bluuebunny/crossref_metadata_2025_split huggingface dataset:
The pharmacokinetics of Casodex enantiomers in subjects with impaired liver function
Authors: COCKSHOTT I. D. , SOTANIEMI E. A. , COOPER K. J. , JONES D. C. 
Published: July 2012

Casodex is a novel non‐steroidal antiandrogen being developed for the treatment of prostatic cancer. The antiandrogenic activity is predominantly in the R(–) enantiomer with little, if any, activity in the S(+) enantiomer.
The pharmacokinetics of the enantiomers of Casodex have been investigated over 28 days following a single oral dose of Casodex (50 mg) to 10 male subjects with histologically verified liver cirrhosis or fatty liver with fibrosis. Ten age matched male subjects with normal hepatic function served as a control group.
For both groups plasma concentrations of (S)‐Casodex were lower than those for (R)‐Casodex; this difference was about 10‐fold at early time points and increased to about 25‐fold by 24 h after dosage.
The kinetics of (R)‐Casodex were similar in subjects with and without liver disease (Cmax: 750 vs 848 ng ml−1; tmax: 24 − 30 h; t1/2;: 7.40 vs 7.22 days; AUC: 182 vs 225μg ml−1 h).
The kinetics of (S)‐Casodex could not be described in the majority of subjects; in the remainder the mean terminal phase half‐life for both groups was less than 1 day.
Patterns of subsequent malignancies after Hodgkin lymphoma in children and adults
Authors: Omer Bilal , Kadan‐Lottick Nina S. , Roberts Kenneth B. , Wang Rong , Demsky Carolyn , Kupfer Gary M. , Cooper Dennis , Seropian Stuart , Ma Xiaomei 
Published: July 2012

SummaryTo evaluate the impact of reduced radiation and combined modality therapy (CMT) in the treatment of Hodgkin lymphoma, we assessed the risk of second malignant neoplasms (SMNs) in patients who received extended‐field radiotherapy only and patients who underwent CMT. Among 404 patients treated at Yale during 1970–2004, the risk of solid SMNs was elevated in the radiotherapy only group (n = 198, median follow‐up = 21·1 years) compared to the general population, with a standardized incidence ratio (SIR) of 1·85 [95% confidence interval (CI): 1·17–2·78]. No increase was observed in the CMT group (n = 206, median follow‐up = 14·3 years), although potential differences in SMN risk were indicated across the age spectrum in subgroup analysis. Patients who received mustard‐containing regimens had increased risks for haematological SMNs (SIR = 8·74) and all SMNs (SIR = 1·85). When the analysis was stratified by age at diagnosis, children (0–20 years) had a significantly higher risk of SMNs (SIR = 5·24, 95% CI: 2·26–10·33), regardless of the treatment received. These findings suggest that recent treatment options utilizing lower dose radiation and less intense alkylator chemotherapy might be associated with lower incidences of SMNs among adults but not necessarily children.
Interleukin‐25 promotes basic fibroblast growth factor expression by human endothelial cells through interaction with IL‐17RB, but not IL‐17RA
Authors: Wang W. , Fan Y. Q. , Lv Z. , Yao X. J. , Wang W. , Huang K. W. , Meng Q. , Fang C. L. , Lee T. H. , Corrigan C. J. , An Y. Q. , Ying S. 
Published: July 2012

SummaryBackgroundUnlike other IL‐17 family members, the Th2‐derived cytokine IL‐25 (IL‐17E) induces (promotes) Th2 responses. One or both of the two receptors for IL‐25 (IL‐17RA, IL‐17RB) is expressed on inflammatory cells and tissue structural cells, suggesting that in addition to promoting Th2‐type inflammation IL‐25 may also act on structural cells at sites of Th2‐type inflammation such as in the asthmatic bronchial mucosa to promote remodelling changes.ObjectiveOur previous studies showed elevated expression of IL‐25 and IL‐17RB immunoreactivity in asthmatic airways with co‐localization of the latter to endothelial cells. We therefore hypothesized that IL‐25 acts on endothelial cells through this receptor to induce production of the key angiogenic and remodelling cytokine basic fibroblast growth factor (bFGF).MethodsPolymerase chain reaction (PCR) immunocytochemistry/immunohistochemistry and ELISA were employed to detect expression of IL‐17RB, IL‐17RA and bFGF by human vascular endothelial cells (HUVEC) and immunoreactivity for IL‐25 and bFGF in asthmatic bronchial biopsies. Receptor‐blocking antibodies, PCR and an in vitro angiogenesis assay were used to investigate whether IL‐25 acts on IL‐17RB or IL‐17RA to induce bFGF expression and angiogenesis. PCR was also employed to investigate the signalling pathways involved in IL‐25‐mediated bFGF expression.ResultsHUVEC constitutively expressed IL‐17RB, IL‐17RA and bFGF. Production of the latter was further increased by IL‐25, but attenuated after blockade of the IL‐17RB, but not the IL‐17RA receptor. Neutralization of endogenous VEGF and bFGF completely abrogated IL‐25‐induced angiogenesis which was also inhibited by blocking IL‐17RB, but not IL‐17RA. The PI3K‐specific inhibitor LY294002 also completely attenuated IL‐25‐induced bFGF expression. Immunoreactivity for IL‐25 and bFGF was elevated in the asthmatic bronchial mucosa and the expression of each correlated with the other.Conclusions and Clinical RelevanceOur data support the hypothesis that IL‐25 contributes to elevated bFGF in asthmatic airways by acting on the endothelial cell IL‐17RB receptor through PI3K‐signalling pathways. Targeting the pathways might benefit therapy of airways remodelling.
Immune responses against islet allografts during tapering of immunosuppression – a pilot study in 5 subjects
Authors: Huurman V A L , van der Torren C R , Gillard P , Hilbrands R , van der Meer-Prins E P M W , Duinkerken G , Gorus F K , Claas F H J , Keymeulen B , Roelen D L , Pipeleers D G , Roep B O 
Published: July 2012

SummaryTransplantation of isolated islet of Langerhans cells has great potential as a cure for type 1 diabetes but continuous immune suppressive therapy often causes considerable side effects. Tapering of immunosuppression in successfully transplanted patients would lower patients' health risk. To identify immune biomarkers that may prove informative in monitoring tapering, we studied the effect of tapering on islet auto- and alloimmune reactivity in a pilot study in five transplant recipients in vitro. Cytokine responses to the graft were measured using Luminex technology. Avidity of alloreactive cytotoxic T Lymphocytes (CTL) was determined by CD8 blockade. The influence of immunosuppression was mimicked by in vitro replenishment of tacrolimus and MPA, the active metabolite of mycophenolate mofetil. Tapering of tacrolimus was generally followed by decreased C-peptide production. T-cell autoreactivity increased in four out of five patients during tapering. Overall alloreactive CTL precursor frequencies did not change, but their avidity to donor mismatches increased significantly after tapering (P = 0·035). In vitro addition of tacrolimus but not MPA strongly inhibited CTL alloreactivity during tapering and led to a significant shift to anti-inflammatory graft-specific cytokine production. Tapering of immunosuppression is characterized by diverse immune profiles that appear to relate inversely to plasma C-peptide levels. Highly avid allospecific CTLs that are known to associate with rejection increased during tapering, but could be countered by restoring immune suppression in vitro. Immune monitoring studies may help guiding tapering of immunosuppression after islet cell transplantation, even though we do not have formal prove yet that the observed changes reflect direct effects of immune suppression on immunity.
Responses of benthic macroinvertebrate communities to altitude and geology in tributaries of the Sepik River (Papua New Guinea): the influence of taxonomic resolution on the detection of environmental gradients
Authors: DUDGEON DAVID 
Published: July 2012

Summary1. Benthic macroinvertebrate communities were sampled in 30 tributary streams at altitudes from sea level to about 3000 m draining three geologically distinct regions within the catchment of the Sepik River, Papua New Guinea. The fauna of this near‐pristine river has been little studied, and the impacts of ongoing and anticipated human impacts on the Sepik are uncertain.2. Data on community composition were analysed at different levels of taxonomic resolution (species or morphospecies versus family) to compare their responses to environmental variables such as altitude and geology (reflected in water chemistry), and to indicate their potential utility for the detection of environmental change.3. A total of 183 000 macroinvertebrates representing 250 species were collected, predominantly insects (232 species and >99% of individuals). The fauna was co‐dominated by Diptera (42% of individuals; 32 morphospecies, mainly Orthocladiinae, Simuliidae and Chironominae) and Ephemeroptera (36%; 48 species), although the Trichoptera showed the highest species (67) and family (13) richness, with Coleoptera ranked third (43 species). Naucoridae (Heteroptera) and Crambidae: Acentropinae (Lepidoptera), each represented by 13 species, were distinctive faunal elements. Mayflies were represented by only four families, one consisting of a single species.4. Multivariate analysis of the species‐level data set revealed that community composition was influenced by geological region, but the effect was largely due to altitude as most streams in one region (the Central Highlands) were at higher elevations (>800 m) than streams in the other two regions (<500 m). However, altitude had no direct effect on species richness. A secondary influence of current speed and a subsidiary effect of water chemistry (pH and N‐NO3) on community composition were also detected. Naucorid bugs showed evidence of altitudinal zonation and some species replacement, plus a tendency for certain genera to be associated with highland or lowland streams.5. Analysis of the family‐level data set failed to uncover strong effects of any environmental variable, either individually or in combination, although some sensitivity to altitude plus slope was detected.6. These findings suggest that attempts to use macroinvertebrates to detect environmental change in New Guinea streams will require species‐level monitoring of community composition.
The signal crayfish is not a single species: cryptic diversity and invasions in the Pacific Northwest range of Pacifastacus leniusculus
Authors: LARSON ERIC R. , ABBOTT CATHRYN L. , USIO NISIKAWA , AZUMA NORIKO , WOOD KIMBERLY A. , HERBORG LEIF‐MATTHIAS , OLDEN JULIAN D. 
Published: July 2012

Summary1. We used historical sources, morphology‐based taxonomy and mtDNA sequence data to address questions about the signal crayfish Pacifastacus leniusculus. These included evaluating unrecognised cryptic diversity and investigating the extent to which P. leniusculus may have been introduced within its presumed native range in the Pacific Northwest region of North America. Our study builds and expands on Pacific Northwest phylogeographic knowledge, particularly related to patterns of glacial refugia for freshwater species.2. Extensive collections (824 specimens) from British Columbia (Canada), Idaho, Nevada, Oregon and Washington (United States) were used to characterise P. leniusculus at the mitochondrial 16S rRNA gene. Genetic groups within the species were elucidated by phylogenetics and amova; evolutionary relationships within the most common and diverse group were investigated using a statistical parsimony haplotype network, a nested amova, and tests of isolation by distance. Morphological measurements were used to relate findings of molecular analyses to three historically recognised P. leniusculus subspecies and characterise cryptic diversity by morphology.3. We found substantial cryptic diversity, with three groups highly distinct from P. leniusculus in discrete geographic regions: the Chehalis River glacial refugium, Central Oregon and the Okanagan Plateau. Disjunct distributions of P. leniusculus relative to these cryptic groups and known patterns of Pleistocene glaciation and landscape evolution cast doubt on whether P. leniusculus is native to some areas such as coastal drainages of northern Washington and southern British Columbia. Morphological traits previously used to characterise P. leniusculus subspecies still persist but may be incapable of distinguishing P. leniusculus from newly discovered cryptic groups.4. Cryptic diversity found within P. leniusculus highlights the pressing need for a thorough investigation of the genus Pacifastacus using data based on more extensive gene and taxon sampling. It also warrants conservation attention, as introductions of P. leniusculus within the Pacific Northwest may carry risks of hybridisation and introgression for cryptic groups. Owing to high genetic diversity and limited dispersal capacity relative to more vagile organisms like freshwater fish, crayfish of the genus Pacifastacus offer powerful potential insights into the geological history and phylogeography of the Pacific Northwest region. Finally, by shedding light on the long‐neglected native range of P. leniusculus, our results should also better inform our understanding of potential source populations for, and the ecology of, this important invasive species in regions including Europe, Japan and elsewhere in North America.
An MRI scale for assessment of haemophilic arthropathy from the International Prophylaxis Study Group
Authors: Lundin B. , Manco‐Johnson M. L. , Ignas D. M. , Moineddin R. , Blanchette V. S. , Dunn A. L. , Gibikote S. V. , Keshava S. N. , Ljung R. , Manco‐Johnson M. J. , Miller S. F. , Rivard G. E. , Doria A. S. ,   The International Prophylaxis Study Group
Published: July 2012

SummaryEvaluation of prophylactic treatment of haemophilia requires sensitive methods. To design and test a new magnetic resonance imaging (MRI) scale for haemophilic arthropathy, two scales of a combined MRI scoring scheme were merged into a single scale which includes soft tissue and osteochondral subscores. Sixty‐one joint MRI's of 46 patients with haemophilia were evaluated by four radiologists using the new and older scales. Forty‐six of the joints were evaluated using two X‐ray scales. For all MRI scores, interreader agreement and correlations with X‐ray scores and lifetime number of haemarthroses were analysed. The interreader agreement intraclass correlation coefficient was 0.82, 0.89 and 0.88 for the soft tissue and osteochondral subscores and the total score, as evaluated according to the new MRI scale, compared to 0.80 and 0.89 as for the older scales. The total score and osteochondral subscore according to the new scale, as well as scores according to the older scales were correlated (P < 0.01) with number of haemarthroses (Spearman correlation 0.35–0.68) and with the X‐ray scores (Spearman correlation 0.40–0.76), but no correlation (P > 0.05) was found between the soft tissue subscore of the new MRI scale and the X‐ray scores. The new MRI scale is simpler to apply than the older and has similar reader reliability and correlation with lifetime number of haemarthroses, and by separating soft tissue and osteochondral changes it gives additional information. The new scale is useful for analyses of early and moderate stages of arthropathy, and may help to evaluate prophylactic haemophilia treatment.
The unsayable: a concept analysis
Authors: Schick Makaroff Kara L. 
Published: July 2012

AbstractAimTo report an analysis of the concept of the unsayable.BackgroundWithin nursing, there is recognition that not all experiences of illness can be fully voiced and therefore may be unsayable. However, focus has been on that which is sayable, those experiences that can be communicated through language, leaving the unsayable unexamined. There is little examination of the meaning or relevance of the concept for nursing practice.Data sourcesThe literature search was not limited by date and includes English, peer‐reviewed texts in the databasesCINAHL, Web of Science, and PsychINFOfrom 1959–2011.DesignRodgers' method of evolutionary concept analysis was used.Review methodsReferences were read and analyzed according to surrogate terms, related concepts, attributes, antecedents, and consequences.ResultsThree surrogate terms, one related concept, four attributes, four antecedents, and two consequences were identified in this concept analysis. Based on this analysis, the unsayable refers to what is not expressed yet alluded to through language and may be conscious or unconscious. The meaning of this concept differs substantially between psychology and nursing.ConclusionAlthough literature on the unsayable has been developed primarily outside the discipline of nursing, exploration of the concept within nursing may assist nurses to consider situations and experiences that are challenging, elusive, and perhaps impossible for patients to language while living amid illness.
Research on nursing handoffs for medical and surgical settings: an integrative review
Authors: Staggers Nancy , Blaz Jacquelyn W. 
Published: July 2012

AbstractAimsTo synthesize outcomes from research on handoffs to guide future computerization of the process on medical and surgical units.BackgroundHandoffs can create important information gaps, omissions and errors in patient care. Authors call for the computerization of handoffs; however, a synthesis of the literature is not yet available that might guide computerization.Data sourcesPubMed, CINAHL, Cochrane, PsycINFO, Scopus and a handoff database from Cohen and Hilligoss.DesignIntegrative literature review.Review methodsThis integrative review included studies from 1980–March 2011 in peer‐reviewed journals. Exclusions were studies outside medical and surgical units, handoff education and nurses' perceptions.ResultsThe search strategy yielded a total of 247 references; 81 were retrieved, read and rated for relevance and research quality. A set of 30 articles met relevance criteria.ConclusionStudies about handoff functions and rituals are saturated topics. Verbal handoffs serve important functions beyond information transfer and should be retained. Greater consideration is needed on analysing handoffs from a patient‐centred perspective. Handoff methods should be highly tailored to nurses and their contextual needs. The current preference for bedside handoffs is not supported by available evidence. The specific handoff structure for all units may be less important than having a structure for contextually based handoffs. Research on pertinent information content for contextually based handoffs is an urgent need. Without it, handoff computerization is not likely to be successful. Researchers need to use more sophisticated experimental research designs, control for individual and unit differences and improve sampling frames.
The role of epiphytism in architecture and evolutionary constraint within mycorrhizal networks of tropical orchids
Authors: MARTOS FLORENT , MUNOZ FRANÇOIS , PAILLER THIERRY , KOTTKE INGRID , GONNEAU CÉDRIC , SELOSSE MARC‐ANDRÉ 
Published: July 2012

AbstractCharacterizing the architecture of bipartite networks is increasingly used as a framework to study biotic interactions within their ecological context and to assess the extent to which evolutionary constraint shape them. Orchid mycorrhizal symbioses are particularly interesting as they are viewed as more beneficial for plants than for fungi, a situation expected to result in an asymmetry of biological constraint. This study addressed the architecture and phylogenetic constraint in these associations in tropical context. We identified a bipartite network including 73 orchid species and 95 taxonomic units of mycorrhizal fungi across the natural habitats of Reunion Island. Unlike some recent evidence for nestedness in mycorrhizal symbioses, we found a highly modular architecture that largely reflected an ecological barrier between epiphytic and terrestrial subnetworks. By testing for phylogenetic signal, the overall signal was stronger for both partners in the epiphytic subnetwork. Moreover, in the subnetwork of epiphytic angraecoid orchids, the signal in orchid phylogeny was stronger than the signal in fungal phylogeny. Epiphytic associations are therefore more conservative and may co‐evolve more than terrestrial ones. We suggest that such tighter phylogenetic specialization may have been driven by stressful life conditions in the epiphytic niches. In addition to paralleling recent insights into mycorrhizal networks, this study furthermore provides support for epiphytism as a major factor affecting ecological assemblage and evolutionary constraint in tropical mycorrhizal symbioses.
The genetics of primary and secondary sexual character trade‐offs in a horned beetle
Authors: House C. M. , Simmons L. W. 
Published: July 2012

AbstractWhen structures compete for shared resources, this may lead to acquisition and allocation trade‐offs so that the enlargement of one structure occurs at the expense of another. Among the studies of morphological trade‐offs, their importance has been demonstrated primarily through experimental manipulations and comparative analyses. Relatively, a few studies have investigated the underlying genetic basis of phenotypic patterns. Here, we use a half‐sibling breeding design to determine the genetic underpinnings of the phenotypic trade‐off between head horns and the male copulatory organ or aedeagus that has been found in the dung beetle Onthophagus taurus. Instead of the predicted negative genetic covariance among characters that trade‐off, we find positive genetic covariance between absolute horn and aedeagus length and zero genetic covariance between relative horn and aedeagus length. Therefore, although the genetic covariance between absolute horn and aedeagus length would constrain the independent evolution of primary and secondary sexual characters in this population, there was no evidence of a trade‐off. We discuss alternative hypotheses for the observed patterns of genetic correlation between traits that compete for resources and the implications that these have for selection and the evolution of such traits.
Ultrio and Ultrio Plus non‐discriminating reactives: false reactives or not?
Authors: Charlewood R. , Flanagan P. 
Published: July 2012

Background  The low, fluctuating levels of DNA characteristic of occult hepatitis B infection make its detection by nucleic acid testing (NAT) a challenge.Methods  Four year’s routine use of the Ultrio and Ultrio Plus assays in blood donations in New Zealand was analysed.Results  0·09% of donations tested with Ultrio and Ultrio Plus assays showed reactivity in the multiplex assay, but non‐reactivity in all three discriminatory assays and relevant mandatory serological assays (anti‐HIV, anti‐HCV, HBsAg). These donations were more likely to be anti‐HBc reactive (Ultrio, 13%; Ultrio Plus, 57%; random donors, 6·8%). Thirty‐four per cent of these anti‐HBc‐reactive donations were also reactive in either an alternate NAT assay or on repeat multiplex testing. Thirteen per cent of the donors of the discriminatory‐negative, anti‐HBc‐reactive donations who had given other Ultrio‐ or Ultrio Plus‐tested donations had at least one other multiplex reactive donation.Conclusion  These findings suggest that their HBV DNA levels are around the assay’s limit of detection, that false reactivity cannot be presumed when a donor fails to discriminate and that caution should be applied when deciding whether to continue accepting donations from such donors.