bluuebunny/crossref_metadata_2025 huggingface dataset:
Increase in vesicular hand eczema after house dust mite inhalation provocation: a double‐blind, placebo‐controlled, cross‐over study
Authors: Schuttelaar Marie Louise A. , Coenraads Pieter Jan , Huizinga Janneke , De Monchy Jan G. , Vermeulen Karin M.
Published: October 2012

Background. It is unclear whether the respiratory tract is involved in eliciting or aggravating eczematous lesions in patients with vesicular hand eczema.

Objectives. To investigate the effect of inhalation of house dust mite (HDM) on vesicular hand eczema.

Methods. Eighteen patients with vesicular hand eczema and HDM allergy received inhalation challenges with four concentrations of HDM in a randomized, double‐blind, placebo‐controlled, cross‐over study. Early asthmatic reactions and late asthmatic reactions were defined as a placebo‐corrected fall of 15% or more from baseline of forced expiratory volume in 1 second. Hand eczema was scored according to the Dyshidrotic Eczema Area and Severity Index (DASI) at baseline, and 1, 6, 24 and 48 hr.

Results. The median DASI increased significantly as compared with baseline at 6 and 48 hr after HDM inhalation. This increase was significantly different between the provocations at 6 hr. The median vesicles score increased significantly from baseline at 24 and 48 hr. Patients with a placebo‐corrected increase in the number of vesicles at 24 hr and 48 hr had significantly more often late asthmatic reactions than those without an increase in the number of vesicles. Patients with a placebo‐corrected increase of the DASI score at 24 hours had as a group a higher mean total IgE level than those without an increase of the DASI score.

Conclusion. Hand eczema increased significantly more after HDM provocation than after placebo provocation. An increase in the number of vesicles was preceded by late asthmatic reactions. The group patients with an increase of hand eczema tended to have a higher mean total IgE level.
A structural voyage toward an understanding of the MHC‐I‐restricted immune response: lessons learned and much to be learned
Authors: Gras Stephanie , Burrows Scott R. , Turner Stephen J. , Sewell Andrew K. , McCluskey James , Rossjohn Jamie
Published: October 2012

T cells that express clonally distributed αβ T‐cell receptors (TCRs) corecognize antigenic peptides (p) bound to major histocompatibility complex class I (MHC‐I) and class II molecules (MHC‐II). Extensive human leukocyte antigen (HLA) polymorphism enables HLA molecules from different haplotypes to capture an array of self‐ and microbe‐derived peptide antigens that is fundamental to adaptive immunity. T cells developing in the thymus are selected for weak binding to self‐peptide‐HLA complexes generating a vast repertoire of clonally distinct T cells in the periphery. Indeed, diversity within germline loci and the finally assembled TCR genes, coupled with inherent TCR cross‐reactivity, enables CD8+ T cells to survey the multitude of pHLA‐I landscapes. Precisely how does the TCR ligate to pHLA‐I, and how does knowledge of the detailed structural interactions inform immunobiology? A recent number of our structural studies concerning the TCR‐pMHC‐I axis, alongside others in the field, have provided insight into HLA‐I polymorphism, pMHC‐I flexibility, TCR bias, TCR polymorphism, maintenance of self‐tolerance, T‐cell cross‐reactivity, and alloreactivity. Collectively, the data also provide an opportunity to address the structural correlates of MHC‐I restriction. Here, we provide our perspective concerning these advances in the field. Although much key information has been gleaned, the structural data show that some of the key concepts surrounding the TCR‐pMHC‐I interaction remain controversial and unresolved.
The structural basis of HLA‐associated drug hypersensitivity syndromes
Authors: Pompeu Yuri A. , Stewart Jon D. , Mallal Simon , Phillips Elizabeth , Peters Bjoern , Ostrov David A.
Published: October 2012

Recent data suggest alternative mechanisms that promote human leukocyte antigen (HLA)‐associated drug syndromes. Hypersensitive responses have been attributed to drug interactions with HLA molecules, peptides presented by HLA molecules and T‐cell antigen receptors. Definition of an increasing number of HLA‐associated drug syndromes suggests that polymorphism in the antigen‐binding cleft residues influence recognition of specific drugs. Recent data demonstrate that small molecule drugs bind within the antigen‐binding cleft of HLA in a manner that alters the repertoire of HLA‐bound peptide ligands. This drug recognition mechanism permits presentation of self‐peptides to which the host has not been tolerized. This altered repertoire mechanism is analogous to massive polyclonal T‐cell responses occurring in mismatched HLA organ transplantation in which the drug in effect creates a novel HLA allele. Alteration of the self‐peptide repertoire by HLA‐binding small molecules may be the mechanistic basis for a diverse set of deleterious T‐cell responses since the antigen‐binding cleft has structural features that are compatible with binding drug‐like small molecules. Small molecule drugs that bind elements of the trimolecular complex (T‐cell receptor, peptide, and HLA) may cause short‐ and long‐term adverse effects by a diverse set of mechanisms.
Molecular basis of lipid antigen presentation by CD1d and recognition by natural killer T cells
Authors: Girardi Enrico , Zajonc Dirk M.
Published: October 2012

Together with peptides, T lymphocytes respond to hydrophobic molecules, mostly lipids, presented by the non‐classical CD1 family (CD1a–e). These molecules have evolved complex and diverse binding grooves in order to survey different cellular compartments for self and exogenous antigens, which are then presented for recognition to T‐cell receptors (TCRs) on the surface of T cells. In particular, most CD1d‐presented antigens are recognized by a population of lymphocytes denominated natural killer T (NKT) cells, characterized by a strong immunomodulatory potential. Among NKT cells, two major subsets (type I and type II NKT cells) have been described, based on their TCR repertoire and antigen specificity. Here we review recent structural and biochemical studies that have shed light on the molecular details of CD1d‐mediated antigen recognition by type I and II NKT cells, which are in many aspects distinct from what has been observed for peptide major histocompatibility complex‐reactive TCRs.
Treatment of spinal cord compression: are we overusing radiotherapy alone compared to surgery and radiotherapy?
Authors: Hutton Jonathon , Leung John
Published: October 2012

Introduction

This article describes how patients with metastatic spinal cord compression (MSCC) were treated from 2005 to 2011 at a single institution. A comparison is made with an international and standardized scoring system which would have predicted which patients would have a better outcome with neurosurgery in addition to radiotherapy in accordance with current best practice standards.

Method

A retrospective audit of allMSCCpatients presenting from 2005 to 2011 was undertaken. An assessment of outcome was made by using ambulatory assessment tool and by comparing overall survival with published standards.

Results

In all, 39 patients were identified, of whom 37 received radiotherapy alone and two (5%) received surgery and postoperative radiotherapy. The international standardized scoring system predicted 28 (72%) of the 39 patients might have had a better outcome with neurosurgery in addition to radiotherapy.MSCCpatients generally had reasonable outcomes, but selected patients could potentially do better with decompressive surgery.

Conclusion

There is a subset ofMSCCpatients who have poor predicted ambulatory rates after radiotherapy alone and who may benefit from decompressive surgery. It is recommended thatMSCCpatients be categorized according to the international scoring system to identify appropriate candidates for surgical intervention and postoperative radiotherapy or radiotherapy alone.
Mitochondrial Composition, Function and Stress Response in PlantsF
Authors: Jacoby Richard P. , Li Lei , Huang Shaobai , Pong Lee Chun , Millar A. Harvey , Taylor Nicolas L.
Published: October 2012

The primary function of mitochondria is respiration, where catabolism of substrates is coupled to ATP synthesis via oxidative phosphorylation. In plants, mitochondrial composition is relatively complex and flexible and has specific pathways to support photosynthetic processes in illuminated leaves. This review begins with outlining current models of mitochondrial composition in plant cells, with an emphasis upon the assembly of the complexes of the classical electron transport chain (ETC). Next, we focus upon the comparative analysis of mitochondrial function from different tissue types. A prominent theme in the plant mitochondrial literature involves linking mitochondrial composition to environmental stress responses, and this review then gives a detailed outline of how oxidative stress impacts upon the plant mitochondrial proteome with particular attention to the role of transition metals. This is followed by an analysis of the signaling capacity of mitochondrial reactive oxygen species, which studies the transcriptional changes of stress responsive genes as a framework to define specific signals emanating from the mitochondrion. Finally, specific mitochondrial roles during exposure to harsh environments are outlined, with attention paid to mitochondrial delivery of energy and intermediates, mitochondrial support for photosynthesis, and mitochondrial processes operating within root cells that mediate tolerance to anoxia and unfavorable soil chemistries.

image

[ A. Harvey Millar (Corresponding author)]
Adsorptive Depletion of CD14+CD16+ Proinflammatory Monocyte Phenotype in Patients With Generalized Pustular Psoriasis: Clinical Efficacy and Effects on Cytokines
Authors: Fujisawa Tomomi , Murase Kana , Kanoh Hiroyuki , Takemura Masao , Ohnishi Hidenori , Seishima Mariko
Published: October 2012

Generalized pustular psoriasis (GPP) is a subtype of psoriasis with strong association with activated neutrophils. Adsorptive granulocyte and monocyte apheresis (GMA) is an extracorporeal intervention for selective depletion of activated granulocytes and monocytes. However, the immunological mechanism(s) for the effect of GMA on patients is not fully defined yet. We investigated the effects of GMA on the ratio of CD14+CD16+ proinflammatory monocytes/CD14+ monocytes and cytokine/chemokine production by these leukocytes including CXCL8, CCL2, CCL3, CCL4, CCL5 and tumor necrosis factor (TNF)‐α in five patients with active GPP. CD14+CD16+ monocytes were significantly elevated in patients with active GPP, and GMA markedly reduced the CD14+CD16+/CD14+ ratio together with improvement of patients' clinical symptoms. The serum levels of CXCL8, CCL3 and CCL4 were increased in active GPP patients. Likewise, CCL2 production from monocytes was increased in active GPP patients. Further, CCL3 and CCL4 production from monocytes in active GPP patients were reduced after a course of GMA. Serum CCL5 level and the release of CCL5 from monocytes in active GPP were significantly reduced, but TNF‐α level in active GPP was similar to controls. Based on these results, we believe that in addition to neutrophils, elevated CD14+CD16+ proinflammatory monocytes are part of the immune pathology in GPP. Accordingly, selective depletion of CD14+CD16+ monocytes by GMA should be therapeutic in this condition.
Selective Plasma Exchange With Dialysis in Patients With Acute Liver Failure
Authors: Nakae Hajime , Igarashi Toshiko , Tajimi Kimitaka
Published: October 2012

Selective plasma exchange with dialysis is a blood purification therapy in which simple plasma exchange is performed using a selective membrane plasma separator while the dialysate flows out of the hollow fibers. To evaluate the effect of plasma exchange with dialysis, biochemical examination of the blood, for example, the oxidative stress regulation system and interleukin 18 levels, was performed in patients with acute liver failure. We studied four patients with acute liver failure in whom the therapy was performed (nine times in total). The degree of hepatic encephalopathy and interleukin 18 levels decreased significantly after treatment. However, total protein levels did not change significantly. The level of reactive oxygen species and total antioxidant capacity did not change significantly. Plasma exchange with dialysis may be a useful blood purification therapy in cases of acute liver failure in terms of the removal of water‐soluble and albumin‐bound toxins.
Fibrinogen Salvage During DF Thermo Using Evaflux‐5A Plasma Fractionators
Authors: Nakashima Momoko , Yasui Masahide , Ihara Akira
Published: October 2012

DF Thermo, a modified form of double‐filtration plasmapheresis (DFPP), has been used for the treatment of various indications such as arteriosclerosis obliterans (ASO). In case of ASO, fibrinogen is a substance to be removed by DFPP. On the other hand, plasmapheresis for chronic viral hepatitis C became an insurance covered treatment in Japan in April 2008. Since then DFPP has also become a treatment of chronic viral hepatitis C as an adjunctive therapy for the purpose of improving the effect of medication. Therefore, there has been a growing concern in recent years about patients' low fibrinogen levels due to DFPP treatment. With the aim of improving fibrinogen retention by DF Thermo, we examined by in vitro trial, the effects when recirculating the filtrate and elevating its temperature. The trial was conducted using bovine plasma, run through experimental circuits with the same configuration as the clinical setting of the One‐Way method and DF Thermo method. The DF Thermo circuit contained a thermostat, on which the temperature was set to 40°C. Two One‐Way method circuits were prepared with different temperature settings, i.e., 20°C and 40°C. With these three different conditions, variance of the fibrinogen retention under different temperatures and the implementation of recirculation were compared. Results show that the DF Thermo circuit tends to have enhanced the fibrinogen retention compared to the One‐Way method 20°C and 40°C. The explanation is likely as follows: viscosity of plasma reduces when warmed, which in turn helps maintain the permeability of membrane, and the recirculation of the plasma helps prevent membrane fouling, thus more fibrinogen is retained in the DF Thermo method.
Researching Transport Choices: The Possibilities of ‘Mobile Methodologies’ to Study Life‐on‐the‐Move
Authors: HARADA THERESA , WAITT GORDON
Published: October 2012

Personal transport choices are under increased government scrutiny as private cars are attributed with exacerbating carbon emissions. This paper appraises the value of mobile methodologies for researching transport choices through paying closer attention to life‐on‐the‐move. Drawing on key debates within geography regarding the ‘new’ mobilities paradigm that challenge ideas which render drivers as lifeless, this paper illustrates the merits and challenges of designing a project that embraced mobile methodologies to explore the unwilled and unforeseen aspects of driving. Examples are drawn from a project conducted inWollongong,NewSouthWales,Australia.
Ambiguity and relational signals in regulator–regulatee relationships
Authors: Etienne Julien
Published: October 2012

Responsive Regulationtranslated an ongoing academic debate about behavior orientation and regulatory enforcement into a synthetic framework. Yet ethnographic studies reveal that ambiguity pervades regulator–regulatee interactions and suggest that the reality of regulatory encounters may be too ambivalent to fit the picture of the regulatory “game” at the heart of Ayres and Braithwaite's theory. This article proposes to address this ambivalence by drawing the outline of a relational signaling approach to regulatory encounters. The regulatory game is deconstructed into several ideal types of regulator–regulatee relationships. Within each ideal type ambiguity is managed with relational signals, namely behaviors that take a specific signification depending on the nature of the relationship. A relational signaling approach can account for the varying meanings of cooperation, defection, and mutual social control across different regulator–regulatee dyads.
An Optimised 1,10‐Phenanthroline Method for the Determination of Ferrous and Ferric Oxides in Silicate Rocks, Soils and Minerals
Authors: Tarafder Pranab K. , Thakur Raghbendra
Published: October 2012

A precise, accurate and rapid method for the sequential determination of FeO and Fe2O3 in rocks, soils and some non‐refractory minerals by 1,10‐phenanthroline spectrophotometry is described. Fe(II) and Fe(III) were leached from the sample (−200 mesh) using a mixture of NH4HF2 and H2SO4 at 40–80 °C for 10 min on a hot plate. Both Fe(II) and Fe(III) could be conveniently estimated sequentially from the same reaction mixture at the μg g−1 to percentage level. The method is better than the existing wet chemical methods, including the commonly used Pratt's titrimetric redox method, for Fe(II) and Fe(III) determinations in rock and soil samples in terms of precision, accuracy and rapidity. The throughput of the method was very high; at least forty to fifty samples could be estimated easily in a day. The results obtained compare favourably with those obtained by Pratt's method, as well as for certified/recommended values of a set of eleven certified reference materials having FeO and Fe2O3 contents in the range 0.21–14.63% and 0.58–8.48%, respectively. The optimised 1,10 phenanthroline method was found to be accurate to within 0.21% m/m FeO and 0.30% m/m Fe2O3 compared with the literature values of the certified reference materials studied.
Using species combinations in indicator value analyses
Authors: De Cáceres Miquel , Legendre Pierre , Wiser Susan K. , Brotons Lluís
Published: October 2012

Indicator species are often determined using an analysis of the relationship between the species occurrence or abundance values from a set of sites and the classification of the same sites into site groups (habitat types, community types, disturbance states, etc.). It may happen, however, that a particular site group has no indicator species even if its sites have a community composition that is clearly distinct from the sites of other site groups. This motivates an exploration of the indicator value of not only individual species but also species combinations.

Here, we present a novel statistical approach to determine indicators of site groups using species data. Unlike traditional indicator value analysis, we allow indicators to be species combinations in addition to single species. We require that all the species forming the combination must occur in the site to use the combination as an indicator. We present a simple algorithm that identifies the set of indicators (each one being either a single species or a species combination) that show high positive predictive value for the target site group. Moreover, we demonstrate the use of the percentage of sites of the site group where at least one of its valid indicators occurs to determine whether the group can be reliably predicted throughout its range.

Using a simulation study, we show that if two species are not strongly correlated and their frequency in the data set is larger than the frequency of sites belonging to the site group, the joint occurrence of the two species has higher positive predictive value for the site group than the two species taken independently.

We illustrate the proposed method by determining which combinations of vascular plants can be used as indicators for 29 shrubland and forest vegetation types of New Zealand.

The proposed methodology extends traditional indicator value analyses and will be useful to develop multispecies ecological or environmental indicators. Further, it will allow newly surveyed sites to be reliably assigned to previously defined vegetation types.
‘Like doing a jigsaw with half the parts missing’: community pharmacists and the management of cancer pain in the community
Authors: Savage Imogen , Blenkinsopp Alison , Closs S Jose , Bennett Michael I
Published: October 2012

Objectives

The aim was to explore and describe community pharmacists' current and potential place in the cancer pain pathway. Objectives were to describe pharmacists' role in advising patients and their carers on optimum use of opioid drugs for pain relief, identify elements of medicines management that could be modified and identify opportunities for improved communication with patients and other professionals.

Methods

Semi-structured interviews were conducted with 25 community pharmacists in three areas of England. Data were analysed using the Framework method.

Key findings

Pharmacists had no reliable method to identify patients with cancer and no access to disease stage and treatment plan information. There was little evidence of any routine communication with other professionals about patient care. Contact with patients was limited. Access to palliative care medicines could be problematic for patients and medicines use reviews (MURs) were rarely done. Interview data suggested variable levels of knowledge about optimal opioid use in cancer pain or awareness of patients' priorities. For some pharmacists, proactive involvement appeared to be inhibited by fear of discussing emotional and wider social aspects and accounts showed that a wide range of issues and concerns were raised by family members, indicating considerable unmet need. Pharmacists tended to assume information had already been provided by others and felt isolated from other care team members. Many felt that their potential contribution to cancer pain management was constrained but aspired to do more.

Conclusions

There is significant scope for improving access to and interaction with, community pharmacists by people with cancer pain and their families. Finding ways to embed pharmacists within palliative care teams could provide a starting point for a greater contribution to cancer pain management.
Some recommended statistical analytic practices when reliability generalization studies are conducted
Authors: Sánchez‐Meca Julio , López‐López José Antonio , López‐Pina José Antonio
Published: October 2012

Precursors of the reliability generalization (RG) meta‐analytic approach have not established a single preferred analytic method. By means of five real RG examples, we examine how using different statistical methods to integrate coefficients alpha can influence results in RG studies. Specifically, we compare thirteen different statistical models for averaging reliability coefficients and searching for moderator variables that differ in terms of: (a) whether to transform or not the coefficients alpha, and (b) the statistical model assumed, distinguishing between ordinary least squares methods, the fixed‐effect (FE) model, the varying coefficient (VC) model, and several versions of the random‐effects (RE) model. The results obtained with the different methods exhibited important discrepancies, especially regarding moderator analyses. The main criterion for the model choice should be the extent to which the meta‐analyst intends to generalize the results. RE models are the most appropriate when the meta‐analyst aims to generalize to a hypothetical population of past or future studies, while FE and VC models are the most appropriate when the interest focuses on generalizing the results to a population of studies identical to those included in the meta‐analysis. Finally, some guidelines are proposed for selecting the statistical model when conducting an RG study.
Revisiting Case IV: A reassessment of bias and standard errors of Case IV under range restriction
Authors: Fife Dustin A. , Mendoza Jorge L. , Terry Robert
Published: October 2012

In 2004, Hunter and Schmidt proposed a correction (called Case IV) that seeks to estimate disattenuated correlations when selection is made on an unmeasured variable. Although Case IV is an important theoretical development in the range restriction literature, it makes an untestable assumption, namely that the partial correlation between the unobserved selection variable and the performance measure is zero. We show in this paper why this assumption may be difficult to meet and why previous simulations have failed to detect the full extent of bias. We use meta‐analytic literature to investigate the plausible range of bias. We also show how Case IV performs in terms of standard errors. Finally, we give practical recommendations about how the contributions of Hunter and Schmidt (2004) can be extended without making such stringent assumptions.
Being flexible and tuning in: professional caregivers' reflections on management of violent behaviour in nursing homes
Authors: Isaksson Ulf , Åström Sture , Graneheim Ulla H.
Published: October 2012

Aims and objectives

This qualitative, descriptive study aimed to illuminate professional caregivers' reflections on managing residents' violent behaviour in nursing homes.

Background

Violence towards caregivers in the care of older people is a challenge attracting increasing attention in nursing research. However, studies that focus on the approaches caregivers in nursing homes resort to and how they manage everyday care situations involving threats and violent situations are relatively few.

Methods

The study was based on 41 interviews in which the caregivers reflected on their own courses of action in violent situations. The interviews were subjected to qualitative content analysis.

Results

This study showed that caregivers were flexible and in tune with the resident by averting and defusing threatening and violent situations. The caregivers tried to give care in line with the residents' condition, control their own spontaneous reactions and interpret the residents' reactions as communicative signs indicating how they should interact with the resident in the situation. As a last resort, when previous approaches had been unsuccessful, the caregivers took a firm stand, confronted the resident and the violent behaviour more directly, but with respect and with the residents' best interests in mind.

Conclusions

These findings illuminate how caregivers successfully can manage threatening and violent behavior in nursing homes by being flexible and tuning in with the resident but also by taking a firm stand with the residents' best interests in mind. To be flexible and in tune with residents, it is important to know the residents' personal histories. This may mean involving stakeholders, such as family members and friends, in the care of residents with violent behaviour.

Implications for practice

We believe that it is important to involve stakeholders in the care of threatening and violent residents in nursing homes as it is important to get information on the residents' personal history. However, there are risks when interpreting residents' behaviour in light of their personal histories as relatives experiences may be subjective and the information may give the caregivers preconceived ideas about the resident.
Genotype‐specific SNP map based on whole chromosome 3B sequence information from wheat cultivars Arina and Forno
Authors: Shatalina Margarita , Wicker Thomas , Buchmann Jan P. , Oberhaensli Simone , Šimková Hana , Doležel Jaroslav , Keller Beat
Published: October 2012

Agronomically important traits are frequently controlled by rare, genotype‐specific alleles. Such genes can only be mapped in a population derived from the donor genotype. This requires the development of a specific genetic map, which is difficult in wheat because of the low level of polymorphism among elite cultivars. The absence of sufficient polymorphism, the complexity of the hexaploid wheat genome as well as the lack of complete sequence information make the construction of genetic maps with a high density of reproducible and polymorphic markers challenging. We developed a genotype‐specific genetic map of chromosome 3B from winter wheat cultivars Arina and Forno. Chromosome 3B was isolated from the two cultivars and then sequenced to 10‐fold coverage. This resulted in a single‐nucleotide polymorphisms (SNP) database of the complete chromosome. Based on proposed synteny with the Brachypodium model genome and gene annotation, sequences close to coding regions were used for the development of 70 SNP‐based markers. They were mapped on a Arina × Forno Recombinant Inbred Lines population and found to be spread over the complete chromosome 3B. While overall synteny was well maintained, numerous exceptions and inversions of syntenic gene order were identified. Additionally, we found that the majority of recombination events occurred in distal parts of chromosome 3B, particularly in hot‐spot regions. Compared with the earlier map based on SSR and RFLP markers, the number of markers increased fourfold. The approach presented here allows fast development of genotype‐specific polymorphic markers that can be used for mapping and marker‐assisted selection.
Comparative in vitro and experimental in vivo studies of the anti–epidermal growth factor receptor antibody nimotuzumab and its aglycosylated form produced in transgenic tobacco plants
Authors: Rodríguez Meilyn , Pérez Lincidio , Gavilondo Jorge V. , Garrido Greta , Bequet‐Romero Mónica , Hernández Ignacio , Huerta Vivian , Cabrera Gleysin , Pérez Marlene , Ramos Osmani , Leyva René , León Mariela , Ramos Pedro Luis , Triguero Ada , Hernández Abel , Sánchez Belinda , Ayala Marta , Soto Jeny , González Ernesto , Mendoza Osmani , Tiel Kenia , Pujol Merardo
Published: October 2012

A broad variety of foreign genes can be expressed in transgenic plants, which offer the opportunity for large‐scale production of pharmaceutical proteins, such as therapeutic antibodies. Nimotuzumab is a humanized anti–epidermal growth factor receptor (EGFR) recombinant IgG1 antibody approved in different countries for the treatment of head and neck squamous cell carcinoma, paediatric and adult glioma, and nasopharyngeal and oesophageal cancers. Because the antitumour mechanism of nimotuzumab is mainly attributed to its ability to interrupt the signal transduction cascade triggered by EGF/EGFR interaction, we have hypothesized that an aglycosylated form of this antibody, produced by mutating the N297 position in the IgG1 Fc region gene, would have similar biochemical and biological properties as the mammalian‐cell‐produced glycosylated counterpart. In this paper, we report the production and characterization of an aglycosylated form of nimotuzumab in transgenic tobacco plants. The comparison of the plantibody and nimotuzumab in terms of recognition of human EGFR, effect on tyrosine phosphorylation and proliferation in cells in response to EGF, competition with radiolabelled EGF for EGFR, affinity measurements of Fab fragments, pharmacokinetic and biodistribution behaviours in rats and antitumour effects in nude mice bearing human A431 tumours showed that both antibody forms have very similar in vitro and in vivo properties. Our results support the idea that the production of aglycosylated forms of some therapeutic antibodies in transgenic plants is a feasible approach when facing scaling strategies for anticancer immunoglobulins.
Boundaries of Citizenship Behavior: Curvilinearity and Context in the Citizenship and Task Performance Relationship
Authors: Rubin Robert S. , Dierdorff Erich C. , Bachrach Daniel G.
Published: October 2012

Resource allocation, attentional capacity, and role theories all suggest that the well‐documented linear relationship between citizenship behavior and task performance may be more complex than previously believed. In a study of 352 incumbents, we develop hypotheses that propose a curvilinear effect of employee citizenship on task performance. We further argue that this nonmonotonic relationship is different across the targets of citizenship performance and is moderated by several factors from the task context. Results support the curvilinear assertion, indicating that the relationship with task performance inflects when citizenship is more frequently performed. These diminishing returns are amplified when the target of citizenship is the organization compared to the individual. Findings further reveal that the task context elements of accountability and autonomy moderate the curvilinear relationship, whereas ambiguity does not. Implications for a reappraisal of the citizenship–task performance relationship are discussed.
Differential effects of intranasal vaccination with recombinant NcPDIin different mouse models ofNeospora caninuminfection
Authors: Debache K. , Hemphill A.
Published: October 2012

In this study, mice were vaccinated intranasally with recombinantN. caninumprotein disulphide isomerase (NcPDI) emulsified in cholera toxin (CT) or cholera toxin subunit B (CTB) fromVibrio cholerae. The effects of vaccination were assessed in the murine nonpregnant model and the foetal infection model, respectively. In the nonpregnant mice, previous results were confirmed, in that intranasal vaccination with recNcPDI in CT was highly protective, and low cerebral parasite loads were noted upon real‐time PCR analysis. Protection was accompanied by an IgG1‐biased anti‐NcPDI response upon infection and significantly increased expression of Th2 (IL‐4/IL‐10) and IL‐17 transcripts in spleen compared with corresponding values in mice treated with CT only. However, vaccination with recNcPDI in CT did not induce significant protection in dams and their offspring. In the dams, increased splenic Th1 (IFN‐γ/IL‐12) and Th17mRNAexpressions was detected. No protection was noted in the groups vaccinated with recNcPDI emulsified in CTB. Thus, vaccination with recNcPDI in CT in nonpregnant mice followed by challenge infection induced a protective Th2‐biased immune response, while in the pregnant mouse model, the same vaccine formulation resulted in a Th1‐biased inflammatory response and failed to protect dams and their progeny.
Neogene exhumation history of the Bergell massif (southeast Central Alps)
Authors: Mahéo Gweltaz , Gautheron Cécile , Leloup Philippe‐Hervé , Fox Matthew , Tassant‐Got Laurent , Douville Eric
Published: October 2012

Terra Nova, 25, 110–118, 2013

The Bergell pluton is an elongated plutonic body emplaced during Oligocene time along the Insubric line in the central Alps. Reconstruction of its exhumation, based on apatite (U–Th)/He dating and one‐dimensional thermal modelling, provides evidence for a three steps history: (i) following initial fast exhumation from >20–25 to ∼17 Ma, slow down of the exhumation rate until ∼10 Ma, (ii) quiescent phase from ∼10 to ∼5–6 Ma and (iii) an apparent increase of exhumation after ∼5–6 Ma. The decrease in exhumation rate is related with migration of thrusting south of the Bergell area in the Southern Alps (Lombardic phase). Increase in exhumation rate after ∼5–6 Ma is possibly related with Messinian base level drop, enhanced climatic variability (3–4 Ma) and intensification of glaciation (∼0.87 Ma).
Biocontainment in Gain-of-Function Infectious Disease Research
Authors: Lipkin W. Ian
Published: October 2012

The discussion of H5N1 influenza virus gain-of-function research has focused chiefly on its risk-to-benefit ratio. Another key component of risk is the level of containment employed. Work is more expensive and less efficient when pursued at biosafety level 4 (BSL-4) than at BSL-3 or at BSL-3 as modified for work with agricultural pathogens (BSL-3-Ag). However, here too a risk-to-benefit ratio analysis is applicable. BSL-4 procedures mandate daily inspection of facilities and equipment, monitoring of personnel for signs and symptoms of disease, and logs of dates and times that personnel, equipment, supplies, and samples enter and exit containment. These measures are not required at BSL-3 or BSL-3-Ag. Given the implications of inadvertent or deliberate release of high-threat pathogens with pandemic potential, it is imperative that the World Health Organization establish strict criteria for biocontainment that can be fairly applied in the developing world, as well as in more economically developed countries.
Enzymatically Active and Inactive Phosphodiesterases and Diguanylate Cyclases Are Involved in Regulation of Motility or Sessility in Escherichia coli CFT073
Authors: Spurbeck Rachel R. , Tarrien Rebecca J. , Mobley Harry L. T.
Published: October 2012

Intracellular concentration of cyclic diguanylate monophosphate (c-di-GMP), a second messenger molecule, is regulated in bacteria by diguanylate cyclases (DGCs) (synthesizing c-di-GMP) and phosphodiesterases (PDEs) (degrading c-di-GMP). c-di-GMP concentration ([c-di-GMP]) affects motility and sessility in a reciprocal fashion; high [c-di-GMP] typically inhibits motility and promotes sessility. A c-di-GMP sensor domain, PilZ, also regulates motility and sessility. Uropathogenic
Escherichia coli
regulates these processes during infection; motility is necessary for ascending the urinary tract, while sessility is essential for colonization of anatomical sites. Here, we constructed and screened 32 mutants containing deletions of genes encoding each PDE (
n
= 11), DGC (
n
= 13), PilZ (
n
= 2), and both PDE and DGC (
n
= 6) domains for defects in motility, biofilm formation, and adherence for the prototypical pyelonephritis isolate
E. coli
CFT073. Three of 32 mutations affected motility, all of which were in genes encoding enzymatically inactive PDEs. Four PDEs, eight DGCs, four PDE/DGCs, and one PilZ regulated biofilm formation in a medium-specific manner. Adherence to bladder epithelial cells was regulated by [c-di-GMP]. Four PDEs, one DGC, and three PDE/DGCs repress adherence and four DGCs and one PDE/DGC stimulate adherence. Thus, specific effectors of [c-di-GMP] and catalytically inactive DGCs and PDEs regulate adherence and motility in uropathogenic
E. coli
.

IMPORTANCE
Uropathogenic
Escherichia coli
(UPEC) contains several genes annotated as encoding enzymes that increase or decrease the abundance of the second messenger molecule, c-di-GMP. While this class of enzymes has been studied in an
E. coli
K-12 lab strain, these proteins have not been comprehensively examined in UPEC. UPEC utilizes both swimming motility and adherence to colonize and ascend the urinary tract; both of these processes are hypothesized to be regulated by the concentration of c-di-GMP. Here, for the first time, in a uropathogenic strain,
E. coli
CFT073, we have characterized mutants lacking each protein and demonstrated that the uropathogen has diverged from
E. coli
K-12 to utilize these enzymes to regulate adherence and motility by distinct mechanisms.
Lung function in volunteers before and after exposure to trichloramine in indoor pool environments and asthma in a cohort of pool workers
Authors: Nordberg Gunnar F , Lundstrom Nils-Goran , Forsberg Bertil , Hagenbjork-Gustafsson Annika , Lagerkvist Birgitta J-son , Nilsson Johan , Svensson Mona , Blomberg Anders , Nilsson Leif , Bernard Alfred , Dumont Xavier , Bertilsson Helen , Eriksson Kare
Published: October 2012

Objectives

Exposure to trichloramine (NCl3) in indoor swimming-pool environments is known to cause mucous membrane irritation, but if it gives rise to changes in lung function or asthma in adults is not known. (1) We determined lung function in volunteers before and after exposure to indoor pool environments. (2) We studied the occurrence of respiratory symptoms and asthma in a cohort of pool workers.

Design/methods/participants

(1) We studied two groups of volunteers, 37 previously non-exposed healthy persons and 14 pool workers, who performed exercise for 2 h in an indoor pool environment. NCl3in air was measured during pool exposures and in 10 other pool environments. Filtered air exposures were used as controls. Lung function and biomarkers of pulmonary epithelial integrity were measured before and after exposure. (2) We mailed a questionnaire to 1741 persons who indicated in the Swedish census 1990 that they worked at indoor swimming-pools.

Results

(1) In previously non-exposed volunteers, statistically significant decreases in FEV1(forced expiratory volume) and FEV%(p=0.01 and 0.05, respectively) were found after exposure to pool air (0.23 mg/m3of NCl3). In pool workers, a statistically significant decrease in FEV%(p=0.003) was seen (but no significant change of FEV1).In the 10 other pool environments the median NCl3concentration was 0.18 mg/m3. (2) Our nested case/control study in pool workers found an OR for asthma of 2.31 (95% CI 0.79 to 6.74) among those with the highest exposure. Exposure-related acute mucous membrane and respiratory symptoms were also found.

Conclusions

This is the first study in adults showing statistically significant decreases in lung function after exposure to NCl3. An increased OR for asthma among highly exposed pool workers did not reach statistical significance, but the combined evidence supports the notion that current workroom exposures may contribute to asthma development. Further research on sensitive groups is warranted.
Economic crisis and smoking behaviour: prospective cohort study in Iceland
Authors: McClure Christopher Bruce , Valdimarsdóttir Unnur A , Hauksdóttir Arna , Kawachi Ichiro
Published: October 2012

Objective

To examine the associations between the 2008 economic collapse in Iceland and smoking behaviour at the national and individual levels.

Design

A population-based, prospective cohort study based on a mail survey (Health and Wellbeing in Iceland) assessed in 2007 and 2009.

Setting

National mail survey.

Participants

Representative cohort (n=3755) of Icelandic adults.

Main outcome measure

Smoking status.

Results

A significant reduction in the prevalence of smoking was observed from 2007 (pre-economic collapse) to 2009 (postcollapse) in both males (17.4–14.8%; p 0.01) and females (20.0–17.5%; p 0.01) in the cohort (n=3755). At the individual level of analysis, male former smokers experiencing a reduction in income during the same period were less likely to relapse (OR 0.37; 95% CI 0.16 to 0.85). Female smokers were less likely to quit over time compared to males (OR 0.65; 95% CI 0.45 to 0.93). Among male former smokers who experienced an increase in income between 2007 and 2009, we observed an elevated risk of smoking relapse (OR 4.02; 95% CI 1.15 to 14.00).

Conclusions

The national prevalence of smoking in Iceland declined following the 2008 economic crisis. This could be due to the procyclical relationship between macro-economic conditions and smoking behaviour (ie, hard times lead to less smoking because of lower affordability), or it may simply reflect a continuation of trends already in place prior to the crisis. In individual-level analysis, we find that former smokers who experienced a decline in income were less likely to relapse; and conversely, an increase in income raises the risk. However, caution is warranted since these findings are based on small numbers.
Pulmonary metastasectomy for sarcoma: a systematic review of reported outcomes in the context of Thames Cancer Registry data
Authors: Treasure Tom , Fiorentino Francesca , Scarci Marco , Møller Henrik , Utley Martin
Published: October 2012

Objectives

Sarcoma has a predilection to metastasis to the lungs. Surgical excision of these metastases (pulmonary metastasectomy) when possible has become standard practice. We reviewed the published selection and outcome data.

Design

Systematic review of published reports that include survival rates or any other outcome data. Survival data were put in the context of those in a cancer registry.

Setting

Specialist thoracic surgical centres reporting the selection and outcome for pulmonary metastasectomy in 18 follow-up studies published 1991–2010.

Participants

Patients having one or more of 1357 pulmonary metastasectomy operations performed between 1980 and 2006.

Interventions

All patients had surgical pulmonary metastasectomy. A first operation was reported in 1196 patients. Of 1357 patients, 43% had subsequent metastasectomy, some having 10 or more thoracotomies. Three studies were confined to patients having repeated pulmonary metastasectomy.

Primary and secondary outcome measures

Survival data to various time points usually 5 years and sometimes 3 or 10 years. No symptomatic or quality of life data were reported.

Results

About 34% and 25% of patients were alive 5 years after a first metastasectomy operation for bone or soft tissues sarcoma respectively. Better survival was reported with fewer metastases and longer intervals between diagnosis and the appearance of metastases. In the Thames Cancer Registry for 1985–1994 and 1995–2004 5 year survival rates for all patients with metastatic sarcoma were 20% and 25% for bone, and for soft tissue sarcoma 13% and 15%.

Conclusions

The 5 year survival rate among sarcoma patients who are selected to have pulmonary metastasectomy is higher than that observed among unselected registry data for patients with any metastatic disease at diagnosis. There is no evidence that survival difference is attributable to metastasectomy. No data were found on respiratory or any other symptomatic benefit. Given the certain harm associated with thoracotomy, often repeated, better evidence is required.
Knowledge of human papillomavirus and cervical cancer among young women recruited using a social networking site
Authors: Gunasekaran Bharathy , Jayasinghe Yasmin , Fenner Yeshe , Moore Elya E , Wark John D , Fletcher Ashley , Tabrizi Sepehr N , Garland Suzanne M
Published: October 2012

Objectives

Human papillomavirus (HPV) is the commonest sexually transmitted infection. Despite the significant morbidity and mortality associated with HPV-related diseases, previous studies have demonstrated low HPV knowledge in the general population. The objectives of this study were to assess knowledge of cervical cancer and HPV among young women and investigate predictors of high knowledge.

Methods

Female subjects, aged 16–25 years living in Victoria, Australia, were recruited using targeted advertising on Facebook from May to September 2010. A web-based questionnaire was used in a cross-sectional pilot study for a large longitudinal study on women's health, The Young Female Health Initiative.

Results

A total of 278 women completed the questionnaire. The geographic region, indigenous status and socio-economic status of participants were representative of the target population. Overall, 63% knew what HPV was, but only 48% knew it was a common virus. Predictors of high HPV knowledge on multivariate analyses were older age (adjusted OR (aOR) 2.78, 95% CI 0.77 to 10.04), higher socio-economic status (aOR 1.39, 95% CI 0.66 to 2.95), being Australian-born (aOR 3.10, 95% CI 1.15 to 8.36), older age at first vaginal intercourse (aOR 1.84, 95% CI 0.66 to 5.14), awareness of HPV vaccines (aOR 2.16, 95% CI 0.68 to 6.85) and chlamydia (aOR 2.57, 95% CI 1.11 to 5.94), and self-reported HPV vaccination status (aOR 1.83, 95% CI 0.76 to 4.41).

Conclusions

HPV and cervical cancer knowledge among participants were relatively high compared with other studies conducted both worldwide and in Australia. However, deficits in knowledge exist and warrant address in educational initiatives.
TIME DELAY AND CALABI INVARIANT IN CLASSICAL SCATTERING THEORY
Authors: GOURNAY A. , TIEDRA DE ALDECOA R.
Published: October 2012

We define, prove the existence and obtain explicit expressions for classical time delay defined in terms of sojourn times for abstract scattering pairs (H0, H) on a symplectic manifold. As a by-product, we establish a classical version of the Eisenbud–Wigner formula of quantum mechanics. Using recent results of Buslaev and Pushnitski on the scattering matrix in Hamiltonian mechanics, we also obtain an explicit expression for the derivative of the Calabi invariant of the Poincaré scattering map. Our results are applied to dispersive Hamiltonians, to a classical particle in a tube and to Hamiltonians on the Poincaré ball.