bluuebunny/crossref_metadata_2025 huggingface dataset:
Erythropoietin enhances immunostimulatory properties of immature dendritic cells
Authors: Rocchetta F , Solini S , Mister M , Mele C , Cassis P , Noris M , Remuzzi G , Aiello S
Published: June 2011

Dendritic cells (DCs) are the most potent antigen-presenting cells and play a crucial role by modulating the T cell immune response against infective agents, tumour antigens and alloantigens. The current study shows that differentiating bone marrow (BM)-derived DCs but not fully differentiated DCs are targets of erythropoietin (EPO). Indeed, DCs emerging from rat bone marrow, but not splenic DCs, express the EPO receptor (Epo-R) and respond to EPO stimulation displaying a more activated phenotype with increased CD86, CD40 and interleukin (IL)-12 expression levels and a higher allostimulatory capacity on T cells than untreated DCs. Moreover, results here presented show that EPO up-regulates Toll-like receptor (TLR)-4 in differentiating DCs rendering these cells more sensitive to stimulation by the TLR-4 ligand lipopolysaccharide (LPS). Indeed, DCs treated with EPO and then stimulated by LPS were strongly allostimulatory and expressed CCR7, CD86, CD40, IL-12 and IL-23 at higher levels than those observed in DCs stimulated with LPS alone. It is tempting to speculate that EPO could act as an additional danger signal in concert with TLR-4 engagement. Thus, EPO, beyond its erythropoietic and cytoprotective effects, turns out to be an immune modulator.
Variation in repeat length and heteroplasmy of the mitochondrial DNA control region along a core–edge gradient in the eastern spadefoot toad (Pelobates syriacus)
Authors: MUNWES INBAR , GEFFEN ELI , FRIEDMANN ADAM , TIKOCHINSKI YARON , GAFNY SARIG
Published: June 2011

Peripheral populations are those situated at the distribution margins of a species and are often subjected to more extreme abiotic and biotic conditions than those at the core. Here, we hypothesized that shorter repeat length and fewer heteroplasmic mitochondrial DNA (mtDNA) copies, which are associated with more efficient mitochondrial function, may be related to improved survival under extreme environmental conditions. We sampled eastern spadefoot toads (mostly as tadpoles) from 43 rain pools distributed along a 300‐km gradient from core to edge of the species’ distribution. We show that mean pool tandem repeat length and heteroplasmy increase from edge to core, even after controlling for body size. We evaluate several alternative hypotheses and propose the Fisher hypothesis as the most likely explanation. However, additional sequential sampling and experimental studies are required to determine whether selection under extreme conditions, or alternative mechanisms, could account for the gradient in heteroplasmy and repeat length in the mtDNA control region.
Reconstructing demographic events from population genetic data: the introduction of bumblebees to New Zealand
Authors: LYE G. C. , LEPAIS O. , GOULSON D.
Published: June 2011

Four British bumblebee species (Bombus terrestris, Bombus hortorum, Bombus ruderatus and Bombus subterraneus) became established in New Zealand following their introduction at the turn of the last century. Of these, two remain common in the United Kingdom (B. terrestris and B. hortorum), whilst two (B. ruderatus and B. subterraneus) have undergone marked declines, the latter being declared extinct in 2000. The presence of these bumblebees in New Zealand provides an unique system in which four related species have been isolated from their source population for over 100 years, providing a rare opportunity to examine the impacts of an initial bottleneck and introduction to a novel environment on their population genetics. We used microsatellite markers to compare modern populations of B. terrestris, B. hortorum and B. ruderatus in the United Kingdom and New Zealand and to compare museum specimens of British B. subterraneus with the current New Zealand population. We used approximate Bayesian computation to estimate demographic parameters of the introduction history, notably to estimate the number of founders involved in the initial introduction. Species‐specific patterns derived from genetic analysis were consistent with the predictions based on the presumed history of these populations; demographic events have left a marked genetic signature on all four species. Approximate Bayesian analyses suggest that the New Zealand population of B. subterraneus may have been founded by as few as two individuals, giving rise to low genetic diversity and marked genetic divergence from the (now extinct) UK population.
CsgE is a curli secretion specificity factor that prevents amyloid fibre aggregation
Authors: Nenninger Ashley A. , Robinson Lloyd S. , Hammer Neal D. , Epstein Elisabeth Ashman , Badtke Matthew P. , Hultgren Scott J. , Chapman Matthew R.
Published: June 2011

Curli are extracellular amyloid fibres produced by Escherichia coli that are critical for biofilm formation and adhesion to biotic and abiotic surfaces. CsgA and CsgB are the major and minor curli subunits, respectively, while CsgE, CsgF and CsgG direct the extracellular localization and assembly of curli subunits into fibres. The secretion and stability of CsgA and CsgB are dependent on the outer membrane lipoprotein CsgG. Here, we identified functional interactions between CsgG and CsgE during curli secretion. We discovered that CsgG overexpression restored curli production to a csgE strain under curli‐inducing conditions. In antibiotic sensitivity and protein secretion assays, CsgG expression alone allowed translocation of erythromycin and small periplasmic proteins across the outer membrane. Coexpression of CsgE with CsgG blocked non‐specific protein and antibiotic passage across the outer membrane. However, CsgE did not block secretion of proteins containing a 22‐amino‐acid putative outer membrane secretion signal of CsgA (A22). Finally, using purified proteins, we found that CsgE prohibited the self‐assembly of CsgA into amyloid fibres. Collectively, these data indicate that CsgE provides substrate specificity to the curli secretion pore CsgG, and acts directly on the secretion substrate CsgA to prevent premature subunit assembly.
Mental health advocacy and African and Caribbean men: good practice principles and organizational models for delivery
Authors: Newbigging Karen , McKeown Mick , French Beverley
Published: June 2011

Background  Advocacy has a critical role to play in addressing concerns about access to appropriate mental health care and treatment for African and Caribbean men.

Aim  To investigate good practice principles and organizational models for mental health advocacy provision for African and Caribbean men.

Study design  The study consisted of: (i) A systematic literature review. Bibliographic and internet searching was undertaken from 1994 to 2006. The inclusion criteria related to mental health, advocacy provision for African and Caribbean men. (ii) Four focus groups with African and Caribbean men to explore needs for and experiences of mental health advocacy. (iii) An investigation into current advocacy provision through a survey of advocacy provision in England, Wales and Northern Ireland. (iv) Twenty‐two qualitative stakeholder interviews to investigate the operation of mental health advocacy for this client group. The study was undertaken in partnership with two service user‐led organizations and an African Caribbean mental health service.

Results  Primary research in this area is scant. Mainstream mental health advocacy services are often poor at providing appropriate services. Services developed by the Black Community and voluntary sector are grounded in different conceptualizations of advocacy and sharper understanding of the needs of African and Caribbean men. The lack of sustainable funding for these organizations is a major barrier to the development of high‐quality advocacy for this group, reflecting a lack of understanding about their distinctive role.

Conclusions  The commissioning and provision of mental health advocacy needs to recognize the distinct experiences of African and Caribbean men and develop capacity in the range of organizations to ensure equitable access.
Stages of change and health‐related quality of life among employees of an institution
Authors: Liau Siow Yen , Shafie Asrul A , Ibrahim Mohamed Izham Mohamed , Hassali Mohamed Azmi , Othman Ahmad Tajuddin , Mohamed Mohamad Haniki Nik , Hamdi Menal A
Published: June 2011

Background  Transtheoretical Model of change has been used successfully in promoting behaviour change.

Objective  To examine the relationships between health‐related quality of life (HRQoL) scores with the stages of change of adequate physical activity and fruit and vegetables intake.

Design  This was a cross‐sectional study conducted among employees of the main campus and Engineering campus of Universiti Sains Malaysia (USM) during October 2009 and March 2010. Main variables studied: Data on physical activity and fruit and vegetable intake was collected using the WHO STEPS instrument for chronic disease risk factors surveillance. The Short Form‐12 health survey (SF‐12) was used to gather information on participants’ HRQoL. The current stages of change are measured using the measures developed by the Pro‐Change Behaviour Systems Incorporation. Statistical analysis: One way ANOVA and its non‐parametric equivalent Kruskal‐Wallis were used to compare the differences between SF‐12 scores with the stages of change.

Results  A total of 144 employees were included in this analysis. A large proportion of the participants reported inadequate fruits and vegetable intake (92.3%) and physical activity (84.6%). Mean physical and mental component scores of SF‐12 were 50.39 (SD = 7.69) and 49.73 (SD = 8.64) respectively. Overall, there was no statistical significant difference in the SF‐12 domains scores with regards to the stages of change for both the risk factors.

Conclusions  There were some evidence of positive relationship between stages of change of physical activity and fruit and vegetable intake with SF‐12 scores. Further studies need to be conducted to confirm this association.
Patients’ decision making to accept or decline an implantable cardioverter defibrillator for primary prevention of sudden cardiac death
Authors: Carroll Sandra L. , Strachan Patricia H. , de Laat Sonya , Schwartz Lisa , Arthur Heather M.
Published: June 2011

Background  Patients are offered implantable defibrillators (ICDs) for the prevention of sudden cardiac death (SCD). However, patients’ decision‐making process (DMP) of whether or not to accept an ICD has not been explored. We asked patients about their decision making when offered an ICD.

Design/Setting  A grounded theory methodology was employed. Patients were recruited from three ICD centres. Those who received an ICD underwent interviews the first month after implant. Declining patients had interviews at their convenience. In‐depth analysis of transcripts was completed. Identified themes were placed along process pathways in a DMP model and tested.

Findings  Forty‐four patients consented to participate (25% women). Thirty‐four accepted an ICD and 10 (23%) declined. Ages ranged from 26 to 87 (mean = 65; SD = 12.5). Participants were retired (65%), had ischaemic heart disease (64%) and some post‐secondary education (52%). The DMP was triggered when patient’s risk for SCD was communicated. The physician’s recommendation and a new awareness SCD risk were motivators to accept the ICD. Patient’s decision‐making approaches fell along a continuum, from active and engaged to passive and indifferent. Patient’s approaches were influenced most by the following: (i) trust; (ii) social influences and (iii) health state.

Conclusions  Health‐care providers need to recognize the DMP pathways in which ICD candidacy and SCD risk are understood. The factors that influence a patient’s decision warrant discussion pre‐implant. It is imperative that patients comprehend the meaning of ICD candidacy to make an informed decision. Participants did not recall alternatives to receiving ICD therapy.
Efficacy of adipose tissue‐derived mesenchymal stem cells for fulminant hepatitis in mice induced by concanavalin A
Authors: Kubo Norihito , Narumi Shunji , Kijima Hiroshi , Mizukami Hiroki , Yagihashi Soroku , Hakamada Kenichi , Nakane Akio
Published: June 2011

Background and Aim:  Fulminant hepatitis is mainly caused by excessive immune response‐mediated liver injury and its definitive therapy is liver transplantation. Mesenchymal stem cells, one of the adult stem cells, have an immunomodulatory effect on immune cells and reside in various tissues. The aim of this study was to investigate a therapeutic effect of adipose tissue‐derived mesenchymal stem cells (ASCs) on fulminant hepatitis induced by concanavalin A (ConA).

Methods:  The ASCs were isolated from adipose tissues of BALB/c mice and confirmed by detection of cell surface markers and induction of multi‐lineage differentiation. BALB/c mice were injected with ConA and treated with ASCs, phosphate buffered saline (PBS) or splenocytes (SPLCs). Survival rates, levels of serum liver enzymes, titers of serum cytokines, histopathology and localization of ASCs were investigated.

Result:  The survival rate of ASC‐injected mice significantly increased compared to PBS or SPLC‐injected mice. This effect was dependent on doses and timing of ASCs injected. Improvement of liver enzyme levels, histopathological changes and suppression of inflammatory cytokine production were observed in ASC‐injected mice. Fluorescent stained ASCs were detected in inflammatory liver, but not in normal liver.

Conclusion:  These results suggest that ASC treatment has a high potential to be an innovative therapy for fulminant hepatitis.
Endosonography‐guided fine needle aspiration cytology of intra‐abdominal lymph nodes with unknown primary in a tuberculosis endemic region
Authors: Dhir Vinay , Mathew Praveen , Bhandari Suryaprakash , Bapat Mukta , Kwek Andrew , Doctor Vatsala , Maydeo Amit
Published: June 2011

Background and Aim:  Intra‐abdominal lymphadenopathy poses a diagnostic and management challenge in highly endemic regions for tuberculosis. Opting for empirical anti‐tuberculosis treatment raises the risk of wrong or delayed treatment. Endoscopic ultrasound‐guided fine needle aspiration (EUS‐FNA) is the procedure of choice for tissue acquisition from peri‐luminal lymph nodes. We studied the utility of EUS‐FNA in evaluating intra‐abdominal lymph nodes of unknown etiology, in the setting of high endemicity of tuberculosis.

Methods:  Consecutive patients with intra‐abdominal lymph nodes of unknown etiology underwent EUS‐FNA using a 22‐gauge needle. Final diagnosis was made on surgical histology or on 6‐months follow‐up. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and diagnostic yield were calculated.

Results:  Sixty‐six patients were included. Final diagnoses were tuberculosis, 35 (53%); metastatic adenocarcinoma, 11 (16.7%); lymphoma, three (4.5%); carcinoid, one (1.5%) and reactive nodes, 16 (24.2%). EUS‐FNA provided a diagnosis in 61 patients (92.4%). Sensitivity, specificity, PPV and NPV for diagnosing tuberculosis via EUS‐FNA were 97.1%, 100%, 100% and 96.9%, respectively. In 10 (15.2%) patients receiving empirical anti‐tuberculosis treatment, the final diagnoses were metastatic adenocarcinoma (5), lymphoma (2), carcinoid (1) and reactive adenopathy (2).

Conclusion:  Despite being in a highly endemic area, almost half of the patients studied have a non‐tuberculosis etiology. EUS‐FNA is a safe and accurate procedure for establishing the diagnosis of unexplained intra‐abdominal lymphadenopathy.
Optimal follow‐up time to determine the sustained virological response in patients with chronic hepatitis C receiving pegylated‐interferon and ribavirin
Authors: Namikawa Masashi , Kakizaki Satoru , Yata Yutaka , Yamazaki Yuichi , Horiguchi Norio , Sato Ken , Takagi Hitoshi , Mori Masatomo
Published: June 2011

Background and Aim:  This study evaluated whether the assessment of hepatitis C virus (HCV)‐RNA at 12 weeks (FW+12) post‐treatment follow‐up was as applicable as FW+24 to evaluate sustained virological response (SVR) using the highly sensitive real‐time polymerase chain reaction (PCR) HCV assay.

Methods and Results:  Two hundred and twenty‐two patients with chronic hepatitis C were included in this study. Pegylated interferon (Peg‐IFN) and ribavirin were administered for 24–72 weeks based on the genotype and viral load. Serum HCV‐RNA was measured using real‐time PCR at pretreatment, the end of treatment, FW+4, FW+8, FW+12, FW+16, FW+20 and FW+24. Two hundred patients had a virological response at the end of treatment. One hundred and forty‐eight of 200 (74.0%) patients with a virological response at the end of treatment had an SVR at the FW+24. The positive predictive value (PPV) to identify patients with SVR at FW+4, FW+8, FW+12 was 87.1, 96.1, 98.0%, respectively. The viral load showed a reversion to the basal level as early as 8 weeks in relapse patients. There were only three patients who relapsed after FW+12 and all three of these patients were females with genotype Ib and a high viral load.

Conclusion:  The assessment of serum HCV‐RNA FW+12, using the highly sensitive real‐time PCR assay, is almost as effective as FW+24 to predict SVR. However, there are false negatives in female patients with a high viral load of genotype Ib when the SVR is predicted by FW+12. The current standard with FW+24 is reasonable, but the assessment of serum HCV‐RNA FW+12 may be effective in most patients.
Susceptibility of rat non‐alcoholic fatty liver to the acute toxic effect of acetaminophen
Authors: Kučera Otto , Roušar Tomáš , Staňková Pavla , Haňáčková Lenka , Lotková Halka , Podhola Miroslav , Červinková Zuzana
Published: June 2011

Background and Aim:  Acetaminophen overdose is the most frequent cause of acute liver failure. Non‐alcoholic fatty liver disease is the most common chronic condition of the liver. The aim was to assess whether non‐alcoholic steatosis sensitizes rat liver to acute toxic effect of acetaminophen.

Methods:  Male Sprague–Dawley rats were fed a standard diet (ST‐1, 10% kcal fat) and high‐fat gelled diet (HFGD, 71% kcal fat) for 6 weeks and then acetaminophen was applied in a single dose (1 g/kg body weight). Animals were killed 24, 48 and 72 h after acetaminophen administration. Serum biochemistry, activities of mitochondrial complexes, hepatic malondialdehyde, reduced and oxidized glutathione, triacylglycerol and cholesterol contents, and concentrations of serum and liver cytokines (TNF‐α, TGF‐β1) were measured and histopathological samples were prepared.

Results:  The degree of liver inflammation and hepatocellular necrosis were significantly higher in HFGD fed animals after acetaminophen administration. Serum markers of liver injury were elevated only in acetaminophen treated HFGD fed animals. Concentration of hepatic reduced glutathione and ratio of reduced/oxidized glutathione were decreased in both ST‐1 and HFGD groups at 24 h after acetaminophen application. Mild oxidative stress induced by acetaminophen was confirmed by measurement of malondialdehyde. Liver content of TNF‐α was not significantly altered, but hepatic TGF‐β1 was elevated in acetaminophen treated HFGD rats. We did not observe acetaminophen‐induced changes in activities of respiratory complexes I, II, and IV and activity of caspase‐3.

Conclusion:  Liver from rats fed HFGD is more susceptible to acute toxic effect of acetaminophen, compared to non‐steatotic liver.
Impact of non‐traditional phosphate binders and cinacalcet on haemodialysis patient biochemistry, pill burden and cost
Authors: GRAY NICHOLAS A , KRISHNASAMY RATHIKA , VARDESH DEEPAK L , HOLLETT PETER R , ANSTEY CHRIS M
Published: June 2011

Aim:  The Australian Pharmaceutical Benefits Scheme (PBS) commenced cost subsidization for haemodialysis patients of sevelamer in December 2007, cinacalcet in July 2008 and lanthanum in May 2009. To determine the impact of PBS listing of these medications, we performed a single centre cross‐sectional, longitudinal study.

Methods:  Dialysis parameters and biochemistry were prospectively collected at 6 monthly intervals for all prevalent haemodialysis patients from October 2007 to April 2010. Medications prescribed to manage chronic kidney disease mineral and bone disorder were recorded. Univariate regression analysis was undertaken for each variable against time.

Results:  Patient numbers ranged from 87 to 114 in each period. At baseline, mean age was 68.8 ± 14.3 years, 71% male, 15.1 ± 3.5 haemodialysis hours/week and urea reduction ratio 71.9 ± 9.8%. These variables were unchanged over time. The use of sevelamer, cinacalcet and lanthanum increased (P < 0.001). There was a decrease in the use of aluminium‐ and calcium‐based phosphate binders (P < 0.001) but no change in the use of magnesium based phosphate binders (P = 0.09) or calcitriol (P = 0.11). Serum phosphate (P = 0.13) and parathyroid hormone (PTH) (P = 0.87) were unchanged. Mean ‘bone pill’ burden fell from 60.3/week to 51.9/week (P = 0.02). Mean pill cost increased from Australian dollars (AUD) 12.85/patient per week to AUD 59.85/patient per week (P < 0.001).

Conclusion:  The PBS subsidization of sevelamer, cinacalcet and lanthanum has changed prescribing patterns, although serum phosphate and PTH remain unchanged. These changes have been at an additional cost of AUD 2444/patient per year. Data to address clinical end‐points of mortality and hospitalization is needed to determine if the cost of these newer agents is warranted.
Incidence and features of dual anti‐GBM‐positive and ANCA‐positive patients
Authors: DE ZOYSA JANAK , TAYLOR DOMINIC , THEIN HLA , YEHIA MAHA
Published: June 2011

Aims:  Goodpasture's syndrome, glomerulonephritis and pulmonary haemorrhage, may be due to a variety of causes. Rarely, patients with Goodpasture's syndrome present with both anti‐glomerular basement membrane (GBM) and antineutrophil cytoplasmic antibody (ANCA). The aim of this report was to determine the incidence, clinical features, management and outcomes of patients presenting with concurrent ANCA and anti‐GBM disease in Auckland.

Methods:  Potential patients were identified by an electronic search of serology for ANCA and anti‐GBM antibody, diagnostic renal biopsy, or in‐hospital admissions using ICD9 and ICD10 codes between 1998 and 2008. A retrospective case‐note review of all potential cases was performed.

Results:  Six cases were identified: two women and four men. The incidence was estimated at 0.47 cases per million people per year. The mean age of presentation was 59 years (range 25–85 years). One patient was a smoker and two patients were ex‐smokers. All subjects were anaemic, had haemoptysis and an abnormal chest X‐ray at presentation. The mean creatinine at presentation was 225 µmol/L (range 126–406 µmol/L); all patients had haematuria and proteinuria. All patients received corticosteroids and cyclophosphamide. Two patients were not plasma exchanged and died. Four patients received plasma exchange and are alive. One patient had a clinical relapse 6 years after their initial presentation and is on renal replacement therapy.

Conclusion:  Concurrent ANCA and anti‐GBM disease is rare. The mortality rate is high. Aggressive immunosuppression with steroids, cyclophosphamide and plasma exchange can induce remission and preserve renal function. Long‐term monitoring for relapses should occur.
MARKET MANIPULATION: A SURVEY
Authors: Putniņš Tālis J.
Published: June 2011

Abstract Despite the significant attention that market manipulation has received in recent years many aspects of it are poorly understood. This article identifies from the theoretical and empirical literature what we do and do not know about market manipulation, and suggests directions for future research. We know that manipulation is possible and that it occurs in a wide variety of markets and circumstances. In contrast, we know little about how often manipulation occurs, its effects and how it responds to regulation. Suggested approaches for future research on these issues include: (1) collecting more comprehensive data sets of manipulation cases; (2) using detection controlled estimation methods to overcome sample selection and partial observability problems and (3) conducting controlled experiments. This article also constructs a novel and broad taxonomy of the different types of market manipulation and discusses approaches to defining manipulation.
GOVERNMENT SIZE AND GROWTH: A SURVEY AND INTERPRETATION OF THE EVIDENCE
Authors: Bergh Andreas , Henrekson Magnus
Published: June 2011

Abstract The literature on the relationship between the size of government and economic growth is full of seemingly contradictory findings. This conflict is largely explained by variations in definitions and the countries studied. An alternative approach – of limiting the focus to studies of the relationship in rich countries, measuring government size as total taxes or total expenditure relative to GDP and relying on panel data estimations with variation over time – reveals a more consistent picture. The most recent studies find a significant negative correlation: an increase in government size by 10 percentage points is associated with a 0.5% to 1% lower annual growth rate. We discuss efforts to make sense of this correlation, and note several pitfalls involved in giving it a causal interpretation. Against this background, we discuss two explanations of why several countries with high taxes seem able to enjoy above average growth. One hypothesis is that countries with higher social trust levels are able to develop larger government sectors without harming the economy. Another explanation is that countries with large governments compensate for high taxes and spending by implementing market‐friendly policies in other areas. Both explanations are supported by ongoing research.
Human α‐mannosidase produced in transgenic tobacco plants is processed in human α‐mannosidosis cell lines
Authors: De Marchis Francesca , Balducci Chiara , Pompa Andrea , Riise Stensland Hilde M. F. , Guaragno Marco , Pagiotti Rita , Menghini Anna R. , Persichetti Emanuele , Beccari Tommaso , Bellucci Michele
Published: June 2011

Deficiency in human lysosomal α‐mannosidase (MAN2B1) results in α‐mannosidosis, a lysosomal storage disorder; patients present a wide range of neurological, immunological, and skeletal symptoms caused by a multisystemic accumulation of mannose‐containing oligosaccharides. Here, we describe the expression of recombinant MAN2B1 both transiently in Nicotiana benthamiana leaves and in the leaves and seeds of stably transformed N. tabacum plants. After purification from tobacco leaves, the recombinant enzyme was found to be N‐glycosylated and localized in vacuolar compartments. In the fresh leaves of tobacco transformants, MAN2B1 was measured at 10 200 units/kg, and the purified enzyme from these leaves had a specific activity of 32–45 U/mg. Furthermore, tobacco‐produced MAN2B1 was biochemically similar to the enzyme purified from human tissues, and it was internalized and processed by α‐mannosidosis fibroblast cells. These results strongly indicate that plants can be considered a promising expression system for the production of recombinant MAN2B1 for use in enzyme replacement therapy.
The New Independent Higher Education Institutions in China: Dilemmas and Challenges
Authors: Zhang Luxi , Adamson Bob
Published: June 2011

One impact of globalisation has been the expansion of higher education to meet changing current socio‐economic and political requirements. This expansion places considerable stress on the public purse and many states have turned to alternative solutions. In China, a new phenomenon has emerged: independent higher education institutions that complement public and private institutions in helping to cater for the expanded numbers of students. These independent institutions are formed through partnerships between existing institutions and the business sector. After analysing the political, socio‐economic and cultural contexts that shape the policy of developing independent institutions, this paper explores the dilemmas and challenges that have arisen at the implementation level and critiques some of the solutions that have been found.
In Praise of the Carceral Tour: Learning from the Grendon Experience
Authors: WILSON DAVID , SPINA ROY , CANAAN JOYCE E.
Published: June 2011

Abstract: This article is a response to Piché and Walby's (2010) criticism of ‘carceral tours’. It uses 40 reflective accounts, completed by final year students at Birmingham City University, of their visit to HMP Grendon – an annual visit which has been ongoing for ten years – to argue that this ‘carceral tour’ has pedagogical value to the students and is also important to the prisoners and prison staff.
Modelling the size and composition of fruit, grain and seed by process‐based simulation models
Authors: Martre Pierre , Bertin Nadia , Salon Christophe , Génard Michel
Published: June 2011

Understanding what determines the size and composition of fruit, grain and seed in response to the environment and genotype is challenging, as these traits result from several linked processes controlled at different levels of organization, from the subcellular to the crop level, with subtle interactions occurring at or between the levels of organization. Process‐based simulation models (PBSMs) implement algorithms to simulate metabolic and biophysical aspects of cell, tissue and organ behaviour. In this review, fruit, grain and seed PBSMs describing the main phases of growth, development and storage metabolism are discussed. From this concurrent work, it is possible to identify generic storage organ processes which can be modelled similarly for fruit, grain and seed. Spatial heterogeneity at the tissue and whole‐plant level is found to be a key consideration in modelling the effects of the environment and genotype on fruit, grain and seed end‐use value. In the future, PBSMs may well become the main link between studies at the molecular and whole‐plant levels. To bridge this phenotype‐to‐genotype gap, future models need to remain plastic without becoming overparameterized.

Contents

Summary
601

I.
Introduction
601

II.
Modelling the morphogenesis and growth of fruit, grain and seed
602

III.
Modelling fruit, grain and seed composition
605

IV.
Next steps in modelling the size and composition of fruit, grain and seed
610

References
612
Heparan sulfate glycosaminoglycan mimetic improves pressure ulcer healing in a rat model of cutaneous ischemia‐reperfusion injury
Authors: Tong Miao , Tuk Bastiaan , Hekking Ineke M. , Pleumeekers Mieke M. , Boldewijn Mireille B. , Hovius Steven E.R. , van Neck Johan W.
Published: June 2011

Pressure ulcers are a major clinical problem, with a large burden on healthcare resources. This study evaluated the effects of the heparan sulfate glycosaminoglycan mimetic, OTR4120, on pressure ulceration and healing. Ischemia‐reperfusion (I‐R) was evoked to induce pressure ulcers by external clamping and then removal of a pair of magnet disks on rat dorsal skin for a single ischemic period of 16 hours. Immediately after magnet removal, rats received an intramuscular injection of OTR4120 weekly for up to 1 month. During the ischemic period, normal skin perfusion was reduced by at least 60% and at least 20–45% reperfused into the ischemic region after compression release. This model caused sustained skin incomplete necrosis for up to 14 days and led to grade 2–3 ulcers. OTR4120 treatment decreased the area of skin incomplete necrosis and degree of ulceration. OTR4120 treatment also reduced inflammation and increased angiogenesis. In OTR4120‐treated ulcers, the contents of vascular endothelial growth factor, platelet‐derived growth factor, and transforming growth factor beta‐1 were increased. Moreover, OTR4120 treatment promoted early expression of alpha‐smooth muscle actin and increased collagen biosynthesis. Long‐term restoration of wounded tissue biomechanical strength was significantly enhanced after OTR4120 treatment. Taken together, we conclude that OTR4120 treatment reduces pressure ulcer formation and potentiates the internal healing bioavailability.
Diagnostic Accuracy of the ID Migraine: A Systematic Review and Meta‐Analysis
Authors: Cousins Gráinne , Hijazze Samira , Van de Laar Floris A. , Fahey Tom
Published: June 2011

(Headache 2011;51:1140‐1148)

Objective.— The purpose of this systematic review with meta‐analysis is to determine the diagnostic accuracy of the identification of migraine (ID Migraine) as a decision rule for identifying patients with migraine.

Background.— The ID Migraine screening tool is designed to identify patients with migraine in primary care settings. Several studies have validated the ID Migraine across various clinical settings, including primary care, neurology departments, headache clinics, dental clinics, ear, nose, and throat (ENT) and ophthalmology.

Methods.— A systematic literature search was conducted to identify all studies validating the ID Migraine, with the International Headache Criteria as the reference standard. The methodological quality of selected studies was assessed using the Quality of Diagnostic Accuracy Studies tool. All selected studies were combined using a bivariate random effects model. A sensitivity analysis was also conducted, pooling only those studies using representative patient groups (primary care, neurology departments, and headache clinics) to determine the potential influence of spectrum bias on the results.

Results.— Thirteen studies incorporating 5866 patients are included. The weighted prior probability of migraine across the 13 studies is 59%. The ID Migraine is shown to be useful for ruling out rather than ruling in migraine, with a greater pooled sensitivity estimate (0.84, 95% confidence interval 0.75‐0.90) than specificity (0.76, 95% confidence interval 0.69‐0.83). A negative ID Migraine score reduces the probability of migraine from 59% to 23%. The sensitivity analysis reveals similar results.

Conclusions.— This systematic review quantifies the diagnostic accuracy of the ID Migraine as a brief, practical, and easy to use diagnostic tool for Migraine. Application of the ID Migraine as a diagnostic tool is likely to improve appropriate diagnosis and management of migraine sufferers.
Serotonin Depletion Leads to Cortical Hyperexcitability and Trigeminal Nociceptive Facilitation via the Nitric Oxide Pathway
Authors: le Grand Supang Maneesri , Supornsilpchai Weera , Saengjaroentham Chonlawan , Srikiatkhachorn Anan
Published: June 2011

(Headache 2011;51:1152‐1160)

Objective.— To investigate the role of nitric oxide (NO) in the development of cortical hyperexcitability and trigeminal nociceptive facilitation induced by serotonin (5‐HT) depletion.

Background.— Nitric oxide and 5‐HT are important in the pathogenesis of primary headaches. An increase in cortical excitability and trigeminal nociception has been demonstrated in animals with low 5‐HT levels. Although the mechanism underlying this increase is unclear, an alteration of the NO system is one possible explanation.

Methods.— Male Wistar rats were divided into control and 5‐HT‐depleted groups. 5‐HT was depleted by i.p. injection of parachlorophenylalanine (100 mg/kg). Three days after injection, a microelectrode was inserted into the cerebral cortex for electrocorticograph recording and waves of cortical spreading depression (CSD) were triggered with KCl application. N‐nitro‐L‐arginine methyl ester (L‐NAME; 10 mg/kg by i.v. injection) or saline was given after the second CSD wave. Following the experiment, the cerebral cortex and brain stem were removed for anti‐neuronal nitric oxide synthase (nNOS) and anti‐Fos immunohistochemistry.

Results.— Relative to the control group, the 5‐HT‐depleted group exhibited a higher frequency of CSD waves, more nNOS‐immunoreactive cells in both the cerebral cortex and brainstem and more Fos‐immunoreactive cells in the trigeminal nucleus caudalis (TNC). In the control group, L‐NAME application led to fewer nNOS‐immunoreactive cells in the cerebral cortex and TNC, and fewer Fos‐immunoreactive cells in the TNC; however, L‐NAME was without effect on the CSD pattern. By contrast, in addition to decreased nNOS and Fos expression, L‐NAME significantly reduced the frequency of CSD events in the 5‐HT‐depleted group.

Conclusions.— Inhibition of NO production can counter both the cortical hyperexcitability and facilitation of trigeminal nociception that develop in the depleted 5‐HT state. Therefore, NO is likely involved in the increase in both CSD events and CSD‐evoked trigeminal nociception under decreased 5‐HT conditions.
Socioeconomic Context and Emotional‐Behavioral Achievement Links: Concurrent and Prospective Associations Among Low‐ and High‐Income Youth
Authors: Ansary Nadia S. , McMahon Thomas J. , Luthar Suniya S.
Published: June 2011

Temporal associations in the relationship between emotional‐behavioral difficulty and academic achievement were explored in 2 samples followed from 6th through 8th grade. The first sample comprised 280 students entering an economically disadvantaged urban middle school and the second comprised 318 students entering an affluent suburban middle school. Among disadvantaged youth, emotional indices were concurrently associated with poorer achievement while prospective associations between substance use and achievement were evident. For privileged adolescents, only a significant concurrent relationship emerged between social anxiety and achievement, although nonsignificant trends in the data suggest other, albeit weak, associations. The findings are discussed in terms of similarities and differences in these temporal associations across 2 samples representing extremes of the socioeconomic continuum.
Progranulin contributes to endogenous mechanisms of pain defense after nerve injury in mice
Authors: Lim Hee‐Young , Albuquerque Boris , Häussler Annett , Myrczek Thekla , Ding Aihao , Tegeder Irmgard
Published: June 2011

Progranulin haploinsufficiency is associated with frontotemporal dementia in humans. Deficiency of progranulin led to exaggerated inflammation and premature aging in mice. The role of progranulin in adaptations to nerve injury and neuropathic pain are still unknown. Here we found that progranulin is up‐regulated after injury of the sciatic nerve in the mouse ipsilateral dorsal root ganglia and spinal cord, most prominently in the microglia surrounding injured motor neurons. Progranulin knockdown by continuous intrathecal spinal delivery of small interfering RNA after sciatic nerve injury intensified neuropathic pain‐like behaviour and delayed the recovery of motor functions. Compared to wild‐type mice, progranulin‐deficient mice developed more intense nociceptive hypersensitivity after nerve injury. The differences escalated with aging. Knockdown of progranulin reduced the survival of dissociated primary neurons and neurite outgrowth, whereas addition of recombinant progranulin rescued primary dorsal root ganglia neurons from cell death induced by nerve growth factor withdrawal. Thus, up‐regulation of progranulin after neuronal injury may reduce neuropathic pain and help motor function recovery, at least in part, by promoting survival of injured neurons and supporting regrowth. A deficiency in this mechanism may increase the risk for injury‐associated chronic pain.
Vacuolar Import of Phosphatidylcholine Requires the ATP‐Binding Cassette Transporter Ybt1
Authors: Gulshan Kailash , Moye‐Rowley W. Scott
Published: June 2011

ATP‐binding cassette (ABC) transporters are well known for their roles as multidrug resistance determinants but also play important roles in regulation of lipid levels. In the yeast Saccharomyces cerevisiae, the plasma membrane ABC transporter proteins Pdr5 and Yor1 are required for normal rates of transport of phosphatidyethanolamine to the surface of the cell. Loss of these ABC transporters causes a defect in phospholipid asymmetry across the plasma membrane and has been linked with slowed rates of trafficking of other membrane proteins. Four ABC transporter proteins are found on the limiting membrane of the yeast vacuole and loss of one of these vacuolar ABC transporters, Ybt1, caused a major defect in the normal delivery of the phosphatidylcholine (PC) analog NBD‐PC (7‐nitro‐2,1,3‐benzoxadiazol‐PC) to the lumen of the vacuole. NBD‐PC accumulates on cytosolic membranes in an ybt1Δ strain. We demonstrated that Ybt1 is required to import NBD‐PC into vacuoles in the presence of ATP in vitro. Loss of Ybt1 prevented vacuolar remodeling of PC analogs. Turnover of Ybt1 was reduced under conditions in which function of this vacuolar remodeling pathway was required. Our data describe a novel vacuolar route for lipid remodeling and reutilization in addition to previously described enzymatic avenues in the cytoplasm.
Long-term depression is a stroke risk factor
Authors: Kocer Emel , Kocer Abdulkadir , Degirmenci Yıldız , Eryılmaz Mehmet
Published: June 2011

Kocer E, Kocer A, Degirmenci Y, Eryılmaz M. Long-term depression is a stroke risk factor.

Background and Aim: Only a few studies have evaluated depression prevalence in pre-stroke period in comparison to controls. We investigated this association based on a hospitalised stroke population.

Methods: One hundred and forty-eight stroke patients were evaluated. The presence of depression was compared with those of 100 healthy controls without stroke, from the same region. Depression was accepted as present or not present after history and clinical evaluation according to Diagnostic and Statistical Manual of Mental Disorders-IV. Socio-demographic variables, other stroke risk factors and the time of diagnosis of depression (how many year or month they got depression) were recorded.

Results: Gender and mean age of patients and controls were similar in comparison. Depression was diagnosed in 27 patients and 24 controls (p > 0.05). The time period passed after diagnosis of depression was longer in stroke patients in comparison to controls (p < 0.001).

Conclusions: The risk of stroke should be considered in elderly with long-term depression. This indicates that treatment of depression is another factor which should be considered in prevention of brain stroke.
A Systematic Review of Methods of Eye Irrigation for Adults and Children with Ocular Chemical Burns
Authors: Chau Janita P.C. , Lee Diana T.F. , Lo Suzanne H.S.
Published: June 2011

Aim: To present the best available research evidence on eye irrigation methods for ocular chemical burns to facilitate better‐informed clinical decisions.

Methods: Randomized, quasi‐randomized controlled trials and observational studies comparing the effectiveness of eye irrigation methods among adults or children as an active form of emergency treatment for ocular chemical burns were reviewed. Electronic databases in English and Chinese were searched from inception to June 2010. Two reviewers made independent decisions on whether to include each publication in the review and critically appraised the study quality independently. Given the clinical and methodological diversity among the studies, the review findings are presented in a narrative form.

Results and Discussion: Four studies involving 302 adults and children were identified. The results of this review indicate that patients who underwent irrigation with tap water immediately following alkali burns at the scene of injury had significantly better clinical and ocular outcomes. The evidence also suggests that in hospital settings, more patients preferred balanced saline solution (BSS) plus than other irrigation fluids. Irrigation with diphoterine was found in one study that resulted in better ocular outcomes following grade 1 and 2 ocular burns. With regard to duration of eye irrigation, patients with ocular chemical burns treated with prolonged irrigation reported shorter duration of treatment at hospital and absence from work. The results should be treated with caution, as there were significant differences between the comparison groups in some studies.

Implications and Conclusions: As prompt eye irrigation with tap water immediately after alkali burns had better outcomes, it would be important to commence eye irrigation immediately after burns are sustained. In this review, irrigating fluids including normal saline, lactated Ringer's, normal saline with sodium bicarbonate added, BSS Plus, and diphoterine solutions all yielded positive ocular outcomes suggesting for its use in hospital settings.
Locally cold flows from large-scale structure
Authors: Aragon-Calvo M. A. , Silk J. , Szalay A. S.
Published: June 2011

We show that the ‘cold’ Hubble flow observed for galaxies around the Milky Way does not represent a problem in cosmology but is due to the particular geometry and dynamics of our local wall. The behaviour of the perturbed Hubble flow around the Milky Way is the result of two main factors: at small scales (R < 1 Mpc) the inflow is dominated by the gravitational influence of the Milky Way and at large scales (R > 1 Mpc) the outflow reflects the expansion of our local wall which ‘cools down’ the peculiar velocities. This is an intrinsic property of walls and is independent of cosmology. We find the dispersion of the local Hubble flow (1 < R < 3 Mpc) around simulated ‘Milky Way’ haloes located at the centre of low-density cosmological walls to be σH∼ 30 km s-1, in excellent agreement with observations. The expansion of our local wall is also reflected in the value of the measured local Hubble constant. For ‘Milky Way’ haloes inside walls, we find super-Hubble flows with hlocal≃ 0.77–1.13 over a range of increasingly ‘clean’ environments. The radius of equilibrium (R0) depends not only on the mass of the central halo and the Hubble expansion, but also on the dynamics given by the local LSS geometry. The super-Hubble flow inside our local wall has the effect of reducing the radius at which the local expansion balances the gravitational influence of the Milky Way. By ignoring the dynamical effect of the local wall, the mass of the Milky Way estimated from R0 can be underestimated by as much as ∼30 per cent.
The correlation structure of dark matter halo properties
Authors: Jeeson-Daniel Akila , Vecchia Claudio Dalla , Haas Marcel R. , Schaye Joop
Published: June 2011

We investigate the correlation between nine different dark matter halo properties using a rank correlation analysis and a Principal Component Analysis for a sample of haloes spanning five orders of magnitude in mass. We consider mass and dimensionless measures of concentration, age, relaxedness, sphericity, triaxiality, substructure, spin and environment, where the latter is defined in a way that makes it insensitive to mass. We find that concentration is the most fundamental property. Except for environment, all parameters are strongly correlated with concentration. Concentration, age, substructure, mass, sphericity and relaxedness can be considered a single family of parameters, albeit with substantial scatter. In contrast, spin, environment and triaxiality are more independent, although spin does correlate strongly with substructure and both spin and triaxiality correlate substantially with concentration. Although mass sets the scale of a halo, all other properties are more sensitive to concentration.