bluuebunny/crossref_metadata_2025 huggingface dataset:
The Tzs Protein and Exogenous Cytokinin Affect Virulence Gene Expression and Bacterial Growth ofAgrobacterium tumefaciens
Authors: Hwang Hau-Hsuan , Yang Fong-Jhih , Cheng Tun-Fang , Chen Yi-Chun , Lee Ying-Ling , Tsai Yun-Long , Lai Erh-Min
Published: April 2013

The soil phytopathogen Agrobacterium tumefaciens causes crown gall disease in a wide range of plant species. The neoplastic growth at the infection sites is caused by transferring, integrating, and expressing transfer DNA (T-DNA) from A. tumefaciens into plant cells. A trans-zeatin synthesizing (tzs) gene is located in the nopaline-type tumor-inducing plasmid and causes trans-zeatin production in A. tumefaciens. Similar to known virulence (Vir) proteins that are induced by the vir gene inducer acetosyringone (AS) at acidic pH 5.5, Tzs protein is highly induced by AS under this growth condition but also constitutively expressed and moderately upregulated by AS at neutral pH 7.0. We found that the promoter activities and protein levels of several AS-induced vir genes increased in the tzs deletion mutant, a mutant with decreased tumorigenesis and transient transformation efficiencies, in Arabidopsis roots. During AS induction and infection of Arabidopsis roots, the tzs deletion mutant conferred impaired growth, which could be rescued by genetic complementation and supplementing exogenous cytokinin. Exogenous cytokinin also repressed vir promoter activities and Vir protein accumulation in both the wild-type and tzs mutant bacteria with AS induction. Thus, the tzs gene or its product, cytokinin, may be involved in regulating AS-induced vir gene expression and, therefore, affect bacterial growth and virulence during A. tumefaciens infection.
Optimal concentrations in transport systems
Authors: Jensen Kaare H. , Kim Wonjung , Holbrook N. Michele , Bush John W. M.
Published: April 2013

Many biological and man-made systems rely on transport systems for the distribution of material, for example matter and energy. Material transfer in these systems is determined by the flow rate and the concentration of material. While the most concentrated solutions offer the greatest potential in terms of material transfer, impedance typically increases with concentration, thus making them the most difficult to transport. We develop a general framework for describing systems for which impedance increases with concentration, and consider material flow in four different natural systems: blood flow in vertebrates, sugar transport in vascular plants and two modes of nectar drinking in birds and insects. The model provides a simple method for determining the optimum concentration
c
opt
in these systems. The model further suggests that the impedance at the optimum concentration
μ
opt
may be expressed in terms of the impedance of the pure (
c
= 0) carrier medium
μ
0
as
μ
opt
∼2

α

μ
0
, where the power
α
is prescribed by the specific flow constraints, for example constant pressure for blood flow (
α
= 1) or constant work rate for certain nectar-drinking insects (
α
= 6). Comparing the model predictions with experimental data from more than 100 animal and plant species, we find that the simple model rationalizes the observed concentrations and impedances. The model provides a universal framework for studying flows impeded by concentration, and yields insight into optimization in engineered systems, such as traffic flow.
Strength in numbers? Effects of multiple natural enemy species on plant performance
Authors: Stephens Andrea E. A. , Srivastava Diane S. , Myers Judith H.
Published: April 2013

While plants are invariably attacked by numerous insects and pathogens, the consequences of multiple enemies for plant performance are poorly understood. In particular, a predictive framework is lacking for when to expect enemies to have independent versus non-independent effects on their host plant. This is problematic for weed biological control programmes where multiple enemies are frequently released with the possibility of antagonistic interactions that may reduce control. Here, we conduct an analysis of 74 unique plant–enemy–enemy combinations from 51 studies to determine the frequency of non-independent effects of natural enemies on host plant performance, and test a number of
a priori
predictions for determinants of independent and antagonistic effects of multiple enemies. For three-quarters of plant response measurements, enemies had independent effects on plant performance. In most of the remainder, multiple enemies led to less reduction in performance than that predicted from each enemy alone. Antagonistic effects occurred when enemies attacked the same plant part concurrently or attacked plant reproductive structures. These two predictors explained why antagonistic effects were particularly prevalent for weeds, plants in the family Asteraceae and enemies in the order Diptera. Our results suggest that a few simple rules about avoiding particular combinations of multiple enemies could improve biological control success.
Evolutionary consequences of self-fertilization in plants
Authors: Wright Stephen I. , Kalisz Susan , Slotte Tanja
Published: April 2013

The transition from outcrossing to self-fertilization is one of the most common evolutionary changes in plants, yet only about 10–15% of flowering plants are predominantly selfing. To explain this phenomenon, Stebbins proposed that selfing may be an ‘evolutionary dead end’. According to this hypothesis, transitions from outcrossing to selfing are irreversible, and selfing lineages suffer from an increased risk of extinction owing to a reduced potential for adaptation. Thus, although selfing can be advantageous in the short term, selfing lineages may be mostly short-lived owing to higher extinction rates. Here, we review recent results relevant to the ‘dead-end hypothesis’ of selfing and the maintenance of outcrossing over longer evolutionary time periods. In particular, we highlight recent results regarding diversification rates in self-incompatible and self-compatible taxa, and review evidence regarding the accumulation of deleterious mutations in selfing lineages. We conclude that while some aspects of the hypothesis of selfing as a dead end are supported by theory and empirical results, the evolutionary and ecological mechanisms remain unclear. We highlight the need for more studies on the effects of quantitative changes in outcrossing rates and on the potential for adaptation, particularly in selfing plants. In addition, there is growing evidence that transitions to selfing may themselves be drivers of speciation, and future studies of diversification and speciation should investigate this further.
Intraspecific morphological and genetic variation of common species predicts ranges of threatened ones
Authors: Fuller Trevon L. , Thomassen Henri A. , Peralvo Manuel , Buermann Wolfgang , Milá Borja , Kieswetter Charles M. , Jarrín-V Pablo , Devitt Susan E. Cameron , Mason Eliza , Schweizer Rena M. , Schlunegger Jasmin , Chan Janice , Wang Ophelia , Schneider Christopher J. , Pollinger John P. , Saatchi Sassan , Graham Catherine H. , Wayne Robert K. , Smith Thomas B.
Published: April 2013

Predicting where threatened species occur is useful for making informed conservation decisions. However, because they are usually rare, surveying threatened species is often expensive and time intensive. Here, we show how regions where common species exhibit high genetic and morphological divergence among populations can be used to predict the occurrence of species of conservation concern. Intraspecific variation of common species of birds, bats and frogs from Ecuador were found to be a significantly better predictor for the occurrence of threatened species than suites of environmental variables or the occurrence of amphibians and birds. Fully 93 per cent of the threatened species analysed had their range adequately represented by the geographical distribution of the morphological and genetic variation found in seven common species. Both higher numbers of threatened species and greater genetic and morphological variation of common species occurred along elevation gradients. Higher levels of intraspecific divergence may be the result of disruptive selection and/or introgression along gradients. We suggest that collecting data on genetic and morphological variation in common species can be a cost effective tool for conservation planning, and that future biodiversity inventories include surveying genetic and morphological data of common species whenever feasible.
Interacting Glutamate Receptor-Like Proteins in Phloem Regulate Lateral Root Initiation in Arabidopsis
Authors: Vincill Eric D. , Clarin Arielle E. , Molenda Jennifer N. , Spalding Edgar P.
Published: April 2013

Molecular, genetic, and electrophysiological evidence indicates that at least one of the plant Glu receptor-like molecules, GLR3.4, functions as an amino acid–gated Ca2+ channel at the plasma membrane. The aspect of plant physiology, growth, or development to which GLR3.4 contributes is an open question. Protein localization studies performed here provide important information. In roots, GLR3.4 and the related GLR3.2 protein were present primarily in the phloem, especially in the vicinity of the sieve plates. GLR3.3 was expressed in most cells of the growing primary root but was not enriched in the phloem, including the sieve plate area. GLR3.2 and GLR3.4 physically interacted with each other better than with themselves as evidenced by a biophotonic assay performed in human embryonic kidney cells and Nicotiana benthamiana leaf cells. GLR3.3 interacted poorly with itself or the other two GLRs. Mutations in GLR3.2, GLR3.4, or GLR3.2 and GLR3.4 caused the same and equally severe phenotype, namely, a large overproduction and aberrant placement of lateral root primordia. Loss of GLR3.3 did not affect lateral root primordia. These results support the hypothesis that apoplastic amino acids acting through heteromeric GLR3.2/GLR3.4 channels affect lateral root development via Ca2+ signaling in the phloem.
Objective algorithm to separate signal from noise in a Poisson-distributed pixel data set
Authors: Straasø Tine , Müter Dirk , Sørensen Henning Osholm , Als-Nielsen Jens
Published: April 2013

A statistical method to determine the background level and separate signal from background in a Poisson-distributed background data set is described. The algorithm eliminates the pixel with the highest intensity value in an iterative manner until the sample variance equals the sample mean within the estimated uncertainties. The eliminated pixels then contain signal superimposed on the background, so the integrated signal can be obtained by summation or by a simple extension by profile fitting depending on the user's preferences. Two additional steps remove `outliers' and correct for the underestimated extension of the peak area, respectively. The algorithm can be easily modified to specific needs, and an application on crystal truncation rods is presented, dealing with a sloping background.
McXtrace: a Monte Carlo software package for simulating X-ray optics, beamlines and experiments
Authors: Bergbäck Knudsen Erik , Prodi Andrea , Baltser Jana , Thomsen Maria , Kjær Willendrup Peter , Sanchez del Rio Manuel , Ferrero Claudio , Farhi Emmanuel , Haldrup Kristoffer , Vickery Anette , Feidenhans'l Robert , Mortensen Kell , Meedom Nielsen Martin , Friis Poulsen Henning , Schmidt Søren , Lefmann Kim
Published: April 2013

This article presents the Monte Carlo simulation packageMcXtrace, intended for optimizing X-ray beam instrumentation and performing virtual X-ray experiments for data analysis. The system shares a structure and code base with the popular neutron simulation codeMcStasand is a good complement to the standard X-ray simulation softwareSHADOW.McXtraceis open source, licensed under the General Public License, and does not require the user to have access to any proprietary software for its operation. The structure of the software is described in detail, and various examples are given to showcase the versatility of theMcXtraceprocedure and outline a possible route to using Monte Carlo simulations in data analysis to gain new scientific insights. The studies performed span a range of X-ray experimental techniques: absorption tomography, powder diffraction, single-crystal diffraction and pump-and-probe experiments. Simulation studies are compared with experimental data and theoretical calculations. Furthermore, the simulation capabilities for computing coherent X-ray beam properties and a comparison with basic diffraction theory are presented.
Perceptions of the design of voice output communication aids
Authors: Judge Simon , Townend Gillian
Published: April 2013

Background

Voice output communication aids (VOCAs) are a key form of aided communication within the field of augmentative and alternative communication (AAC). In recent years, rapid developments in technology have resulted in an explosion of devices available commercially, yet little research has been conducted into what people who use VOCAs think about them.

Aims

The aim of this research was to explore the perceptions of communication aid design from the perspective of end users and AAC professionals, with the objective being to inform and influence the design of future devices.

Methods & Procedures

A two‐part study was conducted: interviews were undertaken with people who use VOCAs, and questionnaires were distributed to those who use aided communication and to AAC professionals. Analysis of the interview data was carried out using a qualitative method based on framework analysis, whilst descriptive statistics were generated from the questionnaire data. Interview participants were an opportunity sample of VOCA users within a defined region of the UK. Those recruited were over the age of 12 years and able to engage in the interview process; they were identified through the caseloads of local Speech and Language Therapists specializing in AAC. The questionnaire was marketed to the AAC community throughout the UK. Respondents were self‐selecting as those using aided communication, their carers and AAC professionals.

Outcomes & Results

Eighteen people participated in the interviews. Questionnaires were completed by 43 people who use aided communication and 68 AAC professionals. The data suggest that current devices are considered to be neither reliable nor durable by users and professionals. Although features given a higher importance ranking are more likely to be perceived as available, a number of important design deficits are identified by users and/or professionals. Simplicity of design (and use) and the desire for devices which support communication that is as fast and spontaneous as possible also emerge as key requirements. Synthesis of the data produced a framework with three main themes covering the range of issues which influence the successful use of a VOCA: specific aspects of the design of a device; the consideration of the wider picture around the person; and the personal context in which someone uses their device.

Conclusions & Implications

Although the original aim of the project was to establish the user requirements of VOCA design, the data indicate that the characteristics of the device cannot be considered in isolation. Those factors uncovered highlight questions about whether the design of communication aids is truly effective in meeting the needs of the people who use them. Based on these data, an initial specification for future device design is proposed.
The Living with Dysarthria group for post‐stroke dysarthria: the participant voice
Authors: Mackenzie C. , Kelly S. , Paton G. , Brady M. , Muir M.
Published: April 2013

Background

The Living with Dysarthria group programme, devised for people with post‐stroke dysarthia and family members, was piloted twice. Feedback from those who experience an intervention contributes to the evaluation of speech and language therapy programmes, giving the participant view of the intervention's value and guiding further developments.

Research Question

What feedback do participants in the Living with Dysarthria programme provide, informing on its perceived usefulness and guiding its future development?

Methods & Procedures

Nine people with chronic dysarthria following stroke and four family members who completed the Living with Dysarthria programme all contributed to Focus Group (FG) discussion, transcribed and thematically analysed, and completed an Anonymous Questionnaire Evaluation (AQE), comprising closed statements and open questions. An anonymous descriptive adjective selection task (ADAST) was also used.

Outcomes & Results

The varied forms of feedback provided complementary information. Thematic analysis of FG data and AQE open question responses were configured around programme benefits, programme structure and content, and programme practicalities. Benefits associated with participation included learning and insight, being supported by peers and professionals, and improved speech and confidence. These are consistent with the main programme elements of education, support and speech practice. All activities were seen as relevant and positively received. Flexibility, recognition of and catering to individual needs were valued characteristics. The community location was approved by all. Most participants thought the format of eight weekly sessions of 2 h was appropriate. Responses to AQE closed statements provided almost unanimous confirmation of the very positive feedback conveyed in FG discussions. The main response to suggested improvements in AQEs was that the number of sessions should be increased. Feedback indicated that for a few individuals there was negative reaction to some facts about stroke, home practice tasks were difficult to complete, the person with dysarthria/family member pair may not be the optimum combination for paired practice activities and pre‐programme information should be extended. The ADAST showed that the programme was enjoyable, interesting, stimulating and useful.

Conclusions & Implications

Participant feedback indicates that group therapy, with family member participation, is a valid form of management for chronic post‐stroke dysarthria. Education, peer and professional support, and speech practice are confirmed as relevant programme components. Consistent majority opinions were communicated in different situations and via varied mediums. Some individuals expressed views relevant to their own needs, and these responses also inform future implementation of the Living with Dysarthria programme.
The Tyranny of Relevance and the Art of Translation
Authors: Flinders Matthew
Published: April 2013

The ‘tyranny of relevance’ captures a widespread sense of concern among social and political scientists that their academic freedom and professional autonomy is under threat from a changing social context in which scholars are increasingly expected to demonstrate some form of social ‘relevance', ‘impact’ or ‘engagement’ beyond academe. This article attempts to reframe the current debate by reflecting upon the history of the discipline and different forms of scholarship in order to craft an argument concerning the need for political scientists to rediscover ‘the art of translation'. This, in turn, facilitates a more sophisticated grasp of key concepts, emphasises the need for the discipline to engage with multiple publics in multiple ways, and suggests that engaging with non-academic audiences is likely to improve not simply the discipline's leverage in terms of funding, or scholarship in terms of quality, but also teaching in terms of energy and relevance. The simple argument of this article is not therefore that political science has become irrelevant, but that it has generally failed to promote and communicate the social value and benefit of the discipline in an accessible manner. Resolving this situation is likely to demand a little political imagination.
Political Science and Publicity
Authors: Isaac Jeffrey C.
Published: April 2013

Should political science be publicly relevant? Instead of furnishing a direct answer, I propose to complicate the question. Yet in doing so, I will indicate an answer. And the answer is yes, political science should be publicly relevant – but not in any simple sense, since ‘political science', ‘should’ and indeed ‘publicly relevant’ are less straightforward than they might seem. In what follows I will first complicate the questions posed to political science. I will proceed to reflect on the connection between publication – one of the central activities of all science, including political science – and publicity. I will then briefly tell a story about the journal that I edit, Perspectives on Politics, and the distinctive mission of this journal, which is to serve as ‘a political science public sphere'. I will conclude with some brief reflections on the best ways of thinking about how political science can and should be ‘publicly relevant'.
Risk Factors for Encapsulating Peritoneal Sclerosis in Long‐Term Peritoneal Dialysis: A Retrospective Observational Study
Authors: Nakao Masatsugu , Yokoyama Keitaro , Yamamoto Izumi , Matsuo Nanae , Tanno Yudo , Ohkido Ichiro , Hayakawa Hiroshi , Ikeda Masato , Yamamoto Hiroyasu , Hosoya Tatsuo
Published: April 2013

Encapsulating peritoneal sclerosis (EPS) is a serious complication that occurs in patients with long‐term peritoneal dialysis (PD). Investigation of risk factors that contribute to EPS in patients on long‐term PD therapy is needed. In a retrospective, observational study, data were collected for 107 patients treated with PD therapy for more than 5 years. Fifty cases of EPS were compared with 57 cases of non‐EPS. To evaluate the impact of PD‐associated peritonitis in EPS, univariate and multivariate logistic regression models were applied. Episodes of peritonitis, number of peritonitis episodes and the duration of peritonitis were included as explanatory variables in addition to previously reported risk factors. D/P Cr and serum β2MG levels in the EPS and non‐EPS groups were: 0.82 ± 0.10 and 0.67 ± 0.12 (P < 0.01), and 33.8 ± 8.54 and 29.2 ± 8.18 mg/L (P < 0.01), respectively. Episodes of peritonitis, number of peritonitis episodes and the duration of peritonitis was 68% and 42% (P < 0.01), 1.80 ± 2.19 and 0.75 ± 1.07 times (P < 0.01), and 18.1 ± 15.3 and 10.2 ± 4.90 days (P < 0.01), in the EPS and non‐EPS groups, respectively. Furthermore, multivariate logistic regression models demonstrated that both D/P Cr and the duration of peritonitis were independently associated with EPS (P < 0.01 and P < 0.05, respectively). In patients on long‐term PD therapy, D/P Cr and the duration of peritonitis are independently associated with EPS. Earlier treatment to promote an early recovery from PD‐associated peritonitis could be critical in preventing EPS.
Quantifying sequence proportions in a DNA‐based diet study using Ion Torrent amplicon sequencing: which counts count?
Authors: Deagle Bruce E. , Thomas Austen C. , Shaffer Amanda K. , Trites Andrew W. , Jarman Simon N.
Published: April 2013

A goal of many environmental DNA barcoding studies is to infer quantitative information about relative abundances of different taxa based on sequence read proportions generated by high‐throughput sequencing. However, potential biases associated with this approach are only beginning to be examined. We sequenced DNA amplified from faeces (scats) of captive harbour seals (Phoca vitulina) to investigate whether sequence counts could be used to quantify the seals’ diet. Seals were fed fish in fixed proportions, a chordate‐specific mitochondrial 16S marker was amplified from scat DNA and amplicons sequenced using an Ion Torrent PGM™. For a given set of bioinformatic parameters, there was generally low variability between scat samples in proportions of prey species sequences recovered. However, proportions varied substantially depending on sequencing direction, level of quality filtering (due to differences in sequence quality between species) and minimum read length considered. Short primer tags used to identify individual samples also influenced species proportions. In addition, there were complex interactions between factors; for example, the effect of quality filtering was influenced by the primer tag and sequencing direction. Resequencing of a subset of samples revealed some, but not all, biases were consistent between runs. Less stringent data filtering (based on quality scores or read length) generally produced more consistent proportional data, but overall proportions of sequences were very different than dietary mass proportions, indicating additional technical or biological biases are present. Our findings highlight that quantitative interpretations of sequence proportions generated via high‐throughput sequencing will require careful experimental design and thoughtful data analysis.
Next‐generation sequencing to inventory taxonomic diversity in eukaryotic communities: a test for freshwater diatoms
Authors: Kermarrec L. , Franc A. , Rimet F. , Chaumeil P. , Humbert J. F. , Bouchez A.
Published: April 2013

The recent emergence of barcoding approaches coupled to those of next‐generation sequencing (NGS) has raised new perspectives for studying environmental communities. In this framework, we tested the possibility to derive accurate inventories of diatom communities from pyrosequencing outputs with an available DNA reference library. We used three molecular markers targeting the nuclear, chloroplast and mitochondrial genomes (SSU rDNA, rbcL and cox1) and three samples of a mock community composed of 30 known diatom strains belonging to 21 species. In the goal to detect methodological biases, one sample was constituted directly from pooled cultures, whereas the others consisted of pooled PCR products. The NGS reads obtained by pyrosequencing (Roche 454) were compared first to a DNA reference library including the sequences of all the species used to constitute the mock community, and second to a complete DNA reference library with a larger taxonomic coverage. A stringent taxonomic assignation gave inventories that were compared to the real one. We detected biases due to DNA extraction and PCR amplification that resulted in false‐negative detection. Conversely, pyrosequencing errors appeared to generate false positives, especially in case of closely allied species. The taxonomic coverage of DNA reference libraries appears to be the most crucial factor, together with marker polymorphism which is essential to identify taxa at the species level. RbcL offers a high resolving power together with a large DNA reference library. Although needing further optimization, pyrosequencing is suitable for identifying diatom assemblages and may find applications in the field of freshwater biomonitoring.
Enrichment and isolation of acidophilic sulfate‐reducing bacteria from Tinto River sediments
Authors: Sánchez‐Andrea Irene , Stams Alfons J. M. , Amils Ricardo , Sanz José Luis
Published: April 2013

Although some acidophilic and alkaliphilic species have been described recently, most of the known sulfate‐reducing bacteria (SRB) grow optimally at neutral pH. In this study, sulfate reduction was studied with sediment samples from the extremely acidic Tinto River basin. Stable enrichments of SRB were obtained at pH 4 with glycerol, methanol and hydrogen; at pH 4.5 with lactate and at pH 5.5 with succinate as substrates. Inhibition of sulfate reduction by organic acids below their pKa was observed. Cloning and sequencing of 16S rRNA gene showed that fermentative bacteria (Paludibacter spp., Oscillibacter spp.) and SRB (Thermodesulfobium spp., Desulfosporosinus spp., Desulfitobacterium spp., Desulfotomaculum spp.) were co‐enriched. By repeated serial dilutions and streaking on agar plates, four strains of SRB belonging to the Firmicutes phylum were obtained. Two of them show 96% 16S rRNA gene sequence similarity with Desulfosporosinus acidophilus, and a third one with Desulfosporosinus orientis. Another isolate has just 93% rRNA gene sequence similarity with the Desulfosporosinus/Desulfitobacterium cluster and might represent a novel species within a novel genus. One of the Desulfosporosinus strains was further investigated showing maximum growth at pH 5.5, and a pH‐dependent inhibitory effect of organic acids and sulfide.
Correlation study and significance of the EGFR expression in serum, lymph nodes and tumor tissue of NSCLC
Authors: Zhuo Yinling , Guo Qisen , Song Pingping , Zhang Qiong , Guo Chen , Zeng Hongsheng , Guan Yan , Liu Xiuju , Zhao Chenqing
Published: April 2013

Background

This study was designed to detect the protein expression of epidermal growth factor receptor (EGFR) among serum, lymph node, and tumor tissues, and to discuss their relationship and clinical significance. We investigated whether EGFR levels in serum and lymph nodes could be used as an effective method for non‐small cell lung cancer (NSCLC) to diagnose and assess clinical stage.

Methods

In 56 patients with NSCLC and 10 individuals with nonmalignant thoracic disease, we measured EGFR levels in serum using an enzyme immunoassay, and EGFR mRNA levels in lymph node and NSCLC tissues by quantitative real‐time‐polymerase chain reaction. We examined the correlation between them and with the clinical parameters.

Results

Serum EGFR levels substantially decreased after surgical treatment (P < 0.001). Serum EGFR levels were correlated with smoking, surgery, and pathological type after surgery (all P < 0.05). EGFR mRNA levels in lymph node and tumor tissues were correlated more closely with lymph node metastasis (P = 0.015. EGFR mRNA in tissues was higher than that of benign pulmonary diseases (P = 0.020). There was an obvious positive correlation among EGFR levels of serum and lymph node tissues (r = 0.764; P < 0.001), serum and tumor tissues (r = 0.616; P < 0.001), and lymph node and tumor tissues (r = 0.904; P < 0.001) in NSCLCs.

Conclusion

The data suggest that detecting EGFR levels in serum and lymph node tissues could be a simple and effective method to diagnose and assess the clinical stage in patients with NSCLC.
Three phenotypes of adult‐onset asthma
Authors: Amelink M. , de Nijs S. B. , de Groot J. C. , van Tilburg P. M. B. , van Spiegel P. I. , Krouwels F. H. , Lutter R. , Zwinderman A. H. , Weersink E. J. M. , ten Brinke A. , Sterk P. J. , Bel E. H.
Published: April 2013

Rationale

Adult‐onset asthma differs from childhood‐onset asthma in many respects. It is more heterogeneous, often severe and frequently associated with loss of lung function. To identify underlying mechanisms of adult‐onset asthma and to capture predictors of disease progression, detailed characterization and phenotyping is necessary.

Objectives

To characterize adult‐onset asthma and identify subphenotypes of adult‐onset asthma.

Methods

A cohort of 200 patients with adult‐onset (>18 year) asthma (age 54 (26–75) year) was recruited from one academic and three nonacademic pulmonary outpatient clinics in Amsterdam, the Netherlands. These patients were fully characterized with respect to clinical, functional and inflammatory markers. After data reduction, K‐means nonhierarchical cluster analysis was performed to identify clusters of adult‐onset asthma.

Measurements and main results

Patients with adult‐onset asthma were predominately female (61%) and nonatopic (55%). Within this group of patients were identified three clusters of adult‐onset asthma. Cluster 1 (n = 69) consisted of patients with severe eosinophilic inflammation‐predominant asthma and persistent airflow limitation despite high‐intensity anti‐inflammatory treatment, with relatively low symptom scores. The second cluster was characterized by obese women with frequent symptoms, high healthcare utilization and low sputum eosinophils. The third cluster consisted of patients with mild‐to‐moderate, well‐controlled asthma with normal lung function and low inflammatory markers. Repeatability accuracy was 98.2%.

Conclusions

Amongst patients with adult‐onset asthma, three subphenotypes can be identified with distinct clinical and inflammatory characteristics. These subphenotypes help to understand the underlying pathobiology and provide clinicians with directions for personalized management.
Postoperative hypothermia and patient outcomes after major elective non‐cardiac surgery
Authors: Karalapillai D. , Story D. , Hart G. K. , Bailey M. , Pilcher D. , Schneider A. , Kaufman M. , Cooper D. J. , Bellomo R.
Published: April 2013

Using a multicentre adult patient database from Australia and New Zealand, we obtained the lowest and highest temperature in the first 24 h after admission to the intensive care unit after elective non‐cardiac surgery. Hypothermia was defined as core temperature < 36 °C; transient hypothermia as a temperature < 36 °C that was corrected within 24 h, and persistent hypothermia as hypothermia not corrected within 24 h. We studied 50 689 patients. Hypothermia occurred in 23 165 (46%) patients, was transient in 22 810 (45%), and was persistent in 608 (1.2%) patients. On multivariate analysis, neither transient (OR = 1.07, 95%CI0.96–1.20) nor persistent (OR = 1.50. 95%CI0.96–2.33) hypothermia was independently associated with increased hospital mortality.
Colposcopically directed cervical biopsy during pregnancy; minor surgical and obstetrical complications and high rates of persistence and regression
Authors: Kärrberg Cecilia , Brännström Mats , Strander Björn , Ladfors Lars , Rådberg Thomas
Published: April 2013

Objective

To evaluate whether colposcopically directed cervical biopsies during pregnancy are associated with surgical/obstetric complications and to examine the natural course (regression, persistence, progression) of dysplasia during pregnancy.

Design

Prospective clinical study.

Setting and population

University Hospital and 251 pregnant women with atypical cervical cytology in early pregnancy.

Methods

The patients were investigated by colposcopically directed punch biopsies, colposcopically directed loop‐biopsies or LEEP‐cones. The histology results during pregnancy were compared with those after delivery to evaluate the natural course of dysplastic lesions during pregnancies. Postoperative complications were recorded. Obstetric outcome was recorded and compared with the 54 919 other births in the same geographical area during the study period.

Main outcome measures

Persistence, regression and progression of cervical dysplasia, surgical complications after diagnostic procedure, incidence of preterm birth, mode of delivery.

Results

Only a minor part (12.3%) of the dysplastic lesions showed progression during pregnancy, with 54.6 and 33.1% showing persistence and regression, respectively. No surgically related postoperative bleeding that needed surgical (diathermy/suture) treatment occurred and the miscarriage rate was low (0.8%). There were no differences in mode of delivery, preterm birth or other obstetrical variables between the study group and the large control cohort.

Conclusion

Investigation of atypical cytology during pregnancy with biopsy including large loop excisions is a safe procedure with regard to surgical complications and obstetrical outcome. There is a high rate of persistence and regression of dysplasia during pregnancy.
Long‐term results of the effect of intravitreal ranibizumab on the retinal arteriolar diameter in patients with neovascular age‐related macular degeneration
Authors: Mendrinos Efstratios , Mangioris Georgios , Papadopoulou Domniki N. , Donati Guy , Pournaras Constantin J.
Published: April 2013

Purpose:  To study the effect of intravitreal (IVT) ranibizumab on the retinal arteriolar diameter in patients with neovascular age‐related macular degeneration (AMD).

Methods:  Ten eyes of 10 patients with previously untreated neovascular AMD were included. All eyes had three monthly IVT injections of ranibizumab and then were retreated as needed, based on visual acuity and optical coherence tomography (OCT) criteria. The diameter of the retinal arterioles was measured in vivo with a retinal vessel analyser (RVA) before the first IVT injection, 7 and 30 days after the first, the second and the third injection, and at month 12 of follow‐up.

Results:  A significant vasoconstriction of the retinal arterioles was observed following each one of the first three IVT injections of ranibizumab. Thirty days following the first, second and third injection, there was a mean decrease of 8.4 ± 3.2%, 11.9 ± 4.5% and 18.5 ± 7.2%, respectively, of the retinal arteriolar diameter compared with baseline (p < 0.01). At month 12, the vasoconstriction was still present with a mean decrease of 19.1 ± 8.3% of the retinal arteriolar diameter compared with baseline (p < 0.01). Median number of ranibizumab injections was 4 (range 3–10). There was no correlation between the number of injections and percentage diameter decrease at month 12 (r = −0.54, p > 0.1). There was no significant change in mean arterial pressure (MAP) during the period of follow‐up (p > 0.05).

Conclusions:  These results suggest that IVT ranibizumab induces sustained retinal arteriolar vasoconstriction in eyes with neovascular AMD.
Structure–function relationship among three types of spectral‐domain optical coherent tomography instruments in measuring parapapillary retinal nerve fibre layer thickness
Authors: Kanamori Akiyasu , Nakamura Makoto , Tomioka Mari , Kawaka Yuki , Yamada Yuko , Negi Akira
Published: April 2013

Purpose:  To compare the relationships of parapapillary retinal nerve fibre layer (RNFL) thickness among three spectral‐domain optical coherence tomography (SD‐OCT) instruments with visual field sensitivity (VFS).

Methods:  One hundred and thirteen eyes of 113 Japanese subjects with glaucoma (mean deviation in standard automated perimetry = −8.9 ± 6.7 dB) were imaged by Cirrus, RTVue and 3D OCT. The average hemi‐superior and hemi‐inferior RNFL thicknesses were obtained. In addition, the structure–function relationship using two retinotopic maps that consisted of six or nine sectors was also evaluated. Decibel (dB) scale and 1/Lamert (1/L) were used to express VFS. RNFL thickness correlation with corresponding VFS in visual field sectors was compared among the three instruments. Background RNFL thickness (non‐neuronal tissue) for each instrument was estimated using a linear regression model at 1/L = 0.

Results:  The correlation between the average hemi‐superior and hemi‐inferior RNFL thickness in the three SD‐OCT instruments with corresponding VFS was similar. In the analysis of retinotopic maps, 3D OCT showed a higher correlation in superotemporal sectors than RTVue, whereas RTVue had a stronger relationship in the nasal sector than Cirrus. The background RNFL thickness extrapolated was approximately 60% that of normal eyes in all the instruments.

Conclusions:  The three SD‐OCT showed similar overall correspondence with VFS with a partially discordant retinotopic relationship. RNFL measured with any SD‐OCT devices likely contains non‐neuronal tissue, comprising 60% of its thickness.
Exploring weather‐related experiences and practices: examining methodological approaches
Authors: de Vet Eliza
Published: April 2013

With projected climate change, it is increasingly important to understand the current role of weather in everyday life and how it may change in the future. This paper evaluates two qualitative research approaches for their ability to generate insight into weather‐related experiences and everyday practices. As these mundane day‐to‐day weather interactions often escape memory over time, the paper calls into question the ability of conventional methodological approaches that rely on recall to accurately excavate these events. The research examined serial one‐on‐one, semi‐structured interviews with an adapted short‐term focus, and daily diary‐photographs. Each approach was applied to one of two Australian cities with sharply contrasting climates – Melbourne and Darwin. Both approaches were able to generate insight into weather‐related experiences and practices. However, both presented problems. In interviews, these problems related to retrospective accounts beyond ‘yesterday’, where physical experience recollections became limited. For diary‐photographs, inspiring participants to continually complete and submit contributions proved problematic. I argue that interviews are better for documenting routine practice and generalised experiences, while diary‐photographs are better at showing fine‐grained detail of physical experiences. Where both aspects are sought, as in this study, a combination is possible. However, using dual methods increases the risk of participant fatigue.
Differences in spatial autocorrelation (SAc), plant species richness and diversity, and plant community composition in grazed and ungrazed grasslands along a moisture gradient, North Dakota, USA
Authors: Meyers Lindsey M. , DeKeyser Edward S. , Norland Jack E.
Published: April 2013

Questions

How are plant species richness and diversity related to spatial autocorrelation under grazed and ungrazed conditions in grassland communities? Is spatial autocorrelation dissimilar within different plant communities?

Location

The grasslands of southeast North Dakota, USA.

Methods

The study was conducted during the summer of 2009 in six grasslands under different management (grazed vs ungrazed with fire) along a moisture gradient. Spatial autocorrelation at each site was measured along 50‐m transects among three different landscape positions representing different moisture levels. Dissimogram multivariate analysis was used to measure the nugget, dissimilarity and patch diameter. Additionally, richness and Shannon diversity indices and nonmetric multidimensional scaling analysis were compared to the dissimogram results.

Results

Mean patch diameter was significantly higher in grazed mid‐slope sites than in ungrazed sites. Spatial autocorrelation was not different between the landscape positions (higher, dry areas were not different from lower, mesic areas). However, plant species richness, diversity and community composition were found to be different between landscape positions and management, with key differences in the presence of certain invasive species.

Conclusions

Disturbance and moisture level were reflected differently in the spatial autocorrelation analysis compared to the richness, diversity and ordination analyses. This indicates that disturbance and management impacted spatial autocorrelation separate from plant community composition and species diversity. This also highlights changes in the plant community caused by different management actions and the spread of invasive species.
A prospective phase II randomized study of deferasirox to prevent iatrogenic iron overload in patients undertaking induction/consolidation chemotherapy for acute myeloid leukaemia
Authors: Kennedy Glen A. , Morris Kirk L. , Subramonpillai Elango , Curley Cameron , Butler Jason , Durrant Simon
Published: April 2013

This prospective randomized phase II study aimed to determine the safety and efficacy of deferasirox in preventing iatrogenic iron overload in patients receiving induction/consolidation chemotherapy for acute myeloid leukaemia (AML) ize. Serum ferritin, transferrin saturation and CRP were measured pre‐, mid‐ and post‐ each chemotherapy cycle. Patients were randomized to receive either therapy with deferasirox vs. no deferasirox therapy once serum ferritin increased to >500 μg/l. The trial was stopped prematurely due to excess gastrointestinal (GI) and infectious toxicity demonstrable in the deferasirox arm, after 10 patients had been randomized to deferasirox and 6 patients to the control arm. Overall, deferasirox was poorly tolerated, with median maximum tolerated dose only 13·8 mg/kg/d and no patient able to tolerate doses >20 mg/kg/d. Median duration of deferasirox therapy was only 72 d (range 19–130 d), with 9/10 patients requiring unplanned dose interruptions and 4/10 patients unable to continue the drug predominantly due to GI effects. Although all 3 treatment‐related deaths occurred in the deferasirox arm (P = 0·25), median overall survival was similar between treatment arms. Use of deferasirox to prevent iatrogenic iron overload in AML patients undertaking induction/consolidation is poorly tolerated and appears to be associated with excess GI and infectious toxicity.
The effect of hydroxcarbamide therapy on survival of children with sickle cell disease
Authors: Lopes de Castro Lobo Clarisse , Pinto Jorge F. C. , Nascimento Emilia M. , Moura Patricia G. , Cardoso Gilberto P. , Hankins Jane S.
Published: April 2013

Although evidence is accumulating that hydroxycarbamide decreases mortality among adults with sickle cell disease (SCD), there are no published data regarding the effect of hydroxycarbamide on mortality among children. The Paediatric Hydroxycarbamide Program was established to treat children with SCD aged 3–18 years if they met disease severity criteria. Mortality data and clinical/laboratorial effects of hydroxycarbamide were retrospectively collected for the first 9 years of the Program. Mortality among those who received hydroxycarbamide was compared to that of untreated children. Among 1760 subjects, 267 received hydroxycarbamide at a median dose of 20·8 mg/kg/d (range 10–32) for a median of 2 years (range 0·1–6·5). Survival among hydroxycarbamide‐treated children was significantly greater than that among untreated ones (99·5% vs. 94·5%, P = 0·01), due primarily to fewer deaths from acute chest syndrome and infection. Hydroxycarbamide therapy was significantly associated with increases in haemoglobin concentration, fetal haemoglobin, mean corpuscular volume, and reduction in platelet counts, reticulocytes and neutrophils. Toxicity was minimal and predominantly mild reversible neutropenia. Significantly fewer hospitalizations and emergency room visits, and shorter admissions were observed among hydroxycarbamide‐treated subjects, when compared to the 12‐month period prior to treatment initiation. Hydroxycarbamide therapy reduces disease severity and is probably associated with decreased mortality among children with SCD.
Paradoxical protection from atherosclerosis and thrombosis in a mouse model of sickle cell disease
Authors: Wang Hui , Luo Wei , Wang Jintao , Guo Chiao , Wolffe Stephanie L. , Wang Julia , Sun Eddy B. , Bradley Kori N. , Campbell Andrew D. , Eitzman Daniel T.
Published: April 2013

Sickle cell disease (SCD) is associated with vascular complications including premature stroke. The role of atherothrombosis in these vascular complications is unclear. To determine the effect of SCD on atherosclerosis and thrombosis, mice with SCD along with controls were generated by transplantation of bone marrow from mice carrying the homozygous sickle cell mutation (Hbbhβs/hβs) or wild‐type mice (Hbb+/+) into C57BL6/J or apolipoprotein E deficient (Apoe−/−) recipient mice. At the time of sacrifice, 23–28 weeks following bone marrow transplantation, anaemia, reticulocytosis, and splenomegaly were present in mice receiving Hbbhβs/hβs bone marrow compared with control mice. Analysis of atherosclerosis involving the aortic root revealed reduced atherosclerotic lesion area with reduced macrophage content and increased collagen content in Apoe−/−, Hbbhβs/hβs mice compared to Apoe−/−, Hbb+/+ mice. In a carotid thrombosis model, the time to thrombosis was prolonged in Hbbhβs/hβs mice compared to Hbb+/+ mice. This apparent protective effect of SCD on atherosclerosis and thrombosis was diminished by inhibition of heme oxygenase‐1 (HMOX1) using zinc protoporphyrin IX.

We conclude that SCD in mice is paradoxically protective against atherosclerosis and thrombosis, highlighting the complexity of vascular events in SCD. This protective effect is at least partially mediated by induction of HMOX1.