIVE TOUCH
Authors: Peters Georgina
Published: June 2012

Infosys' European head, BG Srinivas, provides a unique, London‐based world view.
EXECUTIVE SUMMARY: THE GIFT THAT KEEPS ON GOING
Authors: Adams Gabrielle S , Flynn Francis J , Norton Michael I
Published: June 2012

Gabrielle S Adams, Francis J Flynn and Michael I Norton, ‘The gifts we keep on giving: Documenting and destigmatising the regifting taboo’, Psychological Science (forthcoming publication).
Essentialism and the Social
Authors: Pratten Stephen
Published: June 2012

In this paper I show that two senses are often assigned to essences in frameworks that award them a significant ontological status. There is both a defining sense and a more concrete-explanatory sense. Once this distinction is recognized, competing forms of essentialism can be differentiated and their implications more easily explored. As an example of work where the defining and the concrete-explanatory senses of essence are tied closely together I consider the essentialism outlined by Rom Harré as part of his analysis of the practices of natural scientists. As an illustration of a position where the two senses are de-coupled and priority given to the defining sense I examine the essentialism Charles Peirce develops in his mature account of natural classes. I show that arguments concerning the scope of essentialism and its relevance for the study of social phenomena depend heavily on the sense of essence prioritized. The focus on these two senses of essence facilitates a better understanding of the forms of essentialism defended by Harré and Peirce and helps identify the challenges contemporary realists face as they seek to defend an essentialism that applies to the social.
A Cosmopolitan Approach to the Explanation of Social Change: Social Mechanisms, Processes, Modernity
Authors: Delanty Gerard
Published: June 2012

In recent years social science has been characterized by a cosmopolitan turn. Of the many questions that arise from this the most important are those that concern the implications for explaining social change. While cosmopolitanism is centrally about social change, much cosmopolitan theory due to its normative orientation lacks a capacity for explanation. The problem of explanation is also a problem that besets all ‘big question’ approaches in social science. In this paper a broad definition of cosmopolitanism is given and elucidated by an outline of its epistemological, ontological and methodological frameworks. Emphasizing the latter two, a relational conception of cosmopolitanism is developed as an alternative to dispositional/agency based and systemic accounts. First I argue that there are four main kinds of cosmopolitan relationships, which together constitute the social ontology of cosmopolitanism. These are the relativization of identity, the positive recognition of the other, the mutual evaluation of cultures, and the creation of a normative world culture. A methodological framework is advanced that distinguishes between the preconditions of cosmopolitanism, its social mechanisms and processes (of which three are specified: generative, transformational and institutionalizing) and trajectories of historical change. The argument is made that cosmopolitan phenomena can be accounted for in terms of this ontological and methodological framework. The advantage of this approach is that it offers cosmopolitan analysis a macro level account of social change that is broadly explanatory and which can also account for both the diachronic and synchronic levels of the emergence of cosmopolitanism as both a counter-factual normative cultural model and as a part of social and political practices and institutional arrangements.
A randomized, ‘head‐to‐head’ pilot study comparing the effects of etanercept monotherapy vs. etanercept and narrowband ultraviolet B (NB‐UVB) phototherapy in obese psoriasis patients
Authors: Park K.K. , Wu J.J. , Koo J.
Published: June 2012

Background  Etanercept is a tumour necrosis factor‐alpha antagonist used for the treatment of moderate‐to‐severe psoriasis. Current opinion suggests that etanercept may have reduced efficacy in obese patients. Narrowband ultraviolet B (NB‐UVB) phototherapy is unaffected by body weight and the addition of NB‐UVB to etanercept therapy may supplement the efficacy of etanercept in these patients.

Objective  To evaluate the efficacy and safety of NB‐UVB phototherapy when administered in conjunction with 50 mg of etanercept once weekly in the treatment of obese patients with moderate‐to‐severe plaque psoriasis.

Methods  Thirty psoriasis patients with a body mass index (BMI) greater than 30 were enrolled into this randomized, ‘head‐to‐head’ comparison study. All subjects received 50 mg of etanercept twice weekly for 12 weeks and then randomized to receive either etanercept monotherapy or combination etanercept and NB‐UVB three times weekly for an additional 12 weeks. Treatment response was evaluated using Psoriasis Area and Severity Index (PASI), body surface area (BSA) and Physician’s Global Assessment (PGA) scores.

Results  Twenty‐five subjects completed the study. At 12 weeks, 48% of all patients achieved PASI 75. By Week 24, 62.5% of all patients achieved PASI 75. Patients in the etanercept monotherapy and combination etanercept and NB‐UVB phototherapy arms had similar rates of achieving PASI 75 (46.7% vs. 53.3% of each group, respectively).

Conclusion  Combination etanercept and NB‐UVB has similar efficacy to etanercept monotherapy in obese patients. This result indicates that even in the setting of obesity, the majority of patients respond well to etanercept, with or without NB‐UVB.
The Civilised Detective: Tomás Eloy Martínez and the Massacre of Trelew
Authors: DUNKERLEY JAMES
Published: June 2012

This article considers the ‘Trelew Massacre’ of August 1972 in Chubút, Argentina, through the primary prism of Tomás Eloy Martínez's journalistic account,La pasión según Trelew, first issued in 1973 and again, in a much expanded second edition, in 2009. The substantive experience of 1972 is assessed in terms of Martínez's construction ofLa pasiónand the events of the ‘Dirty War’ (known asEl Procesoby its authors) opened by the coup of March 1976. Martínez's impressive work of documentary reportage is also reconsidered in comparison with that of Rodolfo Walsh and, at deeper historical remove, that of Domingo Faustino Sarmiento, as well as in the context of Hannah Arendt's notion of ‘the banality of evil’ and a putative national history of ‘bloodletting’ in Argentina.
Clinical, hematologic, and electrolyte changes with 0.9% sodium chloride or acetated fluids in endurance horses
Authors: Fielding C. Langdon , Gary Magdesian K. , Meier Chloe A. , Rhodes Diane M.
Published: June 2012

Objective

To describe the clinical and laboratory changes associated with the use ofIV0.9% sodium chloride and a commercially available acetated fluid (CAF) to treat endurance horses requiring emergency medical treatment.

Design

Randomized, controlled clinical trial from 2007 to 2010.

Setting

Emergency treatment centers of the Western States 100‐mile (220 km) endurance ride.

Animals

Twelve horses requiring emergency medical treatment in the form ofIVfluids completed the study.

Interventions

Horses were assigned to either the 0.9% sodium chloride group (6 horses) or CAF group (6 horses) and received a total of 20 L of fluid. Clinical, hematologic, and electrolyte data were collected prior to and during fluid therapy.

Measurements and Main Results

As compared to results prior to fluid therapy, horses treated with 0.9% sodium chloride had a decrease in heart rate (P < 0.01), PCV (P < 0.001), total plasma protein (TPP) (P < 0.001), and the sodium‐chloride difference (P < 0.05). These horses also had an increase in plasma chloride (P < 0.01) and sodium (P < 0.01) concentrations. Horses treated with CAF showed a decrease in PCV (P < 0.01) and TPP (P < 0.001).

Conclusions

These findings should aid in the design a larger clinical trial to provide further clarification on the effects of type of fluid therapy on clinical and biochemical parameters in endurance horses. The use of 0.9% sodium chloride may not be ideal for the emergency management of endurance horses as it was associated with an increase in plasma chloride concentration.
Position statement on visiting in adult critical care units in the UK
Authors: Gibson Vanessa , Plowright Catherine , Collins Tim , Dawson Deborah , Evans Sara , Gibb Peter , Lynch Fiona , Mitchell Kay , Page Pam , Sturmey Gordon
Published: June 2012

To provide nurses with an evidence‐based Position Statement on the standards patients and visitors should expect when visiting an adult critical care unit in the 21st century in the UK. The British Association of Critical Care Nurses (BACCN) is a leading organization for critical care nursing in the UK and regularly receives enquiries about best practice regarding visiting policies. Therefore, in keeping with the BACCN's commitment to provide evidence‐based guidance for nurses, a Position Statement on visiting practices in adult critical care units was commissioned. This brought together experts from the field of critical care nursing and representatives from patient and relatives' groups to review visiting practices and the literature and produce a Position Statement. An extensive search of the literature was undertaken using the following databases: Blackwell Synergy, CINAHL, Medline, Swetswise, Cochrane Data Base of Systematic Reviews, National Electronic Library for Health, Institute for Healthcare Improvement and Google Scholar. After obtaining selected articles, the references from these articles were then evaluated for their relevance to this Position Statement and were retrieved. The evidence suggests a disparity between what nurses believe is best practice and what patients and visitors actually want. Historically, visitors have been perceived as being responsible for increasing noise, taking up space, taking up nursing time, hindering nursing care and spreading infection. The evidence reviewed for this Position Statement suggests there are many benefits to patients and nurses from visitors. There was no evidence to suggest that visitors pose a direct infection risk to patients. Clear visiting policies based on evidence will negate arbitrary decisions by nurses regarding who can visit and will lessen confusion and dispel myths which can only bring benefits to patients, staff and organizations. To make nurses aware of the physical and psychological benefits of visiting to patients. Visitors bring a positive energy to patients and can act as advocates. They can supply nurses with vital information about patients which will enable the nurse to provide more individualized care. Being cognizant of the evidence will help nurses develop policies on visiting which are up to date for the 21st century.
Copy Number Variations in 6q14.1 and 5q13.2 are Associated with Alcohol Dependence
Authors: Lin Peng , Hartz Sarah M. , Wang Jen‐Chyong , Agrawal Arpana , Zhang Tian‐Xiao , McKenna Nicholas , Bucholz Kathleen , Brooks Andrew I. , Tischfield Jay A. , Edenberg Howard J. , Hesselbrock Victor M. , Kramer John R. , Kuperman Samuel , Schuckit Marc A. , Goate Alison M. , Bierut Laura J. , Rice John P.
Published: June 2012

Background

Excessive alcohol use is the third leading cause of preventable death and is highly correlated with alcohol dependence, a heritable phenotype. Many genetic factors for alcohol dependence have been found, but many remain unknown. In search of additional genetic factors, we examined the association between Diagnostic and StatisticalManual of Mental Disorders, Fourth Edition (DSM‐IV) alcohol dependence and all common copy number variations (CNVs) with good reliability in the Study of Addiction: Genetics and Environment (SAGE).

Methods

All participants in SAGE were interviewed using the Semi‐Structured Assessment for the Genetics of Alcoholism, as a part of 3 contributing studies. A total of 2,610 non‐Hispanic European American samples were genotyped on the Illumina Human 1M array. We performed CNV calling by CNVPartition, PennCNV, and QuantiSNP, and only CNVs identified by all 3 software programs were examined. Association was conducted with the CNV (as a deletion/duplication) as well as with probes in the CNV region. Quantitative polymerase chain reaction (qPCR) was used to validate the CNVs in the laboratory.

Results

CNVs in 6q14.1 (p = 1.04 × 10−6) and 5q13.2 (p = 3.37 × 10−4) were significantly associated with alcohol dependence after adjusting multiple tests. On chromosome 5q13.2, there were multiple candidate genes previously associated with various neurological disorders. The region on chromosome 6q14.1 is a gene desert that has been associated with mental retardation and language delay. The CNV in 5q13.2 was validated, whereas only a component of the CNV on 6q14.1 was validated by qPCR. Thus, the CNV on 6q14.1 should be viewed with caution.

Conclusions

This is the first study to show an association between DSM‐IV alcohol dependence and CNVs. CNVs in regions previously associated with neurological disorders may be associated with alcohol dependence.
Associations Between Selected State Laws and Teenagers' Drinking and Driving Behaviors
Authors: Cavazos‐Rehg Patricia A. , Krauss Melissa J. , Spitznagel Edward L. , Chaloupka Frank J. , Schootman Mario , Grucza Richard A. , Bierut Laura Jean
Published: June 2012

Background

We examined the associations between selected state‐level graduated driving licensing (GDL) laws and use‐and‐lose laws (laws that allow for the suspension of a driver's license for underage alcohol violations including purchase, possession, or consumption) with individual‐level alcohol‐related traffic risk behaviors among high school youth.

Methods

Logistic regression models with fixed effects for state were used to examine the associations between the selected state‐level laws and drinking and driving behaviors youth aged 16 to 17 years (obtained from the Youth Risk Behavior Surveillance System (YRBSS); responses dichotomized as “0 times” or “1 or more times”) over an extended period of time (1999 to 2009).

Results

A total of 11.7% of students reported having driven after drinking any alcohol and 28.2% reported riding in a car with a driver who had been drinking on 1 or more occasions in the past 30 days. Restrictive GDL laws and use‐and‐lose laws were associated with decreased driving after drinking any alcohol and riding in a car with a driver who had been drinking alcohol.

Conclusions

Restrictive GDL and use‐and‐lose laws may help to bolster societal expectations and values about the hazards of drinking and driving behaviors and are therefore partly responsible for the decline in these alcohol‐related traffic risk behaviors.
Explicating Hearing the Voice of the Customer as a Manifestation of Customer Focus and Assessing its Consequences
Authors: Bharadwaj Neeraj , Nevin John R. , Wallman Jeffrey P.
Published: June 2012

It is often asserted that hearing the voice of the customer (VOC) can generate meaningful product and process innovation. Minimal empirical attention has, however, been devoted to evaluating this claim. The paucity of academic research exists, in part, due to the lack of an underlying conceptual foundation for the VOC concept. An opportunity thereby exists to impart theory, and evaluate whether hearing the VOC can indeed lead to favorable consequences. This research construes customer focus as a market‐sensing capability which manifests itself in the key organizational processes (i.e., intelligence generation and continual performance assessment) and values (i.e., a customer orientation serves as the guiding principle) that allow the VOC to be heard throughout the organization. Those manifestations are hypothesized to impact positions (i.e., relative [task‐related] performance) and outcomes (i.e., customer loyalty). The results based on data obtained from a cross‐sectional survey research design fielded in a supplier‐business customer context provide empirical support for the favorable consequences of being customer‐focused, and support the need to consider moderating variables. This paper advances theory by (1) answering the call to examine the capabilities that underlie a customer‐focused organization; (2) establishing empirical support for the (a) linkage between hearing the VOC and acting on that information, (b) elusive relationship between acting on the VOC and future buyer intentions, and (c) sources→positions→outcomes model as a path to achieving competitive advantage; (3) demonstrating that being customer‐focused does not have a direct effect on customer loyalty, thereby revealing a result different than that obtained in the consumer empowerment literature; and (4) demonstrating the importance of key moderators, namely (a) that relative (operational) performance has a strong positive effect on loyalty in relationships characterized by lower switching costs, and (b) that the effect of customer focus may lessen over time, implying that core capabilities may evolve into core rigidities. Additionally, this research contributes to business practice by providing managers with an understanding of how to hear the VOC throughout the firm (i.e., how to become a customer‐focused organization), and offering guidance on how to manage buyer–seller relationships.
Physical examination: How to examine the arm with arteriovenous fistula
Authors: Sousa Clemente Neves , Apóstolo João Luís , Figueiredo Maria Henriqueta , Martins Maria Manuela , Dias Vanessa Filipa
Published: June 2012

Physical examination has demonstrated its effectiveness in identifying complications of arteriovenous fistula (AVF). It should be initiated at the stage prior to the construction of the AVF and continue in its accomplishment, maturation, and subsequent use in the treatment of hemodialysis. Nurses should incorporate the physical examination in their practices, in order to preserve the vascular net of patients and assist in the recognition of complications of AVF. It is intended to describe aspects of the physical examination that enable the identification of the AVF complications including: infection, accessory veins, venous stenosis, steal syndrome, high‐output cardiac failure, and venous hypertension.
Factor Structure of the Farsi Version of the Ways of Coping Questionnaire
Authors: PADYAB MOJGAN , GHAZINOUR MEHDI , RICHTER JÖRG
Published: June 2012

Despite burgeoning research on coping with stress and its crucial role on people's psychological and physical well‐being, there is a dearth of psychometrically established instrument for use in Iran to measure coping. A Farsi translation of the Ways of Coping questionnaire (WOC) was administered to 739 participants from Tehran, Iran. The factor structure of the WOC was assessed with both explanatory and confirmatory factor analyses. A 7‐factor structure model with some important similarities and differences to the original version from the United States was confirmed. The Farsi version of WOC was found to have good construct reliability and model fit and has considerable potential to be used in future coping research among Iranian populations.
Exploring the Relationship Among the Undesired Self, Health, and Mood in Older Adults1
Authors: MORA PABLO A. , MUSUMECI‐SZABO TAMARA , POPAN JASON , BEAMON TEERAH , LEVENTHAL HOWARD
Published: June 2012

Longitudinal data from older adults were analyzed to examine the impact of health factors on undesired and ideal self‐discrepancies; and the association of these 2 self‐discrepancies on moods. Results showed that after controlling for self‐assessed health (SAH), fatigue/lack of energy was associated with the undesired but not the ideal self. A second set of analyses revealed that the undesired self‐discrepancy predicted moods only at high levels of SAH. The ideal self was only associated with anxiety, but only at low levels of SAH. This evidence supports the idea that health‐related factors are relevant for the self‐discrepancies of older adults, especially the undesired self‐discrepancy. We expanded prior evidence by demonstrating that the effects of self‐discrepancies on mood are moderated by SAH.
Implant‐supported single tooth restoration in the aesthetic zone: transmucosal and submerged healing provide similar outcome when simultaneous bone augmentation is needed
Authors: Cordaro Luca , Torsello Ferruccio , Chen Stephen , Ganeles Jeffrey , Brägger Urs , Hämmerle Christoph
Published: June 2012

Aim

The aim of this study was to compare the clinical outcomes after 2 years with bone level implants placed to restore a single missing teeth that needed simultaneous augmentation and were treated with a transmucosal or submerged approach.

Methods

This study analyzed a subset of patients included in an ongoing prospective multicenter randomized clinical trial (RCT) involving12 centers where patients were to be followed‐up to 5 years after loading. Of the 120 implants that were placed in the original study, and randomly assigned to submerged or non‐submerged healing, 52 needed simultaneous augmentation (28 women patients and 24 men patients, between 23 and 78 years of age). Twenty‐seven of them received implants with submerged healing (AuS), while in 25 patients the implants were inserted with a non‐submerged protocol (AuNS).

At the 2‐year follow‐up visit, radiographic crestal bone level changes were recorded as well as soft tissue parameters included Pocket probing depth (PPD), bleeding on probing (BoP) and clinical attachment level (CAL) at teeth adjacent to the implant site.

Results

After 2 years a small amount of bone resorption was found in both groups (0.37 ± 0.49 mm in the AuS group and 0.54 ± 0.76 in the AuNS group; P < 0.001).

There was no statistically significant difference between AuS Group and AuNS group for PPD (2.5 vs. 2.4 mm), BOP (BOP + sites: 8.8% vs. 11.5%) and CAL (2.8 vs. 2.4 mm) at the 2‐year follow‐up visit.

Conclusions

When a single implant is placed in the aesthetic zone in conjunction with bone augmentation for a moderate peri‐implant defect, submerged and transmucosal healing determine similar outcome, hence there is no need to submerge an implant in this given clinical situation.
A modified method using the SonoPrep® ultrasonic skin permeation system for sampling human interstitial fluid is compatible with proteomic techniques
Authors: Lecomte Marie M. J. , Atkinson Kelly R. , Kay Daniel P. , Simons Joanne L. , Ingram John R.
Published: June 2012

Background

The use of biomarkers in skin is a novel diagnostic tool. Interstitial fluid (ISF) from skin provides a snapshot of proteins secreted at the time of sampling giving insights into the patient's health status.

Methods

A minimally invasive technique for the transdermal collection of human ISF proteins. A low frequency ultrasonic skin permeation device (SonoPrep® ultrasonic skin permeation system) was used to produce micropores in the stratum corneum through which ISF was extracted using a portable pulsed vacuum ISF collection device.

Results

On average, protein concentrations recovered ranged between 0.064 and 4.792 μg/μL (mean 1.258 μg/μL). Two‐dimensional gel electrophoresis revealed that this sample type was amenable to this type of analysis. Gel images indicated that both highly abundant proteins and lower abundance proteins were isolated from the skin. Western blot analysis confirmed the presence of proteins commonly found in plasma and the epidermis.

Conclusion

A minimally invasive method for the transdermal recovery of ISF proteins has been developed. We have demonstrated that ISF samples obtained using this approach can be analysed with proteomic techniques, such as two‐dimensional gel electrophoresis and western blots, providing another tool for the identification of disease specific protein biomarkers.
Identifying malnutrition risk in acute medical patients: Validity and utility of Malnutrition Universal Screening Tool and Modified Malnutrition Screening Tool
Authors: GIBSON Simone , SEQUEIRA Jennifer , CANT Robyn , KU Christopher
Published: June 2012

Aim:  Nutrition screening is increasingly conducted in hospitals during the patient admission process. We aimed to explore the ease of use of two tools in the conduct of screening by nutrition technicians (NTs), and to compare validity. The tools are Malnutrition Universal Screening Tool (MUST) and Modified Malnutrition Screening Tool (Mod‐MST).

Methods:  A sample of 262 consecutive adult hospital patients in medical wards was screened during December 2008 to January 2009. Trained NTs used both tools to screen each patient. Dietitians who were blinded to screening results then assessed each patient using Subjective Global Assessment as a reference tool. Time taken for screening was recorded and ease of tool use was explored in interviews with technicians.

Results:  The specificity of MUST and Mod‐MST was 85% and 83%, respectively, with sensitivity of 80% and 77%. Both tools were easy to use and could be applied to all patients, including those unable to answer interview questions. However, the MUST took two to three times longer to complete (5–7 min) using objective data. The Mod‐MST collected subjective data that required interpretation by technicians.

Conclusion:  Specificity and sensitivity of the two tools were less than optimum at ≤85%, as some patients would be misclassified. Both tools were valid and feasible to use with all medical patients, including those with whom communication cannot be established. The Mod‐MST is recommended, as choice of malnutrition screening tool needs to balance efficacy with time taken to be useful for mass screening programs.