bluuebunny/crossref_metadata_2025 huggingface dataset:
Government effectiveness and support for democracy
Authors: Magalhães Pedro C.
Published: May 2013

Diffuse support for democracy, as captured in mass surveys, tends to be treated as impervious to regime performance. Such a finding is often presented as confirmation of the basic distinction between ‘diffuse’ and ‘specific’ support as proposed by David Easton. This study argues that this line of argument stems from an incomplete reading of important aspects of Easton's theorisation about the relationship between system outputs and diffuse support. Using multilevel models, evidence from more than 100 surveys in close to 80 countries, and different measures of democratic support, it is shown that government effectiveness is the strongest macro‐level predictor of such support. In democratic regimes, government effectiveness, understood as the quality of policy‐making formulation and implementation, is linked to higher levels of support for democracy. Furthermore, in non‐democracies, effectiveness and support for democracy are, under some model specifications, negatively related.
The potential of distance‐based thresholds and character‐basedDNAbarcoding for defining problematic taxonomic entities byCO1 andND1
Authors: Bergmann T. , Rach J. , Damm S. , DeSalle R. , Schierwater B. , Hadrys H.
Published: May 2013

The mitochondrialCO1 gene (cytochromecoxidaseI) is a widely accepted metazoan barcode region. In insects, the mitochondrialNADHdehydrogenase subunit 1 (ND1) gene region has proved to be another suitable marker especially for the identification of lower level taxonomic entities such as populations and sister species. To evaluate the potential of distance‐based thresholds and character‐basedDNAbarcoding for the identification of problematic species‐rich taxa, both markers,CO1 andND1, were used as test parameters in odonates. We sequenced and compared gene fragments ofCO1 andND1 for 271 odonate individuals representing 51 species, 22 genera and eight families. Our data suggests that (i) the combination of theCO1 andND1 fragment forms a better identifier than a single region alone; and (ii) the character‐based approach provides higher resolution than the distance‐based method inOdonata especially in closely related taxonomic entities.
A fracture prevention service reduces further fractures two years after incident minimal trauma fracture
Authors: Van der Kallen John , Giles Michelle , Cooper Kerry , Gill Kerry , Parker Vicki , Tembo Agness , Major Gabor , Ross Linda , Carter Jan
Published: May 2013

Aim

To evaluate the impact of a fracture prevention clinic service on initiation of treatment, continuing treatment and subsequent minimal trauma fractures (MTF).

Method

Participants were people aged 50 and over, with a minimal trauma fracture presenting to the Emergency Department (ED) in a large tertiary referral hospital in New South Wales, Australia, between February 2007 and March 2009. A cohort of patients who attended a Fracture Prevention Clinic (clinic group) were compared with a cohort who did not attend the clinic (non‐clinic group). A telephone questionnaire was conducted with participants or their carers between December 2010 and April 2011 at least 12 months post‐fracture presentation. Questionnaire items included demographics, fracture types, osteoporosis treatment, recurrent fractures and smoking and dietary habits. Data were compared using chi‐squared test for categorical variables and Student's t‐test or Mann–Whitney U‐test for continuous variables.

Results

Two hundred and fourteen clinic attendees and 220 non‐clinic attendees were surveyed between 12 and 40 months (mean 24 months) post‐initial fracture. New fracture rates were lower in the clinic group (5.1%) than the non‐clinic group (16.4%, P < 0.001). Treatment rates for bone fragility were higher in the clinic group (81.3%) than in the non‐clinic group (54.1%, P < 0.001) with 66.8% of the clinic group and 34.1% of the non‐clinic group on a bisphosphonate or strontium ranelate at the time of the survey (P < 0.001).

Conclusion

Patients managed by a fracture prevention clinic service following a MTF have fewer new fractures and are more likely to be on treatment for bone fragility.
DRD4 and TH gene polymorphisms are associated with activity, impulsivity and inattention in Siberian Husky dogs
Authors: Wan Michele , Hejjas Krisztina , Ronai Zsolt , Elek Zsuzsanna , Sasvari‐Szekely Maria , Champagne Frances A. , Miklósi Ádám , Kubinyi Enikő
Published: May 2013

Both dopamine receptor D4 (DRD4) exon 3 and tyrosine hydroxylase (TH) intron 4 repeat polymorphisms have been linked to activity and impulsivity in German Shepherd dogs (GSDs). However, the results in GSDs may not be generalisable to other breeds, as allelic frequencies vary markedly among breeds. We selected the Siberian Husky for further study, because it is highly divergent from most dog breeds, including the GSD. The study sample consisted of 145 racing Siberian Huskies from Europe and North America. We found that this breed possesses seven DRD4 length variants, two to five more variants than found in other breeds. Among them was the longest known allele, previously described only in wolves. Short alleles of the DRD4 and TH repeat polymorphisms were associated with higher levels of activity, impulsivity and inattention. Siberian Huskies possessing at least one short allele of the DRD4 polymorphism displayed greater activity in a behavioural test battery than did those with two long alleles. However, the behavioural test was brief and may not have registered variation in behaviour across time and situations. Owners also completed the Dog‐Attention Deficit Hyperactivity Disorder Rating Scale (Dog‐ADHD RS), a more general measure of activity and attention. Siberian Huskies from Europe with two short alleles of the TH polymorphism received higher ratings of inattention on the Dog‐ADHD RS than did those with the long allele. Investigation of the joint effect of DRD4 and TH showed that dogs possessing long alleles at both sites were scored as less active–impulsive than were others. Our results are aligned with previous studies showing that DRD4 and TH polymorphisms are associated with activity–impulsivity related traits in dogs. However, the prevalence of variants of these genes differs across breeds, and the functional role of specific variants is unclear.
Prenatal Metanephrogenesis of The Camel: Morphological Evidence of Epithelial–Mesenchymal Interaction
Authors: Osman A.‐H. K. , Farouk S. M. , Eidaroos H. , Abbott L. C. , Ahmed A. A.
Published: May 2013

The present investigation examined histogenesis of epithelial, stromal and angiogenic elements of the prenatal camel permanent or metanephric kidney. The primitive metanephros was first observed at the 13‐mm crown vertebral rump length (CVRL) stage as an ovoid structure composed of a centrally located epithelial ureteric bud and peripheral circumscribed masses of undifferentiated mesenchymal cells. The first morphological evidence of glomerulogenesis was observed at the 28‐mm CVRL stage. Developing renal corpuscles became obvious at the 35‐mm CVRL stage. At the 60‐mm CVRL stage, the epithelial renal pelvis gave rise to tubular branches that extended towards the cortical zone. These branches represented the presumptive collecting ducts. Differentiation of renal tubules into the proximal and distal convoluted tubules was observed at the 95‐mm CVRL stage. At the 130‐mm CVRL stage, the renal medulla was clearly delineated into medullary pyramids, which in association with the corresponding cortical caps formed the morphological basis of the renal lobar formation. A gradual nephrogenic decline was noticed from the 940‐mm CVRL on; however, the process of nephrogenesis persisted throughout all the studied foetal stages.
The experience of pregnant women with a body mass index >30 kg/m2 of their encounters with healthcare professionals
Authors: Lindhardt Christina L. , Rubak Sune , Mogensen Ole , Lamont Ronald F. , Joergensen Jan Stener
Published: May 2013

Objective

To examine the experience of women with a pre‐pregnant BMI >30 kg/m2, in their encounters with healthcare professionals during pregnancy.

Design

Qualitative study using a phenomenological methodology approach.

Setting

Face‐to‐face interviews with pregnant women in their own home who were referred from their general practitioner to specialist antenatal follow‐up at their local hospital.

Sample

Sixteen women with pre‐pregnant BMI >30 kg/m2.

Methods

Qualitative in‐depth interviews. Participant's experiences of their encounters with health care professionals were recorded verbatim, transcribed and analysed using a phenomenological approach.

Results

Two main themes were identified, an accusatorial response from healthcare professionals and a lack of advice and helpful information on how being obese and pregnant might affect the women's health and that of their child.

Conclusions

Pregnant women with obesity may experience prejudice from healthcare professionals. These women felt they were treated with a lack of respect, an accusatorial response, and the feeling that information which could have been helpful was not forthcoming. Communication between obese pregnant woman and healthcare professionals appears to be lacking. Improved training in communication skills, less judgemental behaviour and better dissemination of information from healthcare professionals working with pregnant women with obesity are needed.
Diagnostic accuracy of ultrasound and MRI in the prenatal diagnosis of placenta accreta
Authors: Maher Mohammad A. , Abdelaziz Ahmed , Bazeed Mohamed F.
Published: May 2013

Objective

To analyze the value of ultrasound followed by magnetic resonance imaging (MRI) in doubtful cases for antenatal detection of placenta accreta.

Design

A prospective observational study.

Setting

Hospital in the southern region, Saudi Arabia.

Sample

Patients with a low‐lying placenta or placenta previa.

Methods

The placentas of all included cases were scanned in a systematic fashion using both gray‐scale and color Doppler (transabdominal and transvaginal).

Main outcome measures

Explicit ultrasound criteria for placenta accreta were carefully applied, and any case with two or more criteria was labeled as highly suspicious. If only one criterion was detected, then the case was labeled as suspicious and MRI was applied.

Results

Five hundred and seventy seven women had a diagnosis of low‐lying placenta or placenta previa. Of these, 42 had placenta accreta confirmed after delivery by pathological examination, and 39 of these were diagnosed prenatally. Ultrasound accurately predicted placenta accreta in 33 of 39 of women and correctly ruled out placenta accreta in 512 of 514 without placenta accreta (sensitivity 95.1% and specificity 95.5%). Twenty (20) women underwent MRI because of suspicion of placenta accreta by ultrasonography. MRI accurately predicted placenta accreta in six of 20 cases and correctly ruled out placenta accreta in 10 of 20 cases (sensitivity 85.7% and specificity 76.9%).

Conclusion

Placenta accreta can be successfully detected prenatally using ultrasound. MRI can provide additional information in doubtful cases.
Predicting Psychological Needs and Well‐Being of Individuals Engaging in Weight Management: The Role of Important Others
Authors: Ng Johan Y.Y. , Ntoumanis Nikos , Thøgersen‐Ntoumani Cecilie , Stott Kyle , Hindle Linda
Published: May 2013

Background: Using the self‐determination theory (SDT) framework, we examined how significant others might support or thwart psychological needs of people with weight management goals, and in turn might affect their psychological well‐being and weight control behaviors. Design: Longitudinal design with three sets of questionnaires administered over a 6‐month period. Methods: One hundred and fifty‐six eligible participants (age = 31.01 ± 13.21 years) were asked to complete questionnaires of SDT‐based constructs, weight management behaviors, and psychological well‐being. Hypotheses were tested using Bayesian path analysis. Results: Perceived autonomy support from significant others was related to psychological need satisfaction, while controlling behaviors by others were associated with need thwarting. In turn, need satisfaction was associated with some beneficial outcomes such as life satisfaction, and need thwarting was related to some maladaptive outcomes such as higher levels of depressive symptoms and increases in unhealthy diet behaviors. Conclusions: Our findings indicate that the quality of interactions between individuals engaged in weight management and their significant others matters in terms of predicting the psychological needs and well‐being of the former.
Natural history of acute upper GI bleeding due to tumours: short‐term success and long‐term recurrence with or without endoscopic therapy
Authors: Sheibani S. , Kim J. J. , Chen B. , Park S. , Saberi B. , Keyashian K. , Buxbaum J. , Laine L.
Published: May 2013

Background

Scant information is available regarding patients with upper gastrointestinal bleeding (UGIB) from tumours.

Aim

To determine the presentation, endoscopic findings, treatment and outcomes in patients with UGIB from malignant tumours and identify risk factors associated with rebleeding.

Methods

Consecutive patients who were hospitalised with haematemesis, melena or haematochezia and underwent upper endoscopy were identified retrospectively by reviewing an endoscopy database. Patients with UGIB due to biopsy‐proven malignant tumours were studied.

Results

Tumours were the source of bleeding in 106 (5%) of 2,166 patients with UGIB. Tumours were oesophageal in 17 (16%), gastric in 77 (73%) and duodenal in 12 (11%). At presentation, 84 (79%) did not have known cancer previously, and 79 (75%) had metastatic disease. Seventy‐seven (73%) received transfusions at index hospitalisation. At endoscopy, 32 (30%) had active bleeding (31 oozing, 1 spurting). Among actively bleeding patients, haemostasis was achieved in 12 (86%) of 14 receiving endoscopic therapy and all 18 not receiving endoscopic treatment. Hospitalisation for rebleeding occurred in 50 (49%) of 103 at a median of 30 days (3–885). On multivariate analysis, age ≤60 years (OR = 2.49, 95% CI 1.06–5.81) and haemodynamic instability (OR = 2.42, 95% CI 1.08–5.46) were associated with rebleeding.

Conclusions

Patients presenting with tumour‐associated UGIB have substantial blood loss, with three‐quarters requiring transfusion at presentation. Initial haemostasis occurs in almost all patients, with or without endoscopic therapy, but rebleeding requiring repeat hospitalisation occurs in approximately half the patients and is more common in patients who are ≤60 years of age and have haemodynamic instability at presentation.
The research and evaluation of serious games: Toward a comprehensive methodology
Authors: Mayer Igor , Bekebrede Geertje , Harteveld Casper , Warmelink Harald , Zhou Qiqi , van Ruijven Theo , Lo Julia , Kortmann Rens , Wenzler Ivo
Published: May 2013

The authors present the methodological background to and underlying research design of an ongoing research project on the scientific evaluation of serious games and/or computer‐based simulation games (SGs) for advanced learning. The main research questions are: (1) what are the requirements and design principles for a comprehensive social scientific methodology for the evaluation of SGs?; (2) to what extent do SGs contribute to advanced learning?; (3) what factors contribute to or determine this learning?; and (4) to what extent and under what conditions can SG‐based learning be transferred to the real world? In the Netherlands between 2005 and 2012, several hundred SG sessions with 12 SGs were evaluated systematically, uniformly and quantitatively to create a dataset, which comprises data on 2488 respondents in higher education or work organizations. The authors present the research model, the quasi‐experimental design and the evaluation instruments. This focus in this paper is on the methodology and dataset, which form a sound foundation for forthcoming publications on the empirical results.
Image visibility of cancer to enhance targeting precision and spatial mapping biopsy for focal therapy of prostate cancer
Authors: Ukimura Osamu , de Castro Abreu Andre Luis , Gill Inderbir S. , Shoji Sunao , Hung Andrew J. , Bahn Duke
Published: May 2013

Objective

To assess the advantages of cancer image visibility when using multiparametric transrectal ultrasonography (TRUS) in potential candidates for focal therapy for prostate cancer.

Patients and Methods

A total of 93 potential candidates for focal cryotherapy underwent grey‐scale and Doppler TRUS‐guided biopsy.

All real‐time TRUS images were recorded, allowing subsequent reviewing for the planning of targeted focal cryotherapy, and/or follow‐up targeted biopsy. The spatial mapping of TRUS‐visible lesions and targeted sampling areas were individually documented in schematic anatomic drawings of the prostate.

Data from the baseline imaging‐targeted biopsies were compared with systematic (non‐targeted) biopsies. Of the 93 patients, 73 patients with low‐ to intermediate‐risk disease were eventually considered to be candidates for hemi‐ablative focal cryosurgery, i.e. cryoablation of one lobe.

Results

Among the 93 patients, a total of 681 biopsy cores were available for analysis, including imaging‐targeted (n = 256, 37.5%) and systematic (n = 425, 62.5%) cores. Of the 256 targeted biopsy cores, 65% (n = 167) were positive for cancer, compared with 6.2% (26/425) in systematic (non‐targeted) cores (P < 0.001). A total of 88% (82/93) of the biopsy‐proven cancer index lesions were TRUS‐visible.

When comparing TRUS‐visible with image‐invisible index lesions, the cancer‐involved core length was 6.1 vs 1.5 mm (P < 0.001), respectively. Furthermore, the percent of core with involved cancer was 48 vs 16% (P < 0.001), and the mean Gleason score was 7.0 vs 6.2 (P < 0.001).

With increasing TRUS‐visible lesion size (<10, 11–15, 16–20, >20 mm), cancer‐involved core length and percent of core with cancer also significantly increased (P = 0.009 and P = 0.008, respectively).

Conclusions

TRUS‐guided targeted biopsies significantly improved the detection and staging of higher grade and larger volume cancer, compared with image‐blind (non‐targeted systematic) biopsies.

Image visibility enhanced the precise targeting and accurate spatial mapping of cancer to help identify more appropriate candidates for focal therapy.
Impact of tumour morphology on renal function decline after partial nephrectomy
Authors: Mehrazin Reza , Palazzi Kerrin L. , Kopp Ryan P. , Colangelo Caroline J. , Stroup Sean P. , Masterson James H. , Liss Michael A. , Cohen Seth A. , Jabaji Ramzi , Park Samuel K. , Patterson Anthony L. , L'Esperance James O. , Derweesh Ithaar H.
Published: May 2013

Objective

To examine the association of renal morphology with renal function after partial nephrectomy (PN).

Patients and Methods

We conducted a multi‐institutional retrospective analysis of 322 PNs performed between 2003 and 2011.

The RENAL nephrometry score for each lesion was determined and the estimated glomerular filtration rate (eGFR) was calculated preoperatively and at last follow‐up.

We divided patients into two RENAL nephrometry score groups, low (<8) and high (≥8), and analysed and compared the outcomes of each group.

The primary outcome was median change in eGFR between preoperative and last follow‐up (ΔeGFR). The secondary outcome was eGFR <60 mL/min/1.73m2 at last follow‐up.

Multivariable analysis was conducted to evaluate the risk factors for eGFR <60 mL/min/1.73 m2 at last follow‐up.

Results

The median (interquartile range) follow‐up was 25.2 (13.5–39.3) months. Low (n = 165) and high (n = 157) RENAL score groups were well‐matched for baseline eGFR. The median tumour size (4.2 vs 2.4 cm, P < 0.001) was greater for the high group.

In all, 64% of the low and 88.2% of the high RENAL score group (P < 0.001) had decreased eGFR at last follow‐up.

Median eGFR was −7 for the low vs −13.8 mL/min/1.73 m2 for the high group (P = 0.001); eGFR <60 mL/min/1.73 m2 at last follow‐up was 27.3% for the low vs 37.6% for the high group (P = 0.057).

Linear regression analysis showed that for each 1‐point increase in RENAL score, there was 2.5% decrease in eGFR (P = 0.002); for each 1‐cm increase in tumour size, there was 1.8% decrease in eGFR (P = 0.013). Area under curve analyses showed no significant difference between RENAL score and tumour size for prediction of de novo eGFR <60 mL/min/1.73 m2 (P = 0.920) and ΔeGFR ≥50% (P = 0.85).

Multivariable analysis showed that increasing RENAL score (odds ratio [OR] 1.24, P = 0.046) and decreasing preoperative eGFR (OR 1.10, P < 0.001) were risk factors for eGFR <60 mL/min/1.73 m2 at last follow‐up.

Conclusions

Increasing RENAL nephrometry score is an independent risk factor for eGFR <60 mL/min/1.73 m2 after PN.

RENAL nephrometry score may serve as an additional measure for risk stratification before PN, but further investigation is required.
Platelet‐mediated angiogenesis is independent of VEGF and fully inhibited by aspirin
Authors: Etulain J , Fondevila C , Negrotto S , Schattner M
Published: May 2013

Background and Purpose

Platelets are major players in every step of vessel development through the local delivery of angiogenesis‐modulating factors, including the pro‐angiogenic protein VEGF and the anti‐angiogenic endostatin. Although thrombin is a potent agonist and is highly elevated in angiogenesis‐related diseases, studies regarding its action on the release of platelet angiogenic factors are scarce and controversial. Herein, we have investigated the role of thrombin not only in VEGF and endostatin release but also in net platelet angiogenic activity.

Experimental Approach

Human platelets were stimulated with thrombin in the presence of the various inhibitors of the signalling pathways involved in platelet activation. Supernatants/releasates were used to determine the levels of angiogenic molecules and to induce angiogenic responses.

Key Results

We found that thrombin induced the secretion of both VEGF and endostatin; however, the overall effect of the releasates was pro‐angiogenic as they promoted tubule‐like formation and increased the proliferation of endothelial cells. Both responses were only slightly suppressed in the presence of a VEGF receptor‐neutralizing antibody. Pharmacological studies revealed that while inhibitors of PKC, p38, ERK1/2, Src kinases or PI3K/Akt exerted only partial inhibitory effects, aspirin fully blocked the pro‐angiogenic activity of the releasate.

Conclusions and Implications

In contrast to current belief, platelet pro‐angiogenic responses are independent of VEGF and appear to be the result of the combined action of several molecules. Moreover, our data reinforce the notion that aspirin is a good candidate for a therapeutic agent to treat angiogenesis‐related diseases.
Postsynaptic mechanisms underlying the excitatory action of histamine on medial vestibular nucleus neurons in rats
Authors: Zhang Xiao‐Yang , Yu Lei , Zhuang Qian‐Xing , Peng Shi‐Yu , Zhu Jing‐Ning , Wang Jian‐Jun
Published: May 2013

Background and Purpose

Anti‐histaminergic drugs have been widely used in the clinical treatment of vestibular disorders and most studies concentrate on their presynaptic actions. The present study investigated the postsynaptic effect of histamine on medial vestibular nucleus (MVN) neurons and the underlying mechanisms.

Experimental Approach

Histamine‐induced postsynaptic actions on MVN neurons and the corresponding receptor and ionic mechanisms were detected by whole‐cell patch‐clamp recordings on rat brain slices. The distribution of postsynaptic histamine H1, H2 and H4 receptors was mapped by double and single immunostaining. Furthermore, the expression of mRNAs for H1, H2 and H4 receptors and for subtypes of Na+–Ca2+ exchangers (NCXs) and hyperpolarization‐activated cyclic nucleotide‐gated (HCN) channels was assessed by quantitative real‐time RT‐PCR.

Key Results

A marked postsynaptic excitatory effect, co‐mediated by histamine H1 and H2 receptors, was involved in the histamine‐induced depolarization of MVN neurons. Postsynaptic H1 and H2 rather than H4 receptors were co‐localized in the same MVN neurons. NCXs contributed to the inward current mediated by H1 receptors, whereas HCN channels were responsible for excitation induced by activation of H2 receptors. Moreover, NCX1 and NCX3 rather than NCX2, and HCN1 rather than HCN2‐4 mRNAs, were abundantly expressed in MVN.

Conclusion and Implications

NCXs coupled to H1 receptors and HCN channels linked to H2 receptors co‐mediate the strong postsynaptic excitatory action of histamine on MVN neurons. These results highlight an active role of postsynaptic mechanisms in the modulation by central histaminergic systems of vestibular functions and suggest potential targets for clinical treatment of vestibular disorders.

Linked Articles

This article is part of a themed issue on Histamine Pharmacology Update. To view the other articles in this issue visit http://dx.doi.org/
10.1111/bph.2013.170.issue‐1
Tying the knot between cytokine and toll‐like receptor signaling in gastrointestinal tract cancers
Authors: Tye Hazel , Jenkins Brendan J.
Published: May 2013

Inflammation‐associated malignancies of the gastrointestinal tract (GI), including those of the stomach and colon, collectively rank as the highest cause of cancer‐related deaths worldwide. It has been well documented that the deregulated activation of the archetypal pro‐inflammatory and oncogenic transcription factors nuclear factor‐kappa B (NF‐κB) and signal transducer and activator of transcription (STAT)3 is a common feature of GI cancers that invariably correlates with poor prognosis. Signal transducer and activator of transcription 3 and NF‐κB are key downstream signal transducers of the interleukin (IL)‐6 cytokine and toll‐like receptor (TLR) families, respectively, and until recently, the potential involvement of these two families in the pathogenesis of cancer has been investigated in isolation. However, there is now emerging evidence of the complex interplay between the IL‐6 cytokine and TLR families in GI tract cancers, with a surprising twist in the identification of a non‐immune role for specific TLR family members. In this review, we discuss the molecular mechanisms associated with cross‐talk between the IL‐6 cytokine family/STAT3 signaling network and the TLR family/NF‐κB signaling network, and we address the potential benefit of their therapeutic targeting in gastric and colorectal cancers.
Bone morphogenetic protein‐6 induces castration resistance in prostate cancer cells through tumor infiltrating macrophages
Authors: Lee Geun Taek , Jung Yeon Suk , Ha Yun‐Sok , Kim Jeong Hyun , Kim Wun‐Jae , Kim Isaac Y.
Published: May 2013

Bone morphogenetic protein (BMP) is a pleiotropic growth factor that has been implicated in inflammation and prostate cancer (CaP) progression. We investigated the potential role of BMP‐6 in the context of macrophages and castration‐resistant prostate cancer. When the androgen‐responsive murine (Tramp‐C1 and PTENCaP8) and human (LNCaP) CaP cell lines were cocultured with macrophages in the presence of dihydrotestosterone, BMP‐6 increased androgen‐responsive promoter activity and cell count significantly. Subsequent studies revealed that BMP‐6 increased the expression level of androgen receptor (AR) mRNA and protein in CaP cell lines only in the presence of macrophages. Simultaneously, the AR antagonists bicalutamide and MDV3100 partially or completely blocked BMP‐6‐induced macrophage‐mediated androgen hypersensitivity in CaP cells. Abolishing interleukin‐6 signaling with neutralizing antibody in CaP/macrophage cocultures inhibited the BMP‐6‐mediated AR upregulation in CaP cells. Using Tramp‐C1 and PTENCaP8 cells with a tetracycline‐inducible expression of BMP‐6, the induction of BMP‐6 in vivo resulted in a significant resistance to castration. However, this resistance was blocked after the removal of macrophages with clodronate liposomes. Taken together, these results show that BMP‐6 induces castration resistance by increasing the expression of AR through macrophage‐derived interleukin‐6.
Mouse models for Aicardi–Goutières syndrome provide clues to the molecular pathogenesis of systemic autoimmunity
Authors: Behrendt R , Roers A
Published: May 2013

Aicardi–Goutières syndrome (AGS) is a hereditary autoimmune disease which overlaps clinically and pathogenetically with systemic lupus erythematosus (SLE), and can be regarded as a monogenic variant of SLE. Both conditions are characterized by chronic activation of anti-viral type I interferon (IFN) responses. AGS can be caused by mutations in one of several genes encoding intracellular enzymes all involved in nucleic acid metabolism. Mouse models of AGS-associated defects yielded distinct phenotypes and reproduced important features of the disease. Analysis of these mutant mouse lines stimulated a new concept of autoimmunity caused by intracellular accumulations of nucleic acids, which trigger a chronic cell-intrinsic antiviral type I IFN response and thereby autoimmunity. This model is of major relevance for our understanding of SLE pathogenesis. Findings in gene-targeted mice deficient for AGS associated enzymes are summarized in this review.
Blood pressure in Afghan male immigrants to Denmark
Authors: Asmar Ali , Bülow Jens , Simonsen Lene , Christensen Niels J. , Frandsen Erik , Norsk Peter
Published: May 2013

Purpose

Immigration from a Third‐World society to a Western society can be associated with higher blood pressure and salt sensitivity. We therefore tested whether immigrants from Afghanistan to Denmark compared with non‐immigrant Danes exhibit a (i) higher 24‐h ambulatory blood pressure (24‐h ABP) and (ii) blunted renin response to a change in salt intake.

Methods

Twenty‐four‐hour ABP was measured in 40 men of Afghan (Afghans) and 40 men of Danish (Danes) origin. Each group was divided into young (20–30 years, n = 20) and middle aged (40–60 years, n = 20). A 3‐day low (70 mmol per 24‐h) and a 3‐day high (250 mmol per 24‐h) salt intake were in addition instituted in subgroups of the young groups (n = 18).

Results

Young and middle‐aged Afghans exhibited a lower 24‐h mean arterial pressure (24‐h MAP) than the same respective age groups of Danes (83 ± 1 versus 90 ± 1 mm Hg, P<0·05, and 89 ± 2 versus 100 ± 1 mm Hg, P<0·05). 24‐h ABP did not change in any of the young groups during increased salt intake, whereas the Danes exhibited a greater decrease in plasma renin activity (PRA) (P<0·05). Plasma noradrenaline (PNA) was significantly higher among the young Afghans.

Conclusions

Afghan immigrants to Denmark exhibit a lower 24‐h ABP than Danes. In young Afghans, PRA is less sensitive to changes in salt intake, while PNA is higher and may reflect their lower systolic blood pressure and/or arterial pulse pressure. Whether these hormonal differences can explain the lower 24‐h ABP in Afghans should be further explored.
The presence of a cytopathologist increases the diagnostic accuracy of endoscopic ultrasound‐guided fine needle aspiration cytology for pancreatic adenocarcinoma: a meta‐analysis
Authors: Hébert‐Magee S. , Bae S. , Varadarajulu S. , Ramesh J. , Frost A. R. , Eloubeidi M. A. , Eltoum I. A.
Published: May 2013

Objective

A meta‐analysis has not been previously performed to evaluate critically the diagnostic accuracy of endoscopic ultrasound‐guided fine needle aspiration (EUS‐FNA) of solely pancreatic ductal adenocarcinoma and address factors that have an impact on variability of accuracy. The aim of this study was to determine whether the presence of a cytopathologist, variability of the reference standard and other sources of heterogeneity significantly impacts diagnostic accuracy.

Methods

We conducted a comprehensive search to identify studies, in which the pooled sensitivity, specificity, likelihood ratios for a positive or negative test (LR+, LR−) and summary receiver‐operating curves (SROC) could be determined for EUS‐FNA of the pancreas for ductal adenocarcinoma using clinical follow‐up, and/or surgical biopsy or excision as the reference standard.

Results

We included 34 distinct studies (3644 patients) in which EUS‐FNA for a solid pancreatic mass was evaluated. The pooled sensitivity and specificity for EUS‐FNA for pancreatic ductal adenocarcinoma was 88.6% [95% confidence interval (CI): 87.2–89.9] and 99.3% (95% CI: 98.7–99.7), respectively. The LR+ and LR– were 33.46 (95% CI: 20.76–53.91) and 0.11 (95% CI: 0.08–0.16), respectively. The meta‐regression model showed rapid on‐site evaluation (ROSE) (P = 0.001) remained a significant determinant of EUS‐FNA accuracy after correcting for study population number and reference standard.

Conclusion

EUS‐FNA is an effective modality for diagnosing pancreatic ductal adencarcinoma in solid pancreatic lesions, with an increased diagnostic accuracy when using on‐site cytopathology evaluation.
Plasticity during childhood and adolescence: innovative approaches to investigating neurocognitive development
Authors: Kadosh Kathrin Cohen , Linden David E.J. , Lau Jennifer Y.F.
Published: May 2013

Adolescence is a period of profound change, which holds substantial developmental milestones, but also unique challenges to the individual. In this opinion paper, we highlight the potential of combining two recently developed behavioural and neural training techniques (cognitive bias modification and functional magnetic neuroimaging‐based neurofeedback) into a research approach that could help make the most of increased levels of plasticity during childhood and adolescence. We discuss how this powerful combination could be used to explore changing brain–behaviour relationships throughout development in the context of emotion processing, a cognitive domain that exhibits continuous development throughout the second decade of life. By targeting both behaviour and brain response, we would also be in an excellent position to define sensible time windows for enhancing plasticity, thereby allowing for targeted intervention approaches that can help improve emotion processing in both typically and atypically developing populations.
Undifferentiated facial electromyography responses to dynamic, audio‐visual emotion displays in individuals with autism spectrum disorders
Authors: Rozga Agata , King Tricia Z. , Vuduc Richard W. , Robins Diana L.
Published: May 2013

We examined facial electromyography (fEMG) activity to dynamic, audio‐visual emotional displays in individuals with autism spectrum disorders (ASD) and typically developing (TD) individuals. Participants viewed clips of happy, angry, and fearful displays that contained both facial expression and affective prosody while surface electrodes measured corrugator supercilli and zygomaticus major facial muscle activity. Across measures of average and peak activity, the TD group demonstrated emotion‐selective fEMG responding, with greater relative activation of the zygomatic to happy stimuli and greater relative activation of the corrugator to fearful stimuli. In contrast, the ASD group largely showed no significant differences between zygomatic and corrugator activity across these emotions. There were no group differences in the magnitude and timing of fEMG response in the muscle congruent to the stimuli. This evidence that fEMG responses in ASD are undifferentiated with respect to the valence of the stimulus is discussed in light of potential underlying neurobiological mechanisms.
Selective and faithful imitation at 12 and 15 months
Authors: Hilbrink Elma E. , Sakkalou Elena , Ellis‐Davies Kate , Fowler Nia C. , Gattis Merideth
Published: May 2013

Research on imitation in infancy has primarily focused on what and when infants imitate. More recently, however, the question why infants imitate has received renewed attention, partly motivated by the finding that infants sometimes selectively imitate the actions of others and sometimes faithfully imitate, or overimitate, the actions of others. The present study evaluates the hypothesis that this varying imitative behavior is related to infants' social traits. To do so, we assessed faithful and selective imitation longitudinally at 12 and 15 months, and extraversion at 15 months. At both ages, selective imitation was dependent on the causal structure of the act. From 12 to 15 months, selective imitation decreased while faithful imitation increased. Furthermore, infants high in extraversion were more faithful imitators than infants low in extraversion. These results demonstrate that the onset of faithful imitation is earlier than previously thought, but later than the onset of selective imitation. The observed relation between extraversion and faithful imitation supports the hypothesis that faithful imitation is driven by the social motivations of the infant. We call this relation the King Louie Effect: like the orangutan King Louie in The Jungle Book, infants imitate faithfully due to a growing interest in the interpersonal nature of interactions.

A video abstract of this article can be viewed at http://youtu.be/qlnIof1k-u8.
Environmental factors driving the effectiveness of European agri‐environmental measures in mitigating pollinator loss – a meta‐analysis
Authors: Scheper Jeroen , Holzschuh Andrea , Kuussaari Mikko , Potts Simon G. , Rundlöf Maj , Smith Henrik G. , Kleijn David
Published: May 2013

In Europe, agri‐environmental schemes (AES) have been introduced in response to concerns about farmland biodiversity declines. Yet, as AES have delivered variable results, a better understanding of what determines their success or failure is urgently needed. Focusing on pollinating insects, we quantitatively reviewed how environmental factors affect the effectiveness of AES. Our results suggest that the ecological contrast in floral resources created by schemes drives the response of pollinators to AES but that this response is moderated by landscape context and farmland type, with more positive responses in croplands (vs. grasslands) located in simple (vs. cleared or complex) landscapes. These findings inform us how to promote pollinators and associated pollination services in species‐poor landscapes. They do not, however, present viable strategies to mitigate loss of threatened or endangered species. This indicates that the objectives and design of AES should distinguish more clearly between biodiversity conservation and delivery of ecosystem services.
Multiscale characterization of partially demineralized superficial and deep dentin surfaces
Authors: Pelin Irina M. , Trunfio‐Sfarghiu Ana‐Maria , Farge Pierre , Piednoir Agnes , Pirat Christophe , Ramos Stella M. M.
Published: May 2013

The objective of this study was to address the following question: ‘Which properties are modified in partially demineralized surfaces, compared with non‐demineralized dentin surfaces, following orthophosphoric acid‐etching as performed in clinical procedures?’. For this purpose, the complementary techniques atomic force microscopy/spectroscopy, scanning electron microscopy, energy‐dispersive X‐ray spectroscopy, and contact angle measurements were used to provide a multiscale characterization of the dentin substrate undergoing the acidic preconditioning designed to enhance wetting. Special attention was given to the influence of the etching pretreatment on the nanomechanical properties at different levels of dentin surfaces, in both dry and hydrated conditions. The four‐sided pyramid model (extended Hertz contact model) proved to be accurate for calculating the apparent Young's modulus, offering new information on the elasticity of dentin. The modulus value notably decreased following etching and surface hydration. This study underlines that after the acid etching pretreatment the contribution of the nanomechanical, morphological, and physicochemical modifications has a strong influence on the dentin adhesion properties and thus plays a significant role in the coupling of the adhesive–resin composite build‐up material at the dentin surface.
Fisetin inhibits growth, induces G2/M arrest and apoptosis of human epidermoid carcinoma A431 cells: role of mitochondrial membrane potential disruption and consequent caspases activation
Authors: Pal Harish C. , Sharma Samriti , Elmets Craig A. , Athar Mohammad , Afaq Farrukh
Published: May 2013

Non‐melanoma skin cancers (NMSCs), one of the most common neoplasms, cause serious morbidity and mortality. Therefore, identification of non‐toxic phytochemicals for prevention/treatment of NMSCs is highly desirable. Fisetin (3,3′,4′,7‐tetrahydroxyflavone), a dietary flavonoid, present in fruits and vegetables possesses anti‐oxidant and antiproliferative properties. The aim of this study was to investigate the chemotherapeutic potential of fisetin in cultured human epidermoid carcinoma A431 cells. Treatment of A431 cells with fisetin (5–80 μm) resulted in a significant decrease in cell viability in a dose‐ and time‐dependent manner. Employing clonogenic assay, we found that fisetin treatment significantly reduced colony formation in A431 cells. Fisetin treatment of A431 cells resulted in G2/M arrest and induction of apoptosis. Furthermore, treatment of A431 cells with fisetin resulted in (i) decreased expression of anti‐apoptotic proteins (Bcl2; Bcl‐xL and Mcl‐1); (ii) increased expression of pro‐apoptotic proteins (Bax, Bak and Bad); (iii) disruption of mitochondrial potential; (iv) release of cytochrome c and Smac/DIABLO from mitochondria; (v) activation of caspases; and (vi) cleavage of Poly(ADP‐ribose) polymerase (PARP) protein. Pretreatment of A431 cells with the pan‐caspase inhibitor (Z‐VAD‐FMK) blocked fisetin‐induced cleavage of caspases and PARP. Taken together, these data provide evidence that fisetin possesses chemotherapeutic potential against human epidermoid carcinoma A431 cells. Overall, these results suggest that fisetin could be developed as a novel therapeutic agent for the management of NMSCs.
A macroecological perspective of trait patterns in stream communities
Authors: Heino Jani , Schmera Dénes , Erős Tibor
Published: May 2013

Other than some classical ideas, large‐scale approaches to understand variation in organismal traits (or the trait composition of an ecological community) across stream ecosystems are rather recent. Recent case studies and review papers show clear evidence for the usefulness of trait‐based analyses in bioassessment, but how community traits vary along natural gradients at large scales has not yet been synthesised. Here, we attempt to fill this gap by providing a synthesis of trait patterns of stream communities from a macroecological perspective.

We argue that although both natural and anthropogenic filters shape community traits, examination of poorly understood natural filters, including those acting at large scales, should receive increasing attention. Such knowledge is vital for reliably inferring anthropogenic impacts on stream communities and ecosystems.

We synthesise knowledge of two large‐scale spatial patterns of stream communities: among drainage basins (i.e. geographical variation) and within drainage basins (i.e. longitudinal variation). We also examine the temporal dimension of organismal traits. Our review highlights clear evidence for large‐scale influences on the trait composition in stream systems. For example, despite previous contentions that organismal traits should vary negligibly across large geographical gradients, there is actually clear geographical variation across near‐pristine systems. Furthermore, in accordance with theory, organismal traits in actual data sets vary along the longitudinal gradient of stream systems.

We provide an overview of empirical and statistical approaches to understanding the trait composition of stream communities in macroecological studies and conclude that the methodology should be carefully considered in comparisons among studies, because contrasting results may reflect not only ecological differences but also differences in methodology (e.g. choice of species traits, trait quantification and analytical methods).

We conclude that the question of how the trait composition of stream communities varies along geographical and environmental gradients is far from settled. A challenge for large‐scale stream ecology is to provide a more specific view of trait variation in multiple taxonomic groups (e.g. do traits vary similarly in different organisms groups?), along major environmental gradients (e.g. is trait variation similar along the same environmental gradients in different regions?) and among different regional entities (e.g. do the traits vary, on average, among different regions?).
Purchasing factor concentrates in the 21st century through competitive tendering
Authors: Hay C. R. M.
Published: May 2013

The increasing intensity of treatment, the widespread adoption of factor VIII and IX prophylaxis and increasing usage over the past decade have led to haemophilia becoming an almost uniquely expensive condition to treat. The average adult with severe haemophilia A in the UK used 250 000 IU of factor VIII in 2011/2012, at a cost in excess of £100 000 p.a. The cost to the end‐user may be considerably higher than this for some US patients supplied by home care companies with high on‐costs. This has led to a high level of administrative scrutiny of treatment and an imperative to procure clotting factor concentrates more efficiently and collectively. National procurement schemes have run successfully in various countries and will become commoner. The UK system of procurement is described. This system, following EU procurement rules, evaluated products technically and by price. The price of bioequivalent products was determined by reverse e‐auction. Considerable cost reductions were achieved whilst retaining all suppliers and maintaining a degree of prescribing freedom. Elements of this system could be more widely applied.
Incidence and clinicopathological characteristics of intraductal carcinoma detected in prostate biopsies: a prospective cohort study
Authors: Watts Katherine , Li Jianbo , Magi‐Galluzzi Cristina , Zhou Ming
Published: May 2013

Aims

Intraductal carcinoma of the prostate (IDC‐P) is a distinct clinicopathological entity and is associated with aggressive, high‐grade and high‐volume prostate carcinoma (PCa). The incidence, clinicopathological characteristics and prognostic significance of IDC‐P have not been reported in prostate biopsies (PBx) that surgical pathologists encounter in their daily practice.

Methods and results

In 1176 prospectively collected PBx, 33 IDC‐P cases were identified (2.8%). The mean age of patients with IDC‐P was 65 (range 46–79) years and mean serum prostate‐specific antigen was 16.2 (range 0.4–105.6) ng/ml. Three (0.26%) IDC‐P cases did not have a concomitant invasive PCa. Of 30 cases with concomitant invasive PCa, Gleason score was 7 in 16 (53.3%), 8 in four (13.3%) and 9 in 10 (33.3%) cases. The mean number of biopsy cores involved by PCa was 7.2 (range 1–14). Nine patients were treated with radical prostatectomy. Seminal vesicle invasion was found in four of nine (44%) cases, significantly higher than the risk of 12% predicted by Partin Tables (P = 0.016).

Conclusions

This is the first prospective study that has investigated the incidence and prognostic significance of IDC‐P diagnosed in PBx encountered in daily practice. It is critical for surgical pathologists to diagnose and report IDC‐P in PBx.