bluuebunny/crossref_metadata_2025_split huggingface dataset:
Beyond gastrointestinal graft‐versus‐host disease. A lesson to learn
Authors: Gassas Adam , Zaidman Irina , Schechter Tal , Doyle John 
Published: April 2010

Gassas A, Zaidman I, Schechter T, Doyle J. Beyond gastrointestinal graft‐versus‐host disease. A lesson to learn. Pediatr Transplantation 2011: 15: E139–E141. © 2010 John Wiley & Sons A/S.Abstract:  The authors present a child with severe GvHD of GI tract with typical presentation of ileus and abdominal pain. However, the severe GvHD has led to multiple intermittent intussusceptions with resultant ischemic segments of the small bowel leading to sub‐acute mechanical intestinal obstruction. The clinical presentation of the mechanical intestinal obstruction was identical to the preceding ileus GvHD presentation. This has led to continuation of the conservative management with immunosuppressant therapy and delaying further investigation and surgical intervention. Once a barium study demonstrated the severe bowel constriction, laparoscopic surgical resection was necessary with excellent results. The resected small bowel showed multiple segments of ischemic ileitis leading to ulceration and severe stricture. The resection margins showed regenerating mucosa with no ulceration, but with focal evidence of mild GvHD.
Engineering pigs for xenotransplantation
Authors: Kramer S. , Schnieke A. 
Published: April 2010

Xenotransplantation using tissues and organs from genetically modified pigs has the potential to fulfil the serious shortage of material available for human transplantation. However, considerable immunological barriers must be overcome before such discordant grafts can be used. The generation of α(1,3)‐galactosyltransferase knock out pig lines has surmounted the initial obstacle of hyperacute rejection. Further improvements are now necessary to provide adequate protection against acute humoral xenograft rejection. The expression of human complement regulator transgenes in existing transgenic animals is inadequate, and a means of achieving abundant uniform expression in the organ is required. Recent findings have also highlighted the need for additional transgenes to alleviate incompatibilities between the porcine and human anticoagulation and anti‐inflammatory systems.Generating multi‐transgenic animals by breeding individual transgenic animals is inefficient and incurs several problems, including: independent Mendelian segregation of multiple transgenes; failure of different transgenes to co‐express at the right time or in the correct tissue; and an increased risk of insertional mutagenesis due to multiple integration events. A novel approach is therefore required to produce what are likely to be increasingly complex multi‐transgenic animals. Ideally, all transgenes should reside at a single Mendelian locus. They should not be subject to the position effect. There should be no limitation on transgene size to allow inclusion of substantial regulatory regions, or genes as multiple copies to obtain abundant expression. Finally, insertional mutagenesis should be excluded if possible. One possible way to achieve these is to use artificial chromosome vectors. De novo formed human artificial chromosomes are being developed as vectors for human gene therapy. The feasibility of this and alternative approaches to deliver sets of xenoprotective transgenes into pigs is being explored.This work is being carried out in close collaboration with the Xeno‐Forschergruppe (FOR 535) and is supported through funding provided by the DFG.
Aims and status of the German DFG ‐ Transregio Research Group Xenotransplantation
Authors: Reichart B. 
Published: April 2010

Allotransplantation is the therapy of choice for endstage diseases. Due to the organ shortage, three times respectively twice as many patients are currently waiting for kidneys or hearts as are actually transplanted annually in Germany. Consequently, the mortality rate on the heart transplant list is around 16%; if patients have to wait more than 24 months for a kidney, the graft survival after 10 years will be less than half when compared to those who are able to receive an organ within 6 months. Therefore, porcine xenotransplantation of kidneys and hearts will be a very much needed alternative clinical technique – including (porcine) xenogenic islet cell transplantation for diabetic patients with hypoglycaemic attacks – a large number of persons, if one considers that the number of people suffering from diabetes worldwide increased by nearly 50% over the last decade.Of course, much more work is needed before clinical xenotransplantation will become a safe and long lasting alternative. The α(1,3)‐galactosyltransferase KO, PERV C free pigs – held in specific pathogen free units – must express several human transgenes, like a complement regulator molecule (in order to suppress non Gal‐AB's) and HLA‐E (protection from NK‐cell cytotoxicity). Some kind of accommodation will be necessary (e.g. via Hemoxygenase‐1 or PDL‐1 – a negative costimulatory receptor which also increases the CD4+ CD25high Fox p3+ subset). An overexpression of thrombomodulin (TM) would finally be necessary in order to overcome the disparity between porcine (TM) and human (Thrombin) proteins and possibly avoid microvascular thrombotic disease.And to top all these desires of a clinical transplant specialist, all the genetic engineering should be achieved in close connection within one chromosome, preferably an artificial one, in order to make all these changes hereditary.The just mentioned strategies are the main topics of the DFG‐Transregio Research Group. The following abstracts will highlight the respective progress and will also inevitably evaluate arising problems. International leaders in our field will give their results and opinion – an interchange which is necessary within the small but very active xenotransplantation research field.It is my sincere belief that a clinical scenario of xenotransplantation will be possible in the near future.
Securing the World and Challenging Civil Society: Before and After the ‘War on Terror’
Authors: Howell Jude , Lind Jeremy 
Published: April 2010

ABSTRACTFollowing President Bush's declaration of a ‘War on Terror’ in 2001, governments around the world introduced a range of counter‐terrorist legislation, policies and practices. These measures have affected not only human rights and civil liberties but also civil society and aid frameworks. Although the Obama administration has renounced the language of the ‘War on Terror’ and taken steps to revoke aspects such as water‐boarding and the detention facility at Guantanamo Bay, the bulk of the legislation and practices associated with the post‐9/11 global security framework remain. The cluster of papers which follow provide detailed studies of the effects of the War on Terror regime on civil society in four contexts: the USA, Spain, Kenya and Uzbekistan. In this way it lays a basis for civil society actors and aid agencies to reflect more strategically on how they should engage with security debates and initiatives in a way that best protects the spaces of civil society and the interests of minority and vulnerable groups. This introduction sets out the three key themes pursued throughout the cluster articles, namely, the selective impact of counter‐terrorist measures on civil society; the particularity of civil society responsiveness to these measures; and the role of aid and diplomacy in pursuing security objectives and its consequences for civil society.
Family policy, economic development and infant mortality: a longitudinal comparative analysis
Authors: Ferrarini Tommy , Norström Thor 
Published: April 2010

Ferrarini T, Norström T. Family policy, economic development and infant mortality: a longitudinal comparative analysisInt J Soc Welfare 2010: ••: ••–••© 2010 The Author(s), Journal compilation © 2010 Blackwell Publishing Ltd and International Journal of Social Welfare.In the present study, the impact of family policy legislation and economic development on infant mortality was estimated. Time series analyses indicate that economic growth decreased infant mortality in the earlier part of the 20th century, while the postwar period showed a zero or even a reversed correlation between economic development and child health. The results from fixed effects modelling of data for 18 welfare democracies for the period 1970–2000 are in line with the hypothesis that the more generous the earnings‐related parental leave benefits, the lower the infant mortality.
Serum‐independent Cardiomyogenic Transdifferentiation in Human Endometrium‐derived Mesenchymal Cells
Authors: Ikegami Yukinori , Miyoshi Shunichiro , Nishiyama Nobuhiro , Hida Naoko , Okamoto Kazuma , Miyado Kenji , Segawa Kaoru , Ogawa Satoshi , Umezawa Akihiro 
Published: April 2010

AbstractMedia with high concentrations of serum are commonly used to induce cardiomyogenic transdifferentiation in mesenchymal stem cells; however, serum contains numerous unknown growth factors and interferes with definition of specific cardiomyogenic transdifferentiation factors secreted from feeder cells. In the present study, we determined whether the transdifferentiation of human mesenchymal cells can be observed in a FBS‐free medium. The efficiency of transdifferentiation was observed in 10% FBS‐containing standard medium (10%FBS) and in FBS‐free medium containing insulin and thyroxin (FBS‐free). In the present study, we used human uterine endometrium‐derived mesenchymal cells (EMC100, EMC214) and menstrual blood‐derived mesenchymal cells (MMCs). After cardiomyogenic transdifferentiation, the efficiency and physiological properties of cardiomyogenesis (fractional shortening of the cell [%FS] and action potential [AP]) were evaluated. The efficiency of transdifferentiation in EMC100 and in MMCs increased 36%* and 163%* (*P < 0.05), respectively. The %FS in EMCs increased to 103%*. AP‐duration more than 250 ms with a marked plateau was only observed in FBS‐free (3/19), and not in 10% FBS (0/41). The cardiomyogenic transdifferentiation of human mesenchymal cells can be observed in the FBS‐free medium. Phenotypes of generated cardiomyocytes were significantly more physiological in FBS‐free than in 10% FBS.
Old Age and Outcome After Primary Angioplasty for Acute Myocardial Infarction
Authors: de Boer Menko‐Jan , Ottervanger Jan Paul , Suryapranata Harry , Hoorntje Jan C.A. , Dambrink Jan‐Henk E. , Gosselink A.T. Marcel , van't Hof Arnoud W.J. , Zijlstra Felix 
Published: April 2010

OBJECTIVES: To assess the influence of age as an independent factor determining the prognosis and outcome of patients with acute myocardial infarction (AMI) treated using primary percutaneous coronary intervention (PCI).DESIGN: A retrospective analysis from a dedicated database.SETTING: A high‐volume interventional cardiology center in the Netherlands.PARTICIPANTS: Four thousand nine hundred thirty‐three consecutive patients with AMI.MEASUREMENTS: Baseline characteristics and clinical outcomes after 30 days and 1 year were compared according to age categorized in three groups: younger than 65, 65 to 74, and 75 and older. A more‐detailed analysis was performed with six age groups, from younger than 40 to 80 and older.RESULTS: Of the 4,933 consecutive patients with AMI treated with PCI between 1992 and 2004, 643 were aged 75 and older. Multivariate analysis revealed that patients aged 65 to 75 had a greater risk of 1‐year mortality than those younger than 65 (adjusted odds ratio (AOR)=1.57, 95% confidence interval (CI)=1.15–2.16) and that those aged 75 and older had a greater risk of 1‐year mortality than those younger than 65 (AOR=3.03, 95% CI=2.14–4.29).CONCLUSION: In this retrospective analysis, older age was independently associated with greater mortality after PCI for AMI. Patients aged 65 and older had a higher risk of mortality than younger patients, and those aged 75 and older had the highest risk of mortality.
The role of the curriculum and other factors in determining the medium‐ to long‐term attitude of the practicing dentist towards life‐long learning
Authors: Polyzois I. , Claffey N. , Attström R. , Kelly A. , Mattheos N. 
Published: April 2010

AbstractObjectives:  To investigate the significance of the undergraduate dental curriculum on the medium‐ to long‐term attitudes of the clinician to life‐long learning, and to identify demographical and professional characteristics which may influence this attitude.Methods:  A specially designed questionnaire targeted 12 cohorts of dentists who qualified from Dublin Dental School and Hospital between 1994 and 2005. The curricula of the cohorts varied from fully didactic, exclusively Problem Based Learning or a hybrid for the oldest, youngest and middle graduates, respectively. Participants were questioned about current professional activities, postgraduate training, practice type, hospital affiliation, use of information services and time dedicated to continuing dental education (CDE), etc. A number of dental scenarios were proposed to determine if participants were adherent to current clinical guidelines. Additionally, a visual analogue scale assessed the overall satisfaction of dentists with their undergraduate programme and determined their opinion regarding its influence on subsequent ability to practice dentistry and keep up‐to‐date with scientific developments.Results:  Contingency analysis of the association between curriculum and continuous educational data did not produce statistical significance. Dentists who work in a hospital environment spend more time on CDE (χ2, Pearson’s, P = 0.001), are more adherent to current guidelines (χ2, Pearson’s, P = 0.005) and found their undergraduate studies more enjoyable (Wilkoxon/Kruskal–Wallis, P = 0.01).Conclusions:  Undergraduate curriculum type was found to have very little or no effect on the graduate’s attitude towards life‐long learning or confidence in their ability to practice dentistry. However, these attitudes did appear to be influenced by certain family, demographical and professional characteristics.
Displacing Indigenous Cultural Landscapes: the Naturalistic Gaze at Fraser Island World Heritage Area
Authors: CARTER JENNIFER 
Published: April 2010

AbstractA naturalistic gaze characterises protected area management in Australia, and reproduces the nature–culture dichotomy that is thoroughly criticised in geographical discourse. This naturalistic gaze is exacerbated by the compartmentalism of agency roles and responsibilities in protected areas. This paper maintains that many agencies, either unconsciously or deliberately, perpetuate the naturalistic gaze in a way that displaces Indigenous people from authentic engagement in protected area management. This paper provides an example of such marginalisation of Indigenous Australians in the world heritage area of Fraser Island, which is located in one of the most rapidly urbanising parts of Australia where Indigenous people have limited rights. The paper argues that a new process is required that networks people and place using concepts of nature/culture hybridity to avoid the current conceptual dualisms and the consequent marginalisation of Indigenous people. Such a dialectic and relational approach introduces contexts, meanings and associations that are excluded by current environmental and heritage paradigms that have the potential to marginalise many local voices. It proposes that those responsible for world heritage and protected area planning and management must fully realise or renominate these areas as landscapes in which people, and perhaps especially Indigenous Australians, are always and everywhere embedded and implicated in ‘natural’ environments. This will require changes in governance and in the predominantly technocratically‐driven processes by which these areas are currently designated and managed.
THE SOURCES OF AUSTRALIAN GROWTH
Authors: HOGAN W. P. 
Published: April 2010

“‘Development’ has, as it were, always been part of Australian religion ever since Arthur Phillip declared that he would not wish convicts to be responsible for the founding of a nation; ‘development’ has nearly always been identified with growth, growth seen as having two dimensions—geographical spread and quantitative increase.”—S. J. Butlin [1]
DEVELOPMENT PROSPECTS AND IMPORT POLICIES1
Authors: HOGAN W. P. 
Published: April 2010

SummaryThe developing economies when viewed collectively met the targets for growth laid down by the United Nations for the First Development Decade. But this achievement was recorded against a background of very diverse experiences from one developing economy to another. Some of these economies gained as a result of the special advantages stemming from natural resources such as crude oil. Other developing economies were less fortunately placed. The Second Development Decade has been set higher targets. The immediate prospects are not so encouraging because of the recent disturbances in international monetary and economic relations. Moreover, the prospects for expanding the flow of official and private assistance are not good. Thus the earning of foreign exchange to finance certain costs of development schemes will become of increasing importance during the seventies. In this respect there is an important need for the developed market economies to maintain if not expand access to their domestic markets for developing economies. But this will call for domestic policy techniques for adjusting the industrial structure to cushion the impact of import flows. As yet these techniques are embryonic both in Australia and other advanced industrial countries. One possibility would be to combine adjustments in the industrial structure with development assistance to neighbouring economies.
Heteroresistance of
Cryptococcus gattii
to Fluconazole
Authors: Varma A. , Kwon-Chung K. J. 
Published: April 2010

ABSTRACT

We analyzed 71 clinical and environmental
Cryptococcus gattii
strains that had been isolated before or after the advent of azole antifungals to determine their level of heteroresistance to fluconazole (LHF). All strains of
C. gattii
manifested heteroresistance, with LHFs that ranged between 4 μg/ml and 32 μg/ml. A considerably higher proportion of the
C. gattii
strains (86%) than
Cryptococcus neoformans
strains (46%) exhibited LHFs that were ≥16 μg/ml. No significant correlation was observed between the molecular type or serotypes of strains and their respective LHF. The strains which expressed a higher LHF were also more resistant to xenobiotics than the strains with a low LHF, and the level of resistance to xenobiotics was significantly higher than that reported for
C. neoformans
. The heteroresistant subpopulation, whose level of drug resistance had been raised in a stepwise manner to 64 μg/ml, reverted to the original LHF upon daily transfers in drug-free medium. Importantly, the strains with high LHFs were significantly more virulent than those with low LHFs. Since all the clinical isolates that had not been exposed to azole drugs as well as the environmental strains manifested heteroresistance to fluconazole, heteroresistance of
C. gattii
to azoles is an intrinsic mechanism as in
C. neoformans
and is associated with the strain's virulence.
Recombinant Phenotyping of Cytomegalovirus UL97 Kinase Sequence Variants for Ganciclovir Resistance
Authors: Chou Sunwen 
Published: April 2010

ABSTRACT
A strain of human cytomegalovirus, T2211, modified from standard laboratory strain AD169 to contain a secreted alkaline phosphatase reporter gene for rapid viral quantitation, was cloned as a bacterial artificial chromosome, BA1, and then mutagenized to create recombinant viruses containing viral UL97 kinase sequence variants found in clinical specimens after ganciclovir treatment, but with no phenotypic data to determine their role in drug resistance. Seven control strains and 14 other recombinant strains were phenotyped for ganciclovir resistance and compared with similar strains created using prior technology to show a good concordance of findings. Sequence changes V466M, H469Y, A478V, N510S, A588V, K599R, L600I, G623S, T659I, and V665I were found to confer no significant ganciclovir resistance, while mutations L405P, M460T, A594E, and C603R conferred 3- to 9-fold increases in ganciclovir 50% inhibitory concentrations. Different mutations at codons 594 (A594V, A594E) and 603 (C603W, C603S) conferred varied amounts of ganciclovir resistance. Advances in recombinant phenotyping make it easier to show that many uncharacterized UL97 sequence variants do not confer ganciclovir resistance, but some are newly confirmed as resistance associated, including one (L405P) which is outside the codon range where such mutations are usually found. This information should improve the interpretation of genotypic data generated by diagnostic laboratories.
AmpN-AmpG Operon Is Essential for Expression of L1 and L2 β-Lactamases inStenotrophomonas maltophilia
Authors: Huang Yi-Wei , Lin Cheng-Wen , Hu Rouh-Mei , Lin Yu-Tzu , Chung Tung-Ching , Yang Tsuey-Ching 
Published: April 2010

ABSTRACTAmpG is an inner membrane permease which transports products of murein sacculus degradation from the periplasm into the cytosol in Gram-negative bacteria. This process is linked to induction of the chromosomalampCbeta-lactamase gene in some members of theEnterobacteriaceaeand inPseudomonas aeruginosa. In this study, theampGhomologue ofStenotrophomonas maltophiliaKJ was analyzed. TheampGhomologue and its upstreamampNgene form an operon and are cotranscribed under the control of the promoterPampN. Expression fromPampNwas found to be independent of β-lactam exposure andampNandampGproducts. A ΔampNallele exerted a polar effect on the expression ofampGand resulted in a phenotype of null β-lactamase inducibility. Complementation assays elucidated that an intactampN-ampGoperon is essential for β-lactamase induction. Consistent withampGofEscherichia coli, theampN-ampGoperon ofS. maltophiliadid not exhibit a gene dosage effect on β-lactamase expression. The AmpG permease ofE. colicould complement the β-lactamase inducibility ofampNorampGmutants ofS. maltophilia, indicating that both species have the same precursor of activator ligand(s) for β-lactamase induction.
Safety and Pharmacokinetics of the Antiorthopoxvirus Compound ST-246 following Repeat Oral Dosing in Healthy Adult Subjects
Authors: Jordan Robert , Chinsangaram Jarasvech , Bolken Tove' C. , Tyavanagimatt Shanthakumar R. , Tien Deborah , Jones Kevin F. , Frimm Annie , Corrado Michael L. , Pickens Margaret , Landis Patrick , Clarke Jean , Marbury Thomas C. , Hruby Dennis E. 
Published: April 2010

ABSTRACT
ST-246, a novel compound that inhibits egress of orthopoxvirus from infected cells, is being evaluated as a treatment for pathogenic orthopoxvirus infections in humans. This phase I, double-blind, randomized, placebo-controlled, escalating multiple-dose study was conducted to determine the safety, tolerability, and pharmacokinetics of ST-246 administered as a single daily oral dose of 250, 400, or 800 mg for 21 days to nonfasting healthy human volunteers. ST-246 appeared to be well tolerated, with no serious adverse events (AEs). Headache, for which one subject in the 800-mg group discontinued the study, was the most commonly reported AE in all treatment groups. The multiple-dose pharmacokinetics of ST-246 was well characterized. The day 21 mean elimination half-lives were calculated at 18.8, 19.8, and 20.7 h for each of the 250-, 400-, and 800-mg/day dose groups, respectively. Steady state was reached by day 6 (within 3 to 5 half-lives), saturable absorption was observed at the 800-mg dose level, and the fraction of parent drug excreted in the urine was very low. Based on these results, administration of 400 mg/day ST-246 can be expected to provide plasma concentrations above the efficacious concentration demonstrated in nonhuman primate models in earlier studies.