bluuebunny/crossref_metadata_2025 huggingface dataset:
Medical Students' Conceptualizations of Quality of Life Associated With Children With IBD
Authors: Salazar Guadalupe , Barker Judith C. , Heyman Melvin B.
Published: June 2013

Objectives:

The aim of the present study was to investigate second‐year medical students' understanding of quality of life associated with childhood inflammatory bowel disease (IBD).

Methods:

A cross‐sectional study in a major teaching institution in San Francisco was carried out. A questionnaire was administered following an hour‐long gastroenterology lecture, which featured 2 young patients with pediatric‐onset IBD who addressed everyday life with the disease. Analyses of numerate responses to the questionnaire were paired with a content and thematic analysis of audiotape recordings of the patients' commentaries.

Results:

Medical students' responses to the patient interviews were extremely positive. Medical students gained a new awareness of the psychosocial complexities associated with living with a pediatric chronic illness and a new way of thinking about the meaning of “healthy.” Despite listening to 2 healthy young patients, however, the medical students still conceptualized pediatric IBD in mostly, although not exclusively, negative terms.

Conclusions:

Medical students' perceptions of pediatric IBD improved as a result of listening to the patient interviews. Although this teaching modality effectively introduced students to a complex condition, it did not overcome their unfavorable impression of the effect of IBD on children's lives. The symptoms associated with IBD have stigma attached to them, and these stereotypes influence how medical students perceive those living with this chronic illness. More research and training in this area is necessary.
Correlation of Health‐Related Quality of Life in Children With Inflammatory Bowel Disease, Their Parents, and Physician as Measured by a Visual Analog Scale
Authors: Teitelbaum Jonathan E. , Rajaraman Rajsekar R. , Jaeger Joseph , Para Sindhu , Rakitt Tina
Published: June 2013

Background and Aims:

Inflammatory bowel disease has been shown to affect children's health‐related quality of life (HRQOL) through the use of lengthy questionnaires. We examined whether a pediatric patient's HRQOL, measured by a rapid visual analog scale (“feeling thermometer”), correlates with the perceptions of the HRQOL as determined by the patient's pediatric gastroenterologist and parent(s). Additionally, we attempted to determine whether the HRQOL correlates with the patient's disease activity as determined by validated activity indices.

Methods:

A cross‐sectional study of pediatric patients (ages 7–21 years) who were diagnosed as having Crohn disease, ulcerative colitis, or indeterminate colitis was conducted from January 2011 to May 2011. Each participant (patient, parent(s), and treating pediatric gastroenterologist) completed feeling thermometers to determine the symptom burden as well as therapeutic burden of the patient. The parent(s) and doctor were blinded to the patient's results. Pediatric Ulcerative Colitis Activity Index or a Short Pediatric Crohn Disease Activity Index (S‐PCDAI) was calculated. Correlations between the participant's perceived burdens as well as their calculated disease activity were determined.

Results:

Sixty‐seven children and their families participated, resulting in 101 visits. Patients had a mean age of 15.0 years, and there were 38 boys. There was a strong significant correlation between the patient's perceived symptom burden and that of the parent's (ρ 0.59, P < 0.001) and physician (ρ 0.48, P < 0.001). Similarly, there was a strong significant correlation between patient's perceived treatment burden and that of the parent treatment burden (ρ 0.49, P < 0.001) and, to a lesser degree, the physician (ρ 0.29, P < 0.003). The correlation coefficient was strongest between the physician's perception of the patient's symptom burden against the standard disease activity indices Pediatric Ulcerative Colitis Activity Index (ρ 0.69, P < 0.001) and Short Pediatric Crohn Disease Activity Index (ρ 0.65, P < 0.001).

Conclusions:

The patient's HRQOL was highly correlated to both the physician's and parent's perceptions as well as their disease activity. The feeling thermometer is a quick, easy‐to‐use, visual analog scale that can be implemented in everyday practice to measure a pediatric patient's HRQOL.
C‐ANCA/Proteinase 3–Positive Colitis in Children
Authors: Van Biervliet Stephanie , Bonroy Carolien , Velde Saskia Vande , De Bruyne Ruth , Van Winckel Myriam , Peeters Harald , Delanghe Joris , Stove Veronique , De Vos Martine
Published: June 2013

Aim:

Anti‐neutrophil cytoplasmic antibodies (ANCAs) detected by indirect immunofluorescence have been found in patients with inflammatory bowel disease (IBD). Nevertheless, specific antibodies against proteinase‐3 (PR3) are rare in this context.

Methods:

Sera from 30 consecutive pediatric patients with IBD were evaluated for ANCA‐indirect immunofluorescence and its specific antibodies to investigate whether PR3‐ANCA positivity (PR3‐ANCA+) identifies a distinct IBD subtype.

Results:

The 5 PR3‐ANCA+ patients (17%) showed significantly more concomitant biliary disease and severe anal blood loss (P < 0.05). None had vasculitis features at diagnosis nor during follow‐up.

Conclusions:

This pilot study demonstrates significant clinical differences between the PR3‐ANCA–positive and –negative IBD subset.
Three Main Factors Define Changes in Fecal Microbiota Associated With Feeding Modality in Infants
Authors: Gomez‐Llorente Carolina , Plaza‐Diaz Julio , Aguilera Margarita , Muñoz‐Quezada Sergio , Bermudez‐Brito Miriam , Peso‐Echarri Patricia , Martinez‐Silla Rosario , Vasallo‐Morillas M. Isabel , Campaña‐Martin Laura , Vives‐Piñera Inmaculada , Ballesta‐Martinez Maria J. , Gil Angel
Published: June 2013

Objectives:

There are many differences in the fecal infant microbiota associated with various feeding methods. The aim of this study was to examine the major differences in the fecal microbiota of breast‐fed (BF) and formula‐fed (FF) infants and to describe the principal bacterial components that would explain the variability in the predominant bacterial families and genus clusters.

Methods:

Fecal samples from 58 infants, 31 of whom were exclusively BF and 27 of whom were exclusively FF with a standard formula in agreement with the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition recommendations, were analyzed by fluorescent in situ hybridization combined with flow cytometry. Principal component analysis was used to maximize the information gained for the predominant bacterial families and genus clusters using a minimal number of bacterial groups.

Results:

The predominant detected group was Bifidobacterium, followed by Enterobacteriaceae and Bacteroides in both BF and FF infants. The Lactobacillus group was the only independent variable associated with FF infants. We also found that 3 principal components were sufficient to describe the association between the bacterial group, genus, and species studied in BF and FF infants; however, these components differed between BF and FF infants. For the former, the 3 factors found were Bifidobacterium/Enterobacteriaceae, Lactobacillus/Bacteroides, and Clostridium coccoides/Atopobium; for the latter, Bifidobacterium/Enterobacteriaceae, Bacteroides and C coccoides were observed.

Conclusions:

There is a clear clustering of components of infant microbiota based on the feeding method.
Transcriptomic and Metabolic Changes Associated with Photorespiratory Ammonium Accumulation in the Model Legume Lotus japonicus
Authors: Pérez-Delgado Carmen M. , García-Calderón Margarita , Sánchez Diego H. , Udvardi Michael K. , Kopka Joachim , Márquez Antonio J. , Betti Marco
Published: June 2013

The transcriptomic and metabolic consequences of the lack of plastidic glutamine (Gln) synthetase in the model legume Lotus japonicus were investigated. Wild-type and mutant plants lacking the plastidic isoform of Gln synthetase were grown in conditions that suppress photorespiration and then transferred for different lengths of time to photorespiratory conditions. Transcript and metabolite levels were determined at the different time points considered. Under photorespiratory active conditions, the mutant accumulated high levels of ammonium, followed by its subsequent decline. A coordinate repression of the photorespiratory genes was observed in the mutant background. This was part of a greater modulation of the transcriptome, especially in the mutant, that was paralleled by changes in the levels of several key metabolites. The data obtained for the mutant represent the first direct experimental evidence for a coordinate regulation of photorespiratory genes over time. Metabolomic analysis demonstrated that mutant plants under active photorespiratory conditions accumulated high levels of several amino acids and organic acids, including intermediates of the Krebs cycle. An increase in Gln levels was also detected in the mutant, which was paralleled by an increase in cytosolic Gln synthetase1 gene transcription and enzyme activity levels. The global panoramic of the transcripts and metabolites that changed in L. japonicus plants during the transfer from photorespiration-suppressed to photorespiration-active conditions highlighted the link between photorespiration and several other cellular processes, including central carbon metabolism, amino acid metabolism, and secondary metabolism.
Four related esters: two 4-(aroylhydrazinyl)-3-nitrobenzoates and two 3-aryl-1,2,4-benzotriazine-6-carboxylates
Authors: Cortés Edwar , Abonía Rodrigo , Cobo Justo , Glidewell Christopher
Published: June 2013

The molecules of both methyl 4-[2-(4-chlorobenzoyl)hydrazinyl]-3-nitrobenzoate, C15H12ClN3O5, (I), and methyl 4-[2-(2-fluorobenzoyl)hydrazinyl]-3-nitrobenzoate, C15H12FN3O5, (II), contain an intramolecular N—H...O hydrogen bond, and both show electronic polarization in the nitrated aryl ring. In both compounds, molecules are linked by a combination of N—H...O and C—H...O hydrogen bonds to form sheets, which are built fromR43(18) rings in (I) and fromR44(28) rings in (II). In each of methyl 3-phenyl-1,2,4-benzotriazine-6-carboxylate, C15H11N3O2, (III), and methyl 3-(4-methylphenyl)-1,2,4-benzotriazine-6-carboxylate, C16H13N3O2, (IV), the benzotriazine unit shows naphthalene-type delocalization. There are no hydrogen bonds in the structures of compounds (III) and (IV), but in both compounds, the molecules are linked into chains by π–π stacking interactions involving the benzotriazine units. The mechanism of chain formation is the same in both (III) and (IV), and the different orientations of the two chains can be related to the approximate relationship between the unit-cell metrics for (III) and (IV).
1,4-Bis[2-(4-ferrocenylphenyl)ethynyl]anthraquinone from synchrotron X-ray powder diffraction
Authors: Sachiko Maki , Nishibori Eiji , Aoyagi Shinobu , Sakata Makoto , Takata Masaki , Kondo Mio , Murata Masaki , Sakamoto Ryota , Nishihara Hiroshi
Published: June 2013

The title compound, [Fe2(C5H5)2(C40H22O2)] or 1,4-(FcPh)2Aq [where FcPh is 2-(4-ferrocenylphenyl)ethynyl and Aq is anthraquinone], was synthesized in an attempt to obtain a new solvent-incorporating porous material with a large void space. Thermodynamic data for 1,4-(FcPh)2Aq show a phase transition at approximately 430 K. The crystal structure of solvent-free 1,4-(FcPh)2Aq was determined at temperatures of 90, 300 and 500 K using synchrotron powder diffraction data. A direct-space method using a genetic algorithm was employed for structure solution. Charge densities calculated from observed structure factors by the maximum entropy method were employed for model improvement. The final models were obtained through multistage Rietveld refinements. In both phases, the structures of which differ only subtly, the planar Aq fragments are stacked alternately in opposite orientations, forming a one-dimensional column. The FcPh arms lie between the stacks and fill the remaining space, leaving no voids. C—H...π interactions between the Ph and Fc fragments mediate crystal packing and stabilization.
Triphenylsilanol–4,4′-bipyridyl (4/1): theZ′ = 4 polymorph revisited
Authors: Cascarano Giovanni L. , Ferguson George , Giacovazzo Carmelo , Glidewell Christopher , Spek Anthony L.
Published: June 2013

A fully ordered structure is reported for the polymorph of triphenylsilanol–4,4′-bipyridyl (4/1), 4C18H16OSi·C10H8N2, havingZ′ = 4. The asymmetric unit contains four similar but distinct five-molecule aggregates, in which the central bipyridyl unit is linked to two molecules of triphenylsilanolviaO—H...N hydrogen bonds, with a further pair of triphenylsilanol molecules linked to the first pairviaO—H...O hydrogen bonds. An extensive series of C—H...π(arene) hydrogen bonds links these aggregates into complex sheets. This structure is compared with a previously reported structure [Bowes, Ferguson, Lough & Glidewell (2003).Acta Cryst.B59, 277–286], which was based on an erroneous disordered structural model arising from a false direct-methods solution with reference to a strong pseudo-inversion centre.
Bis(4-picoline-κN)gold(I) dibromidoaurate(I) and bis(4-picoline-κN)gold(I) dichloridoaurate(I): space-group ambiguity?
Authors: Döring Cindy , Jones Peter G.
Published: June 2013

Bis(4-picoline-κN)gold(I) dibromidoaurate(I), [Au(C6H7N)2][AuBr2], (I), crystallizes in the monoclinic space groupP21/n, with two half cations and one general anion in the asymmetric unit. The cations, located on centres of inversion, assemble to form chains parallel to theaaxis, but there are no significant contacts between the cations. Cohesion is provided by flanking anions, which are connected to the cations by short Au...Au contacts and C—H...Br hydrogen bonds, and to each other by Br...Br contacts. The corresponding chloride derivative, [Au(C6H7N)2][AuCl2], (II), is isotypic. A previous structure determination of (II), reported in the space groupP\overline{1} with very similar axis lengths to those of (I) [Linet al.(2008).Inorg. Chem.47, 2543–2551], might be identical to the structure presented here, except that its γ angle of 88.79 (7)° seems to rule out a monoclinic cell. No phase transformation of (II) could be detected on the basis of data sets recorded at 100, 200 and 295 K.
A trait‐based ecosystem model suggests that long‐term responsiveness to rising atmospheric CO2 concentration is greater in slow‐growing than fast‐growing plants
Authors: Ali Ashehad A. , Medlyn Belinda E. , Crous Kristine Y. , Reich Peter B.
Published: June 2013

Atmospheric carbon dioxide concentration (Ca) has a direct and measurable effect on plant growth. However, it does not affect all plant species equally, which could lead to shifts in competitive dominance of species in ecosystems.

We used a dynamic plant carbon–nitrogen model to systematically examine how species traits affect the long‐term Ca responsiveness of C3 plants when growing as established monocultures in the field. The model was tested against responses of 7 C3 herbaceous species growing in a free‐air Ca enrichment (FACE) experiment (BioCON) in Minnesota, USA.

Model simulations showed that several species traits affected the Ca response strongly, giving rise to a number of testable hypotheses about interspecific differences in responsiveness to Ca. The largest responses to rising Ca were obtained for species with low carbon‐use efficiency (net primary production: gross primary production ratio), low foliar carbon allocation, low stomatal conductance, low instantaneous photosynthetic nitrogen use efficiency and low specific leaf area.

In general, our model predicted that, for established plants growing in resource‐limited field conditions, species with slow growth rates would be most responsive to elevated Ca. This prediction was supported by data from the BioCON experiment.

Our model also predicts that, for young plants growing in non‐resource‐limited conditions, species with high growth rates will be most responsive to elevated Ca. This difference in species ranking under different resource availabilities is largely explained by the indirect effects of Ca on leaf area. Leaf‐area feedbacks favour fast‐growing species the most during leaf‐area expansion, but following stand maturation they favour slow‐growing species the most.

These results imply that species that respond strongly to elevated Ca in short‐term (non‐resource‐limited) glasshouse experiments are unlikely to also be the most responsive in resource‐limited field conditions, and therefore that we cannot directly extrapolate from glasshouse experiments to predict which species will be most responsive to elevated Ca in the long term.
Indirect effects and facilitation among native and non‐native species promote invasion success along an environmental stress gradient
Authors: Zarnetske Phoebe L. , Gouhier Tarik C. , Hacker Sally D. , Seabloom Eric W. , Bokil Vrushali A.
Published: June 2013

The spatial distribution of species is mediated by a combination of biotic interactions and environmental conditions. Understanding the relative importance of these factors and how they interact is particularly important for predicting the spread of non‐native species and their impact on resident communities.

We used a 3‐species Lotka–Volterra model parameterized with field and experimental data to understand the potential for continued spread by an introduced, non‐native, dune‐building beach grass (Ammophila breviligulata) and whether this invasion will result in coexistence or displacement in the resident beach grass communities (native Elymus mollis and introduced, non‐native Ammophila arenaria) of the US Pacific Northwest.

We also used the model to investigate to what extent different rates of ocean‐driven sand supply mediate the outcomes of beach grass species interactions.

Our model suggests that A. breviligulata could invade and dominate dunes across the range of sand supply rates observed in the region. We found that sand supply influenced intra‐ vs. interspecific interactions, the strength of positive and indirect effects among beach grasses and the long‐term abundances of the beach grass species themselves.

Of the two non‐natives, A. breviligulata is the inferior dune‐building species. Thus, our results suggest that further invasions by A. breviligulata could reduce the coastal protection services afforded by tall dunes currently dominated by A. arenaria.

Synthesis: In systems with strong environmental forcing and stressful conditions such as coastal dunes, environmentally mediated positive and indirect species interactions can govern invasion success and long‐term native–non‐native coexistence. In doing so, these interactions ultimately shape community structure and ecosystem function. Understanding the joint effects of environmental forcing and species interactions on community assembly is particularly important in cases where species introductions can alter ecosystem services, such as coastal protection, which are vulnerable to the effects of climate change.
Hayek's Slippery Slope, the Stability of the Mixed Economy and the Dynamics of Rent Seeking
Authors: Alves André Azevedo , Meadowcroft John
Published: June 2013

F. A. Hayek's The Road to Serfdom continues to provoke intense scholarly debate focused on the validity of Hayek's central claim that a mixed economy is inherently unstable and economic intervention will inexorably lead to totalitarianism if pursued for a sustained period. This article presents empirical evidence which shows conclusively that it is the mixed economy that has proved remarkably stable, whereas laissez-faire and totalitarian regimes have proved inherently unstable. It is argued that this empirical outcome can be explained by the dynamics of rent seeking and Hayek's failure to anticipate that the state could control more than half of national income without requiring a totalitarian apparatus to control and direct production and consumption. The implications of the failure of Hayek's argument for our conceptualisation of freedom and power in the context of the modern democratic state and our understanding of the relationship between economic and political freedom are considered.
Buying Low, Flying High: Carbon Offsets and Partial Compliance
Authors: Spiekermann Kai
Published: June 2013

Many companies offer their customers voluntary carbon ‘offset’ certificates to compensate for greenhouse gas emissions. Voluntary offset certificates are cheap because the demand for them is low, allowing consumers to compensate for their emissions without significant sacrifices. Regarding the distribution of emission reduction responsibilities I argue that excess emissions are permissible if they are offset properly. However, if individuals buy offsets only because they are cheap, they fail to be robustly motivated to choose a permissible course of action. This suspected lack of robust motivation raises both pragmatic questions about the functioning of offsetting schemes and moral questions about the worth of such unstable motives. The analysis provided here also has wider implications for the normative analysis of partial compliance and ‘many hands' problems, especially for those cases where compliance levels and costs interact.
A genome‐wide association study to detect genetic variation for postpartum dysgalactia syndrome in five commercial pig breeding lines
Authors: Preissler Regine , Tetens Jens , Reiners Kerstin , Looft Holger , Kemper Nicole
Published: June 2013

Postpartum dysgalactia syndrome (PDS) in sows is an important disease after parturition with a relevant economic impact, affecting the health and welfare of both sows and piglets. The genetic background of this disease has been discussed and its heritability estimated, but further genetic analyses are lacking in detail. The aim of the current study was to detect loci affecting the susceptibility to PDS through a genome‐wide association approach. The study was designed as a family‐based association study with matched sampling of affected sows and healthy half‐ or full‐sib control sows on six farms. For the study, 597 sows (322 affected vs. 275 healthy control sows) were genotyped on 62 163 single nucleotide polymorphisms (SNPs) using the Illumina PorcineSNP60 BeadChip. After quality control, 585 sows (314 affected vs. 271 healthy control sows) and 49 740 SNPs remained for further analysis. Statistics were performed mainly with the r package genabel and included a principal component analysis. A statistically significant genome‐wide associated SNP was identified on porcine chromosome (SSC) 17. Further promising results with moderate significance were detected on SSC 13 and on an unplaced scaffold with an older annotation on SSC 15. The PRICKLE2 and NRP2 genes were identified as candidate genes near associated SNPs. Several quantitative trait loci (QTL) have been previously described in these genomic regions, including QTL for mammary gland condition, as teat number and non‐functional nipples QTL, as well as QTL for body temperature and gestation length.
Fine mapping of the chicken congenital loco locus on chromosome 12
Authors: Okumura Y. , Ohtake T. , Uemoto Y. , Sato S. , Sato S. , Kobayashi E.
Published: June 2013

Congenital loco in chicks is characterized by an apparent lack of control of the muscles of the neck. This disorder is inherited as a simple Mendelian recessive disease, caused by an autosomal recessive gene, lo. To date, there are no reports on the localization of this gene. The objective of this study was therefore to identify the genomic region of the lo locus. The experimental congenital loco population used here were selected from a Rhode Island Red (RIR) line and consisted of six generations, resulting in 124 chickens. A total of 113 DNA samples from offspring of four generations (G3, G4, G5, and G6) were used for genotyping. At first, genome‐wide linkage mapping was performed using 122 microsatellite markers on 22 autosomal chromosomes, and the lo locus was mapped to chromosome 12. We then performed fine mapping in two steps on chromosome 12. First, the lo locus was mapped to the interval between GGA12_5 and GGA12_11 using 13 new polymorphic markers. In the second step, fine mapping was performed by adding new families and 11 additional new polymorphic markers. Linkage mapping and haplotype information enabled the localization of the lo locus to a 1.1‐Mb region between GGA12_28 and GGA12_30. Genetic markers between GGA12_28 and GGA12_30 may be used to remove the carriers of congenital loco through this RIR line.
Agriculture and small towns in Africa
Authors: Dorosh Paul , Thurlow James
Published: June 2013

Africa is urbanizing rapidly. Yet most dual economy models focus on the sectoral rather than spatial dimensions of development. This article adopts a “dual–dual” approach to measuring rural/urban and farm/nonfarm linkages. We develop an economy‐wide model of Ethiopia that distinguishes between cities, towns, and rural areas. The model captures detailed sectoral and regional linkages, internal migration flows, and externalities from urban agglomeration. We find larger linkages between agricultural production and small towns and show that redirecting urban growth toward towns rather than cities leads to broader‐based economic growth and poverty reduction. In contrast, industry and services, particularly within cities, are far less effective in reaching rural areas and the poor. Africa's current urbanization pattern—toward major cities rather than towns—will weaken national growth–poverty linkages. Urbanization that takes advantage of the synergistic relationship between agriculture and small towns has the potential to result in a more inclusive growth trajectory.
Dry eye disease in French elderly subjects: the Alienor Study
Authors: Malet Florence , Le Goff Mélanie , Colin Joseph , Schweitzer Cédric , Delyfer Marie‐Noëlle , Korobelnik Jean‐François , Rougier Marie‐Bénédicte , Radeau Thierry , Dartigues Jean‐François , Delcourt Cécile
Published: June 2013

Purpose:  To describe dry eye disease in French elderly subjects.

Methods:  The Alienor Study is a population‐based study on age‐related eye disease in 963 residents of Bordeaux (France), aged 73 years or more. Self‐reported dry eye disease and use of artificial tears were documented through face‐to‐face interview. Dry eye symptoms were assessed using the Ocular Surface Disease Index (OSDI) questionnaire and tear film stability by tear break‐up time measurements (TBUT). Definite dry eye disease was defined as self‐reported dry eye, confirmed by use of artificial tears and/or OSDI greater or equal to 22.

Results:  Nine hundred and fifteen subjects, with mean age of 80 ± 4 years, returned the OSDI questionnaire. Of these, 271 (29.6%) subjects reported a dry eye disease and 135 (14.7%) were using artificial tears. An OSDI score > 22 was found in 359 (39.2%) subjects and a TBUT < 5 seconds in 335/746 (44.9%) subjects. Overall, definite dry eye affected 21.9% of subjects and was more frequent in women (27.1%) than in men (13.6%). After multivariate adjustment, dry eye disease was also significantly less frequent in subjects with high educational level (odds ratio (OR) = 0.49, 95% confidence interval (CI): 0.31–0.78 for long secondary school) and more frequent in subjects with ocular hypertension (OR = 1.61, 95% CI: 1.02–2.57) and those using anxiolytics (OR = 1.53, 95% CI: 1.02–2.29).

Conclusions:  This large observational study confirmed the high prevalence of dry eye symptoms among elderly subjects and confirmed some of the previously identified risk factors (in particular female gender and use of anxiolytics).
Magnetic resonance imaging (MRI)‐guided transurethral ultrasound therapy of the prostate: a preclinical study with radiological and pathological correlation using customised MRI‐based moulds
Authors: Partanen Ari , Yerram Nitin K. , Trivedi Hari , Dreher Matthew R. , Oila Juha , Hoang Anthony N. , Volkin Dmitry , Nix Jeffrey , Turkbey Baris , Bernardo Marcelino , Haines Diana C. , Benjamin Compton J. , Linehan W. Marston , Choyke Peter , Wood Bradford J. , Ehnholm Gösta J. , Venkatesan Aradhana M. , Pinto Peter A.
Published: June 2013

Objective

To characterise the feasibility and safety of a novel transurethral ultrasound (US)‐therapy device combined with real‐time multi‐plane magnetic resonance imaging (MRI)‐based temperature monitoring and temperature feedback control, to enable spatiotemporally precise regional ablation of simulated prostate gland lesions in a preclinical canine model.

To correlate ablation volumes measured with intra‐procedural cumulative thermal damage estimates, post‐procedural MRI, and histopathology.

Materials and Methods

Three dogs were treated with three targeted ablations each, using a prototype MRI‐guided transurethral US‐therapy system (Philips Healthcare, Vantaa, Finland).

MRI provided images for treatment planning, guidance, real‐time multi‐planar thermometry, as well as post‐treatment evaluation of efficacy.

After treatment, specimens underwent histopathological analysis to determine the extent of necrosis and cell viability.

Statistical analyses (Pearson's correlation, Student's t‐test) were used to evaluate the correlation between ablation volumes measured with intra‐procedural cumulative thermal damage estimates, post‐procedural MRI, and histopathology.

Results

MRI combined with a transurethral US‐therapy device enabled multi‐planar temperature monitoring at the target as well as in surrounding tissues, allowing for safe, targeted, and controlled ablations of prescribed lesions.

Ablated volumes measured by cumulative thermal dose positively correlated with volumes determined by histopathological analysis (r2 0.83, P < 0.001).

Post‐procedural contrast‐enhanced and diffusion‐weighted MRI showed a positive correlation with non‐viable areas on histopathological analysis (r2 0.89, P < 0.001, and r2 0.91, P = 0.003, respectively).

Additionally, there was a positive correlation between ablated volumes according to cumulative thermal dose and volumes identified on post‐procedural contrast‐enhanced MRI (r2 0.77, P < 0.01).

There was no difference in mean ablation volumes assessed with the various analysis methods (P > 0.05, Student's t‐test).

Conclusions

MRI‐guided transurethral US therapy enabled safe and targeted ablations of prescribed lesions in a preclinical canine prostate model.

Ablation volumes were reliably predicted by intra‐ and post‐procedural imaging.

Clinical studies are needed to confirm the feasibility, safety, oncological control, and functional outcomes of this therapy in patients in whom focal therapy is indicated.
Serum prostate‐specific antigen (PSA) concentration is positively associated with rate of disease reclassification on subsequent active surveillance prostate biopsy in men with low PSA density
Authors: Umbehr Martin H. , Platz Elizabeth A. , Peskoe Sarah B. , Bhavsar Nrupen A. , Epstein Jonathan I. , Landis Patricia , Partin Alan W. , Carter H. Ballentine
Published: June 2013

Objective

To investigate the association between serum prostate‐specific antigen (PSA) concentration at active surveillance (AS) entry and disease reclassification on subsequent AS biopsy (‘biopsy reclassification’) in men with low PSA density (PSAD).

To investigate whether a clinically meaningful PSA threshold for AS eligibility/ineligibility for men with low PSAD can be identified based on risk of subsequent biopsy reclassification.

Patients and Methods

We included men enrolled in the Johns Hopkins AS Study (JHAS) who had a PSAD of <0.15 ng/mL/g (640 men).

We estimated the incidence rates (IRs; per 100 person years) and hazard ratios (HR) of biopsy reclassification (Gleason score ≥ 7, any Gleason pattern 4 or 5, ≥3 positive cores, or ≥50% cancer involvement/biopsy core) for categories of serum PSA concentration at the time of entry into AS.

We generated predicted IRs using Poisson regression to adjust for age and prostate volume, mean percentage free PSA (ratio of free to total PSA) and maximum percentage biopsy core involvement with cancer.

Results

The unadjusted IRs (per 100 person years) of biopsy reclassification across serum PSA concentration at entry into JHAS showed, in general, an increase; however, the pattern was not linear with higher IRs in the group ≥ 4 to <6 ng/mL (14.2, 95% confidence interval [CI] 11.8–17.2%) when compared with ≥6 to <8 ng/mL (8.4, 95% CI 5.7–12.3%) but almost similar IRs when compared with the group ≥ 8 to <10 ng/mL (14.8, 95% CI 8.4–26.1%).

The adjusted predicted IRs of reclassification showed a similar non‐linear increase in IRs, whereby the rates around 4 ng/mL were similar to the rates around 10 ng/mL.

Conclusion

Risk for biopsy reclassification increased non‐linearly across PSA concentration in men with low PSAD, whereby no obvious clinically meaningful threshold could be identified. This information could be incorporated into decision‐making for AS. However, longer follow‐up times are needed to warrant final conclusions.
Histological inflammation and risk of subsequent prostate cancer among men with initially elevated serum prostate‐specific antigen (PSA) concentration in the Finnish prostate cancer screening trial
Authors: Yli‐Hemminki Tytti H. , Laurila Marita , Auvinen Anssi , Määttänen Liisa , Huhtala Heini , Tammela Teuvo L.J. , Kujala Paula M.
Published: June 2013

Objective

To assess whether histological signs of inflammation are associated with an increased risk of subsequent prostate cancer (PCa) in men with elevated serum prostate‐specific antigen (PSA) concentrations and benign initial biopsy.

Materials and Methods

Study subjects were men aged 54–67 years with an elevated PSA (≥4 ng/mL or 3–4 ng/mL and free to total PSA ratio ≤0.16 or positive digital rectal examination), but a benign biopsy result within the Finnish population‐based randomised screening trial for PCa, which started in 1996.

A total of 293 prostate biopsies without PCa or suspicion of malignancy from the first screening round in the Tampere centre were re‐evaluated by a uropathologist to assess histological inflammation.

Results of the subsequent screening rounds were obtained from the trial database and PCa diagnoses made outside the screening were obtained from the Finnish Cancer Registry.

The median length of follow‐up was 10.5 years.

Cox regression analysis was used to assess PCa risk after the initial benign biopsy.

Results

Histological inflammation was found in 66% of the biopsies.

Subjects with inflammation at the biopsy had a slightly lower PCa risk in the second screening round (18 vs 27%, rate ratio 0.69, 95% confidence interval [CI] 0.35–1.34) relative to men without inflammation. In further follow‐up, the PCa risk remained nonsignificantly lower (hazard ratio [HR] 0.71, CI 0.46–1.10; P = 0.13). The risk was not appreciably affected by adjustment for age, PSA, prostate volume and family history of PCa (HR 0.67, CI 0.42–1.07; P = 0.092).

Conclusions

Histological inflammation in a prostate biopsy among men with an initial false‐positive screening test was not associated with an increased risk of subsequent PCa, but instead with a decreased risk which was of borderline significance.

Inflammation in prostate biopsy is not a useful risk indicator in PCa screening.
Receptor tyrosine kinases MET and RON as prognostic factors in diffuse large B‐cell lymphoma patients receiving R‐CHOP
Authors: Koh Young Wha , Hwang Hee Sang , Jung Se Jin , Park Chansik , Yoon Dok Hyun , Suh Cheolwon , Huh Jooryung
Published: June 2013

Receptor tyrosine kinases MET and RON (MST1R) form non‐covalent complexes on the cell surface, a critical step in tumor progression. A recent study suggested a prognostic role for MET expression in diffuse large B‐cell lymphoma (DLBCL). The aim of this study was to examine the impact of MET and RON expression in uniformly treated DLBCL patients. The expression of MET and RON was retrospectively examined by immunohistochemistry in 120 DLBCL patients treated with rituximab combined with a CHOP regimen (cyclophosphamide, doxorubicin, vincristine, and prednisone). The median follow‐up time was 42.5 months (range, 1–89 months). Thirty‐two (26%) and 30 patients (25%) expressed MET or RON, respectively. Seventy‐five patients (62.5%) were negative for both MET and RON (MET−RON−). MET negativity was associated with worse overall survival (P = 0.029). In multivariate analysis, negativity for both MET and RON (MET−RON−) was strongly associated with inferior overall survival (P = 0.008). Interestingly, the MET−RON− phenotype retained its prognostic impact after subgroup analysis according to the international prognostic index or by the cell of origin by immunohistochemical algorithm by Choi et al. This study suggests that the MET−RON− phenotype is an independent prognostic factor in DLBCL patients receiving R‐CHOP, and may identify a subgroup of DLBCL patients who require more intensive therapy.
Preptin Analogues: Chemical Synthesis, Secondary Structure and Biological Studies
Authors: Buchanan Christina M. , Peng Zhenzhen , Cefre Aiko , Sarojini Vijayalekshmi
Published: June 2013

Peptide hormones that modulate insulin secretion have been recognized to have therapeutic potential, with peptides such as amylin (pramlintide acetate, Symlin) and exendin‐4 (exenatide, Byetta) now commercially available. Preptin is a peptide that has been shown to increase insulin secretion in vitro and in vivo. Here, we describe the first chemical synthesis and analysis of a short series of preptin analogues based on the rat preptin sequence. Phe 21 in the preptin sequence was substituted with the non‐protein amino acids D‐Phe, D‐Hphe, 3‐aminobenzoic acid and 1‐aminocyclooctane‐1‐carboxylic acid, which rendered the preptin analogues resistant to chymotryptic protease hydrolysis at this position. Substitution of Phe 21 with these non‐protein amino acids did not abrogate the insulin secretory effect of preptin, with analogues showing a similar dose‐dependent effect on insulin secretion from βTC6‐F7 mouse β‐cells in both the presence and absence of glucose as unmodified rat preptin. Further studies on the stability of the preptin analogues and their effect on insulin secretion are in progress.
Sigma‐1 Receptor Knockout Impairs Neurogenesis in Dentate Gyrus of Adult Hippocampus Via Down‐Regulation of NMDA Receptors
Authors: Sha Sha , Qu Wei‐Jun , Li Lin , Lu Zi‐Hong , Chen Lei , Yu Wen‐Feng , Chen Ling
Published: June 2013

Aims

This study investigated the influence of sigma‐1 receptor (σ1R) deficiency on adult neurogenesis.

Methods

We employed 8‐week‐old male σ1R knockout (σ1R−/−) mice to examine the proliferation and differentiation of progenitor cells, and the survival and neurite growth of newborn neurons in hippocampal dentate gyrus (DG).

Results

In comparison with wild‐type (WT) littermates, the numbers of 24‐h‐old BrdU+ cells and Ki67+ cells in σ1R−/− mice increased, while the number of 28‐day‐old BrdU+ cells decreased without changes in proportion of BrdU+/NeuN+ cells and BrdU+/GFAP+ cells. The neurite density of newborn neurons was slightly reduced in σ1R−/− mice. In DG granular cells, N‐methyl‐d‐aspartate (NMDA)‐activated current (INMDA) and phosphorylation of NMDA receptor (NMDAr) NR2B were reduced in σ1R−/− mice without the alteration of NR2B expression and membrane properties compared to WT mice. The NR2B antagonist abolished the difference in INMDA between σ1R−/− mice and WT mice. The application of NMDAr agonist in σ1R−/− mice prevented the over‐proliferation of cells and reduction in newborn neurons, but it had no effects on the hypoplastic neurite. The administration of NMDAr antagonist in WT mice enhanced the cell proliferation and depressed the survival of newborn neurons.

Conclusion

The σ1R deficiency impairs neurogenesis in DG through down‐regulation of NMDArs.
Closing the Knowing–Doing Gap in Invasive Plant Management: Accessibility and Interdisciplinarity of Scientific Research
Authors: Matzek Virginia , Covino Justin , Funk Jennifer L. , Saunders Martin
Published: June 2013

Like many conservation disciplines, invasion biology may suffer from a knowing–doing gap, where scientific research fails to inform management actions. We surveyed California resource managers to evaluate engagement with scientific research and to identify research priorities. We examined managers’ access to information, judgment of the usefulness of existing research, ability to generate scientific information, and priorities for future research. We found that practitioners rely on their own experience, and largely do not read the peer‐reviewed literature, which they regard as only moderately useful. Less than half of managers who do research carry out experiments conforming to the norms of hypothesis testing, and their results are not broadly disseminated. Managers’ research needs are not restricted to applied science, or even basic ecology, but include social science questions. Scientists studying invasions can make their research more useful by crossing disciplinary boundaries, sourcing research questions from practitioners, and reporting results in accessible venues.
A Transparent Process for “Evidence‐Informed” Policy Making
Authors: Dicks Lynn V. , Hodge Ian , Randall Nicola P. , Scharlemann Jörn P.W. , Siriwardena Gavin M. , Smith Henrik G. , Smith Rebecca K. , Sutherland William J.
Published: June 2013

Political institutions are keen to use the best available scientific knowledge in decision‐making. For environmental policy, relevant scientific evidence can be complex and extensive, so expert judgment is frequently relied upon, without clear links to the evidence itself. We propose a new transparent process for incorporating research evidence into policy decisions, involving independent synopsis of evidence relating to all possible policy options combined with expert evaluation of what the evidence means for specific policy questions. We illustrate the process using reforms of the European Union's Common Agricultural Policy currently being negotiated. Under the reform proposals, 30% of direct payments to farmers will become conditional upon three “compulsory greening measures.” Independently, we compiled and evaluated experimental evidence for the effects of 85 interventions to protect wildlife on northern European farmland, 12 of which correspond to aspects of the compulsory greening measures. Our evaluation clearly indicates evidence of consistent wildlife benefits for some, but not all, of the greening measures. The process of evidence synopsis with expert evaluation has three advantages over existing efforts to incorporate evidence into policy decisions: it provides a clear evidence audit trail, allows rapid response to new policy contexts, and clarifies sources of uncertainty.
ALLOCATING INFECTION: THE POLITICAL ECONOMY OF THE SWINE FLU (H1N1) VACCINE
Authors: RYAN MATT E.
Published: June 2013

Previous research has isolated the effect of “congressional dominance” in explaining bureaucracy‐related outcomes. This analysis extends the concept of congressional dominance to the allocation of H1N1, or swine flu, vaccine doses. States with Democratic United States Representatives on the relevant House oversight committee received roughly 60,000 additional doses per legislator during the initial allocation period, though this political advantage dissipated after the first 3 weeks of vaccine distribution. As a result political factors played a role in determining vaccine allocation only when the vaccine was in particularly short supply. At‐risk groups identified by the Centers for Disease Control (CDC), such as younger age groups and first responders, do not receive more vaccine doses, and in fact receive slightly fewer units of vaccine. (JEL D72, D73, I18)
CONSOLIDATING THE EVIDENCE ON INCOME MOBILITY IN THE WESTERN STATES OF GERMANY AND THE UNITED STATES FROM 1984 TO 2006
Authors: BAYAZ‐OZTURK GULGUN , BURKHAUSER RICHARD V. , COUCH KENNETH A.
Published: June 2013

The cross‐national intragenerational literature has often analyzed income mobility within short time periods over which mobility might reasonably be thought of as invariant. Here, we argue that a great social transformation—German reunification—abruptly and permanently altered mobility. Using standard measures (with panel data for the western states of Germany and the United States) over the period 1984–2006, we find the conventional result that income mobility is greater in Germany. But when we cut the data into 5‐year windows, we find that income mobility declines significantly over the years immediately following reunification in Germany but not in the United States, using both measures. (JEL J1, J6)
DO HIGHER TOBACCO TAXES REDUCE ADULT SMOKING? NEW EVIDENCE OF THE EFFECT OF RECENT CIGARETTE TAX INCREASES ON ADULT SMOKING
Authors: CALLISON KEVIN , KAESTNER ROBERT
Published: June 2013

There is a general consensus among policymakers that raising tobacco taxes reduces cigarette consumption. However, evidence that tobacco taxes reduce adult smoking is relatively sparse. In this paper, we extend the literature in two ways: using data from the Current Population Survey Tobacco Use Supplements we focus on recent, large tax changes, which provide the best opportunity to empirically observe a response in cigarette consumption, and employ a novel paired difference‐in‐differences technique to estimate the association between tax increases and cigarette consumption. Estimates indicate that, for adults, the association between cigarette taxes and either smoking participation or smoking intensity is negative, small, and not usually statistically significant. Our evidence suggests that increases in cigarette taxes are associated with small decreases in cigarette consumption and that it will take sizable tax increases, on the order of 100%, to decrease smoking by as much as 5%. (JEL I18, I12)
Political Proximity and International Trade
Authors: Umana Dajud C.
Published: June 2013

The impact of politics on international trade has often been excluded by economists both from theoretical and empirical analysis. In this study, we examine empirically the impact of politics on trade flows. Results indicate that political differences have an impact on bilateral trade that is robust to a wide range of econometric specifications. However, the impact of political differences on trade flows vanishes when the costs of reducing the latter become fairly important.
Reduced brain corticotropin‐releasing factor receptor activation is required for adequate maternal care and maternal aggression in lactating rats
Authors: Klampfl Stefanie M. , Neumann Inga D. , Bosch Oliver J.
Published: June 2013

The brain corticotropin‐releasing factor (CRF) system triggers a variety of neuroendocrine and behavioural responses to stress. Whether maternal behaviour and emotionality in lactation are modulated by CRF has rarely been investigated. In the present study, we measured CRF mRNA expression within the parvocellular part of the paraventricular nucleus in virgin and lactating Wistar rats bred for high (HAB) and low (LAB) anxiety‐related behaviour or non‐selected for anxiety (NAB). Further, we intracerebroventricularly infused synthetic CRF or the CRF receptor (CRF‐R) antagonist D‐Phe to manipulate CRF‐R1/2 non‐specifically in lactating HAB, LAB, and NAB dams, and monitored maternal care, maternal motivation, maternal aggression, and anxiety. The CRF mRNA expression in the parvocellular part of the paraventricular nucleus was higher in HAB vs. LAB rats independent of reproductive status. The lactation‐specific decrease of CRF mRNA was confirmed in LAB and NAB dams but was absent in HAB dams. Intracerebroventricular CRF decreased maternal care under basal conditions in the home cage in all breeding lines and reduced attack behaviour in HAB and LAB dams during maternal defence. In contrast, D‐Phe rescued maternal care after exposure to maternal defence in the home cage without influencing maternal aggression. Furthermore, D‐Phe decreased and CRF tended to increase anxiety in HAB/NAB and LAB dams, respectively, suggesting an anxiogenic effect of CRF in lactating females. In conclusion, low CRF‐R activation during lactation is an essential prerequisite for the adequate occurrence of maternal behaviour.