bluuebunny/crossref_metadata_2025 huggingface dataset:
Anti‐donor immune responses elicited by allogeneic mesenchymal stem cells: what have we learned so far?
Authors: Griffin Matthew D , Ryan Aideen E , Alagesan Senthilkumar , Lohan Paul , Treacy Oliver , Ritter Thomas
Published: December 2012

Mesenchymal stem (stromal) cells (MSCs) have potent anti‐inflammatory/immunosuppressive properties which underlie much of their therapeutic potential. This fact has led to the widely accepted belief that MSCs from genetically unrelated individuals (allogeneic (allo)‐MSCs) can be used therapeutically with equal efficacy to autologous MSCs and without triggering the donor‐specific immune responses that are typically associated with allo‐transplants. In this article, we critically review available experimental data to determine whether good in vivo evidence exists in support of the ‘immune privileged’ status of allo‐MSCs. We also examine published studies regarding the immunogenicity of allo‐MSCs following activation (‘licensing’) by inflammatory stimuli or following differentiation. Among the identified studies which have addressed in vivo immunogenicity of allo‐MSCs, there was substantial variability as regards experimental species, disease model, route of MSC administration, cell dose and stringency of the immunological assays employed. Nonetheless, the majority of these studies has documented specific cellular (T‐cell) and humoral (B‐cell/antibody) immune responses against donor antigens following administration of non‐manipulated, interferon‐γ‐activated and differentiated allo‐MSCs. The consequences of such anti‐donor immune responses were also variable and ranged from reduced in vivo survival of allo‐MSCs with accelerated rejection of subsequent allogeneic transplants to apparent promotion of donor‐specific tolerance. On the basis of these findings and on existing knowledge of allo‐antigen recognition from the field of transplant immunology, we propose that the concept of the immune privileged nature of allo‐MSCs should be reconsidered and that the range and clinical implications of anti‐donor immune responses elicited by allo‐MSCs be more precisely studied in human and animal recipients.
Polymer–Graphene Nanocomposites
Authors:   Royal Society of Chemistry,   Royal Society of Chemistry
Published: December 2012

Graphene is an emerging material for generating polymer nanocomposites. Its heat conducting properties are greater than any other material, yet so dense not even helium can pass through its honeycomb lattice. The inclusion of small amounts of graphene to polymer matrices has the possibility of significantly improving their electrical, barrier and mechanical properties. Since the Nobel prize for Physics was awarded in 2010 for the isolation of graphene there has been an explosion in graphene research and the discovery of new applications. This book discusses the current state-of-the-art in graphene nanocomposites with expertise drawn from across the globe. Insights into the functionalisation of graphene are presented, in the context of various polymer systems, along with appropriate methodologies to be adopted. Grasping this view from several active researchers in the field gives the editor the opportunity to look where future trends are heading. This is an important handbook for anyone wishing to get a comprehensive view of the field and bring established methodologies into their laboratory and will benefit post-graduate students and established researchers alike.
Enhanced charge detection of spin qubit readout via an intermediate state
Authors: Studenikin S. A. , Thorgrimson J. , Aers G. C. , Kam A. , Zawadzki P. , Wasilewski Z. R. , Bogan A. , Sachrajda A. S.
Published: December 2012

We employ an intermediate excited charge state of a lateral quantum dot device to increase the charge detection contrast during the qubit state readout procedure, allowing us to increase the visibility of coherent qubit oscillations. This approach amplifies the coherent oscillation magnitude but has no effect on the detector noise resulting in an increase in the signal to noise ratio. In this letter, we apply this scheme to demonstrate a significant enhancement of the fringe contrast of coherent Landau-Zener-Stückelberg oscillations between singlet S and triplet T+ two-spin states.
Diffusion of the vacancy defect leading to the formation of multi-shell structures in the nanowire and nanobridge
Authors: Lee Wen-Jay , Pao Chun-Wei , Wang Yeng-Tseng , Su Wan-Sheng , Chang Jee-Gong
Published: December 2012

Accelerated molecular dynamics has been employed to study the phase transformation of the Au nanobridge and freestanding nanowire from a face center cubic structure with 15 atoms in the cross section to a helical multi-shell structure at room temperature. The translation of vacancy defect displays an important role to cause the transformation of the nanowire and nanobridge. Due to the difference in boundary conditions, the different defect dynamics are observed for nanobridge and nanowire. The fact leads the formation of 11-4 and 12-4 structures in the nanobridge and nanowire, respectively. The 11-4 nanowire has been verified to be a metastable structure, which prefers becoming a 12-4 structure if the defect exists. In addition, the atomic arrangements of 11-4 and 12-4 structures were analyzed by the angular correlation function, and were found to possess a specific coordinated relationship between their inner and outer shells.
P-type behavior of Sb doped ZnO from p-n-p memory structure
Authors: Huang Jian , Li Zonglin , Chu Sheng , Liu Jianlin
Published: December 2012

Antimony (Sb) doped p-type ZnO was studied by using Sb-ZnO/ZnO/Sb-ZnO p-n-p structure. Secondary ion mass spectrometry result confirmed the formation of the structure. Rectifying current-voltage characteristics between Sb-ZnO and undoped ZnO layers were achieved, proving the p-n junction was formed. The p-type behavior from the p-n-p structure was studied by using the capacitance-voltage measurement and small signal model. The voltage operation led to the charging/discharging of the structure, showing nonvolatile memory effect. Very long retention time was achieved. This research suggests that p-type ZnO can be evaluated by a p-n-p structure, which could be promising for future nonvolatile memory applications.
2-Methoxyestradiol inhibits experimental autoimmune encephalomyelitis through suppression of immune cell activation
Authors: Duncan Gordon S. , Brenner Dirk , Tusche Michael W. , Brüstle Anne , Knobbe Christiane B. , Elia Andrew J. , Mock Thomas , Bray Mark R. , Krammer Peter H. , Mak Tak W.
Published: December 2012

The endogenous metabolite of estradiol, 2-Methoxyestradiol (2ME2), is an antimitotic and antiangiogenic cancer drug candidate that also exhibits disease-modifying activity in animal models of rheumatoid arthritis (RA). We found that 2ME2 dramatically suppresses development of mouse experimental autoimmune encephalomyelitis (EAE), a rodent model of multiple sclerosis (MS). 2ME2 inhibits in vitro lymphocyte activation, cytokine production, and proliferation in a dose-dependent fashion. 2ME2 treatment of lymphocytes specifically reduced the nuclear translocation and transcriptional activity of nuclear factor of activated T-cells (NFAT) c1, whereas NF-κB and activator protein 1 (AP-1) activation were not adversely affected. We therefore propose that 2ME2 attenuates EAE through disruption of the NFAT pathway and subsequent lymphocyte activation. By extension, our findings provide a molecular rationale for the use of 2ME2 as a tolerable oral immunomodulatory agent for the treatment of autoimmune disorders such as MS in humans.
The science in social science
Authors: Bernard H. Russell
Published: December 2012

A recent poll showed that most people think of science as technology and engineering—life-saving drugs, computers, space exploration, and so on. This was, in fact, the promise of the founders of modern science in the 17th century. It is less commonly understood that social and behavioral sciences have also produced technologies and engineering that dominate our everyday lives. These include polling, marketing, management, insurance, and public health programs.
Identification of Oct4-activating compounds that enhance reprogramming efficiency
Authors: Li Wendong , Tian E , Chen Zhao-Xia , Sun GuoQiang , Ye Peng , Yang Su , Lu Dave , Xie Jun , Ho Thach-Vu , Tsark Walter M. , Wang Charles , Horne David A. , Riggs Arthur D. , Yip M. L. Richard , Shi Yanhong
Published: December 2012

One of the hurdles for practical application of induced pluripotent stem cells (iPSC) is the low efficiency and slow process of reprogramming. Octamer-binding transcription factor 4 (Oct4) has been shown to be an essential regulator of embryonic stem cell (ESC) pluripotency and key to the reprogramming process. To identify small molecules that enhance reprogramming efficiency, we performed a cell-based high-throughput screening of chemical libraries. One of the compounds, termed Oct4-activating compound 1 (OAC1), was found to activate both
Oct4
and
Nanog
promoter-driven luciferase reporter genes. Furthermore, when added to the reprogramming mixture along with the quartet reprogramming factors (Oct4, Sox2, c-Myc, and Klf4), OAC1 enhanced the iPSC reprogramming efficiency and accelerated the reprogramming process. Two structural analogs of OAC1 also activated Oct4 and Nanog promoters and enhanced iPSC formation. The iPSC colonies derived using the Oct4-activating compounds along with the quartet factors exhibited typical ESC morphology, gene-expression pattern, and developmental potential. OAC1 seems to enhance reprogramming efficiency in a unique manner, independent of either inhibition of the p53-p21 pathway or activation of the Wnt-β-catenin signaling. OAC1 increases transcription of the
Oct4-Nanog-Sox2
triad and
Tet1
, a gene known to be involved in DNA demethylation.
Theory and data in diachronic Construction Grammar
Authors: Trousdale Graeme
Published: December 2012

Constructionalization (the diachronic creation of conventional symbolic units at different levels of schematicity and complexity) is a process which involves a series of micro-changes at different linguistic levels. The development of what with constructions in English is argued to be a case of grammatical constructionalization, whereby aspects of a construction become more general, productive, and less compositional. Equally, parts of the construction become more fixed (involving a reduction in variability), while other parts of the construction expand. The application of principles of construction grammar to aspects of diachronic change helps to clarify the relationship between theoretical principles of language change and the analysis of naturally occurring data; equally, the study of the what with construction reveals areas of potential convergence between formal and functional approaches to syntactic change, as well as areas of difference.
Word classes
Authors: Hollmann Willem B.
Published: December 2012

Structuralists and generativists define word classes distributionally (Palmer 1971, Baker 2003, Aarts 2007), while cognitive linguists take a semantic (Langacker 1987a) or semantic-pragmatic approach (Croft 1991, 2001). Psycholinguistic research, by contrast, has shown that phonological properties also play a role (Kelly 1992, Monaghan et al. 2005). This study reports on a production experiment involving English nonce nouns and verbs. The data confirm the importance of phonology, whilst also suggesting that distributional facts are involved in lexical categorisation. Together with the existing psycholinguistic evidence, the results show that both the generative and cognitive models of word classes are too restricted. However, the usage-based model can accommodate the facts straightforwardly. This was already anticipated by Taylor (2002) but is worked out in more detail here by elaborating on his notion of phonological “sub-schemas” and by bringing together insights from Croft (1991, 2001) related to discourse propositional act constructions and recent suggestions by Langacker (2008b) concerning “summary scanning” and “sequential scanning”.
Development and Evaluation of a Bioenergetics Model for Bull Trout
Authors: Mesa Matthew G. , Weiland Lisa K. , Christiansen Helena E. , Sauter Sally T. , Beauchamp David A.
Published: December 2012

We conducted laboratory experiments to parameterize a bioenergetics model for wild Bull Trout Salvelinus confluentus, estimating the effects of body mass (12–1,117 g) and temperature (3–20°C) on maximum consumption (Cmax) and standard metabolic rates. The temperature associated with the highest Cmax was 16°C, and Cmax showed the characteristic dome‐shaped temperature‐dependent response. Mass‐dependent values of Cmax (N = 28) at 16°C ranged from 0.03 to 0.13 g·g−1·d−1. The standard metabolic rates of fish (N = 110) ranged from 0.0005 to 0.003 g·O2·g−1·d−1 and increased with increasing temperature but declined with increasing body mass. In two separate evaluation experiments, which were conducted at only one ration level (40% of estimated Cmax), the model predicted final weights that were, on average, within 1.2 ± 2.5% (mean ± SD) of observed values for fish ranging from 119 to 573 g and within 3.5 ± 4.9% of values for 31–65 g fish. Model‐predicted consumption was within 5.5 ± 10.9% of observed values for larger fish and within 12.4 ± 16.0% for smaller fish. Our model should be useful to those dealing with issues currently faced by Bull Trout, such as climate change or alterations in prey availability.
Estimating Effective Sample Size for Monitoring Length Distributions: A Comparative Study of Georges Bank Groundfish
Authors: Zhang Yuying , Cadrin Steve X.
Published: December 2012

Because of the aggregative behavior of fish, effective sample size is more meaningful than total sample size for estimating the length distribution of a fish stock. We estimated the effective sample sizes for mean length distributions of six groundfish species from Georges Bank using data collected by a Study Fleet Program implemented by the School for Marine Science and Technology (SMAST) at the University of Massachusetts–Dartmouth. Both statistical and simulation methods were applied. Skewness and kurtosis were also used as proxies for length distributions. The statistical result suggests that the estimated effective sample size is much less than the number of fish measured in the initial SMAST Study Fleet Program, while the simulation method suggests that for most groundfish species reducing the total number of fish to 20% will not affect the variance, skewness, and kurtosis of the population length. For the SMAST Study Fleet Program, increasing the number of sampling stations can improve sampling precision better than increasing the number of fish measured within each station. This study helps to develop an optimal sampling design that balances the quality of the data collected and costs of the sampling effort.
Validating Back‐Calculation Models Using Population Data
Authors: Perez K. O. , Munch S. B.
Published: December 2012

Otolith back‐calculation, an estimation of size and growth at some previous age, is a valuable and widely used method of tracking the traits of surviving individuals. Although numerous back‐calculation models have been developed, the accuracy of model prediction is rarely assessed before using a model on wild populations. Using the Atlantic SilversideMenidia menidia, we tested the precision of four commonly used back‐calculation models (body proportional hypothesis, modified Fry, biological intercept, and time‐varying growth). We calculated the moments of the observed length frequency distribution (mean, variance, skewness, and kurtosis) and compared them with the moments of the back‐calculated length frequency distribution predicted by each model. We also compared how the most accurate back‐calculation model changed under various scenarios of size‐selective mortality and found that bias in back‐calculation could not be explained by size‐selective mortality. The differences between functional forms over a wide range of fish sizes were slight for the biological intercept and modified Fry models, whereas the time‐varying growth and body proportional hypothesis models differed considerably. We found that all models performed well for at least one measure of accuracy. However, the modified Fry model was the most accurate overall when back‐calculating to the observed population moments.
Farp1 gives both sides of the story
Authors: Short Ben
Published: December 2012

Postsynaptic signaling protein helps organize both pre- and postsynapses.
Eco-evolutionary feedbacks, adaptive dynamics and evolutionary rescue theory
Authors: Ferriere Regis , Legendre Stéphane
Published: December 2012

Adaptive dynamics theory has been devised to account for feedbacks between ecological and evolutionary processes. Doing so opens new dimensions to and raises new challenges about evolutionary rescue. Adaptive dynamics theory predicts that successive trait substitutions driven by eco-evolutionary feedbacks can gradually erode population size or growth rate, thus potentially raising the extinction risk. Even a single trait substitution can suffice to degrade population viability drastically at once and cause ‘evolutionary suicide’. In a changing environment, a population may track a viable evolutionary attractor that leads to evolutionary suicide, a phenomenon called ‘evolutionary trapping’. Evolutionary trapping and suicide are commonly observed in adaptive dynamics models in which the smooth variation of traits causes catastrophic changes in ecological state. In the face of trapping and suicide, evolutionary rescue requires that the population overcomeevolutionarythreats generated by the adaptive process itself. Evolutionary repellors play an important role in determining how variation in environmental conditions correlates with the occurrence of evolutionary trapping and suicide, and what evolutionary pathways rescue may follow. In contrast with standard predictions of evolutionary rescue theory, low genetic variation may attenuate the threat of evolutionary suicide and small population sizes may facilitate escape from evolutionary traps.
Evolutionary and plastic rescue in multitrophic model communities
Authors: Kovach-Orr Caolan , Fussmann Gregor F.
Published: December 2012

Under changing environmental conditions, intraspecific variation can potentially rescue populations from extinction. There are two principal sources of variation that may ultimately lead to population rescue: genetic diversity and phenotypic plasticity. We compared the potential for evolutionary rescue (through genetic diversity) and plastic rescue (through phenotypic plasticity) by analysing their differential ability to produce dynamical stability and persistence in model food webs. We also evaluated how rescue is affected by the trophic location of variation. We tested the following hypotheses: (i) plastic communities are more likely to exhibit stability and persistence than communities in which genetic diversity provides the same range of traits. (ii) Variation at the lowest trophic level promotes stability and persistence more than variation at higher levels. (iii) Communities with variation at two levels have greater probabilities of stability and persistence than communities with variation at only one level. We found that (i) plasticity promotes stability and persistence more than genetic diversity; (ii) variation at the second highest trophic level promotes stability and persistence more than variation at the autotroph level; and (iii) more than variation at two trophic levels. Our study shows that proper evaluation of the rescue potential of intraspecific variation critically depends on its origin and trophic location.
Evolutionary rescue in vertebrates: evidence, applications and uncertainty
Authors: Vander Wal E. , Garant D. , Festa-Bianchet M. , Pelletier F.
Published: December 2012

The current rapid rate of human-driven environmental change presents wild populations with novel conditions and stresses. Theory and experimental evidence for evolutionary rescue present a promising case for species facing environmental change persisting via adaptation. Here, we assess the potential for evolutionary rescue in wild vertebrates. Available information on evolutionary rescue was rare and restricted to abundant and highly fecund species that faced severe intentional anthropogenic selective pressures. However, examples from adaptive tracking in common species and genetic rescues in species of conservation concern provide convincing evidence in favour of the mechanisms of evolutionary rescue. We conclude that low population size, long generation times and limited genetic variability will result in evolutionary rescue occurring rarely for endangered species without intervention. Owing to the risks presented by current environmental change and the possibility of evolutionary rescue in nature, we suggest means to study evolutionary rescue by mapping genotype → phenotype → demography → fitness relationships, and priorities for applying evolutionary rescue to wild populations.
Evolutionary rescue beyond the models
Authors: Gomulkiewicz Richard , Shaw Ruth G.
Published: December 2012

Laboratory model systems and mathematical models have shed considerable light on the fundamental properties and processes of evolutionary rescue. But it remains to determine the extent to which these model-based findings can help biologists predict when evolution will fail or succeed in rescuing natural populations that are facing novel conditions that threaten their persistence. In this article, we present a prospectus for transferring our basic understanding of evolutionary rescue to wild and other non-laboratory populations. Current experimental and theoretical results emphasize how the interplay between inheritance processes and absolute fitness in changed environments drive population dynamics and determine prospects of extinction. We discuss the challenge of inferring these elements of the evolutionary rescue process in field and natural settings. Addressing this challenge will contribute to a more comprehensive understanding of population persistence that combines processes of evolutionary rescue with developmental and ecological mechanisms.
Reproductive senescence in female Soay sheep: variation across traits and contributions of individual ageing and selective disappearance
Authors: Hayward Adam D. , Wilson Alastair J. , Pilkington Jill G. , Clutton‐Brock Tim H. , Pemberton Josephine M. , Kruuk Loeske E. B.
Published: December 2012

Although senescence in reproductive success has been observed in a number of wild animal populations, longitudinal analyses determining the actual processes responsible for population‐level patterns of ageing, and in particular, the relative contributions of within‐individual senescence vs. selective mortality, are rare. Furthermore, many studies also only consider single traits in isolation, despite evidence that different aspects of physiology and fitness may show varying patterns of senescence.

We used data from an unmanaged population of Soay sheep on the islands of St Kilda, NW Scotland to analyse age‐related change in four aspects of female reproductive performance: annual fecundity, twinning rate and the maternally influenced offspring traits of lamb birth weight and early survival. We present the results of three analytical techniques, which attempt to disentangle the contributions of within‐individual ageing, selective mortality and terminal effects to the observed population‐level patterns of age‐specific change.

All four traits showed considerable age‐related change, but population‐level trajectories varied markedly across them. Population‐level patterns were underpinned by considerable within‐individual senescence including within‐individual terminal declines in performance occurring only in the final year of life. However, at the population level, these processes were also masked to some extent by selective disappearance (mortality) of poor breeders.

The contributions of individual‐level ageing and selective mortality to population‐level ageing patterns varied considerably between traits, as did the nature of individual‐level senescence. We did not observe detectable significant late‐life declines in all four traits: in particular, there was no evidence of senescence in twinning rate. The results indicate that senescence may not be ubiquitous across all aspects of reproductive performance within a population.
Propagule pressure, not fire or cattle grazing, promotes invasion of buffel grass Cenchrus ciliaris
Authors: Fensham Rod J. , Donald Sam , Dwyer John M.
Published: December 2012

The invasion of exotic grasses into savannas is occurring globally. Despite threats to ecosystem processes and biodiversity, few studies have investigated factors that facilitate invasion success.

The abundance of the exotic perennial Cenchrus ciliaris buffel grass was assessed across woodland clearings at 46 sites in Queensland, Australia. The influence of fire and grazing on the invasion success were also examined experimentally within 18 sampling stations (including cattle grazed and ungrazed treatment pairs) with unburnt, low‐intensity and high‐intensity fire treatments.

Mixed‐effects logistic regressions suggest that the probability of buffel grass occurring in remnants was predominantly a function of the abundance of buffel grass in adjoining paddocks. The abundance of buffel grass in remnants was greater where the boundaries with clearings faced the prevailing wind adjacent to paddocks with high buffel grass abundance.

There was a significant positive association between buffel grass and tree canopies at approximately half of the sites, and the strength of this association was positively related to the amount of coarse sand in the surface soil. This association was interpreted as nutrient enrichment from litter fall on sandy infertile soils being a requirement for invasion. The invasion of buffel grass at the experimental site accelerated with above‐average rainfall after a prolonged drought, and invasion continued even after imposing all combinations of fire and grazing.

Cattle grazing modestly enhanced invasion, relative to the absence of grazing, but this difference was only significant without burning. The occurrence of fire in both the survey and experiment was not associated with enhanced buffel grass invasion.

Invasion of buffel grass may be inevitable over large areas of savanna, especially when abundant rainfall follows periods of drought. However, invasion will be minimized in areas where buffel grass has not been planted, areas without cattle grazing and in areas with low soil fertility.

Synthesis and applications. The invasion of buffel grass accelerates during abundant rainfall after drought and is enhanced by propagule pressure, dispersal trajectories and under trees, probably as a result of nutrient enrichment. Disturbance had little influence on invasion, and there is no support for fire‐promoted invasion as predicted by the grass–fire cycle theory.
Ranolazine Maintained Sinus Rhythm in a Patient with Refractory Symptomatic Atrial Fibrillation
Authors: Sossalla Samuel , Sohns Christian , Seegers Joachim , Lüthje Lars , Vollmann Dirk , Zabel Markus
Published: December 2012

We report on a patient who was treated with several antiarrhythmic drugs as well as different ablation strategies. Nevertheless, symptomatic atrial fibrillation always recurred until an off‐label use with ranolazine was started. We could demonstrate potent effects of ranolazine on atrial fibrillation in a “wash‐in wash‐out” situation. Although promising controlled studies are needed to investigate a potential role of ranolazine for the treatment of atrial fibrillation.
Longitudinal growth of very low birth weight neonates during first year of life and risk factors for malnutrition in a developing country
Authors: Mukhopadhyay Kanya , Mahajan Rama , Louis Deepak , Narang Anil
Published: December 2012

Aims

To study growth of very low birth weight neonates (VLBW) during first year and identify risk factors for malnutrition.

Methods

Neonates ≤34 weeks and ≤1500 g enrolled in a human milk fortification trial were prospectively followed till 1 year corrected age (CA). Anthropometry was plotted on WHO charts. Risk factors were compared between well nourished and underweight infants.

Results

One hundred and thirty‐two, 127, 110, 99 and 101 neonates were followed at CA of 40 weeks, 3, 6, 9 and 12 months. Weight (Mean Z score −2.3 ± 1.2 to –1.7 ± 1.4; p = 0.005) and length (−2.1 ± 1.5 to –1.5 ± 1.3; p = 0.004) improved significantly, from 40 weeks to one year while head circumference declined (−0.92 ± 1.1 to –1.2 ± 1.1; p < 0.001). Incidence of underweight, stunting, microcephaly and wasting changed from 63%, 53%, 13% and 52% neonates at 40 weeks to 41%, 32%, 21% and 27% at one year. Growth between fortified and unfortified or small for gestational age (SGA) and appropriate for gestational age (AGA) groups were similar, while extremely low birth weight (ELBW) neonates showed poorer growth. Z score of weight at 3 months emerged as an independent predictor of malnutrition at one year.

Conclusion

VLBW neonates, especially the ELBW group remained growth retarded at CA of one year. Z score of weight at 3 months was a significant risk factor for malnutrition at one year.
Red blood cell transfusion is associated with increased rebleeding in patients with nonvariceal upper gastrointestinal bleeding
Authors: Restellini S. , Kherad O. , Jairath V. , Martel M. , Barkun A. N.
Published: December 2012

Background

There exists considerable practice variation and little evidence to guide red blood cell (RBC) transfusion in patients with nonvariceal upper gastrointestinal bleeding (NVUGIB). Studies in other critically ill cohorts suggest associations between transfusions and adverse patient outcomes.

Aim

To characterise any possible clinically‐relevant association between RBC transfusion following NVUGIB with rebleeding and mortality.

Methods

Observational study utilising the Canadian Registry of patients with Upper Gastrointestinal Bleeding and Endoscopy (RUGBE). Multivariable logistic regression models were used to examine and quantify independent associations between RBC transfusion and clinical outcomes.

Results

Overall, 1677 patients were included (66.2 ± 16.8 years, 61.7% male, 2.5 ± 1.7 comorbid conditions, initial haemoglobin, 96.8 ± 27.2 g/L); 53.7% received RBC transfusions (2.9 ± 1.6 units of blood), 31.6% had haemodynamic instability, 5.1% fresh blood on rectal examination and 8.6% in the nasogastric tube aspirate. Endoscopic haemostasis was performed in 35.2%. Overall rebleeding (defined as continuous bleeding, rebleeding or surgery) and mortality rates were 17.9% and 5.4%, respectively. After adjusting for potential confounders, transfusion of RBC within 24 h of presentation was significantly and independently associated with an increased risk of rebleeding (OR: 1.8, 95% CI: 1.2–2.8), but not death (OR: 1.0, 95% CI: 0.6–1.8).

Conclusions

This study suggests an association between RBC transfusion following NVUGIB and subsequent rebleeding, after appropriate and extensive adjustment for confounding. Prospective randomised trial evidence is needed to identify the most efficacious and cost‐effective transfusional strategies in these patients.
Duration of vancomycin treatment for coagulase‐negative Staphylococcus sepsis in very low birth weight infants
Authors: Linder Nehama , Lubin Daniel , Hernandez Adriana , Amit Limor , Ashkenazi Shai
Published: December 2012

Aim

Vancomycin is widely used to treat late onset coagulase‐negative Staphylococcus (CoNS) sepsis in very low birth weight (VLBW) infants. Although vancomycin is associated with a risk of toxicity and bacterial resistance, the appropriate duration of use has not been established. This study sought to investigate the association between the duration of vancomycin therapy and clinical outcome in VLBW infants with CoNS sepsis.

Methods

The files of all VLBW infants treated for CoNS sepsis at a tertiary paediatric medical centre from 1995–2003 were reviewed for clinical data, laboratory variables and outcome. Only patients with two positive diagnostic blood cultures were included. The findings were analyzed by duration of vancomycin treatment after the last positive blood culture.

Results

The study cohort included 126 infants, 48 treated for 5 days, 32 for 6–7 days, 31 for 8–10 days and 15 for >10 days. There were no differences among the groups in perinatal characteristics, central catheter dwell time, laboratory data including haematologic, renal and liver function tests, or rate of complications of prematurity. Five infants were diagnosed with infective endocarditis or aortic thrombi and were treated for >10 days. CoNS sepsis recurred in two infants (1.6%). No toxicity of vancomycin treatment was observed.

Conclusions

In VLBW infants with uncomplicated CoNS sepsis, treatment with vancomycin for 5 days after the last positive blood culture appears to be associated with a satisfactory outcome and no adverse effects. A well‐controlled prospective multicentre study is needed to confirm these findings.
A semi‐mechanistic absorption model to evaluate drug–drug interaction with dabigatran: application with clarithromycin
Authors: Delavenne Xavier , Ollier Edouard , Basset Thierry , Bertoletti Laurent , Accassat Sandrine , Garcin Arnauld , Laporte Silvy , Zufferey Paul , Mismetti Patrick
Published: December 2012

Aim

The aim of this study was to develop a PK/PD model to assess drug–drug interactions between dabigatran and P‐gp modulators, using the example of clarithromycin, a strong inhibitor of P‐gp.

Methods

Ten healthy male volunteers were randomized to receive in the first treatment period a single 300 mg dose of dabigatran etexilate (DE) and in the second treatment period 500 mg clarithromycin twice daily during 3 days and then 300 mg DE plus 500 mg clarithromycin on the fourth day, or the same treatments in the reverse sequence. Dabigatran plasma concentration and ecarin clotting time (ECT) were measured on 11 blood samples. Models were built using a non‐linear mixed effect modelling approach.

Results

The best PK model was based on an inverse Gaussian absorption process with two compartments. The relationship between dabigatran concentration and ECT was implemented as a linear function. No continuous covariate was associated with a significant decrease in the objective function. The concomitant administration of clarithromycin induced a significant change only in DE bioavailability, which increased from 6.5% to 10.1% in the presence of clarithromycin. Clarithromycin increased peak concentration and AUC by 60.2% and 49.1% respectively.

Conclusion

The model proposed effectively describes the complex PK of dabigatran and takes into account drug–drug interactions with P‐gp activity modulators, such as clarithromycin.
Strong Genetic Contribution to Peer Relationship Difficulties at School Entry: Findings From a Longitudinal Twin Study
Authors: Boivin Michel , Brendgen Mara , Vitaro Frank , Dionne Ginette , Girard Alain , Pérusse Daniel , Tremblay Richard E.
Published: December 2012

This study assessed the genetic and environmental contributions to peer difficulties in the early school years. Twins' peer difficulties were assessed longitudinally in kindergarten (796 twins, Mage = 6.1 years), Grade 1 (948 twins, Mage = 7.1 years), and Grade 4 (868 twins, Mage = 10 years) through multiple informants. The multivariate results revealed that genetic factors accounted for a strong part of both yearly and stable peer difficulties. At the univariate level, the genetic contributions emerged progressively, as did a growing consensus among informants with respect to those who experienced peer difficulties. These results underline the need to intervene early and persistently, and to target the child and the peer context to prevent peer difficulties and their consequences.
Comparative phylogeography reveals deep lineages and regional evolutionary hotspots in the Mojave and Sonoran Deserts
Authors: Wood Dustin A. , Vandergast Amy G. , Barr Kelly R. , Inman Rich D. , Esque Todd C. , Nussear Kenneth E. , Fisher Robert N.
Published: December 2012

Aim

We explored lineage diversification within desert‐dwelling fauna. Our goals were (1) to determine whether phylogenetic lineages and population expansions were consistent with younger Pleistocene climate fluctuation hypotheses or much older events predicted by pre‐Pleistocene vicariance hypotheses, (2) to assess concordance in spatial patterns of genetic divergence and diversity among species and (3) to identify regional evolutionary hotspots of divergence and diversity and assess their conservation status.

Location

Mojave, Colorado, and Sonoran Deserts, USA.

Methods

We analysed previously published gene sequence data for twelve species. We used Bayesian gene tree methods to estimate lineages and divergence times. Within each lineage, we tested for population expansion and age of expansion using coalescent approaches. We mapped interpopulation genetic divergence and intra‐population genetic diversity in a GIS to identify hotspots of highest genetic divergence and diversity and to assess whether protected lands overlapped with evolutionary hotspots.

Results

In seven of the 12 species, lineage divergence substantially predated the Pleistocene. Historical population expansion was found in eight species, but expansion events postdated the Last Glacial Maximum (LGM) in only four. For all species assessed, six hotspots of high genetic divergence and diversity were concentrated in the Colorado Desert, along the Colorado River and in the Mojave/Sonoran ecotone. At least some proportion of the land within each recovered hotspot was categorized as protected, yet four of the six also overlapped with major areas of human development.

Main conclusions

Most of the species studied here diversified into distinct Mojave and Sonoran lineages prior to the LGM – supporting older diversification hypotheses. Several evolutionary hotspots were recovered but are not strategically paired with areas of protected land. Long‐term preservation of species‐level biodiversity would entail selecting areas for protection in Mojave and Sonoran Deserts to retain divergent genetic diversity and ensure connectedness across environmental gradients.
Family dynamics through time: brood reduction followed by parental compensation with aggression and favouritism
Authors: Shizuka Daizaburo , Lyon Bruce E.
Published: December 2012

Parental food allocation in birds has long been a focal point for life history and parent–offspring conflict theories. In asynchronously hatching species, parents are thought to either adjust brood size through death of marginal offspring (brood reduction), or feed the disadvantaged chicks to reduce the competitive hierarchy (parental compensation). Here, we show that parent American coots (Fulica americana) practice both strategies by switching from brood reduction to compensation across time. Late‐hatching chicks suffer higher mortality only for the first few days after hatching. Later, parents begin to exhibit parental aggression towards older chicks and each parent favours a single chick, both of which are typically the youngest of the surviving offspring. The late‐hatched survivors can equal or exceed their older siblings in size prior to independence. A mixed allocation strategy allows parents to compensate for the costs of competitive hierarchies while gaining the benefits of hatching asynchrony.
Habitat‐related patterns in phenotypic variation in a New Zealand freshwater generalist fish, and comparisons with a closely related specialist
Authors: VANDERPHAM JEFFREY P. , NAKAGAWA SHINICHI , CLOSS GERARD P.
Published: December 2012

1. Within‐species phenotypic variation is hugely variable and may play a role in determining the range of habitats a species can exploit. Our study addressed two main questions: 1. does phenotypic variation allow some species (i.e. habitat‐generalists) to use heterogeneous habitats and 2. are habitat‐generalists more variable than species occupying relatively homogeneous environments (i.e. habitat‐specialists)?

2. We examined the morphology of the common bully (Gobiomorphus cotidianus), a habitat‐generalist eleotrid fish found in lakes and rivers throughout New Zealand. We also compared the level of morphological variability in common bullies with that in the closely related redfin bully (Gobiomorphus huttoni), a habitat‐specialist of moderate‐ and fast‐flowing rivers.

3. Common and redfin bullies were collected from the South Island of New Zealand. A series of body and fin measurements were made, and cephalic dorsal head pores of the mechanosensory lateral‐line system were counted. The pores and associated canal neuromasts are important for prey detection and predator avoidance in other species, particularly, in turbulent conditions where the effectiveness of superficial neuromasts may be compromised.

4. The common bully had more dorsal head pores in fish from rivers than in those from lakes. This pattern was apparent only in adults, suggesting that selective pressures associated with adult habitat, be it rivers or lakes, are responsible.

5. As expected, there was greater phenotypic variability in the generalist common bully than in the specialist redfin bully, particularly with regard to the sensory pores, suggesting their importance for survival in turbulence.

6. We identified habitat‐related patterns in phenotypic variability in a generalist species and demonstrated a link between phenotypic variability and habitat breadth. Variation in the common bully may explain its ability to occupy a range of habitats.
Linking temperature sensitivity of soil organic matter decomposition to its molecular structure, accessibility, and microbial physiology
Authors: Wagai Rota , Kishimoto‐Mo Ayaka W. , Yonemura Seiichiro , Shirato Yasuhito , Hiradate Syuntaro , Yagasaki Yasumi
Published: December 2012

Temperature sensitivity of soil organic matter (SOM) decomposition may have a significant impact on global warming. Enzyme‐kinetic hypothesis suggests that decomposition of low‐quality substrate (recalcitrant molecular structure) requires higher activation energy and thus has greater temperature sensitivity than that of high‐quality, labile substrate. Supporting evidence, however, relies largely on indirect indices of substrate quality. Furthermore, the enzyme‐substrate reactions that drive decomposition may be regulated by microbial physiology and/or constrained by protective effects of soil mineral matrix. We thus tested the kinetic hypothesis by directly assessing the carbon molecular structure of low‐density fraction (LF) which represents readily accessible, mineral‐freeSOMpool. Using five mineral soil samples of contrastingSOMconcentrations, we conducted 30‐days incubations (15, 25, and 35 °C) to measure microbial respiration and quantified easily soluble C as well as microbial biomass C pools before and after the incubations. Carbon structure of LFs (<1.6 and 1.6–1.8 g cm−3) and bulk soil was measured by solid‐state13C‐NMR. DecompositionQ10was significantly correlated with the abundance of aromatic plus alkyl‐C relative to O‐alkyl‐C groups inLFs but not in bulk soil fraction or with the indirect C quality indices based on microbial respiration or biomass. The warming did not significantly change the concentration of biomass C or the three types of soluble C despite two‐ to three‐fold increase in respiration. Thus, enhanced microbial maintenance respiration (reduced C‐use efficiency) especially in the soils rich in recalcitrantLFmight lead to the apparent equilibrium betweenSOMsolubilization and microbial C uptake. Our results showed physical fractionation coupled with direct assessment of molecular structure as an effective approach and supported the enzyme‐kinetic interpretation of widely observed C quality‐temperature relationship for short‐term decomposition. Factors controlling long‐term decompositionQ10are more complex due to protective effect of mineral matrix and thus remain as a central question.
Dok adaptors play anti‐inflammatory roles in pulmonary homeostasis
Authors: Mashima Ryuichi , Arimura Sumimasa , Kajikawa Shuhei , Oda Hideaki , Nakae Susumu , Yamanashi Yuji
Published: December 2012

Asthma is a chronic inflammatory disease of the lung with airflow obstruction and bronchospasm, characterized by pulmonary eosinophilia, airway remodeling, increased airway hyperresponsiveness to environmental stimuli, and excessive Th2‐type cytokine production. Recent studies indicate that crosstalk between the innate and adaptive immune systems is crucial for this disease. We and others have showed that the Dok (downstream of tyrosine kinases) family adaptors, Dok‐1, Dok‐2, and Dok‐3, play essential roles in negative regulation of a wide variety of signaling pathways in both innate and adaptive immunities. Here, histopathology and bronchoalveolar lavage fluid (BALF) cellularity showed spontaneous pulmonary inflammation in Dok‐1−/−Dok‐2−/−Dok‐3−/− (TKO) mice, but not in Dok‐1−/−Dok‐2−/− or Dok‐3−/− mice, with hallmarks of asthma, including eosinophilia, goblet cell hyperplasia, and subepithelial fibrosis. Consistently, TKO mice, but not the other mutants, showed increased airway hyperresponsiveness to methacholine inhalation. In addition, Th2‐type cytokine concentrations in BALF were increased in TKO mice. These findings provide strong evidence that Dok‐1, Dok‐2, and Dok‐3 cooperatively play critical anti‐inflammatory roles in lung homeostasis.
Differential diagnosis of facial acne on black skin
Authors: Poli Florence
Published: December 2012

The diagnosis of acne is usually easy, but there are some pitfalls to be avoided. ‘Keloid acne of the neck’ and beard folliculitis are not acnes in the usual sense: both are inflammatory and fibrous reactions of the hair follicles and frizzy hair; no retentional lesions, blackheads and microcysts – are visible. Gram negative folliculitis classically occurs in acneic male subjects who have undergone extensive treatment with general antibiotics or local antiseptics, but ‘de novo’ cases do exist. On black skin, this condition is not exceptional, it occurs in both sexes and usually takes the nodular form. The diagnosis should be considered if there is any aggravation of acne which is resistant to classic treatment, with painful nodules on the cheeks. Treatment is based on appropriate antibiotherapy for several weeks and possibly, in a second phase, on Isotretinoin. Pityrosporum folliculitis occurs mainly on the trunk. More frequent in men than in women, it is chiefly observed in subjects living in a hot, humid climate. Demodicidosis is manifested by outbreaks of papular or papulopustular lesions of the face. On black skin the principal differential diagnosis is acne. The presence of numerous parasites is necessary for diagnosis. Clinically speaking, an important sign is when the eyelids are affected. Ivermectin is effective. Acneiform dermatitis may be induced by depigmenting preparations containing powerful dermocorticoids. It is therefore important, in cases of very inflammatory acne, to look for the other clinical signs of voluntary depigmentation. In countries where it is endemic, lepromatous leprosy should be considered. Other common dermatitis may simulate acne or else be associated with it, such as eruptive hidradenoma or molluscum contagiosum. Analysis of the different elementary lesions and the absence of retentional lesions generally enable a diagnosis to be established.