bluuebunny/crossref_metadata_2025 huggingface dataset:
Visual function following photodynamic therapy for central serous chorioretinopathy: a comparison of automated macular microperimetry versus best‐corrected visual acuity
Authors: Ehrlich Rita , Mawer Nick P , Mody Christopher H , Brand Christopher S , Squirrell David
Published: July 2011

Abstract

Background:  The study compares the change in best‐corrected visual acuity with the change in central retinal sensitivity before treatment and 6 months after treatment with photodynamic therapy in patients with symptomatic central serous chorio retinopathy.

Design:  Prospective, single‐centre, interventional case series.

Participants:  Eleven consecutive patients with previously untreated central serous chorio retinopathy.

Methods:  Patients had microperimetry and best‐corrected visual acuity recorded before and 6 months after treatment with photodynamic therapy. Refracted best‐corrected visual acuity was assessed at 2 m and adjusted to give the number of letters read at 1 m. Threshold microperimetry was performed by presenting a Goldman III stimulus to 29 points over the central 12° around fixation. Significant visual improvement at 6 months was defined as a best‐corrected visual acuity ≥10 letters or, microperimetry change in mean retinal sensitivity ≥2 decibels (dB).

Main Outcome Measures:  Improvement in best‐corrected visual acuity compared with microperimetry following photodynamic therapy treatment in patients with central serous chorio retinopathy.

Results:  All patients reported a subjective improvement in vision and had complete resolution of subretinal fluid at 6 months. Two patients had a significant improvement in best‐corrected visual acuity (mean ± SD +4.2 ± 5.8 letters), compared with all 11 patients who recorded a significant improvement in mean retinal sensitivity (mean ± SD 4.6 ± 1.9 dB) (P < 0.001).

Conclusions:  These data suggest that compared with microperimetry, best‐corrected visual acuity is underestimating the effectiveness of photodynamic therapy in the treatment of central serous chorio retinopathy.
Investigation into the acceptability of door locking to staff, patients, and visitors on acute psychiatric wards
Authors: Muir‐Cochrane Eimear , van der Merwe Marie , Nijman Henk , Haglund Kristina , Simpson Alan , Bowers Len
Published: July 2011

There is disagreement among psychiatric professionals about whether the doors of acute psychiatric wards should be kept locked to prevent patients from leaving and harming themselves or others. This study explored patient, staff, and visitor perceptions about the acceptability of locking the ward door on acute psychiatric inpatient wards. Interviews were conducted with 14 registered nurses, 15 patients, and six visitors from three different acute wards. Findings revealed commonalities across all groups, with general agreement that locking the door reduced absconding. Staff expressed feelings of guilt, embarrassment, and fear of being blamed when a patient absconded. Staff also reported that open wards created anxious vigilance to prevent an abscond and increased workload in allocating staff to watch the door, whereas staff on partially‐locked doors also perceived an increased workload in letting people in and out of the ward. Patients had mixed feelings about the status of the door, expressing depression, a sense of stigma, and low self‐esteem when the door was locked. The issue of balancing safety and security on acute psychiatric wards against the autonomy of patients is not easily resolved, and requires focused research to develop innovative nursing practices.
Recombinant plant‐expressed tumour‐associated MUC1 peptide is immunogenic and capable of breaking tolerance in MUC1.Tg mice
Authors: Pinkhasov Julia , Alvarez M. Lucrecia , Rigano M. Manuela , Piensook Khanrat , Larios Dalia , Pabst Martin , Grass Josephine , Mukherjee Pinku , Gendler Sandra J. , Walmsley Amanda M. , Mason Hugh S.
Published: July 2011

The human epithelial mucin MUC1 is a heavily glycosylated transmembrane protein that is overexpressed and aberrantly glycosylated on over 90% of human breast cancers. The altered glycosylation of MUC1 reveals an immunodominant peptide along its tandem repeat (TR) that has been used as a target for tumour immunotherapy. In this study, we used the MUC1 TR peptide as a test antigen to determine whether a plant‐expressed human tumour‐associated antigen can be successfully expressed in a plant system and whether it will be able to break self‐antigen tolerance in a MUC1‐tolerant mouse model. We report the expression of MUC1 TR peptide fused to the mucosal‐targeting Escherichia coli enterotoxin B subunit (LTB‐MUC1) in a plant host. Utilizing a rapid viral replicon transient expression system, we obtained high yields of LTB‐MUC1. Importantly, the LTB‐MUC1 fusion protein displayed post‐translational modifications that affected its antigenicity. Glycan analysis revealed that LTB‐MUC1 was glycosylated and a MUC1‐specific monoclonal antibody detected only the glycosylated forms. A thorough saccharide analysis revealed that the glycans are tri‐arabinans linked to hydroxyprolines within the MUC1 tandem repeat sequence. We immunized MUC1‐tolerant mice (MUC1.Tg) with transiently expressed LTB‐MUC1, and observed production of anti‐MUC1 serum antibodies, indicating breach of tolerance. The results indicate that a plant‐derived human tumour‐associated antigen is equivalent to the human antigen in the context of immune recognition.
A Survey on Shape Correspondence
Authors: van Kaick Oliver , Zhang Hao , Hamarneh Ghassan , Cohen‐Or Daniel
Published: July 2011

We review methods designed to compute correspondences between geometric shapes represented by triangle meshes, contours or point sets. This survey is motivated in part by recent developments in space–time registration, where one seeks a correspondence between non‐rigid and time‐varying surfaces, and semantic shape analysis, which underlines a recent trend to incorporate shape understanding into the analysis pipeline. Establishing a meaningful correspondence between shapes is often difficult because it generally requires an understanding of the structure of the shapes at both the local and global levels, and sometimes the functionality of the shape parts as well. Despite its inherent complexity, shape correspondence is a recurrent problem and an essential component of numerous geometry processing applications. In this survey, we discuss the different forms of the correspondence problem and review the main solution methods, aided by several classification criteria arising from the problem definition. The main categories of classification are defined in terms of the input and output representation, objective function and solution approach. We conclude the survey by discussing open problems and future perspectives.
Money‐output Causality Revisited – A Bayesian Logistic Smooth Transition VECM Perspective*
Authors: Gefang Deborah
Published: July 2011

This article proposes a Bayesian approach to examining money‐output causality within the context of a logistic smooth transition vector error correction model. Our empirical results provide substantial evidence that the postwar US money‐output relationship is nonlinear, with regime changes mainly governed by the output growth and price levels. Furthermore, we obtain strong support for nonlinear Granger causality from money to output, although there is also some evidence for models indicating that money is not Granger causal or long‐run causal to output.
Long‐term changes in sickness and health: further evidence from the Hampshire Friendly Society1
Authors: HARRIS BERNARD , GORSKY MARTIN , GUNTUPALLI ARAVINDA MEERA , HINDE ANDREW
Published: July 2011

This article presents new evidence on long‐term trends in sickness rates in England and Wales using data from the Hampshire Friendly Society. In previous work, Edwards, Gorsky, Harris, and Hinde argued that this Society contained a uniquely detailed set of records for the study of individual sickness histories. However, their initial findings were based on the records of a relatively small number of men who joined the Society at different points in time between 1871 and 1912. The current article draws on a much larger body of evidence, based on the records of over 5,500 men who joined between 1824 and 1939. It examines trends in the seasonality of sickness episodes, changes in the relationship between sickness and age, and cause‐specific sickness rates. The results indicate that there was little change in age‐specific morbidity rates over time, but morbidity did increase with age, mainly because older men remained off work for longer, even when they succumbed to the same conditions as men in younger age groups.
How much do we know about market integration in Europe?1
Authors: FEDERICO GIOVANNI
Published: July 2011

The literature on commodity market integration has boomed in the last 15 years, and a sort of consensus is slowly emerging, at least with regard to trends in the last two centuries. This article argues that this consensus is fragile because the research is haunted by serious methodological shortcomings. The results are not really comparable because authors use a bewildering array of statistical techniques, without bothering too much about their assumptions and, more generally, about the theoretical foundations of their work. Market integration is a multi‐faceted process and available techniques can be classified according to the issues they are suitable to tackle. In other words, the methodological choices, together with the available data, have steered the research towards a quite narrow set of issues. Thus we know much less than we suppose. The final section sketches out a research agenda beyond pure measurement.
Doing Good by Splitting Hairs? Analytic Philosophy and Applied Ethics
Authors: GLOCK HANS‐JOHANN
Published: July 2011

abstract

This article explores the connections between analytic philosophy and applied ethics — both historical and substantive. Historically speaking, applied ethics is a child of analytic philosophy. It arose as the result of two factors in the 1960s: the re‐emergence of normative ethics on the one hand, and urgent social and political challenges on the other. But is there a significant substantive link between applied ethics and analytic philosophy? I argue that applied ethics inherited important ‘analytic’ ideals such as clarity and argumentative rigour. At the same time these ideals are not the exclusive preserve of analytic philosophy and applied ethics. Moreover, they are under threat from various trends within applied ethics. In this context I rebut the allegation that the anti‐revisionist reliance on pre‐theoretical moral judgements (aka ‘intuitions’) is less rational than their revisionist dismissal. The article ends with a plea for an analytic approach within applied ethics.
Evolutionary causes and consequences of sequential polyandry in anuran amphibians
Authors: Byrne Phillip G. , Roberts J. Dale
Published: July 2011

Among anuran amphibians (frogs and toads), there are two types of polyandry: simultaneous polyandry, where sperm from multiple males compete to fertilize eggs, and sequential polyandry, where eggs from a single female are fertilized by multiple males in a series of temporally separate mating events, and sperm competition is absent. Here we review the occurrence of sequential polyandry in anuran amphibians, outline theoretical explanations for the evolution of this mating system and discuss potential evolutionary implications. Sequential polyandry has been reported in a limited number of anurans, but its widespread taxonomic and geographic distribution suggests it may be common. There have been no empirical studies that have explicitly investigated the evolutionary consequences of sequential polyandry in anurans, but species with this mating pattern share an array of behavioural, morphological and physiological characteristics, suggesting that there has been common sexual selection on their reproductive system. Sequential polyandry may have a number of adaptive benefits, including spreading the risk of brood failure in unpredictable environments, insuring against male infertility, or providing genetic benefits, either through good genes, intrinsic compatibility or genetic diversity effects. Anurans with sequential polyandry provide untapped opportunities for innovative research approaches that will contribute significantly to understanding anuran evolution and also, more broadly, to the development of sexual‐selection and life‐history theory.
Number and location of venous valves within the popliteal and femoral veins – a review of the literature
Authors: Moore H. M. , Gohel M. , Davies A. H.
Published: July 2011

Although deep venous insufficiency is common and important, the anatomy of deep vein valves is poorly understood. The aim of this study was to investigate the location, number and consistency of venous valves in the femoral and popliteal veins in normal subjects. A detailed literature search of PubMed was performed. Abstracts and selected full text articles were scrutinised and relevant studies published between 1949 and 2010 reporting anatomical details of deep vein valves were included. From 7470 articles identified by the initial search strategy, nine studies with a total of 476 legs were included in this review. All studies were cadaveric and subjects ranged from stillborn fetuses to 103 years of age. Studies suggested that femoral veins contain between one and six valves, and popliteal veins contain between zero and four valves. Deep vein valves were consistently located in the common femoral vein (within 5 cm of the inguinal ligament), the femoral vein (within 3 cm of the deep femoral vein tributary) and in the popliteal vein near the adductor hiatus. Valves are consistently located at specific locations in the deep veins of the leg, although there is often significant variability between subjects. Further anatomical and functional studies using new imaging modalities available should target these areas to identify whether certain valves play a more important role in venous disease. This may guide us in the development of new treatment options for patients with deep venous disease.
Spatially‐dense 3D facial asymmetry assessment in both typical and disordered growth
Authors: Claes Peter , Walters Mark , Vandermeulen Dirk , Clement John Gerald
Published: July 2011

Mild facial asymmetries are common in typical growth patterns. Therefore, detection of disordered facial growth patterns in individuals characterized by asymmetries is preferably accomplished by reference to the typical variation found in the general population rather than to some ideal of perfect symmetry, which rarely exists. This presents a challenge in developing an asymmetry assessment tool that is applicable, without modification, to detect both mild and severe facial asymmetries. In this paper we use concepts from geometric morphometrics to obtain robust and spatially‐dense asymmetry assessments using a superimposition protocol for comparison of a face with its mirror image. Spatially‐dense localization of asymmetries was achieved using an anthropometric mask consisting of uniformly sampled quasi‐landmarks that were automatically indicated on 3D facial images. Robustness, in the sense of an unbiased analysis under increasing asymmetry, was ensured by an adaptive, robust, least‐squares superimposition. The degree of overall asymmetry in an individual was scored using a root‐mean‐squared‐error, and the proportion was scored using a novel relative significant asymmetry percentage. This protocol was applied to a database of 3D facial images from 359 young healthy individuals and three individuals with disordered facial growth. Typical asymmetry statistics were derived and were mainly located on, but not limited to, the lower two‐thirds of the face in males and females. The asymmetry in males was more extensive and of a greater magnitude than in females. This protocol and proposed scoring of asymmetry with accompanying reference statistics will be useful for the detection and quantification of facial asymmetry in future studies.
Fetal surgery for myelomeningocele: progress and perspectives
Authors: DANZER ENRICO , JOHNSON MARK P , ADZICK N SCOTT
Published: July 2011

Myelomeningocele (MMC), one of the most common congenital malformations, can result in severe lifelong disabilities, including paraplegia, hydrocephalus, Chiari II malformation, bowel and bladder dysfunction, skeletal deformations, and neurocognitive impairment. Experimental studies provide compelling evidence that the neurological deficits associated with MMC are not simply caused by incomplete neurulation but rather by the prolonged exposure of the vulnerable neural elements to the intrauterine environment. MMC is the first non‐lethal anomaly considered for fetal surgical intervention, necessitating a careful analysis of risks and benefits. Retrospective and prospective randomized studies suggest that fetal surgery of MMC before 26 weeks of gestation may preserve neuromotor function, reverse hindbrain herniation, and reduce the need for ventriculoperitoneal shunting. However, these studies also demonstrate that fetal surgery is associated with significant maternal and fetal risks. Consequently, additional research is necessary to further elucidate the pathophysiology of MMC, to define the ideal timing and technique of fetal closure, and to evaluate the long‐term implications of prenatal intervention.
PIGMENTS AND PLASTERS FROM THE ROMAN SETTLEMENT OF THAMUSIDA (RABAT, MOROCCO)
Authors: GLIOZZO E. , CAVARI F. , DAMIANI D. , MEMMI I.
Published: July 2011

A total of 22 samples were taken both from plasters still in situ and from collapsed material recovered by French, Italian and Moroccan teams at the Roman settlement of Thamusida (Rabat, Morocco). The sample characterization was obtained using optical microscopy, scanning electron microscopy, image analysis and Raman micro‐spectroscopy. Plaster aggregate was made using a mixture of sands and clays that outcrop nearby, while lime was probably produced using the local limestone crust, as was further verified for the mortars. The plasters from the bath complexes (public buildings) and the Temple à trois cellae (sacred building) were very poorly made, while those from areas VII and XX (private buildings) indicated the involvement of more expert masons. The pigments used were cinnabar, red ochre, yellow ochre, Egyptian blue, green earth, chalk white and carbon black. The overall manufacture was of low quality, and hence perfectly comparable to that observed in other Roman Provinces. With respect to Italy and to other Mediterranean Roman sites, Thamusida fits well within an aesthetic and technical koinè that differentiates sites of the Italian peninsula from those in the Provinces.
Cannabinoids mediate opposing effects on inflammation‐induced intestinal permeability
Authors: Alhamoruni A , Wright KL , Larvin M , O'Sullivan SE
Published: July 2011

BACKGROUND AND PURPOSE Activation of cannabinoid receptors decreases emesis, inflammation, gastric acid secretion and intestinal motility. The ability to modulate intestinal permeability in inflammation may be important in therapy aimed at maintaining epithelial barrier integrity. The aim of the present study was to determine whether cannabinoids modulate the increased permeability associated with inflammation in vitro.

EXPERIMENTAL APPROACH Confluent Caco‐2 cell monolayers were treated for 24 h with IFNγ and TNFα (10 ng·mL−1). Monolayer permeability was measured using transepithelial electrical resistance and flux measurements. Cannabinoids were applied either apically or basolaterally after inflammation was established. Potential mechanisms of action were investigated using antagonists for CB1, CB2, TRPV1, PPARγ and PPARα. A role for the endocannabinoid system was established using inhibitors of the synthesis and degradation of endocannabinoids.

KEY RESULTS Δ9‐Tetrahydrocannabinol (THC) and cannabidiol accelerated the recovery from cytokine‐induced increased permeability; an effect sensitive to CB1 receptor antagonism. Anandamide and 2‐arachidonylglycerol further increased permeability in the presence of cytokines; this effect was also sensitive to CB1 antagonism. No role for the CB2 receptor was identified in these studies. Co‐application of THC, cannabidiol or a CB1 antagonist with the cytokines ameliorated their effect on permeability. Inhibiting the breakdown of endocannabinoids worsened, whereas inhibiting the synthesis of endocannabinoids attenuated, the increased permeability associated with inflammation.

CONCLUSIONS AND IMPLICATIONS These findings suggest that locally produced endocannabinoids, acting via CB1 receptors play a role in mediating changes in permeability with inflammation, and that phytocannabinoids have therapeutic potential for reversing the disordered intestinal permeability associated with inflammation.

LINKED ARTICLES This article is part of a themed section on Cannabinoids in Biology and Medicine. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2012.165.issue‐8. To view Part I of Cannabinoids in Biology and Medicine visit http://dx.doi.org/10.1111/bph.2011.163.issue‐7
Amelioration of renal ischaemia–reperfusion injury by liposomal delivery of curcumin to renal tubular epithelial and antigen‐presenting cells
Authors: Rogers NM , Stephenson MD , Kitching AR , Horowitz JD , Coates PTH
Published: July 2011

BACKGROUND AND PURPOSE Renal ischaemia–reperfusion (IR) injury is an inevitable consequence of renal transplantation, causing significant graft injury, increasing the risk of rejection and contributing to poor long‐term graft outcome. Renal injury is mediated by cytokine and chemokine synthesis, inflammation and oxidative stress resulting from activation of the NF‐κB pathway.

EXPERIMENTAL APPROACH We utilized liposomal incorporation of a potent inhibitor of the NF‐κB pathway, curcumin, to target delivery to renal tubular epithelial and antigen‐presenting cells. Liposomes containing curcumin were administered before bilateral renal ischaemia in C57/B6 mice, with subsequent reperfusion. Renal function was assessed from plasma levels of urea and creatinine, 4 and 24 h after reperfusion. Renal tissue was examined for NF‐κB activity and oxidative stress (histology, immunostaining) and for apoptosis (TUNEL). Cytokines and chemokines were measured by RT‐PCR and Western blotting.

KEY RESULTS Liposomal curcumin significantly improved serum creatinine, reduced histological injury and cellular apoptosis and lowered Toll‐like receptor‐4, heat shock protein‐70 and TNF‐α mRNA expression. Liposomal curcumin also reduced neutrophil infiltration and diminished inflammatory chemokine expression. Curcumin liposomes reduced intracellular superoxide generation and increased superoxide dismutase levels, decreased inducible NOS mRNA expression and 3‐nitrotyrosine staining consistent with limitations in nitrosative stress and inhibited renal tubular mRNA and protein expression of thioredoxin‐interacting protein. These actions of curcumin were mediated by inhibition of NF‐κB, MAPK and phospho‐S6 ribosomal protein.

CONCLUSIONS AND IMPLICATIONS Liposomal delivery of curcumin promoted effective, targeted delivery of this non‐toxic compound that provided cytoprotection via anti‐inflammatory and multiple antioxidant mechanisms following renal IR injury.
Phenotype pharmacology of lower urinary tract α1‐adrenoceptors
Authors: Nishimune A , Yoshiki H , Uwada J , Anisuzzaman ASM , Umada H , Muramatsu I
Published: July 2011

α1‐Adrenoceptors are involved in numerous physiological functions, including micturition. However, the pharmacological profile of the α1‐adrenoceptor subtypes remains controversial. Here, we review the literature regarding α1‐adrenoceptors in the lower urinary tract from the standpoint of α1L phenotype pharmacology. Among three α1‐adrenoceptor subtypes (α1A, α1B and α1D), α1a‐adrenoceptor mRNA is the most abundantly transcribed in the prostate, urethra and bladder neck of many species, including humans. In prostate homogenates or membrane preparations, α1A‐adrenoceptors with high affinity for prazosin have been detected as radioligand binding sites. Functional α1‐adrenoceptors in the prostate, urethra and bladder neck have low affinity for prazosin, suggesting the presence of an atypical α1‐adrenoceptor phenotype (designated as α1L). The α1L‐adrenoceptor occurs as a distinct binding entity from the α1A‐adrenoceptor in intact segments of variety of tissues including prostate. Both the α1L‐ and α1A‐adrenoceptors are specifically absent from Adra1A (α1a) gene‐knockout mice. Transfection of α1a‐adrenoceptor cDNA predominantly expresses α1A‐phenotype in several cultured cell lines. However, in CHO cells, such transfection expresses α1L‐ and α1A‐phenotypes. Under intact cell conditions, the α1L‐phenotype is predominant when co‐expressed with the receptor interacting protein, CRELD1α. In summary, recent pharmacological studies reveal that two distinct α1‐adrenoceptor phenotypes (α1A and α1L) originate from a single Adra1A (α1a‐adrenoceptor) gene, but adrenergic contractions in the lower urinary tract are predominantly mediated via the α1L‐adrenoceptor. From the standpoint of phenotype pharmacology, it is likely that phenotype‐based subtypes such as the α1L‐adrenoceptor will become new targets for drug development and pharmacotherapy.

LINKED ARTICLE This article is commented on by Ventura, pp. 1223–1225 of this issue. To view this commentary visit http://dx.doi.org/10.1111/j.1476‐5381.2011.01663.x
Autocrine activation of human monocyte/macrophages by monocyte‐derived microparticles and modulation by PPARγ ligands
Authors: Bardelli C , Amoruso A , Federici Canova D , Fresu LG , Balbo P , Neri T , Celi A , Brunelleschi S
Published: July 2011

BACKGROUND AND PURPOSE Microparticles (MPs), small membrane‐bound particles originating from different cell types during activation or apoptosis, mediate intercellular communication, exert pro‐coagulant activity and affect inflammation and other pathophysiological conditions. Monocyte‐derived MPs have undergone little investigation and, to our knowledge, have never been evaluated for their possible autocrine effects. Therefore, we assessed the ability of monocyte‐derived MPs to stimulate human monocytes and monocyte‐derived macrophages (MDM).

EXPERIMENTAL APPROACH MPs were generated from supernatants of human monocytes stimulated by the calcium ionophore A23187 (12 µM), and then characterized. Human monocytes and MDM of healthy donors were isolated by standard procedures. Cells were challenged by MPs or phorbol 12‐myristate 13‐acetate (PMA, used as standard stimulus), in the absence or presence of PPARγ agonists and antagonists. Superoxide anion production (measured spectrophotometrically), cytokine release (elisa), PPARγ protein expression (immunoblotting) and NF‐κB activation (EMSA assay) were evaluated.

KEY RESULTS Monocyte‐derived MPs induced, in a concentration‐dependent manner, oxygen radical production, cytokine release and NF‐κB activation in human monocytes and macrophages, with lower effects than PMA. In both cell types, the PPARγ agonists rosiglitazone and 15‐deoxy‐Δ12,14‐prostaglandin J2 (15d‐PGJ2) inhibited MPs‐induced stimulation and this inhibition was reversed by a PPARγ antagonist. In human monocyte/macrophages, MPs as well as rosiglitazone and 15d‐PGJ2 induced PPARγ protein expression.

CONCLUSION AND IMPLICATIONS In human monocyte/macrophages, monocyte‐derived MPs exert an autocrine activation that was modulated by PPARγ ligands, inducing both pro‐inflammatory (superoxide anion production, cytokine release and NF‐κB activation) and anti‐inflammatory (PPARγ expression) effects.
Activated T cells from umbilical cord blood armed with anti‐CD3 × anti‐CD20 bispecific antibody mediate specific cytotoxicity against CD20+ targets with minimal allogeneic reactivity: a strategy for providing antitumor effects after cord blood transplants
Authors: Thakur Archana , Sorenson Carly , Norkina Oxana , Schalk Dana , Ratanatharathorn Voravit , Lum Lawrence G.
Published: July 2011

BACKGROUND: In this study, we asked whether anti‐CD3–activated T cells (ATCs) from cord blood (CB) could be expanded and targeted to solid tumors or hematologic malignancies for infusions after unrelated CB stem cell transplant and whether cord blood ATCs (CBATCs) could reduce alloresponsiveness.

STUDY DESIGN AND METHODS: CB mononuclear cells (MNCs) were activated with anti‐CD3 (20 ng/mL) and expanded for 14 days in interleukin‐2 (100 IU/mL). CBATCs were armed with anti‐CD3 × anti‐CD20 (CD20Bi) or anti‐CD3 × anti‐Her2 (Her2Bi) bispecific antibodies (CBaATCs) and tested for specific cytotoxicity, cytokine secretion, and alloresponsiveness.

RESULTS: Our results show the mean expansion of CBATCs to be 37‐fold after 14 days of culture from either frozen (n = 4) or fresh (n = 4) CB units. Cytotoxicity was optimal when CBATCs were armed with 50 ng of CD20Bi/106 cells. Cytotoxicity peaked between Day 8 and Day 10 for both bispecific antibodies. At an effector‐to‐target ratio of 25:1, the mean cytotoxicities of CBATCs armed with Her2Bi or CD20Bi were 40% (n = 4) and 30% (n = 4), respectively. CBaATCs exhibited peak specific interferon‐γ enzyme‐linked immunosorbent spots on Day 10. CBATCs and CBaATCs suppressed responsiveness to alloantigens by 20% to 50% when compared with normal allogeneic peripheral blood MNC response.

CONCLUSION: We showed that armed CBATCs mediate specific cytotoxicity, secrete low levels of cytokines and chemokines, and demonstrate attenuated response to alloantigens.
Vitamin K‐dependent coagulation factor deficiency in trauma: a comparative analysis between international normalized ratio and thromboelastography (CME)
Authors: Nascimento Bartolomeu , Al Mahoos Mohammed , Callum Jeannie , Capone Antonio , Pacher Jennifer , Tien Homer , Rizoli Sandro
Published: July 2011

BACKGROUND: The use of international normalized ratio (INR) to diagnose vitamin K‐dependent coagulation factor (VitK‐CF) deficiency in trauma has limitations (inability to predict bleeding and long turnaround times). Thromboelastography (TEG) assesses the entire coagulation process. With TEG, reaction time (TEG‐R) is used to assess global coagulation factor activity and takes less than 10 minutes. We assessed the ability of TEG‐R to detect VitK‐CF deficiency in trauma, compared to the INR.

STUDY DESIGN AND METHODS: A total of 219 trauma patients with INR, TEG, and all VitK‐CF measured at admission were included. Demographics and laboratory tests, drugs, blood transfusions, and severity scores were analyzed. Specificity, sensitivity, positive predictive value (PPV), and negative predictive value (NPV) of INR (≥1.3 and ≥1.5) and TEG‐R (>8 min) to diagnose VitK‐CF deficits (≤50%) were calculated. Secondary outcomes included time to INR and TEG results.

RESULTS: Overall, TEG‐R performed worse than INR. TEG‐R had a sensitivity of 33% (95% CI, 16%‐55%), specificity of 95% (95% CI, 91%‐98%), PPV of 47% (95% CI, 23%‐72%), and NPV of 92% (95% CI, 87%‐95%). An INR of 1.5 or greater had a sensitivity of 67% (95% CI, 45%‐84%), specificity of 98% (95% CI, 96%‐99.7%), PPV of 84% (95% CI, 60%‐97%), and NPV of 96% (95% CI, 92%‐98%). An INR of 1.3 or greater also had better sensitivity, PPV, and NPV. For patients on warfarin, the times to INR results and TEG completion were 58 (±23) and 92 (±40) minutes (p = 0.07), respectively. TEG‐R was abnormal in only one patient on warfarin.

CONCLUSION: Our study suggests that TEG‐R is not superior at identifying VitK‐CF deficiency compared to INR in trauma.
Ethnohistorical geography and aboriginal rights litigation in Canada: memoir of an expert witness
Authors: Ray Arthur J.
Published: July 2011

Since the early 1950s, evidence from ethnohistorical geography has played an important role in aboriginal rights claims and litigation in North America. I became involved in Canadian aboriginal and treaty rights litigation over 35 years ago. My participation has included several landmark cases: Regina v. Horseman (treaty rights), Delgamuukw v. Regina (Comprehensive title claim), and Regina v. Powley (Métis rights). Most of the evidence that I have presented over the years has dealt with various aspects of the changing spatial economies of First Nations and Métis communities from Ontario to British Columbia. The Hudson's Bay Company's vast archive has been the primary source for this data.
Predicting the Sintering Curve of Porcelain by Support Vector Regression
Authors: Blanchart Pierre , Azzou Adila , Blanchart Philippe
Published: July 2011

The densification and deformation of porcelain samples during firing with different compression load were investigated by loading dilatometry. Porcelain has a viscous behavior above 1000°C and the global densification is due to the applied stress and due to the behavior of the material itself. Moreover, the density of the powder compact is very influent in thermal transformations and in the global densification rate. Consequently, dilatometry curves are difficult to explain by analytical methods due to the complex response of porcelain and due to the cost and time required to conduct many experiments, which lead to sparse data sets. In this article, Support Vector Regression (SVR) was applied to predict the behavior of porcelain during sintering from a small set of experiments of densification against time, green density, and applied pressure. The SVR method was used to reconstruct any two‐dimensional densification–temperature curves at any applied pressure, from the experimental data. It is shown that SVR is able to calculate a unique optimum from a very limited number of experiments. Moreover, only two main parameters are required for the calculation. Results provide more information about sintering and creep phenomena as extrapolation at very low applied pressure of densification can be performed.
R‐Curve Behavior of 3Y‐TZP at Cryogenic Temperatures
Authors: Xue Weijiang , Xie Zhipeng , Liu Guanwei , Liu Wei , Yi Jian
Published: July 2011

We reported, for the first time, the R‐curve behavior of zirconia ceramic stabilized with 3 mol% Y2O3 (3Y‐TZP) at cryogenic temperatures down to liquid nitrogen temperature of 77 K, measured using direct indentation method and analyzed together with the Weibull statistical analysis of fracture strength data. The results provided a detailed understanding on the effect of decreasing temperature to the steady‐state fracture toughness K∞ that only the increase in the transformation toughening shielding term ΔKT contributed to the K∞ value at cryogenic temperatures, whereas the intrinsic fracture toughness K0 is independent of temperature. A more pronounced R‐curve behavior unanticipated by the conventional interpretation was found at cryogenic temperatures, which could be of great significance to the concomitant increment of the fracture strength and toughness. Therefore, it is believed that 3Y‐TZP could be one of the most promising materials in cryogenic structural applications.
Mandibular Overdentures Supported by 6‐mm Dental Implants: A 1‐Year Prospective Cohort Study
Authors: Guljé Felix , Raghoebar Gerry M. , Ter Meulen Jan‐Willem P. , Vissink Arjan , Meijer Henny J. A.
Published: July 2011

Background: The extremely resorbed edentulous mandible, with a bone height of 8 mm or less, is still a challenge in implant dentistry. Recently, dental implants of 6 mm in length have been developed.

Purpose: The purpose of this 1‐year prospective cohort study was to evaluate treatment outcome of mandibular overdentures supported by four 6‐mm dental implants.

Materials and Methods: Twelve edentulous patients with a mandibular height between 6 and 8 mm participated. The patients were treated with an overdenture supported by four 6‐mm OsseoSpeed™ dental implants (Astra Tech AB, Mölndal, Sweden). Clinical and radiographic parameters were evaluated 1 year after completion of the prosthetic treatment. Patients' satisfaction was scored before implant surgery and 1 year after prosthetic treatment.

Results: One‐year implant survival rate was 96% (two implants were lost). One patient had a fracture of the mandible in the region of one of the implants 3 weeks after implant surgery. Mean scores for plaque, calculus, gingiva, bleeding, and pocket probing depth were low. Patients' satisfaction was high.

Conclusion: One‐year follow‐up data revealed that four 6‐mm dental implants inserted in an extremely resorbed edentulous mandible provided a solid basis for a bar‐retained overdenture.
Long‐Term Clinical, Microbiological, and Radiographic Outcomes of Brånemark™ Implants Installed in Augmented Maxillary Bone for Fixed Full‐Arch Rehabilitation
Authors: De Bruyn Hugo , Bouvry Peter , Collaert Bruno , De Clercq Calix , Persson G. Rutger , Cosyn Jan
Published: July 2011

Purpose: The purpose of this study was to document the long‐term outcome of Brånemark implants installed in augmented maxillary bone and to identify parameters that are associated with peri‐implant bone level.

Material and Methods: Patients of a periodontal practice who had been referred to a maxillofacial surgeon for iliac crest bone grafting in the atrophic maxilla were retrospectively recruited. Five months following grafting, they received 7–8 turned Brånemark implants. Following submerged healing of another 5 months, implants were uncovered and restorative procedures for fixed rehabilitation were initiated 2–3 months thereafter. The primary outcome variable was bone level defined as the distance from the implant‐abutment interface to the first visible bone‐to‐implant contact. Secondary outcome variables included plaque index, bleeding index, probing depth, and levels of 40 species in subgingival plaque samples as identified by means of checkerboard DNA–DNA hybridization.

Results: Nine out of 16 patients (eight females, one male; mean age 59) with 71 implants agreed to come in for evaluation after on average 9 years (SD 4; range 3–13) of function. One implant was deemed mobile at the time of inspection. Clinical conditions were acceptable with 11% of the implants showing pockets ≥ 5 mm. Periodontopathogens were encountered frequently and in high numbers. Clinical parameters and bacterial levels were highly patient dependent. The mean bone level was 2.30 mm (SD 1.53; range 0.00–6.95), with 23% of the implants demonstrating advanced resorption (bone level > 3 mm). Regression analysis showed a significant association of the patient (p < .001) and plaque index (p = .007) with bone level.

Conclusions: The long‐term outcome of Brånemark implants installed in iliac crest‐augmented maxillary bone is acceptable; however, advanced peri‐implant bone loss is rather common and indicative of graft resorption. This phenomenon is patient dependent and seems also associated with oral hygiene.
Bone Graft Healing in Reconstruction of Maxillary Atrophy
Authors: Sjöström Mats , Sennerby Lars , Lundgren Stefan
Published: July 2011

Purpose: Evaluate correlations between volume change for iliac crest bone grafts in maxillary reconstruction (graft volume change [GVC]) and bone mineral density (BMD), bone volume fraction (BVF), hematologic bone metabolic factors (I), and identify indicators of implant failure (II).

Material and Methods: Forty‐six consecutive patients had their edentulous atrophic maxilla reconstructed with free autogenous bone grafts from anterior iliac crest. Endosteal implants were placed 6 months after graft healing. Computer tomography was performed after 3 weeks and 6 months after grafting. Bone biopsies were taken from the internal table of donor site for calculation (BVF), and blood samples were collected. Implant stability was measured at placement with resonance frequency analysis and expressed as implant stability quotient (ISQ). Implant failure was registered.

Results: GVC in onlay bone graft was 37%. The BVF in iliac crest biopsies was 32%. Serum‐IGFBP3 differed with 79% of the samples over normal range. Fifteen patients had one or more implant failures prior to loading (early failures). Forty‐two patients were followed for a minimum of 3 years after implant loading and, in addition, 6/42 patients had one or more implants removed during the follow‐up (late failures). GVC correlated to decreased BMD of lumbar vertebrae L2‐L4 (Kruskal–Wallis test, p = .017). No correlation was found between GVC and hematologic factors (Pearson correlation test) or between GVC and BVF (Kruskal–Wallis test). No correlation was found between ISQ and GVC (Pearson correlation test, p = .865). The association between implant failures and the described factors were evaluated, and no significant correlations were found (unconditional logistic regression).

Conclusion: Onlay bone grafts decrease 37% during initial healing period, which correlate to BMD of lumbar vertebrae L2‐L4. No other evaluated parameters could explain GVC. The evaluated factors could not explain implant failure.
Reimplantation of Dental Implants following Ligature‐Induced Peri‐Implantitis: A Pilot Study in Dogs
Authors: Levin Liran , Zigdon Hadar , Coelho Paulo G. , Suzuki Marcelo , Machtei Eli E.
Published: July 2011

Objectives: This preliminary investigation aimed to evaluate the potential of contaminated implants to reosseointegrate into pristine sites and, in addition, to assess the potential of osseointegration of new implants in peri‐implantitis sockets in a canine model.

Methods: All mandibular premolars were bilaterally extracted from two mongrel dogs. Following 12 weeks of healing, two dental implants were inserted on each hemiarch. Forty‐five days following implant placement, a silk ligature secured with cyanoacrylate was placed around the implants' cervical region in order to induce peri‐implantitis. After another 45 days from ligature placement, the implants were mechanically removed using counter rotation with a ratchet and were reimplanted without any decontamination (neither rinsing nor chemical or mechanical cleaning) in adjacent pristine zones. In sites where implants were removed, new, wider‐diameter implants were placed in the infected sockets. Forty‐five days following reimplantation surgery, the dogs were sacrificed; nondecalcified specimens were processed and toluidine blue stained for morphologic and morphometric (bone‐to‐implant contact [BIC]) assessment under an optical microscope.

In dog 1 all the implants (both in the pristine and in the infected sites) survived and osseointegrated while in dog 2, six out of eight implants failed to osseointegrate and exfoliated. Overall, the mean BIC of all implants was 51.08% (SD 20.54). The mean BIC for the infected implants placed into pristine sites was 51.48% ± 26.29% (SD) and the mean BIC for the new implants in peri‐implantitis socket was 50.58% ± 14.27% (SD).

Conclusions: Within the limitations of this preliminary investigation, especially the small number of animals, osseointegration seems to be achievable both in infected sites and around contaminated implant surfaces.
Alveolar Bone Regeneration around Immediate Implants Using an Injectable nHAC/CSH Loaded with Autogenic Blood‐Acquired Mesenchymal Progenitor Cells: An Experimental Study in the Dog Mandible
Authors: Han Xue , Liu Hongchen , Wang Dongsheng , Su Fang , Zhang Yong , Zhou Wei , Li Shujun , Yang Rui
Published: July 2011

Background: Lack of osseointegration between a dental implant and the walls of the alveolar bone is a common problem in immediate implantation. Injectable tissue‐engineered bone (ITB) may be an effective and minimally invasive solution to the problem. In this study, an injectable bone cement, nHAC/CSH, which consists of nano‐hydroxyapatite/collagen (nHAC) and calcium sulfate hemihydrate (CaSO4.½H2O; CSH) was investigated as a tissue‐engineered scaffold material with blood‐acquired mesenchymal progenitor cells (BMPC) as seeding cells.

Purpose: The aim of the study was to assess the new bone formation around immediate dental implants using nHAC/CSH loaded with dog blood‐acquired mesenchymal progenitor cells (dBMPC) in a canine model.

Materials and Methods: dBMPC were first isolated from peripheral blood of healthy adult dogs. Alizarin red and oil red O staining were then used to evaluate the potential of dBMPC to differentiate into bi‐lineage mesenchymal tissues in vitro. Four healthy mongrel dogs were used in this study. The alveolar bone defects around immediate implants of dogs were created. Each defect was randomly assigned to one of the following three groups: (1) the ITB group (dBMPC + nHAC/CSH); (2) injectable bone cement nHAC/CSH; or (3) no materials (controls). Methylene blue staining was used to examine the bone formation after 3 months.

Results: Studies in vitro revealed that dBMPC could be induced to osteoblasts and adipocytes. The ITB group (dBMPC + nHAC/CSH) showed significantly more bone‐implant contact and bone density than either nHAC/CSH or control groups in the areas with peri‐implant defects 3 months after implantation.

Conclusion: The results indicate that the ITB composed of nHAC/CSH and dBMPC may represent a useful strategy for the clinical reconstruction of bone defects around immediate implantation. However, further investigation is needed involving the use of human BMPC as well as possible use of stem cells.
Foetal Exposure to Food and Environmental Carcinogens in Human Beings
Authors: Myöhänen Kirsi , Vähäkangas Kirsi
Published: July 2011

Abstract:  Exposure to many different chemicals during pregnancy through maternal circulation is possible. Transplacental transfer of xenobiotics can be demonstrated using human placental perfusion. Also, placental perfusion can give information about the placental kinetics as well as metabolism and accumulation in the placenta because it retains the tissue structure and function. Although human placental perfusion has been used extensively to study the transplacental transfer of drugs, the information on food and environmental carcinogens is much more limited. This review deals with the foetal exposure to food and environmental carcinogens in human beings. In particular, human transplacental transfer of the food carcinogens such as acrylamide, glycidamide and nitrosodimethylamine are in focus. Because these carcinogens are genotoxic, the functional capacity of human placenta to induce DNA adduct formation or metabolize these above mentioned CYP2E1 substrates is of interest in this context.
Runaway accretion of metals from compact discs of debris on to white dwarfs
Authors: Rafikov Roman R.
Published: July 2011

It was recently proposed that metal-rich white dwarfs (WDs) accrete their metals from compact discs of debris found to exist around more than a dozen of them. At the same time, elemental abundances measured in atmospheres of some WDs imply vigorous metal accretion at rates up to 1011 g s−1, far in excess of what can be supplied solely by Poynting–Robertson drag acting on such discs of debris. To explain this observation we propose a model, in which rapid transport of metals from the disc on to the WD naturally results from interaction between this particulate disc and a spatially coexisting disc of metallic gas. The latter is fed by evaporation of debris particles at the sublimation radius located at several tens of WD radii. Because of pressure support the gaseous disc orbits the WD slower than the particulate disc. Resultant azimuthal drift between them at speed ≲1 m s−1 causes aerodynamic drag on the disc of solids and drives inward migration of its constituent particles. Upon reaching the sublimation radius, particles evaporate, enhancing the density of the metallic gaseous disc and leading to positive feedback. Under favourable circumstances (low viscosity in the disc of metallic gas and efficient aerodynamic coupling between the discs) a system evolves in a runaway fashion, destroying the discs of debris on time-scale of ∼105 yr, and giving rise to high metal accretion rates up to g s−1, in agreement with observations.