bluuebunny/crossref_metadata_2025 huggingface dataset:
Addiction Research Centres and the Nurturing of Creativity. RAND's Drug Policy Research Center
Authors: Reuter Peter , Pacula Rosalie Liccardo , Caulkins Jonathan P.
Published: July 2010

In September 1989, amid an emotional and ideological debate regarding problematic drug use in the United States and the ‘war on drugs’, RAND's Drug Policy Research Center (DPRC) was created through private foundation funds. The purpose of this new research center was to provide objective empirical analysis on which to base sound drug policy. Twenty years later, RAND's DPRC continues its work, drawing on a broad range of analytical expertise to evaluate, compare and assess the effectiveness of a similarly broad range of drug policies. More than 60 affiliated researchers in the United States and Europe make up the Center, which attempts to provide objective empirical analyses to better inform drug policies within the United States and abroad. This paper provides a look back at the creation, evolution and growth of the Center. It then describes how the Center operates today and how it has maintained its clear identity and focus by drawing on the analytical capabilities of a talented group of researchers from a broad range of academic disciplines.
Extended spectrum beta‐lactamase‐producing bacteria and Clostridium difficile in patients with pouchitis
Authors: McLaughlin S. D. , Clark S. K. , Roberts C. H. , Perry‐Woodford Z. L. , Tekkis P. P. , Ciclitira P. J. , Nicholls R. J.
Published: July 2010

Aliment Pharmacol Ther 2010; 32: 664–669

Background  Treatment with fluoroquinolones is associated with the development of Clostridium difficile and extended spectrum beta‐lactamase‐producing bacteria (ESBL). Clostridium difficile and ESBL are resistant to many antibiotics and each may cause pouchitis after restorative proctocolectomy (RPC) refractory to empirical antibiotic therapy.

Aim  To assess the prevalence and establish risk factors for the development of ESBL and Clostridium difficile toxins (CDT) in RPC patients with recurrent or refractory pouchitis under follow‐up at our institution over a 1‐year period.

Method  An enzyme‐linked immunosorbent assay was used to detect CDT and a culture technique was used to identity ESBL in faecal samples. All patients had previously received fluoroquinolone treatment.

Results  Forty‐eight patients (35 (74%) men; median age 42 years) underwent testing at a median interval from RPC of 8 (range 1–25) years. No patient had a positive CDT result, but ESBL bacteria were identified in 16 (33%) samples. ESBL positivity was significantly related to prepouch ileitis (P = 0.035) and maintenance antibiotic therapy (P = 0.039).

Conclusions  Extended spectrum beta‐lactamase, but not CDT, is a common finding in faecal samples from patients with recurrent or refractory pouchitis. Treatment with maintenance antibiotics and prepouch ileitis are risk factors for developing ESBL‐producing bacteria.
research paper: IL1RN VNTR and IL2−330 polymorphic genes are independently associated with chronic immune thrombocytopenia
Authors: Rocha Andreia Maria Camargos , De Souza Cláudia , Rocha Gifone Aguiar , De Melo Fabrício Freire , Saraiva Isadora Sofia Borges , Clementino Nelma Cristina Diogo , Marino Marília Campos Abreu , Queiroz Dulciene Maria Magalhães
Published: July 2010

Chronic Immune Thrombocytopenia (cITP) is an acquired immune‐mediated disease associated with a T‐helper cell type 1 (Th1) immune polarization, whose genetic risk factors, however, are largely unknown. We investigated polymorphisms in promoter regions of genes that code molecules involved in proinflammatory immune response [IL1B−31T/C, IL1RN variable number tandem repeats (VNTR), IL2−330T/G, and TNF−307G/A] as well as in genes that code Toll like receptors (TLR) (TLR2 Arg753Gln, TLR4 Asp299Gly and TLR5 Arg392stop) in 122 patients with cITP and 541 blood donors. The frequencies of the IL1RN polymorphic allele 2 (P = 0·001) and of the IL2−330 polymorphic allele G (P = 0·004) were significantly higher in cITP patients than in blood donors. In logistic analysis adjusting for age and gender, the polymorphisms remained independently associated with cITP. Enhanced serum concentrations of interleukin (IL)‐1α and IL‐1β were observed in cITP (P < 10−3) and blood donor (P = 0·04) carriers of the IL1RN*2. Also, the serum levels of IL‐2 and γ‐interferon (IFN‐γ) were increased in cITP patients (P < 10−3 and P = 0·04 respectively) and blood donors (P < 10−3 and P = 0·03 respectively) harbouring the IL2−330G allele. Here we demonstrated that IL2−330G and IL1RN*2 are independently associated with cITP and are functional in vivo, which strongly suggests that they contribute to the pathogenesis of cITP.
IgG4‐related tumour‐forming mastitis with histological appearances of granulomatous lobular mastitis: comparison with other types of tumour‐forming mastitis
Authors: Ogura Kanako , Matsumoto Toshiharu , Aoki Yuji , Kitabatake Toshiaki , Fujisawa Minoru , Kojima Kuniaki
Published: July 2010

Ogura K, Matsumoto T, Aoki Y, Kitabatake T, Fujisawa M & Kojima K (2010) Histopathology 57, 39–45 IgG4‐related tumour‐forming mastitis with histological appearances of granulomatous lobular mastitis: comparison with other types of tumour‐forming mastitis

Aims:  Sometimes, mastitis needs to be differentiated from carcinoma because of its association with induration and with ultrasound findings (such as low‐echo lesions) that resemble those in carcinoma. The aim was to define this type of mastitis and to examine 18 cases to clarify its clinicopathological features.

Methods and results:  All cases were categorized into three types: non‐specific mastitis with neutrophilic infiltration (n = 7); non‐specific mastitis with lymphoplasmacytic infiltration (n = 9); and granulomatous lobular mastitis (n = 2). The three types of mastitis presented similar ultrasound findings and shared certain histological features including fibrosis and diffuse or lobulocentric inflammation. Granulomatous lobular mastitis showed specific clinicopathological features including lobulocentric inflammation with giant cells, diffuse IgG4+ plasma cells, and also a high level of serum IgG4.

Conclusions:  Granulomatous lobular mastitis could be categorized into IgG4‐related and non‐IgG4‐related granulomatous lobular mastitis. IgG4 immunohistochemistry serum IgG4 might be useful for diagnosis of IgG4‐related granulomatous lobular mastitis and could help to avoid overtreatment such as wide excision.
The weight of the prostate gland is an excellent surrogate for gland volume
Authors: Varma Murali , Morgan John M
Published: July 2010

Varma M & Morgan J M (2010) Histopathology 57, 55–58 The weight of the prostate gland is an excellent surrogate for gland volume

Aims:  Prostate gland volume is generally assessed by transrectal ultrasound examination or magnetic resonance imaging at the time of prostatic biopsy or pre‐brachytherapy planning. The volume is most commonly measured using the formula, prostate volume = height × width × length × π/6, which is derived considering the gland as ellipsoid. There are conflicting data regarding the accuracy of this method, with most studies comparing this calculated volume with that measured radiologically using planimetry with summation of sequential area measurements. The aim was to determine the relationship between prostate gland volume and weight.

Methods and results:  The accuracy of prostate gland volume calculated from three‐dimensional measurements of the gland in 20 radical prostatectomy specimens relative to the true gland volume determined using water displacement was prospectively evaluated. Since volume measurement by water displacement is not practical in routine practice, the relationship between prostate weight and volume was also evaluated. Our findings indicate that the calculated gland volume consistently underestimates the true volume. The volume of the prostate gland (in cm3) very closely correlates with its weight (in g).

Conclusions:  The weight of the prostate gland (without the seminal vesicles) is an excellent surrogate for prostate volume. The prostate gland in radical prostatectomy specimens should be weighed after transecting the seminal vesicles at the base.
Preferential up‐regulation of heparanase and cyclooxygenase‐2 in carcinogenesis of Barrett’s oesophagus and intestinal‐type gastric carcinoma
Authors: Sonoda Ryotaro , Naomoto Yoshio , Shirakawa Yasuhiro , Fujiwara Yasuhiro , Yamatsuji Tomoki , Noma Kazuhiro , Tanabe Shunsuke , Takaoka Munenori , Gunduz Mehmet , Tsujigiwa Hidetsugu , Nagatsuka Hitoshi , Ohara Nobuya , Yoshino Tadashi , Takubo Kaiyo , Vieth Michael , Tanaka Noriaki
Published: July 2010

Sonoda R, Naomoto Y, Shirakawa Y, Fujiwara Y, Yamatsuji T, Noma K, Tanabe S, Takaoka M, Gunduz M, Tsujigiwa H, Nagatsuka H, Ohara N, Yoshino T, Takubo K, Vieth M & Tanaka N (2010) Histopathology 57, 90–100 Preferential up‐regulation of heparanase and cyclooxygenase‐2 in carcinogenesis of Barrett’s oesophagus and intestinal‐type gastric carcinoma

Aims:  Metaplastic changes secondary to chronic inflammation at the gastro–oesophageal junction and at the pyloric antrum are recognized as the premalignant conditions of Barrett’s oesophageal adenocarcinoma and intestinal‐type gastric carcinoma (GC), respectively. Heparanase (HPSE) and cyclooxygenase (COX)‐2 have been proved to play critical roles in inflammation as well as in cancer. The aim was to examine the meaning of their expression in inflammation‐related carcinogenesis.

Methods and results:  First, expression of HPSE and COX‐2 in 78 clinical tissues of Barrett’s oesophagus was examined by immunohistochemistry and in situ hybridization. Their expression was increased during the metaplasia–dysplasia sequence with increased neovascularization. Successively, their expression in Barrett’s dysplasia was compared with that of GC (22 cases of diffuse‐type and 10 of intestinal‐type). Interestingly, the expression pattern in Barrett’s dysplasia was similar to that in intestinal‐type GC, which mainly arises from chronic inflammation. Furthermore, cultured cell lines isolated from differentiated GC tissues, which are often found to be of intestinal‐type, revealed up‐regulated mRNA expression of HPSE and COX‐2.

Conclusions:  HPSE and COX‐2 are preferentially up‐regulated in Barrett’s oesophagus and intestinal‐type GC. These molecules may play an important role during the development of inflammation‐related adenocarcinoma of the upper gastrointestinal tract.
Matrix metalloproteinases, TIMPs and growth factors regulating ameloblastoma behaviour
Authors: Siqueira Adriane S , Carvalho Marcia R D , Monteiro Ana C D , Freitas Vanessa M , Jaeger Ruy G , Pinheiro Joao J V
Published: July 2010

Siqueira A S, Carvalho M R D, Monteiro A C D, Freitas V M, Jaeger R G & Pinheiro J J V. (2010) Histopathology 57, 128–137 Matrix metalloproteinases, TIMPs and growth factors regulating ameloblastoma behaviour

Aims:  Ameloblastoma is an odontogenic neoplasm with local invasiveness and recurrence. We have previously suggested that growth factors and matrix metalloproteinases (MMPs) influence ameloblastoma invasiveness1. The aim was to study expression of MMPs, tissue inhibitor of metalloproteinases (TIMPs) and growth factors in ameloblastoma.

Methods and results:  Thirteen cases of solid/multicystic ameloblastoma were examined. As a control, calcifying cystic odontogenic tumour (CCOT), a non‐invasive odontogenic neoplasm with ameloblastomatous epithelium was also studied. Immunohistochemistry detected MMPs, TIMPs and growth factors in ameloblastoma and CCOT. The labelling index (LI) of MMP‐9 and TIMP‐2 was significantly higher in ameloblastoma compared with CCOT. The LI of epidermal growth factor (EGF), transforming growth factor (TGF)‐α and epidermal growth factor receptor (EGFR) was also increased in ameloblastoma. This neoplasm showed greater expression of MMPs, TIMPs and growth factors compared with CCOT. We then analysed these molecules in ameloblastoma cells and stroma. Ameloblastoma cells exhibited increased LI of MMP‐1, ‐2 and EGFR. We found a positive correlation between EGF and TIMP‐1, and between TGF‐α and TIMP‐2. It is known that signals generated by growth factors are transduced by the ERK pathway. Ameloblastoma stroma exhibited the phosphorylated (activated) form of ERK.

Conclusions:  These results suggest an interplay involving growth factors MMPs and TIMPs that may contribute to ameloblastoma behaviour. Signals generated by this molecular network would be transduced by ERK 1/2 pathway.
Differential gene expression in classic giant cell tumours of bone: Tenascin C as biological risk factor for local relapses and metastases
Authors: Pazzaglia Laura , Conti Amalia , Chiechi Antonella , Novello Chiara , Magagnoli Giovanna , Astolfi Annalisa , Pession Andrea , Krenacs Tibor , Alberghini Marco , Picci Piero , Benassi Maria Serena
Published: July 2010

Pazzaglia L, Conti A, Chiechi A, Novello C, Magagnoli G, Astolfi A, Pession A, Krenacs T, Alberghini M, Picci P & Benassi M S (2010) Histopathology 57, 59–72 Differential gene expression in classic giant cell tumours of bone: Tenascin C as biological risk factor for local relapses and metastases

Aims:  To identify candidate prognostic biological markers useful in selecting high‐risk patients with classic primary giant cell tumours (GCT). GCT specimens with different behaviour associated with an increased risk of local and/or distant relapses were studied.

Methods and results:  Screening mRNA microarray analysis followed by real‐time polymerase chain reaction and immunohistochemistry on tissue microarray sections was used to validate the prognostic role of differentially expressed genes on a larger series by statistical analysis tests. Global gene expression profiling identified 109 differentially expressed genes according to prognosis. A correlation was found between mRNA levels and clinical outcome identifying Tenascin C (TNC) as the most significant prognostic biological marker. By means of backward Wald logistic regression, TNC overexpression defined an eightfold increased risk for metastasis and fourfold for local recurrence. At the protein level, TNC immunoreactivity resulted in a significant difference in the disease‐free survival probability curves, providing a stratification for GCT patients, useful for predicting relapse.

Conclusions:  Our study provides important data for the selection of biomarkers with a significant clinical impact and suggests the importance of TNC expression in identifying GCT patients at a higher risk of relapse for closer follow‐up and adjuvant medical therapy.
Factor structure, internal consistency and construct validity of the Sheehan Disability Scale in a Spanish primary care sample
Authors: Luciano Juan V. , Bertsch Jordan , Salvador‐Carulla Luis , Tomás José M. , Fernández Ana , Pinto‐Meza Alejandra , Haro Josep M. , Palao Diego J. , Serrano‐Blanco Antoni
Published: July 2010

Rationale, aims and objectives The Sheehan Disability Scale (SDS) is a three‐item instrument that measures disability in three inter‐related domains: work, family life/home responsibilities and social/leisure activities. The main objective of the present study was to examine the factor structure, reliability and construct validity of the SDS in a wide Spanish sample of primary care (PC) patients.

Methods One phase cross‐sectional survey. A total of 3815 patients, aged 18 years or older attending PC for a medical visit, were interviewed between October 2005 and March 2006. The interviews included the Structured Clinical Interview for DSM‐IV Axis I Disorders for depressive and anxiety disorders, the Mini‐International Neuropsychiatric Interview for the rest of mental disorders, a medical conditions checklist, the 2.0 version of the 12‐item Short‐Form Health Survey (SF‐12) for measuring quality of life and the SDS.

Results The principal component analysis and the subsequent confirmatory factor analysis indicated that the SDS is one‐dimensional (normed fit index = 0.990, non‐normed fit index = 0.987, comparative fit index = 0.991, goodness‐of‐fit index = 0.993, standardized root mean‐square residual = 0.037, root mean‐square error of approximation = 0.053). The internal consistency of the scale was good (α = 0.83) and it was significantly associated with the physical and mental component of the SF‐12. Concerning discriminative validity, patients with major depression or panic disorder scored higher on the SDS than patients with chronic medical conditions or with no chronic pathology. We also found that a cut‐off point of 8 in the SDS adequately discriminated between patients with and without depression (area under the curve = 0.814, sensitivity = 81.60%, specificity = 70.60%).

Conclusions The SDS seems a reliable, valid and useful clinical tool for measuring disability in Spanish PC patients.
Pharmacokinetics of oxytetracycline in hemolymph from the Chinese mitten crab,Eriocheir sinensis
Authors: FENG Q. , WU G. H. , LIANG T. M. , JI H. Y. , JIANG X. J. , GU W. , WANG W.
Published: July 2010

Feng, Q., Wu, G. H., Liang, T. M., Ji, H. Y., Jiang, X. J., Gu, W., Wang, W. Pharmacokinetics of oxytetracycline in hemolymph from the Chinese mitten crab,Eriocheir sinensis. J. vet. Pharmacol. Therap.34, 51–57.

The purpose of this study was to investigate the hemolymph kinetics and depuration time of oxytetracycline following intramuscular administration at doses of 2, 8 and 40 mg/kg body weight, respectively. The concentration of OTC in hemolymph was assayed using solid phase extraction and high performance liquid chromatography. The elimination half‐life of the terminal part of the elimination phase (t1/2β) ranged from 87.9 to 114.3 h. The total body clearance (CLb) was 0.0430 L/kg/h at the lower dose, 0.0123 L/kg/h at the medium dose and 0.0013 L/kg/h at the higher dose. The apparent volume of the central compartment (Vc) was found to be 1.383, 0.699 and 0.143 L/kg respectively. The depuration time for each dose was 13.6, 29.6 and 57.6 days, respectively. Results from the present study suggest that the 40 mg/kg dose might have the best therapeutic efficacy following intramuscular administration.
Pharmacokinetics of yohimbine following intravenous administration to horses
Authors: DiMAIO KNYCH H. K. , STEFFEY E. P. , DEUEL J. L. , SHEPARD R. A. , STANLEY S. D.
Published: July 2010

DiMaio Knych, H.K., Steffey, E.P., Deuel, J.L., Shepard, R.A., Stanley, S.D. Pharmacokinetics of yohimbine following intravenous administration to horses. J. vet. Pharmacol. Therap.34, 58–63.

Yohimbine is an alpha 2 adrenergic receptor antagonist used most commonly in veterinary medicine to reverse the effects of the alpha 2 receptor agonists, xylazine and detomidine. Most notably, yohimbine has been shown to counteract the CNS depressant effects of alpha 2 receptor agonists in a number of species. The recent identification of a yohimbine positive urine sample collected from a horse racing in California has led to the investigation of the pharmacokinetics of this compound. Eight healthy adult horses received a single intravenous dose of 0.12 mg/kg yohimbine. Blood samples were collected at time 0 (prior to drug administration) and at various times up to 72 h post drug administration. Plasma samples were analyzed using liquid chromatography–mass spectrometry (LC‐MS) and data analyzed using both noncompartmental and compartmental analysis. Peak plasma concentration was 114.5 + 31.8 ng/mL and occurred at 0.09 + 0.03 h. Mean ± SD systemic clearance (Cls) and steady‐state volume of distribution (Vdss) were 13.5 + 2.1 mL/min/kg and 3.3 + 1.3 L/kg following noncompartmental analysis. For compartmental analysis, plasma yohimbine vs. time data were best fitted to a two compartment model. Mean ± SD Cls and Vdss of yohimbine were 13.6 ± 2.0 mL/min/kg and 3.2 ± 1.1 L/kg, respectively. Mean ± SD terminal elimination half‐life was 4.4 ± 0.9 h following noncompartmental analysis. Immediately following administration, two horses showed signs of sedation, while the other six appeared behaviorally unaffected. Gastrointestinal sounds were moderately increased compared to baseline while fecal consistency appeared normal.
Silybin inhibits interleukin‐1β‐induced production of pro‐inflammatory mediators in canine hepatocyte cultures
Authors: AU A. Y. , HASENWINKEL J. M. , FRONDOZA C. G.
Published: July 2010

Au, A. Y., Hasenwinkel, J. M., Frondoza, C. G. Silybin inhibits interleukin‐1β‐induced production of pro‐inflammatory mediators in canine hepatocyte cultures. J. vet. Pharmacol. Therap.34, 120–129.

Hepatocytes are highly susceptible to cytokine stimulation and are fundamental to liver function. We established primary canine hepatocyte cultures to study effects of anti‐inflammatory agents with hepatoprotective properties. Hepatocyte cultures were incubated with control media alone, silybin (SB), or the more bioavailable silybin–phosphatidylcholine complex (SPC), followed by activation with interleukin‐1 beta (IL‐1β; 10 ng/mL). Inflammatory response was measured by prostaglandin E2 (PGE2), interleukin‐8 (IL‐8), and monocyte chemotactic protein‐1 (MCP‐1) production and also nuclear factor‐kappa B (NF‐κB) translocation. Hepatocyte cultures continued production of the phenotypic marker albumin for more than 7 days in culture. IL‐1β exposure increased PGE2, IL‐8, and MCP‐1 production, which was paralleled by NF‐κB translocation from the cytoplasm to the nucleus. Pretreatment with SB and SPC significantly inhibited IL‐1β‐induced production of pro‐inflammatory markers and attenuated NF‐κB nuclear translocation. We demonstrate for the first time that primary canine hepatocyte cultures can be maintained in culture without phenotypic loss. The observation that hepatocyte cultures respond to pro‐inflammatory IL‐1β activation indicates hepatocytes as primary cellular targets of extrinsic IL‐1β. The ability of SB and SPC to inhibit hepatocyte culture activation by IL‐1β reinforces the notion of their hepatoprotective effects. Our primary canine hepatocyte culture model facilitates identification of hepatoprotective agents and their mechanism of action.
Association of ADH4 genetic variants with alcohol dependence risk and related phenotypes: results from a larger multicenter association study
Authors: Preuss Ulrich W. , Ridinger Monika , Rujescu Dan , Samochowiec Jerzy , Fehr Christoph , Wurst Friedrich M. , Koller Gabriele , Bondy Brigitta , Wodarz Norbert , Debniak Tadeusz , Grzywacz Anna , Soyka Michael , Zill Peter
Published: July 2010

Genetic variants of the alcohol‐metabolizing enzyme ADH4, located on chromosome 4q22–4q23, have been related to alcohol dependence (AD) risk in previous research. The aim of this association study in a large multicenter sample of alcohol‐dependent individuals and controls is to confirm ADH4 single nucleotide polymorphism (SNP) and haplotype association with AD and relevant related phenotypes. One thousand, six hundred and twenty‐two (1622) inpatient subjects and 1469 control subjects with DSM‐IV. AD from four addiction treatment centres were included. Characteristics of AD and related phenotypes including alcohol withdrawal, Cloninger's type I and II and first ages of drinking, regular drinking and AD onset were obtained using standardized structured interviews. After subjects were genotyped for 2 ADH4 polymorphisms, single SNP case‐control and haplotype analyses were conducted. Both variants—rs1800759 and rs1042364—and the A‐A and C‐G haplotypes were significantly related to AD across samples. Furthermore, associations with AD‐related phenotypes and subtypes revealed a potential protective influence of this haplotype. This study confirms the significant relationship of ADH4 variants with AD and related phenotypes. While the rs1800759 and rs1042364 A‐A haplotype had a potential protective influence on the risk for several AD‐related phenotypes, this effect is rather small compared to functional variants of other alcohol or acetaldehyde‐metabolizing enzymes like ALDH2*2 or ADH1B*2.
Why values elicitation techniques enable people to make informed decisions about cancer trial participation
Authors: Abhyankar Purva , Bekker Hilary L. , Summers Barbara A. , Velikova Galina
Published: July 2010

Background Decision aids help patients make informed treatment decisions. Values clarification (VC) techniques are part of decision aids that help patients assimilate the information with their personal values. There is little evidence that these techniques contribute to enhanced decision making over and above the provision of good quality information.

Objectives To assess whether VC techniques are active ingredients in enhancing informed decision making and explain how and why they work.

Methods Participants were randomly assigned to one of three groups: (i) information only, (ii) information plus implicit task, (iii) information plus explicit task. Thirty healthy women from a UK University participated by making a hypothetical choice between taking part in a clinical trial and having the standard treatment for breast cancer. Verbal protocols were elicited by think‐aloud method and content analysed to assess informed decision making; a questionnaire was completed after the decision assessing decision preference, perceptions of decisional conflict and ambivalence. Data were analysed using multivariate statistics.

Findings No participants changed their decision preference as a result of the VC techniques. Women in the explicit VC group evaluated more information in accord with personal values, expressed lower ambivalence, decisional uncertainty and greater clarity of personal values than those in the implicit VC and control groups. Feelings of ambivalence about both options were related to decisional conflict.

Conclusion Explicit VC techniques are likely to be active ingredients in decision aids. They work by enabling people to deliberate about the decision information in accord with their personal values, which is associated with a better decision experience.
Neural correlates of the orthographic neighborhood size effect in Chinese
Authors: Li Qing‐Lin , Bi Hong‐Yan , Zhang J. X.
Published: July 2010

Word recognition research with alphabetical scripts has revealed a facilitatory neighborhood size effect, whereby naming of words with more orthographic neighbors is faster than that of words with fewer neighbors. Preliminary behavioral evidence in Chinese revealed both facilitatory and inhibitory neighborhood size effects, depending on whether there are higher‐frequency neighbors (HFNs) than the target. This functional magnetic resonance imaging study examined the neural substrates of the neighborhood size effect with silent naming. Neighborhood size and the HFN factor were factorially manipulated. Behavioral results replicated previous findings showing that larger neighborhood size facilitated naming in the absence of HFNs, but inhibited naming in their presence. Imaging results identified greater activation in the left middle frontal gyrus for small than larger neighborhood size, and bilateral inferior frontal activations for the with‐HFN condition as compared with the without‐HFN condition. Critically, there was an interaction in the right middle occipital gyrus showing greater activation for large than for small neighborhood size in the absence of HFNs but no neighborhood size effect in their presence. The results support a proposal that, in addition to a facilitatory contribution from orthographic activation of neighborhoods, naming is also affected by whether there are higher‐frequency neighbors, particularly in scripts with deep orthography, where orthographically similar words can be pronounced very differently.
Flight ability and reproductive development in newly‐emerged pine weevil Hylobius abietis and the potential effects of climate change
Authors: Tan Janine Y. , Wainhouse David , Day Keith R. , Morgan Geoffrey
Published: July 2010

Adult pine weevils Hylobius abietis emerge from conifer root‐stumps, on which larvae develop, over an extended period during summer and autumn. Newly‐emerged weevils were tested for their ability to fly and assessed for wing muscle and reproductive development. In addition, the effect of summer–autumn maturation feeding on reproductive development was assessed in field bioassays.

There was considerable variation in development between newly‐emerged weevils that was related to the timing of emergence. The first weevils, emerging in early July, weighed less than later‐emerging ones, had undeveloped flight muscles and did not fly. Over the emergence period, wing muscle size and flight ability increased markedly, with 50–60% flying by mid‐September. Differences between emerging adults are likely to have been affected by temporal changes in the quality of the bark on which the larvae feed.

Reproductive development lagged behind that of wing muscles but, in early August, there was a rapid increase in the proportion of weevils with immature eggs and a corresponding increase in oocyte size. However, although wing muscles were fully formed in later‐emerging weevils, immature eggs were only approximately 10% of the volume of mature eggs.

In field bioassays of summer–autumn maturation feeding, eggs continued to develop and some weevils laid mature eggs. Feeding and development during the pre‐overwinter period is likely to influence winter survival and also dispersal and reproduction in the following spring.

The potential effects of climate change on the weevil life cycle are briefly discussed. Weevils are likely to benefit from the higher temperatures and later autumns predicted under climate change, resulting in an increase in damage to transplants.
The effect of agrochemicals on indicator bacteria densities in outdoor mesocosms
Authors: Staley Zachery R. , Rohr Jason R. , Harwood Valerie J.
Published: July 2010

Water bodies, which are monitored for microbial water quality by quantification of faecal indicator organisms (IOs), can contain various zoonotic pathogens contributed by livestock waste and other sources. Sediments can serve as reservoirs of IOs and other enteric microorganisms, including pathogens. Agrochemicals may influence the survival of these microorganisms in water bodies impacted by livestock waste by enhancing or reducing their survival. Complex, 1100 l, freshwater mesocosms containing leaf litter, zooplankton, periphyton, phytoplankton, and invertebrate and vertebrate animals were used to investigate the response of Escherichia coli and enterococci to agrochemicals. Replicate tanks were treated with atrazine, malathion, chlorothalonil and inorganic fertilizer, either alone at 1× or 2× their expected environmental concentrations (EECs) or in pair‐wise combinations at their EECs. IOs inoculated in sediment (∼104 cfu per 100 ml) were enumerated over 28 days. IOs generally declined over time, but manova revealed that addition of fertilizer and atrazine resulted in significantly greater IO densities. Malathion, chlorothalonil and agrochemical concentration (1× vs 2×) did not significantly affect IO densities and no significant interactions between agrochemicals were noted. The augmentation of IO densities in sediments by fertilizer and atrazine may impact their reliability as accurate predictors of water quality and human health risk, and indicates the need for a better understanding of the fate of IOs and enteric pathogens in sediments exposed to agrochemicals.
One Uniform Welfare State or a Multitude of Welfare Municipalities? The Evolution of Local Variation in Swedish Elder Care
Authors: Trydegård Gun‐Britt , Thorslund Mats
Published: July 2010

The Nordic welfare states, including Sweden, have an inbuilt dilemma between two main principles: universalism and local autonomy. The concept of ‘welfare municipalities’ has been used to characterize the social policy construction of independent local authorities implementing national welfare policies. The aim of the article is to study the evolution of the balance between universal, centralized versus local, decentralized principles in Swedish welfare services, using elder care as a case. The article follows up previous studies on the extensive diversity and the local path dependency in the distribution of elder‐care services in Sweden. A predominant impression from the present exploration is that the pattern has changed in many aspects during the first decade of the new millennium, and in a complex way. The coverage of home help and residential care has become less generous, a sign of weaker universalism. On the other hand, the decentralization tendencies have decreased, the earlier reported geographical disparity appears to have been reduced and the municipalities are increasingly adjusting to the national average. Also, the earlier strong local path dependency has faded out and therefore the concepts ‘welfare municipality’ and ‘local social policy’ appear to be less accurate than heretofore when describing the Swedish model of elder care.
Reforming Long‐term Care in Portugal: Dealing with the Multidimensional Character of Quality
Authors: Santana Silvina
Published: July 2010

This article provides an overview of the informal and institutional setting of long‐term care in Portugal and focuses on service quality, discussing it alongside broader problems related to the organization of long‐term care in the country. We argue that quality assessment and management are critical actions that must be implemented alongside major efforts being made and that quality must be understood, researched and pursued as a multidimensional and complex aspect, entailing objective but also subjective dimensions and a plethora of actors and modelling factors. We conclude that the information and data available are clearly insufficient to support any deep analysis of the situation and field action, and that this represents an important opportunity for further investigation and practice improvement.
Reducing the size distortion of the KPSS test
Authors: Kurozumi Eiji , Tanaka Shinya
Published: July 2010

This article proposes a new stationarity test based on the KPSS test with less size distortion. We extend the boundary rule proposed by Sul et al. (2005) to the autoregressive spectral density estimator and parametrically estimate the long‐run variance. We also derive the finite sample bias of the numerator of the test statistic up to the 1/T order and propose a correction to the bias term in the numerator. Finite sample simulations show that the correction term effectively reduces the bias in the numerator and that the finite sample size of our test is close to the nominal one as long as the long‐run parameter in the model satisfies the boundary condition.
Gov 2.0: Towards a User Generated State?
Authors: Morison John
Published: July 2010

New elements associated with Web 2.0 relating to interactivity and end‐user focus have combined with the availability of new levels of information to encourage the development of what may be termed a Gov 2.0 approach. This, in combination with recent initiatives in the modernising government programme, has emphasised new levels of public participation and engagement with government as well as a re‐engineering of public services to make them more responsive to their end users. Adopting a governmentality perspective, it is argued that this involves a wider process of governing through constructing and reconstructing ideas of the public, community and individual citizen‐consumers who take on a role in their own governance. It is argued that this fundamental re‐working of the nature of what is public represents a constitutional change that is perhaps more significant than the constitutional reform programme directed to formal government which attracts more attention.
The European Commission's Guidance on Article 102TFEU: From Inferno to Paradiso?
Authors: Akman Pιnar
Published: July 2010

The European Commission has for the first time issued a document expressing its official position on the enforcement of Article 102TFEU which prohibits the abuse of a dominant position on the Common Market. The Commission Guidance on enforcement priorities in applying Article 102TFEU to exclusionary abuses (adopted in December 2008) has ended a review of about four years. Given the increased enforcement of Article 102TFEU at the European level and the fact that many national provisions in the EU on unilateral conduct are modelled after Article 102TFEU, how the Commission intends to enforce Article 102TFEU is crucial for the application of competition law and the undertakings subject to it under European and/or national laws. The review period was preceded by severe criticisms of the Commission's approach to Article 102TFEU for protecting competitors instead of competition and for being insufficiently grounded in modern economic thinking. At the heart of the review and the discussions surrounding it lay the question of the objective of Article 102TFEU. Some, including the Directorate General for Competition claimed the objective to be ‘consumer welfare’, whereas some argued that ‘consumer welfare’ cannot be adopted as the objective at the expense of the protection of the competitive process. This article critically reviews the Commission Guidance, with an eye to assessing the ultimate objective of and the test of harm under Article 102TFEU. After discussing whether the Guidance indeed sets priorities, it examines the general approach of the Guidance to exclusionary conduct. It points out that despite there being some welcome novelties in the Guidance, there are also suggestions therein whose legitimacy and legality are questionable. Reflecting on the Guidance as a soft‐law instrument, the article argues that although regarding the objective of Article 102TFEU, the Commission's apparent tendency towards ‘consumer welfare’ is not unlawful, the reform of Article 102TFEU to bring it more in line with modern economic and legal thinking seems to be far from complete.
Expectation of life and unexpected death in open spina bifida: a 40‐year complete, non‐selective, longitudinal cohort study
Authors: OAKESHOTT PIPPA , HUNT GILLIAN M , POULTON ALISON , REID FIONA
Published: July 2010

Aim  The aim of our study was to investigate survival and causes of death in a complete cohort of open spina bifida at the mean age of 40 years.

Method  We conducted a community‐based, prospective study of 117 consecutive infants (50 males, 67 females) with open spina bifida whose backs were closed non‐selectively within 48 hours of birth between 1963 and 1971 at Addenbrooke’s Hospital, Cambridge, UK. Of those who survived to age 1 year, 89% (82 out of 92) had a cerebrospinal fluid shunt. In 2007, all survivors were surveyed by postal questionnaire backed up by telephone interview. Details of deaths were obtained from the Office for National Statistics, medical records, and autopsy reports, and Kaplan–Meier survival curves were constructed.

Results  One in three of the cohort (40/117) died before the age of 5 years. A further 26% (31/117) died during the next 35 years, over 10 times the national average. Half the deaths (16/31) after the age of 5 were sudden and unexpected. All occurred in the community and were followed by a coroner’s autopsy. The most frequent causes of these unexpected deaths were epilepsy, pulmonary embolus, acute hydrocephalus, and acute renal sepsis. The prognosis for survival was strikingly poor in those with the most extensive neurological deficit. Only 17% (7/42) of those born with a high sensory level (above T11) survived to the mean age of 40 years, compared with 61% (23/38) of those with a low sensory level (below L3; p=0.001).

Interpretation  Doctors and care planners need to be aware that, contrary to previous suggestions, there is continuing high mortality throughout adult life in individuals with open spina bifida, and many deaths are unexpected.
Fractures in children and adolescents with spina bifida: the experience of a Portuguese tertiary‐care hospital
Authors: MARREIROS HUMBERTO , MONTEIRO LUÍSA , LOFF CLARA , CALADO EULÁLIA
Published: July 2010

Aim  The morbidity associated with osteoporosis and fractures in children and adolescents with spina bifida highlights the importance of osteoporosis prevention and treatment in these patients. The aim of this study was to examine the occurrence and pattern of bone fractures in paediatric patients with spina bifida.

Method  We reviewed the data of all paediatric patients with spina bifida who were treated in our centre between 1999 and 2008.

Results  One hundred and thirteen patients were included in the study (63 females, 50 males; mean age 10y 8mo, SD 4y 10mo, range 6mo–18y). The motor levels were thoracic in six, upper lumbar in 22, lower lumbar in 42, and sacral in 43 patients. Of the 113 patients, 58 (51.3%) had shunted hydrocephalus. Thirty‐six (31.8%) were non‐ambulatory (wheelchair–dependent [unable to self‐propel wheelchair] n=3, wheelchair‐independent [able to self‐propel wheelchair] n=33), 13 were partial ambulators, 61 were full ambulators, and three were below the age of walking. Forty‐five fractures were reported in 25 patients. The distal femur was the most common fracture site. Statistical analyses showed that patients with higher levels of involvement and in wheelchairs had a significantly increased risk of having a second fracture (p<0.001). Spontaneous fractures were the principal mechanism of injury, and an association was identified between fracture mechanism, type of ambulation, and lesion level: the fractures of patients with higher levels of motor functioning and those in wheelchairs were mainly pathological (p=0.01). We identified an association between risk of a second fracture, higher motor level lesion, and non‐ambulation. There was an increased risk of having a second fracture after a previous spontaneous fracture (p=0.004).

Interpretation  Data in this study indicate a high prevalence of fractures in patients with spina bifida.
Intracerebral large artery disease in Aicardi–Goutières syndrome implicates SAMHD1 in vascular homeostasis
Authors: RAMESH VENKATESWARAN , BERNARDI BRUNO , STAFA ALTIN , GARONE CATERINA , FRANZONI EMILIO , ABINUN MARIO , MITCHELL PATRICK , MITRA DIPAYAN , FRISWELL MARK , NELSON JOHN , SHALEV STAVIT A , RICE GILLIAN I , GORNALL HANNAH , SZYNKIEWICZ MARCIN , AYMARD FRANÇOIS , GANESAN VIJEYA , PRENDIVILLE JULIE , LIVINGSTON JOHN H , CROW YANICK J
Published: July 2010

Aim  To describe a spectrum of intracerebral large artery disease in Aicardi–Goutières syndrome (AGS) associated with mutations in the AGS5 gene SAMHD1.

Method  We used clinical and radiological description and molecular analysis.

Results  Five individuals (three males, two females) were identified as having biallelic mutations in SAMHD1 and a cerebral arteriopathy in association with peripheral vessel involvement resulting in chilblains and ischaemic ulceration. The cerebral vasculopathy was primarily occlusive in three patients (with terminal carotid occlusion and basal collaterals reminiscent of moyamoya syndrome) and aneurysmal in two. Three of the five patients experienced intracerebral haemorrhage, which was fatal in two individuals. Post‐mortem examination of one patient suggested that the arteriopathy was inflammatory in origin.

Interpretation  Mutations in SAMHD1 are associated with a cerebral vasculopathy which is likely to have an inflammatory aetiology. A similar disease has not been observed in patients with mutations in AGS1 to AGS4, suggesting a particular role for SAMHD1 in vascular homeostasis. Our report raises important questions about the management of patients with mutations in SAMHD1.
Defined inflammatory states in astrocyte cultures: correlation with susceptibility towards CD95‐driven apoptosis
Authors: Falsig Jeppe , Latta Markus , Leist Marcel
Published: July 2010

A complete cytokine mix (CCM) or its individual components tumour necrosis factor‐alpha (TNF‐α), interleukin‐1beta (IL‐1β) and interferon‐gamma (IFN‐γ) were used to switch resting murine astrocytes to reactive states. The transformation process was characterized by differential up‐regulation of interleukin‐6 (IL‐6), cyclooxygenase‐2 (COX‐2) and inducible nitric oxide synthetase (iNOS) mRNA and protein and a subsequent release of prostaglandin E2, nitric oxide (NO) and IL‐6. Both CD95L and anti‐CD95 antibodies triggered caspase activation followed by apoptotic death in fully pro‐inflammatory astrocytes, whereas resting cells were totally resistant. Two other death‐inducing ligands, TNF and TNF‐related apoptosis‐inducing ligand (TRAIL) did not induce apoptosis in reactive astrocytes. The switch in astrocyte sensitivity was accompanied by up‐regulation of caspase‐8 and CD95 as well as the capacity to recruit Fas‐associated death domain (FADD) to the activated death receptor complex. Neither CD95‐mediated death, nor other inflammatory parameters were affected by inhibition of iNOS or COX, respectively. Accordingly, IFN‐γ was absolutely essential for up‐regulation of iNOS, but not for the switch in apoptosis sensitivity. In contrast, p38 kinase activity was identified as an important controller of both the inflammatory reaction and apoptosis both in astrocytes stimulated with CCM and in glia exposed to TNF and IL‐1 only.
Role of proline residues in the expression and function of the human noradrenaline transporter
Authors: Paczkowski F. A. , Bryan‐Lluka L. J.
Published: July 2010

The aim was to investigate the roles of proline residues in extracellular loop 2 (P172, P183, P188 and P209) and transmembrane domains 2, 5, 11 and 12 (P108, P270, P526, P551, P552 and P570) in determining noradrenaline transporter (NET) expression and function. Mutants of human NET with these residues mutated to alanine were pharmacologically characterized. Mutation of P108, P270 and P526 disrupted cell surface expression, from [3H]nisoxetine binding and confocal microscopy data. Mutations of P526, P551 and P570 reduced transporter turnover (Vmaxof [3H]noradrenaline uptake/Bmaxof [3H]nisoxetine binding) by 1.5–1.7‐fold compared with wild‐type NET, so these residues might be involved in conformational changes associated with substrate translocation. Conversely, mutations of P172, P183, P188 and P209 increasedVmax/Bmaxby 2–3‐fold compared with wild‐type, indicating that the presence of these proline residues limits turnover of the NET. The mutations had few effects on apparent affinities of substrates or affinities of inhibitors, except decreases in inhibitor affinities after mutations of the P270 and P570 residues, and increases after mutation of the P526 residue. Hence, proline residues in extracellular loop 2 and in transmembrane domains have a range of roles in determining expression and function of the NET.