bluuebunny/crossref_metadata_2025 huggingface dataset:
Cytosine–phosphate–guanosine-DNA induces CD274 expression in human B cells and suppresses T helper type 2 cytokine production in pollen antigen-stimulated CD4-positive cells
Authors: Kubo S , Yamada T , Osawa Y , Ito Y , Narita N , Fujieda S
Published: March 2012

Co-stimulatory molecules are important for regulating T cell activation and immune response. CD274 [programmed death ligand 1 (PD-L1), B7-H1] has emerged as an important immune modulator that can block T cell receptor signalling. We have investigated whether PD-L1 and other co-stimulatory ligands could be expressed in human B cells stimulated by cytosine–phosphate–guanosine (CpG)-DNA. CpG-DNA strongly induced the co-inhibitory molecule ligand, PD-L1, of human B cells. Results show that nuclear factor-kappa B (NF-κB) signalling is involved directly in CpG-DNA-induced PD-L1 expression in human B cells. We sought to determine the effect of CpG-DNA-treated B cells on T helper type 2 (Th2) cytokine production in Cry j 1 (Japanese pollen antigen)-stimulated human CD4-positive cells from patients with seasonal allergic rhinitis caused by Japanese cedar pollen. CpG-DNA-treated B cells reduced Cry j 1-induced interleukin (IL)-5 and IL-13 production in CD4-positive cells. When the binding of PD-1 to PD-L1 was inhibited by PD-1-immunoglobulin (Ig), this chimera molecule reversed the previously described reductions in IL-5 and IL-13 production. In contrast, the CpG B-treated B cells increased both interferon (IFN)-γ and IL-12 production in the presence of Cry j 1-stimulated CD4-positive cells. CpG-DNA simultaneously reduced the expression of B7RP-1 [also known as inducible co-stimulator ligand (ICOSL), B7-H2] and the ligand of CD30 (CD30L). These results indicate that CpG-DNA induces co-inhibitory molecule ligand PD-L1 expression in human B cells and PD-L1 can suppress Th2 cytokine production in Cry j 1-stimulated CD4-positive cells, while CpG-DNA increased Th1 cytokine production and reduced the expression of co-stimulatory molecule ligands that can promote Th2 inflammatory responses.
Child protection training, experience, and personal views of dentists in the prefecture of Attica, Greece
Authors: LAUD ALEXANDRA , GIZANI SOTIRIA , MARAGKOU SYGKLITIKI , WELBURY RICHARD , PAPAGIANNOULIS LISA
Published: March 2012

International Journal of Paediatric Dentistry 2013; 23: 64–71

Background.  The abuse and neglect of children constitutes a social phenomenon that unfortunately is widespread irrespective of geographic, ethnic, or social background. Dentists may be the first health professionals to recognize signs of child maltreatment (CM) and have an important role in dealing with such incidents.

Aim.  To describe the training, experience, and personal views of dentists practicing in the Prefecture of Attica regarding the recognition and referral of abused and neglected children.

Design.  A random sample was drawn from a target population of dentists registered with two of the largest dental associations in Greece. The dental practitioners were interviewed by two paediatric dentists using a specially designed questionnaire. Information was collected regarding their awareness on child maltreatment, the frequency of suspected incidents as well as the reasons for not reporting them.

Results.  With a response rate of 83%, findings are reported from 368 interviews (54% male, mean age 43 years). Only 21% of respondents had received training on child protection at undergraduate level. Suspected abuse was 13% and suspected neglect was 35%. Only six of the 368 respondents made an official report of a suspected case of child maltreatment. The most common reason that might prevent a dentist from reporting a case was doubt over the diagnosis (44%). Ninety‐seven per cent of dentists believed that recognition and referral of incidents should be part of undergraduate training.

Conclusions.  Dental practitioners did not feel adequately informed on recognizing and referring child abuse and neglect cases. The low percentage of reported incidents and the lack of legislation indicate a great need for continuously educating dentists on child maltreatment as well as for setting up an organized system in Greece for reporting such incidents to protect the dentist referring the case as well as the child being victimized.
Registered nurses’ attention to and perceptions of pressure ulcer prevention in hospital settings
Authors: Sving Eva , Gunningberg Lena , Högman Marieann , Mamhidir Anna‐Greta
Published: March 2012

Aim.  To describe how registered nurses perform, document and reflect on pressure ulcer prevention in a specific nurse–patient care situation, as well as generally, on hospital wards.

Background.  Registered nurses should provide safe and qualified pressure ulcer prevention, but pressure ulcers remain a problem. Compliance with evidence‐based guidelines impedes pressure ulcer formation.

Design.  A descriptive design with a multimethods approach.

Method.  Nine registered nurses at three wards and hospitals participated. The registered nurses were observed in a specific nurse–patient care situation with patients at risk for pressure ulcers. Interviews followed and patients’ records were reviewed. Quantitative and qualitative data analysis methods were used.

Results.  Pressure ulcer prevention performed by the registered nurses was dependent on the cultural care, which ranged from planned to unplanned prevention. Diversity was found in compliance with evidence‐based guidelines across the wards. Although all patients involved were at risk and the nurses described pressure ulcer prevention as basic care, the nurses’ attention to prevention was lacking. Few prevention activities and no structured risk assessments using risk assessment tools were observed, and few care plans were identified. The lack of attention was explained by registered nurses’ trust in assistant nurses’ knowledge, and prevention was seen as an assistant nurse task.

Conclusion.  Registered nurses paid little attention to pressure ulcer prevention among patients at risk. The planned and unplanned care structures affected the prevention. The nurses trusted and largely delegated their responsibility to the assistant nurses.

Relevance to clinical practice.  Evidence‐based pressure ulcer prevention is fundamental to patient safety. Care quality is created in situations where patients and care providers meet. How registered nurses work with pressure ulcer prevention, their role and communication, particularly with assistant nurses, should be of major concern to them as well as to healthcare managers.
Let us take a Yale open course: a Chinese view of open educational resources provided by institutions in the West
Authors: Xia J.
Published: March 2012

This research examines selected online comments from open courses available on Chinese websites. These courses were created by universities in the West as an effort to build open educational resources (OER) and were recently translated into Chinese and were relocated to some popular Chinese websites. This research aimed to understand why the Chinese viewers value open courses offered by foreign institutions. A statistical cluster analysis was applied to identify patterns of viewers' behaviour. OER were analysed in a social context and the significance of cross‐cultural communication in information sharing and knowledge delivery was explored. It finds that subject, rather than provider, of a course has a positive impact on the number of meaningful comments.
Didanosine (ddI) associates with increased liver fibrosis in adult HIV–HCV coinfected patients
Authors: Suárez‐Zarracina T. , Valle‐Garay E. , Collazos J. , Montes A. H. , Cárcaba V. , Carton J. A. , Asensi V.
Published: March 2012

Summary. The role of exposure to antiretrovirals (ARV) and serum matrix metalloproteases (MMPs) on liver fibrosis (LF) progression in human immunodeficiency virus (HIV) mono or HIV– hepatitis C virus (HCV) coinfection is unclear. Thus, 213 Caucasian adult HIV‐infected patients were studied, 111 of whom had HCV‐coinfection and 68 were HCV‐monoinfected. Patients with ethanol consumption >50 g/day, hepatitis B coinfection, non‐infective liver diseases or HAART adherence <75% were excluded. LF was assessed by transient elastometry (TE, Fibroscan). Serum levels of MMPs (MMP ‐1,‐2,‐3,‐8,‐9,‐10 and ‐13) and their tissue inhibitors (TIMP‐1,‐2 and ‐4) were measured by ELISA microarrays. Associations with LF were statistically analysed. Protease inhibitors, usually administered to patients with advanced LF were excluded from the analysis. Increased LF was significantly associated with d4T (P = 0.006) and didanosine (ddI) use (P = 0.007), months on d4T (P = 0.001) and on ARV (P = 0.025), duration of HIV (P < 0.0001) and HCV infections (P < 0.0001), higher HIV (P = 0.03) and HCV loads (P < 0.0001), presence of lipodystrophy (P = 0.02), male gender (P = 0.02), older age (P = 0.04), low nadir (P = 0.02) and current CD4+T‐cells (P < 0.0001), low gain of CD4+T‐cells after HAART (P = 0.01) and higher MMP‐2 (P = 0.02) and TIMP‐2 serum levels (P = 0.02). By logistic regression the only variables significantly associated with increased LF were: use of ddI (OR 8.77, 95% CI: 2.36–32.26;P = 0.005), male gender (OR 7.75, 95% CI: 2.33–25.64,P = 0.0008), HCV viral load (in log) (OR 3.53, 95% CI: 2.16–5.77;P < 0.0001) and age (in years) (OR 1.21, 95% CI: 1.09–1.34,P = 0.0003). We conclude that only higher HCV viral load, older age, male gender, and use of ddI associated independently with increased LF in our study.
Factors influencing residents’ evaluations of clinical faculty member teaching qualities and role model status
Authors: Arah Onyebuchi A , Heineman Maas J , Lombarts Kiki M J M H
Published: March 2012

Medical Education 2012: 46: 381–389

Objectives  Evaluations of faculty members are widely used to identify excellent or substandard teaching performance. In order to enable such evaluations to be properly interpreted and used in faculty development, it is essential to understand the factors that influence resident doctors’ (residents) evaluations of the teaching qualities of faculty members and their perceptions of faculty members as role‐model specialists.

Methods  We carried out a cross‐sectional survey within a longitudinal study of the System for Evaluation of Teaching Qualities (SETQ) of clinical teachers. The study sample included 889 residents and 1014 faculty members in 61 teaching programmes spanning 22 specialties in 20 hospitals in the Netherlands. Main outcome measures included residents’ (i) global and (ii) specific ratings of faculty member teaching qualities, and (iii) global ratings of faculty members as role‐model specialists. Statistical analysis was conducted using adjusted multivariable logistic generalised estimating equations.

Results  In total, 690 residents (77.6%) completed 6485 evaluations of 962 faculty members, 848 (83.6%) of whom also self‐evaluated. More recently certified faculty members, those who had attended a teacher training programme, and those who spent more time teaching than seeing patients or conducting research were more likely to score highly on most teaching qualities. However, faculty members who had undergone teacher training were less likely to be seen as role models (odds ratio [OR] 0.72, 95% confidence interval [CI] 0.59–0.88). In addition, faculty members were evaluated slightly higher by male than female residents on core teaching domains and overall teaching quality, but were less likely to be seen as role models by male residents (OR 0.80, 95% CI 0.67–0.97). Lastly, faculty members had higher odds of receiving top scores in specific teaching domains from residents in the first 4 years of residency and were less likely to be considered as role models by more senior residents.

Conclusions  Younger faculty members who dedicated more time to teaching, had attended a teacher training programme, and were evaluated by male residents in the early years of residency were more likely to receive higher scores for teaching performance.
Tracking nickel‐adaptive biomarkers in Pisolithus albus from New Caledonia using a transcriptomic approach
Authors: MAJOREL CLARISSE , HANNIBAL LAURE , SOUPE MARIE‐ESTELLE , CARRICONDE FABIAN , DUCOUSSO MARC , LEBRUN MICHEL , JOURAND PHILIPPE
Published: March 2012

The fungus Pisolithus albus forms ectomycorrhizal (ECM) associations with plants growing on extreme ultramafic soils, which are naturally rich in heavy metals such as nickel. Both nickel‐tolerant and nickel‐sensitive isolates of P. albus are found in ultramafic soils in New Caledonia, a biodiversity hotspot in the Southwest Pacific. The aim of this work was to monitor the expression of genes involved in the specific molecular response to nickel in a nickel‐tolerant P. albus isolate. We used pyrosequencing and quantitative polymerase chain reaction (qPCR) approaches to investigate and compare the transcriptomes of the nickel‐tolerant isolate MD06‐337 in the presence and absence of nickel. A total of 1 071 375 sequencing reads were assembled to infer expression patterns of 19 518 putative genes. Comparison of expression levels revealed that 30% of the identified genes were modulated by nickel treatment. The genes, for which expression was induced most markedly by nickel, encoded products that were putatively involved in a variety of biological functions, such as the modification of cellular components (53%), regulation of biological processes (27%) and molecular functions (20%). The 10 genes that pyrosequencing analysis indicated were induced the most by nickel were characterized further by qPCR analysis of both nickel‐tolerant and nickel‐sensitive P. albus isolates. Five of these genes were expressed exclusively in nickel‐tolerant isolates as well as in ECM samples in situ, which identified them as potential biomarkers for nickel tolerance in this species. These results clearly suggest a positive transcriptomic response of the fungus to nickel‐rich environments. The presence of both nickel‐tolerant and nickel‐sensitive fungal phenotypes in ultramafic soils might reflect environment‐dependent phenotypic responses to variations in the effective concentrations of nickel in heterogeneous ultramafic habitats.
Colonic inflammation up‐regulates voltage‐gated sodium channels in bladder sensory neurons via activation of peripheral transient potential vanilloid 1 receptors
Authors: Lei Q. , Malykhina A. P.
Published: March 2012

Background  Primary sensory neurons express several types of ion channels including transient receptor potential vanilloid 1 (TRPV1) and voltage‐gated Na+ channels. Our previous studies showed an increased excitability of bladder primary sensory and spinal neurons triggered by inflammation in the distal colon as a result of pelvic organ cross‐sensitization. The goal of this work was to determine the effects of TRPV1 receptor activation by potent agonists and/or colonic inflammation on voltage‐gated Na+ channels expressed in bladder sensory neurons.

Methods  Sprague–Dawley rats were treated with intracolonic saline (control), resiniferatoxin (RTX, 10−7 mol L−1), TNBS (colonic irritant) or double treatment (RTX followed by TNBS).

Key Results  TNBS‐induced colitis increased the amplitude of total Na+ current by two‐fold and of tetrodotoxin resistant (TTX‐R) Na+ current by 78% (P ≤ 0.05 to control) in lumbosacral bladder neurons during acute phase (3 days post‐TNBS). Instillation of RTX in the distal colon caused an enhancement in the amplitude of total Na+ current at −20 mV from −112.1 ± 18.7 pA/pF (control) to −183.6 ± 27.8 pA/pF (3 days post‐RTX, P ≤ 0.05) without changes in TTX resistant component. The amplitude of net Na+ current was also increased by 119% at day 3 in the group with double treatment (RTX followed by TNBS, P ≤ 0.05 to control) which was significantly higher than in either group with a single treatment.

Conclusions & Inferences  These results provide evidence that colonic inflammation activates TRPV1 receptors at the peripheral sensory terminals leading to an up‐regulation of voltage gated Na+ channels on the cell soma of bladder sensory neurons. This mechanism may underlie the occurrence of peripheral cross‐sensitization in the pelvis and functional chronic pelvic pain.
Blood donation in Morocco: a 20‐year retrospective study of blood collection in the Rabat blood centre
Authors: Tazi‐Mokha A. , Soulaymani A. , Mokhtari A. , Alami R.
Published: March 2012

Objectives: We trace the history of blood donors and the recruitment strategies developed between 1988 and 2008 in the regional blood transfusion centre of Rabat. Beside, we draw a distribution map of the blood donors' population in Morocco during the year 2008.

Background: Limited resource countries face considerable obstacles to ensuring a safe blood supply and safe blood transfusions. Many countries used and some of them still depend on replacement blood donors.

Methods: Data published in this article had been collected from the CRTS of Rabat archives and reports. Data from all the 16 regional blood transfusion centres were collected from the report annually presented by the different regions.

Results: We found that during the 20 years period studied, the number of blood units collected by Rabat recorded many fluctuations. In the mean time, many measures were taken to promote the recruitment of voluntary blood donors. The proportion of these later jumped from 16·55% in 1988 to reach almost 80% in 2008. Beside, the whole country's blood collection map for the year 2008 showed that 190 504 of whole blood units were collected. This means that there are only six donations per 1000 people.

Conclusion: This is the first study conducted in Morocco that provided detailed information on ongoing trends in blood donor profiles. The creation and development of new mobile drive units and maintaining them over time was the key to increase the collection of blood units from voluntary, non‐remunerated blood donors.
How to infer reliable diploid genotypes from NGS or traditional sequence data: from basic probability to experimental optimization
Authors: CHENUIL A.
Published: March 2012

The use of diploid sequence markers is still challenging despite the good quality of the information they provide. There is a common problem to all sequencing approaches [traditional cloning and sequencing of PCR amplicons as well as next‐generation sequencing (NGS)]: when no variation is found within the sequences from a given individual, homozygozity can never be asserted with certainty. As a consequence, sequence data from diploid markers are mostly analysed at the population (not the individual level) particularly in animal studies. This study aims at contributing to solve this. Using the Bayes theorem and the binomial law, useful results are derived, among which: (i) the number of sequence reads per individual (or sequencing depth) which is required to ensure, at a given probability threshold, that some heterozygotes are not considered erroneously as homozygotes, as a function of the observed heterozygozity (Ho) of the locus in the population; (ii) a way of estimating Ho from low coverage NGS data; (iii) a way of testing the null hypothesis that a genetic marker corresponds to a single and diploid locus, in the absence of data from controlled crosses; (iv) strategies for characterizing sequence genotypes in populations minimizing the average number of sequence reads per individual; (v) a rationale to decide which are the variations that one needs to consider along the sequence, as a function of the sequencing depth affordable, the level of polymorphism desired and the risk of sequencing error. For traditional sequencing technology, optimal strategies appear surprisingly different from the usual empirical ones. The average number of sequence reads required to obtain 99% of fully determined genotypes never exceeds six, this value corresponding to the worst situation when Ho equals 0.6. This threshold value of Ho is strikingly stable when the tolerated proportion of nonfully resolved genotypes varies in a reasonable range. These results do not rely on the Hardy–Weinberg equilibrium assumption or on diallelism of nucleotidic sites.
Pathogens of the bark beetle Ips cembrae: microsporidia and gregarines also known from other Ips species
Authors: Holuša J. , Lukášová K. , Wegensteiner R. , Grodzki W. , Pernek M. , Weiser J.
Published: March 2012

The objective of the current study was to identify pathogens of the large larch bark beetle, Ips cembrae, which is a secondary pest that has produced several local outbreaks across Europe in recent years. Beetles were collected from pheromone traps, trap trees and emergence traps (Larix decidua) during 2007 to 2011 at 10 study sites in central Europe. A total of 3379 mature and callow beetles were examined with a light microscope, and only two microsporidian pathogens [Chytridiopsis typographi and a diplokaryotic microsporidium (probably Nosema sp.)] and two gregarines (Gregarina typographi and Mattesia schwenkei) were found. Within the I. cembrae populations, the infection rate for C. typographi ranged from 2 to 58%. Nosema sp. occurred in only two beetles in 2007 (at two study sites). G. typographi was recorded only in Austria and Croatia and only in 1–2% of the beetles in those countries. Mattesia schwenkei was observed solely in Croatia in 0.6% of the beetles in that country. Only one fungal pathogen in the genus Fusarium was found and only in two mature beetles (0.7%) in 2010. The pathogen species found during our study of I. cembrae were very similar to the pathogens previously identified for Ips typographus. No species‐specific pathogen was detected.
Lactation Weight Loss in Primiparous Sows: Consequences for Embryo Survival and Progesterone and Relations with Metabolic Profiles
Authors: Hoving LL , Soede NM , Feitsma H , Kemp B
Published: March 2012

Contents

Our objective was to study reproductive consequences of lactation bodyweight loss occurring in primiparous sows with mild feed restriction and to relate these lactation weight losses and its consequences to metabolic profiles during lactation and subsequent early gestation. After weaning, 47 first‐litter sows were retrospectively assigned to a high– (HWL, >13.8%, n = 24) or low (LWL, ≤13.8%, n = 23)–weight loss group. Thirty‐six animals received an indwelling jugular vein catheter to determine lactational and gestational profiles of insulin‐like growth factor‐1 (IGF‐1), non‐esterified fatty acids (NEFA) and urea and gestational profiles of progesterone. At day 35 after insemination, sows were euthanized and their reproductive tract collected. Pregnancy rate was 75% (18/24) for HWL and 96% (22/23) for LWL sows. High–weight loss sows had a lower number of implantation sites (17.2 ± 0.8 vs 19.5 ± 0.7, respectively, p = 0.03) and a lower embryonic survival (65.6 ± 3.4 vs 77.4 ± 2.9%, p = 0.02), resulting in fewer vital embryos (14.9 ± 0.9 vs 16.8 ± 0.7, p = 0.07) than LWL sows. Progesterone peak values were reached later in HWL than in LWL sows (day 13.4 ± 0.5 vs 12.0 ± 0.5, respectively, p = 0.05). Gestational concentrations of IGF‐1, NEFA and urea were almost identical for HWL and LWL sows, whilst numerical differences were seen during lactation. The current study shows negative consequences of lactational weight loss in mildly feed‐restricted primiparous sows for embryonic survival and shows that these consequences seem only mildly related with metabolic alterations during lactation and not with metabolic alterations during subsequent gestation.
Breast cancer pathology: The impact of molecular taxonomy on morphological taxonomy
Authors: Masuda Shinobu
Published: March 2012

The concept of having an ‘intrinsic subtype,’ or a molecular taxonomy, lets us clearly recognize that breast cancers have characteristically different patterns of gene expression, thus giving newfound significance to morphological taxonomy. In this review, the concept of the ‘intrinsic subtype’ is discussed, research questions are introduced to refine the significance of morphological taxonomy, and a corresponding example is presented between microarray analysis and ‘immunohistochemical subtype,’ or histological taxonomy.
Extended gastritis cystica profunda associated with Epstein‐Barr virus‐positive dysplasia and carcinoma with lymphoid stroma
Authors: Kim Lucia , Kim Joon Mee , Hur Yoon Seok , Shin Yong Woon , Park In Suh , Choi Suk Jin , Han Jee Young , Chu Young Chae , Kim Kyu Ho
Published: March 2012

We report a case of gastritis cystica porfunda (GCP) associated with gastric carcinoma with lymphoid stroma (CLS). There was dysplastic change in the transitional area between GCP and CLS. Epstein‐Barr virus (EBV) in situ hybridization (ISH) revealed positive reaction at the dysplastic area as well as at the CLS area. Immunohistochemical staining disclosed that dysplastic epithelium was similar to GCP in CK 20, MUC5AC, and E‐cadherin expression, but similar to CLS in MUC6, CEA, p53, c‐erb‐B2, and EBV‐ISH expression. Results of the EBV‐ISH suggested that EBV infection may play a role in dysplastic change.
Development of ulcerative colitis and its associated colorectal neoplasia as a model of the organ‐specific chronic inflammation‐carcinoma sequence
Authors: Okayasu Isao
Published: March 2012

The organ‐specific chronic inflammation‐carcinoma sequence was summarized and proposed. As a typical model, the ulcerative colitis (UC)—UC‐associated carcinoma sequence was selected, and the mechanism of development of UC and UC‐associated carcinoma was reviewed, referring mainly to our data. Intestinal commensal bacteria, including Fusobacterium varium, obtained from the colonic mucosa of UC patients, can enter colonic epithelia and induce secretion of inflammatory cytokines, resulting in early inflammatory lesions consisting of cryptitis and crypt abscess. Inflammatory oxidative stress causes epithelial cell DNA‐damage followed by p53 dependent G1 checkpoint activation and overloading, which causes p53 mutation. In long‐standing UC, mucosal remodeling, including possible loss of crosstalk between epithelium and stroma may be critical for the development of UC‐associated carcinoma, as well as accumulation of early p53 mutation at the crypt level and increase of other stem cell mutated crypts, telomere shortening, and genomic instability of epithelial and stromal cells, including subepithelial myofibroblasts (corresponding to colonic stellate cells or Ito cells) and interstitial cells. Thus, the stochastic (probabilistic) pathway to tumor development over time gains commonalty through chronic inflammation stimulation. For the prevention of cancer development, appropriate anti‐inflammatory therapy is important with an accurate assessment of the inflammation status in the colorectum.
Compliance with home non‐invasive ventilation
Authors: CHENG SUET‐LAI , CHAN VERONICA L. , CHU CHUNG‐MING
Published: March 2012

Home non‐invasive ventilation (NIV) is being increasingly employed to treat chronic hypercapnic respiratory failure. However, there is little data on compliance with home NIV. Sixty‐five patients, aged 72.6 ± 9.4 years, who were using home NIV were administered a questionnaire on symptomatology and adverse effects associated with home NIV. Mean daily use of home NIV was 7.3 ± 2.9 h/day, and the median percentage of days on which home NIV was used for ≥4 h/day was 96.7%.
Provisional unicentric experience with an electronic incident reporting form in pediatric anesthesia
Authors: Montobbio Giovanni , Pini‐Prato Alessio , Guida Edoardo , Disma Nicola , Mameli Leila , Avanzini Stefano , Scali Roberto , Tuo Pietro , Jasonni Vincenzo , Mattioli Girolamo
Published: March 2012

Objective:  To present and compare with literature our experience with an electronic anesthesia‐related incident reporting form as a quality control measure at Gaslini Children’s Hospital over a 19‐month period.

Methods:  All events that occurred between March 2009 and September 2010 were recorded. We adopted an electronic reporting form included in the online recording process of every anesthetic procedure. Events were divided into near misses and adverse events. Adverse events were further divided into incidents, minor events, and major events. Patients were divided into three age‐groups: <1, between 1 and 3, and >3 years.

Results:  A total of 12 850 anesthetics were performed. Eight (0.06%) near misses and 108 (0.8%) adverse events were reported. Adverse events occurred more frequently in infants. Of 108 events, 35 (32.4%), 61 (56.5%), and 12 (11.1%) were classified as incidents, minor, and major events, respectively. Of all the adverse events, 66 (61%) were respiratory, 27 (25%) organizational, six (5%) drug‐related, four (4%) cardiocirculatory, and five (5%) miscellaneous.

Conclusions:  Infants were at the highest risk to experience adverse events. Although experimental electronic incident reporting proved to be feasible, there is reason to suspect that there was underreporting of near misses. Overreporting of near miss events may be enhanced by easier and more straightforward reporting forms as well as by better education for anesthetic providers about the importance of recognizing and reporting near misses.
INSTITUTIONALISING TECHNICAL EDUCATION: THE CASE OF WEAVING DISTRICTS IN MEIJI JAPAN
Authors: HASHINO TOMOKO
Published: March 2012

This paper explores the institutionalisation of technical education for the indigenous Japanese weaving industry and studies the necessity of such education for traditional weavers operating in the modern economy of Meiji Japan. It focuses on how these institutions influenced the government's subsequent institutionalisation of formal technical education. Differing from the state's industrial modernisation programmes that were led by the establishment of technical high schools and engineering universities, trade associations played a major role in the institutes in the weaving districts. The paper also highlights the importance of grass roots activities in the successful adoption of new Western technology among locals.
HEALTH, VITAL GOALS, AND CENTRAL HUMAN CAPABILITIES
Authors: VENKATAPURAM SRIDHAR
Published: March 2012

I argue for a conception of health as a person's ability to achieve or exercise a cluster of basic human activities. These basic activities are in turn specified through free‐standing ethical reasoning about what constitutes a minimal conception of a human life with equal human dignity in the modern world. I arrive at this conception of health by closely following and modifying Lennart Nordenfelt's theory of health which presents health as the ability to achieve vital goals. Despite its strengths I transform Nordenfelt's argument in order to overcome three significant drawbacks. Nordenfelt makes vital goals relative to each community or context and significantly reflective of personal preferences. By doing so, Nordenfelt's conception of health faces problems with both socially relative concepts of health and subjectively defined wellbeing. Moreover, Nordenfelt does not ever explicitly specify a set of vital goals. The theory of health advanced here replaces Nordenfelt's (seemingly) empty set of preferences and society‐relative vital goals with a human species‐wide conception of basic vital goals, or ‘central human capabilities and functionings’. These central human capabilities come out of the capabilities approach (CA) now familiar in political philosophy and economics, and particularly reflect the work of Martha Nussbaum. As a result, the health of an individual should be understood as the ability to achieve a basic cluster of beings and doings—or having the overarching capability, a meta‐capability, to achieve a set of central or vital inter‐related capabilities and functionings.
Screening and Signaling in Communication*
Authors: Andina‐Díaz Ascensión
Published: March 2012

In this paper, we analyze a model of repeated strategic communication between a sender and a receiver. The sender has private information on a policy‐relevant variable but does not know the receiver's motives. Together with the desire of the sender to please the receiver and the desire of the receiver to be pleased, the two‐sided incomplete information creates an interesting communication problem in which players can choose to use information strategically. We analyze various modes of communication, which allow for information transmission, and we compare them in terms of both the quality of the policy implemented and the welfare of the players.
Learning Out of Leaders
Authors: Mougeot Mathilde , Picard Dominique , Tribouley Karine
Published: March 2012

The paper investigates the estimation problem in a regression-type model. To be able to deal with potential high dimensions, we provide a procedure called LOL—for learning out of leaders—with no optimization step. LOL is an autodriven algorithm with two thresholding steps. A first adaptive thresholding helps to select leaders among the initial regressors to obtain a first reduction of dimensionality. Then a second thresholding is performed on the linear regression on the leaders. The consistency of the procedure is investigated. Exponential bounds are obtained, leading to minimax and adaptive results for a wide class of sparse parameters, with (quasi) no restriction on the number p of possible regressors. An extensive computational experiment is conducted to emphasize the practical good performances of LOL.
TLR2 and TLR4 gene polymorphisms in Turkish vitiligo patients
Authors: Karaca N. , Ozturk G. , Gerceker B.T. , Turkmen M. , Berdeli A.
Published: March 2012

Background  It has been shown that toll like receptors (TLR) may be involved in some inflammatory skin diseases such as psoriasis, atopic dermatitis. Vitiligo is an acquired pigmentation disorder of unknown aetiology. A number of genes playing a role in inflammatory response may be associated with development of vitiligo.

Objectives  To investigate whether there is an association between TLR 2 and TLR4 gene polymorphisms in Turkish patients with vitiligo.

Methods  A total of 100 patients (59 women and 41 men) with vitiligo and 100 controls (58 women and 42 men) were included in the study. The TLR2 gene Arg753Gln and TLR4 gene Asp299Gly and Thr399Ile polymorphisms were genotyped by using polymerase chain reaction and restriction fragment length polymorphism method. The data were analysed by Mann–Whitney U‐test, chi‐squared test and logistic regression analysis.

Results  Significant difference was found in the distribution of TLR2 Arg753Gln genotype and in the allele frequencies TLR2 753Gln between vitiligo patients and healthy subjects (P < 0.05). The distribution of TLR4 Asp299Gly genotype was significantly higher in the patient group (10%) than in the control group (%2) (P < 0.05). The TLR4 Thr399Ile distribution did not show any difference in both vitiligo and healthy groups.

Conclusions  Our findings suggest that Toll‐like receptor 2 gene Arg753Gln and Toll‐like receptor 4 Asp299Gly gene polymorphisms are associated with vitiligo susceptibility in Turkish patients.
Long‐term outcomes of interruption and retreatment vs. continuous therapy with adalimumab for psoriasis: subanalysis of REVEAL and the open‐label extension study
Authors: Papp K. , Menter A. , Poulin Y. , Gu Y. , Sasso E.H.
Published: March 2012

Background  REVEAL was a 52‐week study of adalimumab for moderate to severe psoriasis. At Week 33, adalimumab‐treated patients with sustained responses (PASI ≥75 at Weeks 16 and 33) were re‐randomized to receive adalimumab or placebo. Subsequently, they could receive adalimumab in an open‐label extension (OLE) study.

Objective  To compare long‐term efficacy and safety of adalimumab 40 mg every other week (eow), given as continuous treatment or with one period of interruption followed by retreatment.

Methods  Patients who were re‐randomized to adalimumab or placebo at REVEAL Week 33 and received ≥1 dose of OLE adalimumab were analysed as the continuous and retreatment groups, respectively, for >2 years of OLE treatment with adalimumab 40 mg eow. LOCF was used for missing efficacy data.

Results  At OLE Weeks 0, 12 and 24, PASI 75 response rates were 84%, 84%, 86% with continuous treatment (N = 233) vs. 45%, 71%, 79% with retreatment (N = 227). Thereafter, efficacies were slightly greater for continuous treatment but similar between groups, with PASI 75 response rates at OLE Week 108 of 75% vs. 73% respectively. Retreatment was most effective for patients with ≥PASI 50 responses when retreatment was initiated. Adverse event rates for retreatment were equal to or lower than those for continuous treatment.

Conclusions  In psoriasis patients with sustained PASI 75 responses to adalimumab, long‐term efficacy of retreatment after a ≤19‐week interruption was similar to efficacy achieved with >3 years continuous treatment. Adalimumab retreatment provided the best results when initiated before responses had declined below PASI 50.
Morphology and development of the placentae in Eulamprus quoyii group skinks (Squamata: Scincidae)
Authors: Murphy Bridget F. , Brandley Matthew C. , Murphy Christopher R. , Thompson Michael B.
Published: March 2012

Frequent evolutionary changes in reproductive mode have produced a wide range of placental structures in viviparous squamate reptiles. Closely related species with different placental structures and resolved phylogenetic relationships are particularly useful for reconstructing how placentae might have transformed during the evolutionary process. We used light microscopy to study placental morphology in mid‐ to late stage embryos of four closely related species of Eulamprus, a genus of viviparous scincid lizards that we had reason to suspect may display significant interspecific variation in placental morphology. Embryos from all four species possess a chorioallantoic placenta, an omphaloplacenta and an interomphalopleuric membrane, characteristics present in other viviparous skinks. However, unlike other viviparous skinks but characteristic of oviparous skinks, the allantois expands to surround the yolk sac in each species, supplanting the omphalopleure with a larger area of chorioallantois until a chorioallantoic placenta surrounds the entire egg in one specimen that is only a few days from birth. All four Eulamprus species share the same extraembryonic membrane morphology, but the cellular morphology of the uterine epithelium in the chorioallantoic placenta and omphaloplacenta varies between species. We determined that the interomphalopleuric membrane is a shared derived character of the Eulamprus quoyii species group. New phylogenetic information indicates that variation in the chorioallantoic placenta is a result of two independent transitions, but that variation in the omphaloplacenta can be explained using a single change within the species studied. Our results indicate that E. quoyii group skinks are a valuable model for investigating the evolution of viviparity, as extraembryonic membrane development in these species shows features characteristic of both oviparous and viviparous skinks.
A national survey of UK health libraries investigating the cost of interlibrary loan services and assessing the accessibility to key orthopaedic journals
Authors: Tahim Arpan , Stokes Oliver , Vedi Vikas
Published: March 2012

Background:  NHS Library Services are utilised by NHS staff and junior trainees to locate scientific papers that provide them with the evidence base required for modern medical practice. The cost of accessing articles can be considerable particularly for junior trainees.

Objectives:  This survey looks at variations in cost of journal article loans and investigates access to particular orthopaedic journals across the country.

Methods:  A national survey of UK Health Libraries was performed. Access to and costs of journals and interlibrary loan services were assessed. Availability of five wide‐reaching orthopaedic journals was investigated.

Results:  Seven hundred and ten libraries were identified. One hundred and ten libraries completed the questionnaire (16.7%). Of these, 96.2% reported free access to scientific journals for users. 99.1% of libraries used interlibrary loan services with 38.2% passing costs on to the user at an average of £2.99 per article. 72.7% of libraries supported orthopaedic services. Journal of Bone and Joint Surgery (British) had greatest onsite availability.

Conclusions:  The study demonstrates fluctuations in cost of access to interlibrary loan services and variation in access to important orthopaedic journals. It provides a reflection of current policy of charging for the acquisition of medical evidence by libraries in the UK.
THE PROBLEMATIZATION OF MEDICAL TOURISM: A CRITIQUE OF NEOLIBERALISM
Authors: SMITH KRISTEN
Published: March 2012

The past two decades have seen the extensive privatisation and marketisation of health care in an ever reaching number of developing countries. Within this milieu, medical tourism is being promoted as a rational economic development strategy for some developing nations, and a makeshift solution to the escalating waiting lists and exorbitant costs of health care in developed nations. This paper explores the need to problematize medical tourism in order to move beyond one dimensional neoliberal discourses that have, to date, dominated the arena. In this problematization, the paper discusses a range of understandings and uses of the term ‘medical tourism’ and situates it within the context of the neoliberal economic development of health care internationally. Drawing on theory from critical medical anthropology and health and human rights perspectives, the paper critically analyzes the assumed independence between the medical tourism industry and local populations facing critical health issues, where social, cultural and economic inequities are widening in terms of access, cost and quality of health care. Finally, medical tourism is examined in the local context of India, critiquing the increasingly indistinct roles played by government and private sectors, whilst linking these shifts to global market forces.
NEWS MEDIA REPORTS OF PATIENT DEATHS FOLLOWING ‘MEDICAL TOURISM’ FOR COSMETIC SURGERY AND BARIATRIC SURGERY
Authors: TURNER LEIGH
Published: March 2012

Contemporary scholarship examining clinical outcomes in medical travel for cosmetic surgery identifies cases in which patients traveled abroad for medical procedures and subsequently returned home with infections and other surgical complications. Though there are peer‐reviewed articles identifying patient deaths in cases where patients traveled abroad for commercial kidney transplantation or stem cell injections, no scholarly publications document deaths of patients who traveled abroad for cosmetic surgery or bariatric surgery. Drawing upon news media reports extending from 1993 to 2011, this article identifies and describes twenty‐six reported cases of deaths of individuals who traveled abroad for cosmetic surgery or bariatric surgery. Over half of the reported deaths occurred in two countries. Analysis of these news reports cannot be used to make causal claims about why the patients died. In addition, cases identified in news media accounts do not provide a basis for establishing the relative risk of traveling abroad for care instead of seeking elective cosmetic surgery at domestic health care facilities. Acknowledging these limitations, the case reports suggest the possibility that contemporary peer‐reviewed scholarship is underreporting patient mortality in medical travel. The paper makes a strong case for promoting normative analyses and empirical studies of medical travel. In particular, the paper argues that empirically informed ethical analysis of ‘medical tourism’ will benefit from rigorous studies tracking global flows of medical travelers and the clinical outcomes they experience. The paper contains practical recommendations intended to promote debate concerning how to promote patient safety and quality of care in medical travel.
The paraoxonase‐1 pathway is not a major bioactivation pathway of clopidogrel in vitro
Authors: Ancrenaz V , Desmeules J , James R , Fontana P , Reny J‐L , Dayer P , Daali Y
Published: March 2012

BACKGROUND AND PURPOSE Clopidogrel is a prodrug bioactivated by cytochrome P450s (CYPs). More recently, paraoxonase‐1 (PON1) has been proposed as a major contributor to clopidogrel metabolism. The purpose of this study was to assess the relative contribution of CYPs and PON1 to clopidogrel metabolism in vitro.

EXPERIMENTAL APPROACH Clopidogrel metabolism was studied in human serum, recombinant PON1 enzyme (rePON1), pooled human liver microsomes (HLMs), HLMs with the CYP2C19*1/*1 genotype and HLMs with the CYP2C19*2/*2 genotype. Inhibition studies were also performed using specific CYP inhibitors and antibodies. Clopidogrel and its metabolites were measured using LC/MS/MS method.

KEY RESULTS PON1 activity was highest in the human serum and there was no difference in PON1 activity between any of the HLM groups. The production of clopidogrel's active metabolite (clopidogrel‐AM) from 2‐oxo‐clopidogrel in pooled HLMs was approximately 500 times that in serum. When 2‐oxo‐clopidogrel was incubated with rePON1, clopidogrel‐AM was not detected. Clopidogrel‐AM production from 2‐oxo‐clopidogrel was lower in CYP2C19*2/*2 HLMs compared with CYP2C19*1/*1 HLMs, while PON1 activity in HLMs with both genotypes was similar. Moreover, incubation with inhibitors of CYP3A, CYP2B6 and CYP2C19 significantly reduced clopidogrel bioactivation while a PON1 inhibitor, EDTA, had only a weak inhibitory effect.

CONCLUSION AND IMPLICATIONS This in vitro study shows that the contribution of PON1 to clopidogrel metabolism is limited at clinically relevant concentrations. Moreover, CYP2C19, CYP2B6 and CYP3A play important roles in the bioactivation of clopidogrel.
Platelet‐derived growth factor‐BB induces cystathionine γ‐lyase expression in rat mesangial cells via a redox‐dependent mechanism
Authors: Hassan Mohamed I. , Boosen Meike , Schaefer Liliana , Kozlowska Jowita , Eisel Florian , von Knethen Andreas , Beck Martina , Hemeida Ramadan A. M. , El‐Moselhy Mohamed A. M. , Hamada Farid M. A. , Beck Karl‐Friedrich , Pfeilschifter Josef
Published: March 2012

BACKGROUND AND PURPOSE So far, there is only limited information about the regulation of the endogenous synthesis of hydrogen sulfide (H2S), an important gaseous signalling molecule. This study was done to evaluate the redox‐dependent signalling events that regulate the expression of the H2S synthesising enzyme cystathionine‐γ‐lyase (CSE) in rat mesangial cells.

EXPERIMENTAL APPROACH The effects of platelet‐derived growth factor (PDGF)‐BB and antioxidants on CSE expression and activity in cultured rat renal mesangial cells were assessed. Activity of nuclear factor erythroid‐2‐related factor‐2 (Nrf2) was measured as the binding capacity to a radiolabelled consensus element by electrophoretic mobility shift assay (EMSA). Furthermore, CSE and Nrf2 expression was analysed in a rat model of anti‐Thy‐1‐induced glomerulonephritis by immunohistochemistry.

KEY RESULTS Treatment of mesangial cells with PDGF‐BB resulted in a marked time‐ and dose‐dependent up‐regulation of CSE mRNA and protein levels, as well as CSE activity accompanied with increased formation of reactive oxygen species. Remarkably, co‐administration of antioxidants, such as N‐acetylcysteine, ebselen or diphenylene iodonium chloride, drastically reduced PDGF‐BB‐induced CSE expression. PDGF‐BB induced binding of Nrf2 to a corresponding consensus antioxidant element in a redox‐dependent manner. Furthermore, PDGF‐BB‐induced CSE expression in mouse mesangial cells was completely abolished in Nrf2 knockout mice compared with wild‐type mice. In a rat model of anti‐Thy‐1‐induced proliferative glomerulonephritis, we observed a marked up‐regulation of CSE protein paralleled by a stabilization of Nrf2 protein.

CONCLUSIONS AND IMPLICATIONS PDGF‐BB regulated CSE via a redox‐mediated activation of Nrf2. Such action would aid the resolution of glomerular inflammatory diseases.

LINKED ARTICLE This article is commented on by Gallyas, pp. 2228–2230 of this issue. To view this commentary visit http://dx.doi.org/10.1111/j.1476‐5381.2012.01976.x