bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficacious treatment of psoriasis with low‐dose and intermittent cyclosporin microemulsion therapy
Authors: Ito Taisuke , Furukawa Fukumi , Iwatsuki Keiji , Matsue Hiroyuki , Shimada Shinji , Takigawa Masahiro , Tokura Yoshiki
Published: March 2014

Cyclosporin is used for moderate to severe psoriasis and improves not only the skin lesions but also quality of life of the patients. To improve its safe use, we evaluated a low‐dose, intermittent regimen of cyclosporin in the treatment of psoriasis vulgaris. Seventy‐three patients received approximately 2.5 mg/kg per day of cyclosporin microemulsion twice daily before breakfast and dinner for 2–12 weeks until 75% reduction was achieved in Psoriasis Area and Severity Index (PASI) score. When the skin lesions relapsed after cessation of cyclosporin and showed less than 50% reduction from baseline in PASI score, cyclosporin was restarted. This cessation and restart cycle was repeated if necessary. Treatment outcomes were assessed at 12, 48 and 96 weeks after initiation of the therapy. The initial dose of cyclosporin was 2.32 ± 0.27 (standard deviation [SD]) mg/kg per day. At baseline, the mean PASI score was 11.3 ± 5.3 (SD). An average of 49.8 ± 23.8 (SD) days of the therapy achieved PASI 75% reduction. In 20 of 73 patients, the second course of cyclosporin was required. The mean interval between the first and second course was 94 days. An average of 60.8 ± 26.9 days was required to achieve PASI 75% reduction in the second course, which was not significantly longer than that in the first course. Only six patients required cyclosporin for 96 weeks. The adverse effects included one case of hypertension. Our study suggests that low‐dose, intermittent cyclosporin microemulsion is efficacious for the treatment of moderate to severe psoriasis.
Heterostyly promotes disassortative pollination and reduces sexual interference in Darwin's primroses: evidence from experimental studies
Authors: Keller Barbara , Thomson James D. , Conti Elena
Published: March 2014

Different strategies to reduce selfing and promote outcrossing have evolved in hermaphroditic flowers. Heterostyly, a complex floral polymorphism that occurs in at least 27 families of angiosperms, is hypothesized to achieve both goals by optimizing cross‐pollination (via disassortative pollen transfer) and restricting gamete wastage to autogamy (via the reduction in sexual interference between male and female organs).

In heterostylous flowers, the reciprocal positioning of sexual organs in different morphs and the pollen incompatibility system within flower or between flowers of the same morph are thought to optimize both male and female functions, reducing the conflicts inherent to the occurrence of both sexual organs in the same reproductive unit. Specific elements of the disassortative‐pollination and sexual‐interference hypotheses have been tested individually before. However, despite the long‐standing interest in heterostyly – ever since Darwin's seminal work on primroses – the predictions derived from these two hypotheses have never been experimentally and systematically examined in the same system.

Using distylous primroses (Primula elatior, P. vulgaris), we compare pollen transfer (i) between reciprocal and non‐reciprocal flowers; (ii) from anthers onto different parts of the pollinator's body; and (iii) within flower and between flowers of the same morph. We further test whether (iv) anther–stigma distance correlates with self‐pollen transfer and whether (v) seed set differs after pollinations with compatible, incompatible and both pollen types.

Reciprocal herkogamy promotes differential placement of pollen onto different parts of the pollinator's body, thus effecting transfer of more pollen to reciprocal than to non‐reciprocal stigmas and realizing the key predictions of the disassortative‐pollination hypothesis. However, short‐styled flowers transfer pollen more disassortatively than long‐styled flowers in both species, whereas long‐styled flowers export more pollen to non‐reciprocal than to reciprocal stigmas in P. vulgaris, thus compromising male function in this species. Furthermore, larger distance between sexual organs lowers self‐ and intra‐morph pollination and the pollen incompatibility system decreases seed production after self‐pollination, thus diminishing sexual interference.

Our results help us understand how the morphological and physiological components of heterostyly contribute to optimizing pollen transfer and minimizing self‐ and intra‐morph pollination, thus promoting more efficient outcrossing in species with this floral polymorphism.
Does body mass convey a digestive advantage for large herbivores?
Authors: Steuer Patrick , Südekum Karl‐Heinz , Tütken Thomas , Müller Dennis W. H. , Kaandorp Jacques , Bucher Martin , Clauss Marcus , Hummel Jürgen
Published: March 2014

A key concept of body mass (BM) in niche separation of large herbivores assumes that the decrease in diet quality inherent to increasing BM (due to less selective feeding behaviour) is balanced by a simultaneous increase in digestive ability (due to longer retention times), resulting in no or less‐than‐expected reduction in digestibility (as measured in the animal as a result of diet quality and digestive ability). However, the second part of this concept has been challenged recently due to theoretical problems and mismatch with empirical data.

A proxy for digestibility, such as metabolic faecal nitrogen (MFN), will comprise both information on diet quality and digestive ability in free‐ranging animals. In captive animals, if diet is kept constant, such a proxy can exclusively indicate digestive ability. Comparing free‐ranging and captive animals under such conditions, one would expect an increase in MFN with BM in captive animals and no relationship between these measures in free‐ranging animals if BM was related to digestive ability.

We compared captive ungulates on a consistent grass hay diet (17 species; 30–4000 kg BM) to a sample of free‐ranging East African ungulates (19 species; 12–4000 kg BM). MFN was used as the major proxy for digestibility.

In captive animals, there was no influence of BM on MFN (P = 0·466); for free‐ranging animals, a significant decreasing effect of body mass on MFN (P = 0·002) and therefore diet quality was found at a scaling of BM−0·15.

In conclusion, scenarios that assume a compensation of the evident decrease in diet quality with BM via an increased digestive ability are not supported by this study. This does not rule out other feeding‐related factors in facilitating large BM, such as compensation by an increased diet intake.
Spatial networks of fleshy‐fruited trees drive the flow of avian seed dispersal through a landscape
Authors: Rodríguez‐Pérez Javier , García Daniel , Martínez Daniel
Published: March 2014

Seed dispersal by animals leads to plant genes, individuals and species flowing across the landscape, but this process has been seldom seen as the explicit result of structural or landscape connectivity.

For two years, we studied avian seed dispersal of fleshy‐fruited trees in a secondary forest of the northern Iberian Peninsula, considering the areas under the canopies of fruiting trees as hubs of seed deposition.

Using graph‐theory models, we set a spatially explicit network in a continuous landscape, with individual fruiting trees as nodes and expected frugivore movements as links between nodes. We calculated the contribution of each tree to network connectivity, finding strong inter‐annual variability derived from tree properties (position, fruit crop and species).

Trees contributing the most to connectivity accumulated larger seed clumps under their canopies, demonstrating agreement between a network structural connectivity and the functional connectivity of seed dispersal flow. This pattern, however, is accentuated when the large‐scale distribution of fruiting crops closely matches that of individual trees, suggesting between‐year variation in resource tracking by avian frugivores.

Our findings reveal connectivity to be an emerging property of plant‐disperser systems, operating at the scale of individual fruiting plants, but contingent on the yearly, large‐scale templates of fruiting crops.
Exploring restoration options for habitats, species and ecosystem services in the European Union
Authors: Egoh Benis N. , Paracchini Maria L. , Zulian Grazia , Schägner Jan Philipp , Bidoglio Giovanni
Published: March 2014

The Convention on Biological Diversity (CBD) and the European Union have set a target of restoring 15% of degraded ecosystems by 2020 with the aim of conserving biodiversity and enhancing the supply of ecosystem services. This target must be implemented alongside other similar targets aimed at reducing the number of threatened habitat and species as assessed under the Birds and Habitats directives. However, there are several uncertainties associated with achieving these targets including the benefits of restoring biodiversity and ecosystem services, the contribution required from member states and the effect of different restoration scenarios on target achievement.

In this study, we evaluate options that exist for meeting anEU‐wide 15% restoration target while conserving habitats and species and enhancing ecosystem services. We explored the effects of different restoration scenarios on the percentage of threatened habitat and species secured. Lastly, we explored the effects of including financial cost into the prioritization procedure.

Focusing restoration efforts on habitats with inadequate conservation status in the reporting of the Habitats Directive provides the largest benefit for species and ecosystem services. If the restoration target is set at 10% for habitat and species with inadequate or most threatened conservation status, and at 2% for all ecosystem services, about 18% ofEUecosystems should be restored to meet these targets.

When the target is set at 15% of habitat and species and 3% of all ecosystem services, results showed that France hosts the highest percentage of identified priority areas (13%) followed by Spain and Finland with about 11% and Sweden with 9%. However, these numbers change when financial cost is included alongside other criteria, with France containing 35% of all areas identified.

Synthesis and applications. These results suggest that to achieve the greatest benefits, funding for restoration should be directed towards habitats with inadequate conservation status rather than to species. Countries with larger areas of threatened habitat and lower restoration costs may offer better opportunities to meet targets, but including cost at theEUlevel may result in unequal burden sharing among countries.
Optimal release strategies for cost‐effective reintroductions
Authors: Canessa Stefano , Hunter David , McFadden Michael , Marantelli Gerry , McCarthy Michael A.
Published: March 2014

Ex situ programmes for endangered species commonly focus on two main objectives: insurance against immediate risk of extinction and reintroduction. Releases influence the size of captive and wild populations and may present managers with a trade‐off between the two objectives. This can be further complicated when considering the costs of the captive population and the possible release of different life stages.

We approached this decision problem by combining population models and decision‐analytic methods, using the reintroduction programme for the southern corroboree frog Pseudophryne corroboree in Australia as an example. We identified the optimal release rates of eggs and subadults which maximized the size of the captive and reintroduced populations while meeting constraints. We explored two scenarios: a long‐term programme for a stable age‐distributed captive population and a short‐term programme with non‐stable age distribution and limited budget. We accounted for uncertainty in the estimated vital rates and demographic stochasticity.

Assuming a stable age distribution, large proportions of individuals could be released without decreasing the captive population below its initial size. The optimal strategy was sensitive to the post‐release survival of both life stages, but subadult releases were generally most cost‐effective, producing a large wild population and requiring a cheaper captive population. Egg releases were optimal for high expected juvenile survival, whereas mixed releases of both life stages were never optimal.

In the short‐term realistic scenario, subadult releases also produced the largest wild population, but they required a large increase in the size and cost of the captive population that exceeded the available budget. Egg releases were cheaper but yielded smaller numbers in the wild, whereas joint releases of both life stages provided more wild individuals, meeting budget constraints without depleting the captive population.

Synthesis and applications. Optimal release strategies for endangered species reflect the trade‐offs between insurance and reintroduction objectives and depend on the vital rates of the released individuals. Although focusing on a single life stage may have practical advantages, mixed strategies can maximize cost‐effectiveness by combining the relative advantages of releasing early and late life stages.
Microbial community composition explains soil respiration responses to changing carbon inputs along anAndes‐to‐Amazon elevation gradient
Authors: Whitaker Jeanette , Ostle Nicholas , Nottingham Andrew T. , Ccahuana Adan , Salinas Norma , Bardgett Richard D. , Meir Patrick , McNamara Niall P.
Published: March 2014

TheAndes are predicted to warm by 3–5 °C this century with the potential to alter the processes regulating carbon (C) cycling in these tropical forest soils. This rapid warming is expected to stimulate soil microbial respiration and change plant species distributions, thereby affecting the quantity and quality ofCinputs to the soil and influencing the quantity of soil‐derivedCO2released to the atmosphere.

We studied tropical lowland, premontane and montane forest soils taken from along a 3200‐m elevation gradient located in south‐eastAndeanPeru. We determined how soil microbial communities and abiotic soil properties differed with elevation. We then examined how these differences in microbial composition and soil abiotic properties affected soilC‐cycling processes, by amending soils withCsubstrates varying in complexity and measuring soil heterotrophic respiration (RH).

Our results show that there were consistent patterns of change in soil biotic and abiotic properties with elevation. Microbial biomass and the abundance of fungi relative to bacteria increased significantly with elevation, and these differences in microbial community composition were strongly correlated with greater soilCcontent andC:N(nitrogen) ratios. We also found thatRHincreased with addedCsubstrate quality and quantity and was positively related to microbial biomass and fungal abundance.

Statistical modelling revealed thatRHresponses to changingCinputs were best predicted by soil pHand microbial community composition, with the abundance of fungi relative to bacteria, and abundance of gram‐positive relative to gram‐negative bacteria explaining much of the model variance.

Synthesis. Our results show that the relative abundance of microbial functional groups is an important determinant ofRHresponses to changingCinputs along an extensive tropical elevation gradient inAndeanPeru. Although we do not make an experimental test of the effects of climate change on soil, these results challenge the assumption that different soil microbial communities will be ‘functionally equivalent’ as climate change progresses, and they emphasize the need for better ecological metrics of soil microbial communities to help predictCcycle responses to climate change in tropical biomes.
Physician Practice Participation in Accountable Care Organizations: The Emergence of the Unicorn
Authors: Shortell Stephen M. , McClellan Sean R. , Ramsay Patricia P. , Casalino Lawrence P. , Ryan Andrew M. , Copeland Kennon R.
Published: March 2014

Objective

To provide the first nationally based information on physician practice involvement in ACOs.

Data Sources/Study Setting

Primary data from the third National Survey of Physician Organizations (January 2012–May 2013).

Study Design

We conducted a 40‐minute phone survey in a sample of physician practices. A nationally representative sample of practices was surveyed in order to provide estimates of organizational characteristics, care management processes, ACO participation, and related variables for four major chronic illnesses.

Data Collection/Extraction Methods

We evaluated the associations between ACO participation, organizational characteristics, and a 25‐point index of patient‐centered medical home processes.

Principal Findings

We found that 23.7 percent of physician practices (n = 280) reported joining an ACO; 15.7 percent (n = 186) were planning to become involved within the next 12 months and 60.6 percent (n = 717) reported no involvement and no plans to become involved. Larger practices, those receiving patients from an IPA and/or PHO, those that were physician‐owned versus hospital/health system‐owned, those located in New England, and those with greater patient‐centered medical home (PCMH) care management processes were more likely to have joined an ACO.

Conclusions

Physician practices that are currently participating in ACOs appear to be relatively large, or to be members of an IPA or PHO, are less likely to be hospital‐owned and are more likely to use more care management processes than nonparticipating practices.
Incident User Cohorts for Assessing Medication Cost‐Offsets
Authors: Stuart Bruce , Loh F. Ellen , Roberto Pamela , Miller Laura
Published: March 2014

Objective

To develop and test incident drug user designs for assessing cost savings from statin use in diabetics.

Data Source

Random 5 percent sample of Medicare beneficiaries, 2006–2008.

Study Design

Seven‐step incident user design to assess impact of statin initiation on subsequent Medicare spending: (1) unadjusted pre/post initiation test; (2) unadjusted difference‐in‐difference (DID) with comparison series; (3) adjusted DID; (4) propensity score (PS)‐matched DID with static and dynamic baseline covariates; (5) PS‐matched DID by drug adherence strata; (6) PS‐matched DID for high adherers controlling for healthy adherer bias; and (7) replication for ACE‐inhibitor/ARB initiators.

Data Collection/Extraction Methods

Subjects with prevalent diabetes and no statin use (January–June 2006) and statin initiation (July 2006–January 2008) compared to nonusers with a random “potential‐initiation” month. Monthly Medicare spending tracked 24 months pre‐ and post‐initiation.

Principal Findings

Statistically significant savings in Medicare spending were observed beginning 7 months post‐initiation for statins and 13 months post‐initiation for ACEIs/ARBs. However, these savings were only observed for adherent patients in steps 5 and 6.

Conclusions

Drug initiator designs are more robust to confounding than prevalent user designs in assessing cost‐offsets from drug use but still require other adjustments and sensitivity analysis to ensure proper inference.
Tissue storage and primer selection influence pyrosequencing‐based inferences of diversity and community composition of endolichenic and endophytic fungi
Authors: U'Ren Jana M. , Riddle Jakob M. , Monacell James T. , Carbone Ignazio , Miadlikowska Jolanta , Arnold A. Elizabeth
Published: March 2014

Next‐generation sequencing technologies have provided unprecedented insights into fungal diversity and ecology. However, intrinsic biases and insufficient quality control in next‐generation methods can lead to difficult‐to‐detect errors in estimating fungal community richness, distributions and composition. The aim of this study was to examine how tissue storage prior to DNA extraction, primer design and various quality‐control approaches commonly used in 454 amplicon pyrosequencing might influence ecological inferences in studies of endophytic and endolichenic fungi. We first contrast 454 data sets generated contemporaneously from subsets of the same plant and lichen tissues that were stored in CTAB buffer, dried in silica gel or freshly frozen prior to DNA extraction. We show that storage in silica gel markedly limits the recovery of sequence data and yields a small fraction of the diversity observed by the other two methods. Using lichen mycobiont sequences as internal positive controls, we next show that despite careful filtering of raw reads and utilization of current best‐practice OTU clustering methods, homopolymer errors in sequences representing rare taxa artificially increased estimates of richness c. 15‐fold in a model data set. Third, we show that inferences regarding endolichenic diversity can be improved using a novel primer that reduces amplification of the mycobiont. Together, our results provide a rationale for selecting tissue treatment regimes prior to DNA extraction, demonstrate the efficacy of reducing mycobiont amplification in studies of the fungal microbiomes of lichen thalli and highlight the difficulties in differentiating true information about fungal biodiversity from methodological artefacts.
Understanding co‐occurrence by modelling species simultaneously with a Joint Species Distribution Model (JSDM)
Authors: Pollock Laura J. , Tingley Reid , Morris William K. , Golding Nick , O'Hara Robert B. , Parris Kirsten M. , Vesk Peter A. , McCarthy Michael A.
Published: March 2014

A primary goal of ecology is to understand the fundamental processes underlying the geographic distributions of species. Two major strands of ecology – habitat modelling and community ecology – approach this problem differently. Habitat modellers often use species distribution models (SDMs) to quantify the relationship between species’ and their environments without considering potential biotic interactions. Community ecologists, on the other hand, tend to focus on biotic interactions and, in observational studies, use co‐occurrence patterns to identify ecological processes. Here, we describe a joint species distribution model (JSDM) that integrates these distinct observational approaches by incorporating species co‐occurrence data into a SDM.

JSDMs estimate distributions of multiple species simultaneously and allow decomposition of species co‐occurrence patterns into components describing shared environmental responses and residual patterns of co‐occurrence. We provide a general description of the model, a tutorial and code for fitting the model in R. We demonstrate this modelling approach using two case studies: frogs and eucalypt trees in Victoria, Australia.

Overall, shared environmental correlations were stronger than residual correlations for both frogs and eucalypts, but there were cases of strong residual correlation. Frog species generally had positive residual correlations, possibly due to the fact these species occurred in similar habitats that were not fully described by the environmental variables included in the JSDM. Eucalypt species that interbreed had similar environmental responses but had negative residual co‐occurrence. One explanation is that interbreeding species may not form stable assemblages despite having similar environmental affinities.

Environmental and residual correlations estimated from JSDMs can help indicate whether co‐occurrence is driven by shared environmental responses or other ecological or evolutionary process (e.g. biotic interactions), or if important predictor variables are missing. JSDMs take into account the fact that distributions of species might be related to each other and thus overcome a major limitation of modelling species distributions independently.
treeNODF: nestedness to phylogenetic, functional and other tree‐based diversity metrics
Authors: Melo Adriano S. , Cianciaruso Marcus V. , Almeida‐Neto Mário
Published: March 2014

Available measures of nestedness consider descriptor variables (e.g. species) as equally associated, ignoring evolutionary or ecological dissimilarities. Here, we introduce treeNODF, a new class of nestedness that takes into account the resemblance of descriptor variables.

The method is an extension of the NODF index and can be applied to systems in which the resemblance of descriptor variables is described by a tree‐like object. Computation of treeNODF is similar to NODF, but uses branch lengths instead of the sum of species occurrences. In this way, we can calculate a phyloNODF for metacommunities if a phylogeny is used to account for differences in phylogenetic diversity (PD) and traitNODF if a functional dendrogram constructed from species ecological traits is used to account for the functional diversity (FD) of communities. Similar to NODF, treeNODF can also be used to assess nestedness among species. In this case, envNODF uses a dendrogram describing the resemblance among the environmental conditions of different sites, to test whether rare species occur in a subset of the environmental conditions in the habitats occupied by frequent species.

treeNODF is a composite metric that can be additively partitioned into compositional (S.fraction) and tree‐topology (topoNODF = treeNODF – S.fraction) components of the descriptor variables. Tests of treeNODF and its components can be carried out using null models and, if a hypothetical factor is used to order metacommunity data, permutation tests. We show that treeNODF is robust for matrix size and fill, as well as for tree topology.

Finally, we illustrate the use of treeNODF by analysing data on Caribbean bats using phyloNODF, traitNODF and envNODF, as well as their composition and tree‐topology components.
Staging bipolar disorder: clinical, biochemical, and functional correlates
Authors: Grande I. , Magalhães P. V. , Chendo I. , Stertz L. , Panizutti B. , Colpo G. D. , Rosa A. R. , Gama C. S. , Kapczinski F. , Vieta E.
Published: March 2014

Objective

There are several models of staging in bipolar disorder (BD), but none has been validated. The aims of this study were to empirically investigate clinical variables that may be useful to classify patients in clusters according to stage and study the association with biomarkers as biological validators.

Method

This was a historical cohort study. Patients (n = 115) diagnosed with BD and not in an acute episode and first‐degree relatives of patients diagnosed with BD (n = 25) were recruited. Sociodemographic, clinical, and functional data were collected. Serum cytokines, brain‐derived neurotrophic factor, and biomarkers of lipid and protein oxidation were assessed. Cluster analysis was carried out to build a model of staging, and logistic regression was conducted to study associations between the model and biomarkers.

Results

Cluster analysis divided the sample into two equitable groups, denominated early and late stage, with empirical cutoffs for the Functioning Assessment Short Test score, number of episodes, age at onset of the disorder, and time elapsed since first episode. In the logistic regression, IL‐6 was associated with late stage (P = 0.029).

Conclusion

This study supports that clinical, functional, and biochemical variables may help to define a classification of staging in BD.
Testing advances in molecular discrimination among Chinook salmon life histories: evidence from a blind test
Authors: Banks Michael A. , Jacobson David P. , Meusnier Isabelle , Greig Carolyn A. , Rashbrook Vanessa K. , Ardren William R. , Smith Christian T. , Bernier‐Latmani Jeremiah , Van Sickle John , O'Malley Kathleen G.
Published: March 2014

The application of DNA‐based markers toward the task of discriminating among alternate salmon runs has evolved in accordance with ongoing genomic developments and increasingly has enabled resolution of which genetic markers associate with important life‐history differences. Accurate and efficient identification of the most likely origin for salmon encountered during ocean fisheries, or at salvage from fresh water diversion and monitoring facilities, has far‐reaching consequences for improving measures for management, restoration and conservation. Near‐real‐time provision of high‐resolution identity information enables prompt response to changes in encounter rates. We thus continue to develop new tools to provide the greatest statistical power for run identification. As a proof of concept for genetic identification improvements, we conducted simulation and blind tests for 623 known‐origin Chinook salmon (Oncorhynchus tshawytscha) to compare and contrast the accuracy of different population sampling baselines and microsatellite loci panels. This test included 35 microsatellite loci (1266 alleles), some known to be associated with specific coding regions of functional significance, such as the circadian rhythm cryptochrome genes, and others not known to be associated with any functional importance. The identification of fall run with unprecedented accuracy was demonstrated. Overall, the top performing panel and baseline (HMSC21) were predicted to have a success rate of 98%, but the blind‐test success rate was 84%. Findings for bias or non‐bias are discussed to target primary areas for further research and resolution.
KIT and melanoma predisposition in pigs: sequence variants and association analysis
Authors: Fernández‐Rodríguez A. , Estellé J. , Blin A. , Muñoz M. , Créchet F. , Demenais F. , Vincent‐Naulleau S. , Bourneuf E.
Published: March 2014

KIT mutations have been detected in different cancer subtypes, including melanoma. The gene also has been extensively studied in farm animals for its prominent role in coat color. The present work aimed at detecting KIT variants in a porcine model of cutaneous melanoma, the melanoblastoma‐bearing Libechov Minipig (MeLiM). By sequencing exons and intron borders, 36 SNPs and one indel were identified. Of 10 coding SNPs, three were non‐synonymous mutations, likely to affect the protein conformation. A promising variant, located in exon 19 (p.Val870Ala), was genotyped in a MeLiM × Duroc cross, and an association analysis was conducted on several melanoma‐related traits. This variant showed a significant association with melanoma development, tumor ulceration and cutaneous invasion. In conclusion, although the KIT gene would not be a major causal gene for melanoma development in pig, its genetic variation could be influencing this trait.
Copy number variation in Fayoumi and Leghorn chickens analyzed using array comparative genomic hybridization
Authors: Abernathy J. , Li X. , Jia X. , Chou W. , Lamont S. J. , Crooijmans R. , Zhou H.
Published: March 2014

Copy number variation refers to regions along chromosomes that harbor a type of structural variation, such as duplications or deletions. Copy number variants (CNVs) play a role in many important traits as well as in genetic diversity. Previous analyses of chickens using array comparative genomic hybridizations or single‐nucleotide polymorphism chip assays have been performed on various breeds and genetic lines to discover CNVs. In this study, we assessed individuals from two highly inbred (inbreeding coefficiency > 99.99%) lines, Leghorn G‐B2 and Fayoumi M15.2, to discover novel CNVs in chickens. These lines have been previously studied for disease resistance, and to our knowledge, this represents the first global assessment of CNVs in the Fayoumi breed. Genomic DNA from individuals was examined using the Agilent chicken 244 K comparative genomic hybridization array and quantitative PCR. We identified a total of 273 CNVs overall, with 112 CNVs being novel and not previously reported. Quantitative PCR using the standard curve method validated a subset of our array data. Through enrichment analysis of genes within CNV regions, we observed multiple chromosomes, terms and pathways that were significantly enriched, largely dealing with the major histocompatibility complex and immune responsiveness. Using an additional round of computational and statistical analysis with a different bioinformatic pipeline, we identified 43 CNVs among these as high‐confidence regions, 14 of which were found to be novel. We further compared and contrasted individuals of the two inbred lines to discover regions that have a significant difference in copy number between lines. A total of 40 regions had significant deletions or duplications between the lines. Gene Ontology analysis of genomic regions containing CNVs between lines also was performed. This between‐line candidate CNV list will be useful in studies with these two unique genetic lines, which may harbor variations that underlie quantitative trait loci for disease resistance and other important traits. Through the global discovery of novel CNVs in chicken, these data also provide resources for further genetic and functional genomics studies.
An Effective Approach to the Repeated Cross‐Sectional Design
Authors: Lebo Matthew J. , Weber Christopher
Published: March 2014

Repeated cross‐sectional (RCS) designs are distinguishable from true panels and pooled cross‐sectional time series (PCSTS) since cross‐sectional units (e.g., individual survey respondents) appear but once in the data. This poses two serious challenges. First, as with PCSTS, autocorrelation threatens inferences. However, common solutions like differencing and using a lagged dependent variable are not possible with RCS since lags for i cannot be used. Second, although RCS designs contain information that allows both aggregate‐ and individual‐level analyses, available methods—from pooled ordinary least squares to PCSTS to time series—force researchers to choose one level of analysis. The PCSTS tool kit does not provide an appropriate solution, and we offer one here: double filtering with ARFIMA methods to account for autocorrelation in longer RCS followed by the use of multilevel modeling to estimate both aggregate‐ and individual‐level parameters simultaneously. We use Monte Carlo experiments and three applied examples to explore the advantages of our framework.
Recommendations for the allergy management in the primary care
Authors: Jutel M. , Papadopoulos N. G. , Gronlund H. , Hoffman H.‐J. , Bohle B. , Hellings P. , Braunsthal G.‐J. , Muraro A. , Schmid‐Grendelmeier P. , Zuberbier T. , Agache I.
Published: March 2014

The majority of patients seeking medical advice for allergic diseases are first seen in a primary care setting. Correct diagnosis with identification of all offending allergens is an absolute prerequisite for appropriate management of allergic disease by the general practitioner. Allergy diagnostic tests recommended for use in primary care are critically reviewed in accordance with the significant workload in a primary care setting. Simplified pathways for recognition and diagnosis of allergic diseases are proposed, that should be further adapted to local (national) conditions.
Initial results from mechanical compression of the cornea during crosslinking for keratoconus
Authors: Beckman Rehnman Jeannette , Behndig Anders , Hallberg Per , Lindén Christina
Published: March 2014

Purpose

To compare refractive changes after corneal crosslinking with and without mechanical compression of the cornea.

Methods

In a prospective, open, randomized case‐control study conducted at the Department of Ophthalmology, Umeå University Hospital, Sweden, sixty eyes of 43 patients with progressive keratoconus aged 18–28 years planned for corneal crosslinking and corresponding age‐ and sex‐matched control subjects were included. The patients were randomized to conventional corneal crosslinking (CXL; n = 30) or corneal crosslinking with mechanical compression using a flat rigid contact lens sutured to the cornea during treatment (CRXL; n = 30). Subjective refraction and ETDRS best spectacle‐corrected visual acuity (BSCVA), axial length measurement, keratometry and pachymetry were performed before and 1 and 6 months after treatment.

Results

The keratoconus patients had poorer BSCVA, higher refractive astigmatism and higher keratometry readings than the control subjects at baseline (p < 0.01). In the CXL group, BSCVA increased from 0.19 ± 0.26 to 0.14 ± 0.18 logMar (p = 0.03), and the spherical equivalent improved from −1.9 ± 2.8 D to −1.4 ± 2.4 D (p = 0.03). Maximum keratometry readings decreased after CXL from 53.1 ± 4.9 D to 52.6 ± 5.2 D (p = 0.02), and the axial length decreased in the CXL group, likely due to post‐treatment corneal thinning (p = 0.03). In the CRXL group, all the above variables were unaltered (p > 0.05).

Conclusion

At 6 months, the refractive results from CRXL did not surpass those of conventional CXL treatment. Rather, some variables indicated a slightly inferior effect. Possibly, stronger crosslinking would be necessary to stabilize the cornea in the flattened configuration achieved by the rigid contact lens.
Minimally invasive surfactant therapy with a gastric tube is as effective as the intubation, surfactant, and extubation technique in preterm babies
Authors: Aguar Marta , Cernada María , Brugada María , Gimeno Ana , Gutierrez Antonio , Vento Máximo
Published: March 2014

Aim

Preterm infants requiring surfactant replacement have been treated using the INSURE technique, which requires sedation and comprises tracheal intubation, surfactant instillation and extubation. However, minimally invasive surfactant therapy (MIST) does not require sedation, minimises airway injury and avoids placing positive pressure ventilation on an immature lung. This study compared the feasibility of the two techniques and the outcomes in preterm babies with respiratory distress syndrome (RDS).

Methods

Preterm infants with RDS prospectively received surfactant via a gastric tube placed in the trachea by direct laryngoscopy with no sedation. Technique‐related complications and respiratory outcomes were analysed.

Results

We compared 44 patients who received MIST with a historic cohort of 31 patients who received INSURE. This showed no differences in the rate of intubation and mechanical ventilation in the first 72 h, or secondary respiratory outcomes and relevant morbidities, between the babies who received INSURE and those who received MIST. More babies in the MIST group (35%) needed a second dose of surfactant than the INSURE group (6.5%) (p < 0.0001).

Conclusion

Surfactant administration using MIST, with no sedation, is feasible in preterm infants with RDS. No significant differences in secondary respiratory outcomes were found between the MIST and INSURE techniques.
Expression of MexAB‐OprM efflux pump system and susceptibility to antibiotics of different Pseudomonas aeruginosa clones isolated from patients hospitalized in two intensive care units at University Hospital in Bialystok (northeastern Poland) between January 2002 and December 2009
Authors: Sacha Paweł , Wieczorek Piotr , Ojdana Dominika , Hauschild Tomasz , Milewski Robert , Czaban Sławomir , Poniatowski Bogusław , Tryniszewska Elżbieta
Published: March 2014

We investigated the genetic similarities and expression of the MexAB‐OprM efflux pump system in different clones of multiresistant Pseudomonas aeruginosa strains collected from 2002 to 2009 at two intensive care units (ICU). Regulatory and structural genes mexB, mexR, and mexA were found in 99%, 98%, and 94% of tested strains, respectively. The presence of class 1 integron was found in 90% of the strains, while class 2 integron in only one strain (Psa506). Class 3 integron was not found in any of the tested strains. Among the eleven clones identified, only two clones, I and D, exhibited higher levels of mexB gene expression than the other clones. Clone I had the highest expression (FC = 10.36, p < 0.05). The results of our study indicated a high level of MexAB‐OprM pump expression in groups of strains isolated in the years 2008–2009 (FC = 12.92, p < 0.03) and 2002–2006 (FC = 5.14, p < 0.03). There were no statistically significant differences in resistance to all tested antibiotics among the various clones. The high level of antimicrobial resistance may have been due to the coexistence of different resistance mechanisms among the studied P. aeruginosa strains. However, this does not exclude the contribution of the MexAB‐OprM pump, particularly in resistance to meropenem and ciprofloxacin.
Saccharomyces boulardii expresses neuraminidase activity selective for α2,3‐linked sialic acid that decreases Helicobacter pylori adhesion to host cells
Authors: Sakarya Serhan , Gunay Necati
Published: March 2014

Helicobacter pylori is a major causative agent of gastritis and peptic ulcer disease and is an established risk factor for gastric malignancy. Antibiotic combination therapy can eradicate H. pylori. As these same regimens can evoke adverse effects and resistance, new alternative therapies or adjunctive treatments are needed. A probiotic approach may provide a novel strategy for H. pylori treatment. In the current study, two probiotic bacteria, Lactobacillus acidophilus and Lactobacillus reuteri, and a probiotic yeast, Saccharomyces boulardii, were evaluated for their ability to influence H. pylori viability, adherence to gastric and duodenal cells, as well as the effect of S. boulardii on cell surface expression of sialic acid. Our results indicate that S. boulardii contains neuraminidase activity selective for α(2‐3)‐linked sialic acid. This neuraminidase activity removes surface α(2‐3)‐linked sialic acid, the ligand for the sialic acid‐binding H. pylori adhesin, which in turn, inhibits H. pylori adherence to duodenal epithelial cells.
The influence of a glucosyltransferase, encoded by gtfP, on biofilm formation by Streptococcus sanguinis in a dual‐species model
Authors: Yoshida Yasuo , Konno Hiroyasu , Nagano Keiji , Abiko Yuki , Nakamura Yoshinori , Tanaka Yoshinobu , Yoshimura Fuminobu
Published: March 2014

Streptococcus sanguinis is an early colonizer of tooth surfaces and forms biofilms with other species of microorganisms. In vitro, S. sanguinis produces water‐soluble glucans from sucrose and releases them into the culture supernatant; however, the role played by these glucans in biofilm formation is unclear. The present study examined both the effect of glucans on biofilm formation by S. sanguinis and the proportion of this bacterial species within the biofilms. Inactivation of the gtfP gene, annotated as glucosyltransferase in the S. sanguinis genome database, caused a marked reduction in the amount of water‐soluble glucans in the culture supernatant, but not in the amount of water‐insoluble glucans expressed on the bacterial cell surface. Scanning electron microscopy revealed that wild‐type S. sanguinis, but not the gtfP‐deficient mutant, produced large amounts of sticky material in the presence of 1% (w/v) sucrose. In addition, biofilm production by wild‐type bacteria was greater than that by the mutant strain. By contrast, co‐culture of mutant bacteria with Streptococcus mutans, S. sobrinus, S. oralis, S. gordonii, S. anginosus, or S. salivarius showed that inactivating the gtfP gene had little effect on the amount of biofilm produced. Furthermore, inactivating the gtfP gene did not greatly alter the proportion of S. sanguinis in the biofilms formed by the co‐cultures. Thus, despite the role of S. sanguinis glucosyltransferase in formation of water‐soluble glucans and biofilms in monoculture, the functional gene contributed little to biofilms in co‐culture experiments.
Decreased susceptibility to chlorhexidine and prevalence of disinfectant resistance genes among clinical isolates of Staphylococcus epidermidis
Authors: Prag Gustaf , Falk‐Brynhildsen Karin , Jacobsson Susanne , Hellmark Bengt , Unemo Magnus , Söderquist Bo
Published: March 2014

Staphylococcus epidermidis is a versatile agent, being both a commensal and a nosocomial pathogen usually with an opportunistic role in association with implanted foreign body materials. Pre‐operative antiseptic preparation is an important strategy for reducing the risk of complications such as surgical site infection (SSI). Currently, the most widely used antiseptics are alcohols, quaternary ammonium compounds (QACs), and the bisbiguanide chlorhexidine. Occurrence of resistance to the latter agent has drawn increasing attention. The aim of this study was to investigate if decreased susceptibility to chlorhexidine among S. epidermidis was present in our setting, a Swedish university hospital. Staphylococcus epidermidis (n = 143), retrospectively collected, were obtained from prosthetic joint infections (PJI) (n = 61), post‐operative infections after cardiac surgery (n = 31), and the skin of the chest after routine disinfection prior to cardiac surgery (n = 27). In addition, 24 commensal isolates were included. Minimum inhibitory concentration (MIC) of chlorhexidine was determined on Mueller Hinton agar plates supplemented with serial dilutions of chlorhexidine. Five QAC resistance genes, qacA/B, smr, qacH, qacJ, and qacG, were detected using PCR. Decreased susceptibility to chlorhexidine was found in 54% of PJI isolates, 68% of cardiac isolates, 21% of commensal isolates, and 7% of skin isolates from cardiac patients, respectively. The qacA/B gene was present in 62/143 isolates (43%), smr in 8/143 (6%), and qacH in one isolate (0.7%). The qacA/B gene was found in 52% of PJI isolates, 61% of cardiac isolates, 25% of commensal isolates, and 19% of the skin isolates. In conclusion, decreased susceptibility to chlorhexidine, as well as QAC resistance genes, were prevalent among S. epidermidis isolates associated with deep SSIs.
Nodal distribution, stage migration due to diameter measurement and the prognostic significance of metastasis volume in melanoma sentinel lymph nodes: a validation study
Authors: Riber‐Hansen Rikke , Hamilton‐Dutoit Stephen J. , Steiniche Torben
Published: March 2014

To validate metastasis location, maximum metastasis diameter (MMD) measurement induced stage migration and the prognostic significance of total metastatic volume (TMV) in melanoma sentinel lymph nodes (SLNs). A new 227 patient SLN cohort examined by complete step sectioning (250 μm) was tested for TMV and MMD prognostic significance; metastasis location by three different three‐level protocols (Central vs Peripheral vs Global); and potential treatment changing down‐staging by two restricted five‐level protocols [Reduced Central (250 μm) vs Reduced Even (500 μm) sections]. Both TMV and MMD independently predicted recurrence (TMV, hazard ratio (HR): 1.21; 95% confidence interval (CI) 1.07–1.37; p = 0.003; and MMD, HR: 1.46; 95% CI 1.08–1.98, p = 0.02) and melanoma‐specific death (TMV, HR: 1.30; 95% CI 1.11–1.51; p = 0.001; and MMD, HR: 1.82; 95% CI 1.25–2.66, p = 0.002). The Central, Peripheral and Global protocols detected 72%, 76% and 83% of metastases found by complete step sectioning. Based on MMD, using the Reduced Central or Reduced Even protocols, potential treatment changing down‐staging occurred in 20 (20%) or 13 (13%) of SLN‐positive patients. This validation study establishes that: (i) metastases are globally located in melanoma SLNs; (ii) MMD but not TMV leads to uni‐directional stage migration; and (iii) TMV analysis is of prognostic significance.