bluuebunny/crossref_metadata_2025 huggingface dataset:
Permutation importance: a corrected feature importance measure
Authors: Altmann André , Toloşi Laura , Sander Oliver , Lengauer Thomas
Published: April 2010

Motivation: In life sciences, interpretability of machine learning models is as important as their prediction accuracy. Linear models are probably the most frequently used methods for assessing feature relevance, despite their relative inflexibility. However, in the past years effective estimators of feature relevance have been derived for highly complex or non-parametric models such as support vector machines and RandomForest (RF) models. Recently, it has been observed that RF models are biased in such a way that categorical variables with a large number of categories are preferred.

Results: In this work, we introduce a heuristic for normalizing feature importance measures that can correct the feature importance bias. The method is based on repeated permutations of the outcome vector for estimating the distribution of measured importance for each variable in a non-informative setting. The P-value of the observed importance provides a corrected measure of feature importance. We apply our method to simulated data and demonstrate that (i) non-informative predictors do not receive significant P-values, (ii) informative variables can successfully be recovered among non-informative variables and (iii) P-values computed with permutation importance (PIMP) are very helpful for deciding the significance of variables, and therefore improve model interpretability. Furthermore, PIMP was used to correct RF-based importance measures for two real-world case studies. We propose an improved RF model that uses the significant variables with respect to the PIMP measure and show that its prediction accuracy is superior to that of other existing models.

Availability: R code for the method presented in this article is available at http://www.mpi-inf.mpg.de/∼altmann/download/PIMP.R

Contact:  altmann@mpi-inf.mpg.de, laura.tolosi@mpi-inf.mpg.de

Supplementary information:  Supplementary data are available at Bioinformatics online.
Multi-objective tag SNPs selection using evolutionary algorithms
Authors: Ting Chuan-Kang , Lin Wei-Ting , Huang Yao-Ting
Published: April 2010

Motivation: Integrated analysis of single nucleotide polymorphisms (SNPs) and structure variations showed that the extent of linkage disequilibrium is common across different types of genetic variants. A subset of SNPs (called tag SNPs) is sufficient for capturing alleles of bi-allelic and even multi-allelic variants. However, accuracy and power of tag SNPs are affected by several factors, including genotyping failure, errors and tagging bias of certain alleles. In addition, different sets of tag SNPs should be selected for fulfilling requirements of various genotyping platforms and projects.

Results: This study formulates the problem of selecting tag SNPs into a four-objective optimization problem that minimizes the total amount of tag SNPs, maximizes tolerance for missing data, enlarges and balances detection power of each allele class. To resolve this problem, we propose evolutionary algorithms incorporated with greedy initialization to find non-dominated solutions considering all objectives simultaneously. This method provides users with great flexibility to extract different sets of tag SNPs for different platforms and scenarios (e.g. up to 100 tags and 10% missing rate). Compared to conventional methods, our method explores larger search space and requires shorter convergence time. Experimental results revealed strong and weak conflicts among these objectives. In particular, a small number of additional tag SNPs can provide sufficient tolerance and balanced power given the low missing and error rates of today's genotyping platforms.

Availability: The software is freely available at Bioinformatics online and http://cilab.cs.ccu.edu.tw/service_dl.html

Contact:  ckting@cs.ccu.edu.tw; ythuang@cs.ccu.edu.tw
The association between long‐term longitudinal trends in guideline adherence and mortality in relation to age and sex
Authors: Frankenstein Lutz , Remppis Andrew , Fluegel Andrea , Doesch Andreas , Katus Hugo A. , Senges Jochen , Zugck Christian
Published: April 2010

Aims

Using a large clinical multi‐site prospective chronic heart failure registry, we sought to determine (i) implementation of guidelines over time and (ii) adjusted survival benefit there from.

Methods and results

Clinical characteristics, mortality, and medication according to guidelines [guideline adherence index (GAI) for ACE‐inhibitors or angiotensin receptor blockers, beta‐blockers, aldosterone antagonists] were compared for 1481 patients included from 1994 to 2000 and 1811 patients from 2001 to 2007. The co‐morbidity corrected GAI significantly increased from 1994–2000 to 2001–07 (P < 0.001). Concomitantly, 1‐ and 3‐year mortality decreased (14.1–4.8 and 29.5–10.9%, respectively, P < 0.001 each). No interaction with age or sex was noted (P = 0.06, P = 0.25, respectively), though age determined complete medication according to guidelines (P < 0.05). The GAI was a significant predictor of lower overall mortality (adjusted HR per 10% increase: 0.92; 95% CI: 0.88–0.97; P = 0.001), again independent from age or sex. Results were essentially unchanged after controlling for co‐morbidities and other potential confounders.

Conclusion

This study shows that increased use of medication according to guidelines might occur without interventions targeting medication use. It seems to be associated with a substantial improvement in survival. Even though causality cannot be proven, the findings underscore the importance of meticulous implementation of guidelines irrespective of age, sex, or co‐morbidities.
Horizontal movements of simulated escaped farmed Atlantic salmon (Salmo salar) in a western Norwegian fjord
Authors: Skilbrei Ove T. , Holst Jens Christian , Asplin Lars , Mortensen Stein
Published: April 2010

Skilbrei, O. T., Holst, J. C., Asplin, L., and Mortensen, S. 2010. Horizontal movements of simulated escaped farmed Atlantic salmon (Salmo salar) in a western Norwegian fjord. – ICES Journal of Marine Science, 67: 1206–1215. The dispersal of simulated escaped farmed Atlantic salmon (Salmo salar) in Hardangerfjord in western Norway was studied by telemetry. Tagged fish were released from fish farms on five different dates in the course of 1 year. Irrespective of the time of year, the fish dispersed rapidly, with a mean displacement from the release site of 5–7 km after 1 d, and 9–12 km after 2 d. Individual rates of movement varied, but were much higher than the rate of displacement from the release site, as fish moved around in the fjord basin in all directions. As a result, the fish were spread over an area of more than 500 km2 after 1 week. The number of released fish recorded in the fjord gradually declined after each release from ∼40% remaining in the fjord after 3 weeks to few or none after 7 weeks. In all, 38% moved out of the fjord, and 36 and 2% were reported as captured inside and outside the fjord, respectively. Their rapid dispersal suggests that concentrating efforts to recapture escaped salmon in the proximity of an escape site will probably not be successful, at least from locations of this type. In fact, the recaptures demonstrate that it is both necessary and possible to expand the fishing effort to cover a large area and to sustain it for several weeks to attain high rates of recapture. The wide dispersal of escaped fish potentially acting as vectors within the fjord basin also has implications for the spread of disease and parasites.
The use of otolith microstructure to estimate age in adult Atlantic cod Gadus morhua
Authors: Hüssy K. , Hinrichsen H.‐H. , Fey D. P. , Walther Y. , Velasco A.
Published: April 2010

Transverse sections of otoliths from Atlantic cod Gadus morhua from the Baltic Sea revealed narrow growth increments. The widths of these increments corresponded to daily increments from fish with known otolith growth rates and were therefore assumed to be daily increments. They exhibited a distinct pattern with increasing distance from the primary primordium. A series of zones with clearly distinguishable increments, first with increasing then with decreasing widths in a dome‐shaped pattern, were separated by zones where no regular increment structure was visible. Increment width seemed to be tightly coupled to the annual cycle in environmental temperature at a depth of 30–60 m, where G. morhua predominantly reside. Between 135 and 200 increments occurred within the different zones, with a non‐significant trend towards lower increment numbers and widths with distance from the primary primordium of the otolith. Increment formation apparently ceased at temperatures < 5–6° C, but growth during the cold months corresponded closely with estimated growth rates. The increment patterns seemed to reflect annual cycles in environmental temperature, and the count of the increment cycles may thus be a promising tool for the determination of the true age of Baltic G. morhua.
Shoaling preference and evidence for maintenance of sibling groups by juvenile black perch Embiotoca jacksoni
Authors: Sikkel P. C. , Fuller C. A.
Published: April 2010

Group sizes in free‐living juvenile black perch Embiotoca jacksoni were quantified and predictions of the hypothesis that such groups comprise sibling brood‐mates were tested. Group sizes in the field were within the range of female brood sizes and often occurred close to each other but did not merge. In captivity, juveniles formed groups immediately after birth. In laboratory experiments, they also associated significantly more with chambers containing familiar members of their own brood than empty chambers but did not associate more with chambers containing similar‐sized juveniles from a different brood. Juvenile E. jacksoni also associated significantly more with chambers containing familiar brood‐mates than with chambers containing unfamiliar members of a different brood. The strength of this preference increased with the number of days fish had been together since birth. When two broods were placed in a large outdoor tank, all individuals from both broods directed significantly more aggressive acts towards members of the other brood than towards members of their own brood. While the relative effects of familiarity and relatedness cannot be completely separated in this viviparous species, associating with familiar individuals would facilitate the maintenance of sibling groups in the field.
Dietary phosphorus availability influences female cricket lifetime reproductive effort
Authors: VISANUVIMOL LAKSANAVADEE , BERTRAM SUSAN M.
Published: April 2010

1. Recent ecological stoichiometric findings indicate that the relationships among key macronutrient elements [e.g. carbon (C), nitrogen (N), and phosphorus (P) of organisms and their resources] may underlie variation in life‐history traits. The amount of phosphorus in an individual's body is often correlated with its rate of growth, and low‐phosphorus diets are known to reduce growth in a number of insect and crustacean herbivores.

2. These findings suggest that the stoichiometric imbalance between organismal biomass requirements and the relative scarcity of nutrients in nature may also underlie variation in lifetime reproductive success.

3. This study investigated how dietary phosphorus availability during adulthood influenced lifetime reproductive effort, compensatory feeding, lifespan, condition, and stoichiometry of adult European House Cricket, Acheta domesticus.

4. Female crickets fed high amounts of phosphorus during adulthood laid significantly more eggs compared to those fed low amounts of phosphorus. Phosphorus availability did not directly influence lifespan, condition, or body stoichiometry, and crickets did not compensate for low phosphorus diets by eating more food.

5. A stoichiometric perspective may help understand the causes of variation in invertebrate fitness.
Functional indicators of stream health: a river‐basin approach
Authors: FEIO M. J. , ALVES T. , BOAVIDA M. , MEDEIROS A. , GRAÇA M. A. S.
Published: April 2010

1. The efficacy of leaf‐litter decomposition, sediment respiration, biofilm biomass, growth, chlorophyll a concentration and the autotrophic index (biofilm ash‐free dry mass/chlorophyll a) and fungal biomass for detecting human‐induced change was evaluated using 24 references and 15 disturbed stream sites located in central Portugal.

2. Decomposition rates of alder (Alnus glutinosa) and oak (Quercus robur) leaves and sediment respiration rates were effective in discriminating impairment. Decomposition was negatively correlated with abiotic factors, such as ammonium and nitrite concentrations, connectivity and alterations in the hydrological regime, and positively correlated with nitrate concentration and oxygen concentration. Sediment respiration rates were correlated with organic contamination, land use and morphological changes.

3. Growth rates of biofilm, concentration of chlorophyll a and the autotrophic index, although 41–73% higher at disturbed compared to reference sites, were not significantly different. These three variables were significantly correlated with total organic carbon, oxygen concentration, pH, nitrite and the presence of dams. Fungal biomass on leaves and biofilm biomass on natural substrata did not differ between reference and disturbed sites.

4. Our findings lend support to the use of functional variables like decomposition and sediment respiration in monitoring and when used together with structural variables should give a more holistic measure of stream health.
Fracture resistance of root filled molar teeth restored with glass fibre bundles
Authors: Rodrigues F. B. , Paranhos M. P. G. , Spohr A. M. , Oshima H. M. S. , Carlini B. , Burnett Jr L. H.
Published: April 2010

Rodrigues FB, Paranhos MPG, Spohr AM, Oshima HMS, Carlini B, Burnett LH Jr. Fracture resistance of root filled molar teeth restored with glass fibre bundles. International Endodontic Journal, 43, 356–362, 2010.

Aim  To evaluate the effect of unidirectional or woven glass fibre tapes inserted into MOD cavity preparations on the fracture resistance of root filled molar teeth.

Methodology  Extracted human molar teeth were randomly divided into six groups (n = 15) : G1 – sound teeth, control; G2 – MOD cavity preparation; G3 – MOD + root canal treatment (Endo); G4 – MOD + Endo + composite resin restoration (Resin); G5 – MOD + Endo + unidirectional fibre (UF) + Resin; G6 – MOD + ;Endo + woven fibre (WF) + Resin. The teeth were subjected to a compressive fracture test in a universal testing machine. After testing, two failure modes were classified: pulp chamber floor or cusp.

Results  The highest and the lowest mean fracture strengths were found in sound teeth (G1) (4960N) and MOD + root canal treatment (G3) (612.84N), respectively, with significant differences from the other groups (P < 0.05). The remaining groups had statistically similar means. In G5 and G6, there was a tendency for fracture to occur in the pulp chamber floor compromising tooth integrity.

Conclusions  The insertion of glass fibres into MOD cavity preparations and restoring them with composite resin was not different than molar teeth filled with composite resin only in terms of fracture resistance. Fibres placed into MOD cavities do not reinforce teeth.
Transdentinal stimulation of tertiary dentine formation and intratubular mineralization by growth factors
Authors: Kalyva M. , Papadimitriou S. , Tziafas D.
Published: April 2010

Kalyva M, Papadimitriou S, Tziafas D. Transdentinal stimulation of tertiary dentine formation and intratubular mineralization by growth factors. International Endodontic Journal, 43, 382–392, 2010.

Aim  To evaluate the effects of recombinant growth factors on tertiary dentine formation and intratubular mineralization after their application on deep dentinal cavities in dog’s teeth.

Methodology  Treatment included dentinal etching (37% phosphoric acid) and applications of bioactive molecules (1 μg mL−1 TGF‐β1, 10 μg mL−1 IGF‐1, 10 μg mL−1 bFGF, 10 μg mL−1 OP‐1 or 1 μg mL−1 monoclonal anti‐human TGF‐β1 in phosphate buffered saline, PBS) at the dentinal base of buccal Class V cavities. Control groups were treated with 0.1% dog serum albumin (DSA) in PBS omitting the growth factors. This was performed both with and without dentinal etching. The dentinal responses regarding tertiary dentine formation and intratubular mineralization were assessed after 3 and 8 weeks, respectively, using light and scanning electron microscopy. Some specimens were also subjected to dentine permeability testing.

Results  The group treated with transforming growth factor‐beta1 (TGF‐β1) and, to a lesser extent, the one treated with osteogenic protein‐1 (OP‐1) showed significantly greater (P < 0.05) tertiary dentine formation and intratubular mineralization over an 8‐week period when compared with the control and the other experimental groups. There were no significant differences between groups in reduction in dentine permeability after treatment.

Conclusion  Treatment of exposed dentinal tubules with biologically active molecules might induce intratubular mineralization and tertiary dentine formation. Further research is needed to substantiate any clinical benefits as opposed to traditional treatments of exposed dentine so as to provide a scientific base for the clinical regulation of dentine reactions.
Wnt5a promotes differentiation of human dental papilla cells
Authors: Peng L. , Ren L. B. , Dong G. , Wang C. L. , Xu P. , Ye L. , Zhou X. D.
Published: April 2010

Peng L, Ren LB, Dong G, Wang CL, Xu P, Ye L, Zhou XD. Wnt5a promotes differentiation of human dental papilla cells. International Endodontic Journal, 43, 404–412, 2010.

Aim  To investigate the role of Wnt5a in the process of differentiation of human dental papilla cells (HDPCs).

Methodology  Recombinant adenovirus encoding full‐length Wnt5a cDNA was constructed to investigate the biological role of Wnt5a on the differentiation of HDPCs. The effect of Wnt5a on HDPCs differentiation was determined by ALP activity assay, ALP staining and mineral induction assay. Mineralization‐related gene expressions were assessed by RT‐PCR.

Results  Immunostaining revealed Wnt5a expression in the odontoblast layer and dental papilla tissue. Over‐expression of Wnt5a by transfecting HDPCs with an Wnt5a‐carrying construct increased ALPase activity and the formation of mineralized nodules of HDPCs. RT‐PCR analysis showed that the expressions of mineralization‐related genes, such as bone sialoprotein, collagen type I, osteonectin, osteopontin (OCN), dentine matrix protein‐1 were up‐regulated by Wnt5a.

Conclusions  Wnt5a promoted differentiation of HDPCs.
Dentinal tubule disinfection with 2% chlorhexidine gel, propolis, morinda citrifolia juice, 2% povidone iodine, and calcium hydroxide
Authors: Kandaswamy D. , Venkateshbabu N. , Gogulnath D. , Kindo A. J.
Published: April 2010

Kandaswamy D, Venkateshbabu N, Gogulnath D, Kindo AJ. Dentinal tubule disinfection with 2% chlorhexidine gel, propolis, morinda citrifolia juice, 2% povidone iodine, and calcium hydroxide. International Endodontic Journal, 43, 419–423, 2010.

Aim  To investigate the antimicrobial activity of 2% chlorhexidine gel, propolis, Morinda citrifolia juice (MCJ), 2% povidone Iodine (POV‐I), and calcium hydroxide on Enterococcus faecalis‐infected root canal dentine at two different depths (200 μm and 400 μm) and three time intervals (day 1, 3 & 5).

Methodology  One hundred and eighty extracted human teeth were infected for 21 days with E. faecalis. Samples were divided into six groups. Group I (Saline) (Negative control), Group II (Propolis), Group III (MCJ), Group IV (2% Povidone Iodine), Group V (2% Chlorhexidine Gel), Group VI (Calcium hydroxide). At the end of 1, 3, and 5 days, the remaining vital bacterial population was assessed. Dentine shavings were collected at two depths (200 μm and 400 μm), and total numbers of colony forming units were determined. The values were analysed statistically with one‐way analysis of variance followed by Tukey multiple comparison test. The paired t‐test was used to check for differences in growth at different time intervals within groups and for differences at the two depths (P < 0.01)

Results  The number of colony‐forming units was statistically significant in all groups compared to the control group (Saline). Group V (chlorhexidine gluconate) (100%) produced better antimicrobial efficacy followed by 2% POV‐I (87%), propolis (71%), MCJ (69%), and calcium hydroxide (55%). There was no significant difference between propolis and MCJ and no significant difference between data at 200 μm and 400 μm.

Conclusion  Propolis and MCJ were effective against E. faecalis in dentine of extracted teeth.
Endodontic treatment of a geminated maxillary second molar using an endoscope as magnification device
Authors: Weinstein T. , Rosano G. , Del Fabbro M. , Taschieri S.
Published: April 2010

Weinstein T, Rosano G, Del Fabbro M, Taschieri S. Endodontic treatment of a geminated maxillary second molar using an endoscope as magnification device. International Endodontic Journal, 43, 443–450, 2010.

Aim  To describe endodontic treatment for a rare case of gemination.

Summary  A case of complex endodontic treatment in a geminated tooth is presented. With the assistance of microinstruments and magnification devices, a geminated maxillary second molar was successfully treated. In such a case, ultrasonic tips and the use of an endoscope were essential to detect the peculiar anatomy of the tooth involved.

Key learning points 

Knowledge of anomalies concerning fused teeth is essential.

Using an endoscope as a magnification device is useful during the inspection of pulp chambers.

Ultrasonic tips are safe and useful to detect canal orifices.
Combined en bloc liver–double kidney transplantation in an infant with IVC thrombosis
Authors: McGuire Margaret M. , Jones Brian A. , Hull Melissa A. , Misra Meghna V. , Smithers Charles J. , Feins Neil R. , Jenkins Roger L. , Lillehei Craig W. , Harmon William E. , Jonas Maureen M. , Kim Heung B.
Published: April 2010

McGuire MM, Jones BA, Hull MA, Misra MV, Smithers CJ, Feins NR, Jenkins RL, Lillehei CW, Harmon WE, Jonas MM, Kim HB. Combined en bloc liver–double kidney transplantation in an infant with IVC thrombosis. Pediatr Transplantation 2011: 15: E142–E144. © 2010 John Wiley & Sons A/S.

Abstract:  We report a case of a pediatric en bloc liver‐double kidney transplant in a patient with IVC thrombosis below the renal veins. The patient is an 11‐month‐old girl diagnosed with congenital nephrotic syndrome at two months of age. Multifocal liver masses were identified on routine ultrasound at eight months of age. Alpha fetoprotein level was 55 319. Biopsy confirmed hepatoblastoma. CT scan confirmed multiple lesions in both lobes, which would require liver transplantation for resection. She was also found to have thrombosis of her infrarenal IVC secondary to multiple central lines. She was listed for combined liver–kidney transplant and began chemotherapy. After four cycles of chemotherapy, she underwent bilateral nephrectomies followed by a combined en bloc liver‐double kidney transplant from a size matched donor. In order to provide adequate venous outflow from the kidneys in the absence of a recipient infrarenal IVC, the donor liver and kidneys were procured en bloc with a common arterial inflow via the infrarenal aorta and common outflow via the suprahepatic IVC. Kidney transplantation in the absence of adequate recipient venous drainage may require unusual vascular reconstruction techniques. This case demonstrates a novel approach in patients who may require combined liver–kidney transplantation.
Foxp3 regulates human natural CD4+CD25+ regulatory T‐cell‐mediated suppression of xenogeneic response
Authors: Sun Lei , Yi Shounan , O’Connell Philip J.
Published: April 2010

Sun L, Yi S, O’Connell PJ. Foxp3 regulates human natural CD4+CD25+ regulatory T‐cell‐mediated suppression of xenogeneic response. Xenotransplantation 2010; 17: 121–130. © 2010 John Wiley & Sons A/S.

Abstract: Backgrounds:  Cellular rejection of xenografts is predominantly mediated by CD4+ T cells. Foxp3 expressing human naturally occurring CD4+CD25+ regulatory T cells (nTregs) have been shown to suppress pathological and physiological immune responses, including the CD4+ T‐cell‐mediated anti‐pig xenogeneic response in vitro. Although Foxp3 is required for nTreg development and their function, the precise role of Foxp3 in regulating Treg suppressive function in xenoimmune response remains to be identified.

Methods:  In vitro expanded human nTregs were transfected with fluorescein isothiocyanate ‐conjugated Foxp3 small interfering RNA (siRNA) by Lipofectamine 2000. Transfected nTregs were sorted by fluorescence‐activated cell sorting, and then analyzed for Foxp3 gene and protein expression as well as their phenotypic characteristics. Human CD4+CD25− T cells were stimulated with xenogeneic pig peripheral blood mononuclear cell in the presence or absence of nTregs in a coculture or transwell system for evaluation of nTreg suppressive activity. The production of effector cytokines by xenoreactive CD4+CD25− T cells as well as suppressive cytokine by nTregs in their cocultures was examined by ELISA.

Results:  The siRNA‐mediated Foxp3 knockdown resulted in impaired nTreg anergic state, downregulated expression of nTreg function associated molecules, and reduced production of suppressive cytokines by nTregs, which together leading to impaired nTreg‐mediated suppression of CD4+CD25− T‐cell proliferation and their effector cytokine production in response to xenogeneic stimulation.

Conclusions:  This study demonstrates that Foxp3 expression is required for human nTregs to maintain their suppressive function in the xenoimmune response.
Insulin secretion and glucose metabolism in alpha 1,3‐galactosyltransferase knock‐out pigs compared to wild‐type pigs
Authors: Casu Anna , Echeverri Gabriel J. , Bottino Rita , Van Der Windt Dirk J. , He Jing , Ekser Burcin , Ball Suyapa , Ayares David , Cooper David K. C.
Published: April 2010

Casu A, Echeverri GJ, Bottino R, van der Windt DJ, He J, Ekser B, Ball S, Ayares D, Cooper DKC. Insulin secretion and glucose metabolism in alpha 1,3‐galactosyltransferase knock‐out pigs compared to wild‐type pigs. Xenotransplantation 2010; 17: 131–139. © 2010 John Wiley & Sons A/S.

Abstract: Background:  Xenotransplantation of porcine islets could be a valuable alternative to the shortage of human islets for transplantation. To overcome the immunological obstacle of antibody‐mediated rejection, pigs homozygous for α1,3‐galactosyltransferase gene knock‐out (GT‐KO) have been produced. The effect of this mutation on glucose metabolism is unknown.

Methods:  Glucose, insulin, C‐peptide and glucagon levels were studied in eight adult pigs (four wild‐type [WT] and four GT‐KO) during intravenous glucose tolerance test (IVGTT), arginine stimulation test (AST), and insulin tolerance test (ITT). Morphological analysis of the pancreata was also performed. The in vitro insulin response to a high glucose concentration and theophylline were studied in a dynamic perfusion system with isolated islets.

Results:  Basal and stimulated blood glucose levels were similar in WT and GT‐KO pigs. Basal insulin, C‐peptide and glucagon were higher in GT‐KO pigs. C‐peptide and insulin responses to arginine and glucose were also higher in GT‐KO animals. The reduction in blood glucose during ITT and IVGTT was similar in WT and GT‐KO pigs. The extent of staining for insulin and glucagon in the pancreata were similar. The basal insulin secretion of isolated islets was higher in GT‐KO pigs, while stimulation indexes for glucose and theophylline were similar to WT.

Conclusions:  GT‐KO pigs demonstrated differences in glucose metabolism compared to WT pigs, the cause for which remains uncertain. It is unlikely that these differences would in any way affect the outcome of GT‐KO porcine islet xenotransplantation.
Viral gene transfer for xenotransplantation
Authors: Pfeifer A.
Published: April 2010

In order to overcome the major immunological barriers to xenotransplantation, genetic strategies have to be developed that ensure long‐term engraftment of the organ. To this end, immune‐modulatory transgenes have to be efficiently expressed and/or the expression of xeno‐relevant porcine genes (xeno‐epitopes) has to be silenced.

Viral vectors are powerful tools for modulating expression of foreign genes in organs and even the whole animal. Using lentiviral gene transfer in early embryos, gain‐of‐function models can be generated with high efficacies in pig (lentiviral transgenesis). Through combination of lentiviral transgenesis and RNA interference (RNAi) loss‐of‐function models for xenotransplantation can be generated. Our goal is to combine lentivector‐mediated RNAi directed against α‐galactosyltransferase (α‐GT) with immune‐modulatory approaches to finally generate multitransgenic pigs. Furthermore, sensitivity to human serum inactivation of porcine endogenous retrovirus produced by pig cells with reduced levels of α‐GT expression was analysed.
Cellular interaction of functional porcine endogenous retrovirus
Authors: Dörrschuck E. , Krämer M. , Tönjes R. R.
Published: April 2010

Human cells might display mechanisms counteracting infections by porcine endogenous retroviruses (PERV) in the course of pig‐to‐human xenotransplantation. Mammals have developed a number of protective strategies against viruses, including an intracellular antiretroviral defense as part of the innate immunity. In addition to the conventional innate and acquired immune responses an array of dominant genes have evolved that are constitutively expressed which suppress or prevent retroviral infections. Several of these antiretroviral restriction mechanisms have been identified including members of the tripartite motif (TRIM) and APOBEC families. The TRIM5 class of inhibitors appears to target incoming retroviral capsids and the APOBEC class of cytidine deaminases hypermutates and destabilizes retroviral genomes.

Our data show that human and porcine cytidine deaminases inhibit PERV replication significantly, thereby reducing the infectious risk raised by PERV in vitro. The exact mechanism of the TRIM5 mediated restriction has not been exactly determined so far. Data published by Wood et al. (2009) indicate that PERV are insensitive to restriction by divergent TRIM5 molecules including human and monkey TRIM5α?proteins. The role of pig TRIM5 has not been clarified. We have identified a single TRIM5 gene in the pig genome. The impact of porcine TRIM5 protein on PERV will be tested using the human TRIM5α as a negative control, expecting that PERV will be insensitive to porcine TRIM5.
Islet cell xenotransplantation: update on recent progress and future perspectives
Authors: Dufrane D.
Published: April 2010

Allogeneic islet transplantation faces difficulties because (i)organ shortage is recurrent; (ii) several pancreas donors are often needed to treat one diabetic recipient; and (iii) the intrahepatic site of islet implantation may not be the most appropriate site. Another source of insulin‐producing cells, therefore, would be of major interest, and pigs represent a possible and serious source for obtaining such cells. Pig islet grafts may appear difficult because of the species barrier, but recent reports demonstrate that pig islets may function in primates for at least 6 months. Pig islet xenotransplantation, however, must still overcome several hurdles prior to becoming clinically applicable. The actual consensus is to produce more preclinical data in the pig‐to‐primate model as a necessary requirement to envisage any pig‐to‐human transplantation of islets; therefore, a summary of the actual acquired knowledge of pig islet transplantation in primates seemed useful.
Hemeoxygenase‐1: a cytoprotective gene with broad therapeutic potential in xenotransplantation and other inflammatory diseases
Authors: Soares M.
Published: April 2010

Cells have a variety of constitutive and inducible defense cytoprotective mechanisms against oxidative stress. These aim at re‐establishing homeostasis in response to oxidative injury. In the particular context of organ (xeno)transplantation, these defense mechanisms contribute in a critical manner to sustain (xeno)graft survival via at least two interrelated mechanisms. First, cytoprotection per se supports survival and function of cells within a (xeno)transplanted organ and as such should have a beneficial effect in terms of sustaining (xeno)graft survival. Second, cytoprotection reduces immunogenicity of the (xeno)transplanted organ and thus should modulate the activation of the recipient's immune response in a manner that sustains (xeno)graft survival. Others and we have gathered evidence, to suggest that the stress‐responsive enzyme hemeoxygenase‐1 (HO‐1 encoded by the gene Hmox1) acts in such a manner. Upon (xeno)transplantation, HO‐1 becomes ubiquitously expressed in the transplanted organ, acting as the rate‐limiting enzyme in the catabolism of free heme into carbon monoxide (CO), iron (Fe) and biliverdin. There is now accumulating evidence to support the notion that HO‐1 expression in a (xeno)graft and/or in the recipient can have salutary effects that prevent the rejection of that (xeno)graft. In this talk I will argue and provide experimental evidence that this salutary effect might be mediated by the ability of HO‐1 to limit the deleterious effects of free heme. The possibility of using this “protective effect” to support the survival of transplanted organs will be addressed in the particular context of xenotransplantation.
Complement depletion with cobra venom factor delays acute cell‐mediated rejection in pig‐to‐mouse corneal xenotransplantation
Authors: Oh Joo Youn , Kim Mee Kum , Lee Hyun Ju , Ko Jung Hwa , Kim Youngji , Park Chan‐Sik , Kang Hee Jung , Park Chung‐Gyu , Kim Sang Joon , Lee Jin Hak , Wee Won Ryang
Published: April 2010

Oh JY, Kim MK, Lee HJ, Ko JH, Kim Y, Park CS, Kang HJ, Park CG, Kim SJ, Lee JH, Wee WR. Complement depletion with cobra venom factor delays acute cell‐mediated rejection in pig‐to‐mouse corneal xenotransplantation. Xenotransplantation 2010; 17: 140–146. © 2010 John Wiley & Sons A/S.

Abstract: Background:  We have demonstrated earlier that porcine corneal xenografts underwent an acute cell‐mediated rejection in mice despite the absence of T cells. In the present study, we investigated the effect of complement depletion by cobra venom factor (CVF) on the corneal xenograft rejection in a pig‐to‐mouse model.

Methods:  Porcine corneas were orthotopically transplanted into C57BL/6 (B6) and severe combined immunodeficiency (SCID) mice. For complement depletion, 25 μg of CVF (1 g/kg bodyweight) was injected intraperitoneally on the day before and 1, 3, 5, and 7 days after transplantation. Graft survival was clinically assessed by slit lamp biomicroscopy and the median survival time (MST) was calculated. The grafts were histologically evaluated serially after transplantation using antibodies against CD4, CD8, NK1.1, and F4/80.

Results:  The CVF treatment significantly prolonged the porcine corneal xenograft survival in both B6 (MST 9.4 vs. 15.5 days; P = 0.0011) and SCID mice (MST 16.4 vs. 20.5 days; P = 0.0474). Histologically, whereas macrophages and CD4+ T cells were progressively infiltrated into porcine corneal grafts in CVF‐untreated B6 mice, the infiltration by both cells was markedly delayed and decreased in the xenografts in CVF‐treated B6 mice. Likewise, macrophage infiltration, which was prominent in rejected porcine xenografts in SCID mice, was also reduced in CVF‐treated SCID mice.

Conclusions:  Our results suggest that complement depletion by CVF delayed, although did not prevent, an acute cell‐mediated rejection in a pig‐to‐mouse corneal xenotransplantation.
Prolonged survival of GalT‐KO swine skin on baboons
Authors: Weiner Joshua , Yamada Kazuhiko , Ishikawa Yoshinori , Moran Shannon , Etter Justin , Shimizu Akira , Neal Smith Rex , Sachs David H.
Published: April 2010

Weiner J, Yamada K, Ishikawa Y, Moran S, Etter J, Shimizu A, Smith RN, Sachs DH. Prolonged survival of GalT‐KO swine skin on baboons. Xenotransplantation 2010; 17: 147–152. © 2010 John Wiley & Sons A/S.

Abstract: Background:  Allogeneic skin is currently the best alternative to autologous skin as a temporary treatment for severe burns, but it has several drawbacks. As a potential alternative, we have evaluated GalT‐KO swine skin, which lacks expression of the Gal epitope, to investigate the effect of eliminating this epitope on survival of pig‐to‐baboon skin grafts.

Methods:  Two adult baboons that had fully recovered from previous T cell depletion received simultaneous skin grafts from: (i) GalT‐KO swine, (ii) Gal‐positive swine, (iii) a third‐party baboon, and (iv) self (control skin). Recipients were treated with cyclosporin for 12 days and the survival, gross appearance, and histology of the grafts were compared.

Results:  In both baboons, the GalT‐KO skin survived longer than either the Gal‐positive swine skin or the allogeneic skin. Early rejection of the Gal‐positive skin appeared to be mediated by cytotoxic preformed anti‐Gal IgM antibodies, while the rejection of GalT‐KO skin appeared to result from cellular mechanisms.

Conclusions:  GalT‐KO skin may have potential clinical benefits as an alternative to allogeneic skin as a temporary treatment for severe skin injuries.
Inbreeding Depression and Inbreeding Avoidance in a Natural Population of Guppies (Poecilia reticulata)
Authors: Johnson Ashley M. , Chappell Grace , Price Anna C. , Helen Rodd F. , Olendorf Robert , Hughes Kimberly A.
Published: April 2010

Maintenance of genetic variation in the face of strong natural selection is a long‐standing problem in evolutionary biology. One of the most extreme examples of within‐population variation is the polymorphic, genetically determined color pattern of male Trinidad guppies (Poecilia reticulata). Female mating preference for rare or novel patterns has been implicated as a factor in maintaining this variation. The origin of this preference is not understood, although inbreeding avoidance has been proposed as a mechanism. Inbreeding avoidance is advantageous when populations exhibit inbreeding depression and the opportunity for mating between relatives exists. To determine whether these conditions are met in a natural guppy population, we assessed mating and reproductive patterns using polymorphic molecular markers. Females produced more offspring with less‐related males than with more‐related ones. In addition, females were more likely to have mated with less‐related males, but this trend was only marginally significant. Male heterozygosity was positively correlated with mating success and with the number of offspring sired, consistent with strong inbreeding depression for adult male fitness. These results provide substantial insight into mating patterns of a wild guppy population: strong inbreeding depression occurs, and individuals tend to avoid mating with relatives.
Osama or the Georges: Shifting Threats and State Policy towards Civil Society in Uzbekistan
Authors: Stevens Daniel
Published: April 2010

In examining the relationship between the War on Terror and restrictions on civil society, Uzbekistan is an important case, given its emergence as a key player in the operations in Afghanistan, its own terrorist threat, and its particularly stringent policy towards civil society. This article argues that while the ‘crackdown’ on civil society has followed a similar pattern to that of other countries where civil society is perceived as harbouring a threat, there has been a significant shift since the War on Terror began as to the perceived nature of the threat. At the time of 9/11, the government of Uzbekistan took Islamic terrorism to be the main threat; yet within the space of just over two years a new threat was perceived. Western support for civil society, a concession made to the US‐led coalition in return for support against Islamic terrorism, emerged as an even greater threat to the regime. It is this perceived threat that has primarily driven state policy towards civil society, raising important questions about how democracy promotion can be best taken forward in the post‐9/11 world.
Understanding the Southern African ‘Anomaly’: Poverty, Endemic Disease and HIV
Authors: Sawers Larry , Stillwaggon Eileen
Published: April 2010

The epicentre of the global HIV epidemic is southern Africa. Previous explanations point to migration patterns and highly skewed income distribution, both thought to promote risky sexual behaviour. This study emphasizes the importance of common infectious and parasitic diseases that increase the likelihood of HIV transmission by increasing contagiousness and vulnerability to infection. Using multiple regression analysis on country‐level data, the authors find that socio‐economic variables explain statistically only one‐tenth of the difference in HIV prevalence between southern Africa and other low‐ and middle‐income countries. Measures of five cofactor infections together with the socio‐economic variables, however, explain statistically about two‐thirds of the southern Africa difference in HIV prevalence. They conclude that the relative affluence of countries in southern Africa and historical migration patterns have tended to mask the vulnerability of the majority of their populations who are poor and who have very high prevalence of infectious and parasitic diseases. Those diseases replicate a cycle of poverty that produces biological vulnerability through coinfections. An important implication of this research is that integrating treatment of endemic diseases with other HIV‐prevention policies may be necessary to slow the spread of HIV.
Attribution and Self‐Efficacy and Their Interrelationship in the Korean EFL Context
Authors: Hsieh Peggy Pei‐Hsuan , Kang Hyun‐Sook
Published: April 2010

This study examined the interrelationships between learners’ attributions and self‐efficacy and their achievements in learning English as a foreign language. Participants were 192 ninth‐grade English learners in Korea who were asked to provide attribution and self‐efficacy ratings upon receiving test grades. Results indicated that learners with different levels of self‐efficacy ratings endorsed attributions differently for successful and unsuccessful outcomes. Learners with higher levels of self‐efficacy attributed their test results to more internal and personal control factors than those who reported lower self‐efficacy levels. For learners who were unsuccessful, those with higher self‐efficacy made stronger personal control attributions than learners with lower self‐efficacy.
Practical Monetary Policies*
Authors: Guender Alfred V. , Gillmore David R.
Published: April 2010

This paper compares a monetary policy that targets average inflation with one that targets the change in the output gap. It shows that the stabilizing properties of monetary policy strategies are sensitive to both the existence of lags in the transmission mechanism and the design of target rules. A strategy focusing on the change in the output gap is likely to prove inferior to targeting the average rate of inflation in a model where monetary policy affects the real economy sooner than inflation. Even more favourable results for average inflation targeting emerge in a framework that also includes forward‐looking expectations. These results stand in marked contrast to those in standard models where policy lags are absent. To ensure sound choice of policy, central banks are advised to examine the stabilizing properties of monetary policies in a variety of models.
Negotiating dilemmas in the practices of street‐level welfare work
Authors: Hjörne Eva , Juhila Kirsi , van Nijnatten Carolus
Published: April 2010

Hjörne E, Juhila K, van Nijnatten C. Negotiating dilemmas in the practices of street‐level welfare work

Int J Soc Welfare 2010: 19: 303–309 © 2010 The Author(s), Journal compilation © 2010 Blackwell Publishing Ltd and International Journal of Social Welfare.

The theme of this mini‐symposium is based on the core ideas of two influential books published about 30 years ago, namelyMichael Lipsky'sStreet‐Level Bureaucracy – Dilemmas of the Individual in Public Services(1980) andJeffrey Prottas'sPeople‐Processing – The Street‐Level Bureaucrat in Public Service Bureaucracies(1979). In these books, three dilemmas were identified that have great importance for welfare workers' position as mediators between institutions and citizens: autonomy versus control, responsiveness versus standardisation, and demand versus supply. In this editorial, we discuss these dilemmas with regard to the present context of street‐level welfare work, which is strongly influenced by managerialist policies (also called new public management). It is emphasised that in the era of managerialism, the dilemmas should be approached as empirical matters: how they are present, talked into being and negotiated in naturally occurring practices of street‐level welfare work, and with what consequences.
Contractual audit and mental health rehabilitation: a study of formulating effectiveness in a Finnish supported housing unit
Authors: Saario Sirpa , Raitakari Suvi
Published: April 2010

Saario S, Raitakari S. Contractual audit and mental health rehabilitation: a study of formulating effectiveness in a Finnish supported housing unit

Int J Soc Welfare 2010: 19: 321–329 © 2010 The Author(s), Journal compilation © 2010 Blackwell Publishing Ltd and International Journal of Social Welfare.

Mental health NGOs in Western Europe are increasingly managed by contractual audit procedures. This article concerns how contractual audit and its emphasis on effectiveness of care impact on the practices of long‐term mental health rehabilitation. To demonstrate this, a case study of a Finnish NGO that provides supported housing is presented. The study looks at how service purchasing practices, as stated in the contract between the municipality and the NGO, are reflected in the meetings among practitioners. Documentary and meeting data were utilised together with Mitchell Dean's notion of technologies of agency. It was found that practitioners actively sought to show the effectiveness of their everyday work in terms of contractual audit by demonstrating both the economic and progressive aspects of care. Thus, professional competency in mental health rehabilitation appears to entail both the skills of care interventions and the ability to perform these interventions as efficient and financially accountable activities.
Cycles of legitimacy and delegitimation across regimes in Argentina, 1900–2008
Authors: Turner Frederick C. , Carballo Marita
Published: April 2010

If we define a crisis of political legitimacy in a nation as one that occurs when sizeable portions of the politically relevant population challenge or deny the normative validity of claims to authority made by its existing leadership, then Argentina has experienced at least seven such legitimacy crises in the past hundred years. The causes of these crises include the actions of political leaders, political institutions that have proven inadequate to the demands made upon them, frustrated economic growth and an inability of groups to compromise on mutually acceptable solutions. Survey data since 1984 show that Argentinians have consistently had much less confidence in the basic institutions of their society than have citizens in the rest of Latin America and in the world as a whole. Moreover, confidence in most institutions dropped precipitously between 1984 and 2006. Although Argentinians show low interest in politics and trust family members far more than outsiders, most of them still find that democracy is the best form of government for their country. In the future, some of the best ways to enhance political legitimacy in Argentina include increasing the efficiency of political institutions, limiting corruption and – perhaps most important of all – assuring that economic prosperity is maintained and that hard work is rewarded.