bluuebunny/crossref_metadata_2025 huggingface dataset:
Advanced technologies for genetically manipulating the silkwormBombyx mori, a model Lepidopteran insect
Authors: Xu Hanfu , O'Brochta David A.
Published: June 2015

Genetic technologies based on transposon-mediated transgenesis along with several recently developed genome-editing technologies have become the preferred methods of choice for genetically manipulating many organisms. The silkworm,Bombyx mori, is a Lepidopteran insect of great economic importance because of its use in silk production and because it is a valuable model insect that has greatly enhanced our understanding of the biology of insects, including many agricultural pests. In the past 10 years, great advances have been achieved in the development of genetic technologies inB. mori, including transposon-based technologies that rely onpiggyBac-mediated transgenesis and genome-editing technologies that rely on protein- or RNA-guided modification of chromosomes. The successful development and application of these technologies has not only facilitated a better understanding ofB. moriand its use as a silk production system, but also provided valuable experiences that have contributed to the development of similar technologies in non-model insects. This review summarizes the technologies currently available for use inB. mori, their application to the study of gene function and their use in genetically modifyingB. morifor biotechnology applications. The challenges, solutions and future prospects associated with the development and application of genetic technologies inB. moriare also discussed.
Allometry of animal–microbe interactions and global census of animal-associated microbes
Authors: Kieft Thomas L. , Simmons Karen A.
Published: June 2015

Animals live in close association with microorganisms, mostly prokaryotes, living in or on them as commensals, mutualists or parasites, and profoundly affecting host fitness. Most animal–microbe studies focus on microbial community structure; for this project, allometry (scaling of animal attributes with animal size) was applied to animal–microbe relationships across a range of species spanning 12 orders of magnitude in animal mass, from nematodes to whales. Microbial abundances per individual animal were gleaned from published literature and also microscopically counted in three species. Abundance of prokaryotes/individual versus animal mass scales as a nearly linear power function (exponent = 1.07,
R
2
= 0.94). Combining this power function with allometry of animal abundance indicates that macrofauna have an outsized share of animal-associated microorganisms. The total number of animal-associated prokaryotes in Earth's land animals was calculated to be 1.3–1.4 × 10
25
cells and the total of marine animal-associated microbes was calculated to be 8.6–9.0 × 10
24
cells. Animal-associated microbes thus total 2.1–2.3 × 10
25
of the approximately 10
30
prokaryotes on the Earth. Microbes associated with humans comprise 3.3–3.5% of Earth's animal-associated microbes, and domestic animals harbour 14–20% of all animal-associated microbes, adding a new dimension to the scale of human impact on the biosphere. This novel allometric power function may reflect underlying mechanisms involving the transfer of energy and materials between microorganisms and their animal hosts. Microbial diversity indices of animal gut communities and gut microbial species richness for 60 mammals did not indicate significant scaling relationships with animal body mass; however, further research in this area is warranted.
Synthetic datasets and community tools for the rapid testing of ecological hypotheses
Authors: Poisot Timothee , Gravel Dominique , Leroux Shawn , Wood Spencer A , Fortin Marie-Josée , Baiser Benjamin , Cirtwill Alyssa R , Araujo Miguel B , Stouffer Daniel B
Published: June 2015

The increased availability of both open ecological data, and software to interact with it, allows to rapidly collect and integrate data over large spatial and taxonomic scales. This offers the opportunity to address macroecological questions in a cost-effective way. In this contribution, we illustrate this approach by forecasting the structure of a stream food web at the global scale. In so doing, we highlight the most salient issues needing to be addressed before this approach can be used with a high degree of confidence.
DNA methylation restrains transposons from adopting a chromatin signature permissive for meiotic recombination
Authors: Zamudio Natasha , Barau Joan , Teissandier Aurélie , Walter Marius , Borsos Maté , Servant Nicolas , Bourc'his Déborah
Published: June 2015

DNA methylation is essential for protecting the mammalian germline against transposons. When DNA methylation-based transposon control is defective, meiotic chromosome pairing is consistently impaired during spermatogenesis: How and why meiosis is vulnerable to transposon activity is unknown. Using two DNA methylation-deficient backgrounds, the Dnmt3L and Miwi2 mutant mice, we reveal that DNA methylation is largely dispensable for silencing transposons before meiosis onset. After this, it becomes crucial to back up to a developmentally programmed H3K9me2 loss. Massive retrotransposition does not occur following transposon derepression, but the meiotic chromatin landscape is profoundly affected. Indeed, H3K4me3 marks gained over transcriptionally active transposons correlate with formation of SPO11-dependent double-strand breaks and recruitment of the DMC1 repair enzyme in Dnmt3L−/− meiotic cells, whereas these features are normally exclusive to meiotic recombination hot spots. Here, we demonstrate that DNA methylation restrains transposons from adopting chromatin characteristics amenable to meiotic recombination, which we propose prevents the occurrence of erratic chromosomal events.
Structure–function studies of histone H3/H4 tetramer maintenance during transcription by chaperone Spt2
Authors: Chen Shoudeng , Rufiange Anne , Huang Hongda , Rajashankar Kanagalaghatta R. , Nourani Amine , Patel Dinshaw J.
Published: June 2015

Cells use specific mechanisms such as histone chaperones to abrogate the inherent barrier that the nucleosome poses to transcribing polymerases. The current model postulates that nucleosomes can be transiently disrupted to accommodate passage of RNA polymerases and that histones H3 and H4 possess their own chaperones dedicated to the recovery of nucleosomes. Here, we determined the crystal structure of the conserved C terminus of human Suppressors of Ty insertions 2 (hSpt2C) chaperone bound to an H3/H4 tetramer. The structural studies demonstrate that hSpt2C is bound to the periphery of the H3/H4 tetramer, mimicking the trajectory of nucleosomal-bound DNA. These structural studies have been complemented with in vitro binding and in vivo functional studies on mutants that disrupt key intermolecular contacts involving two acidic patches and hydrophobic residues on Spt2C. We show that contacts between both human and yeast Spt2C with the H3/H4 tetramer are required for the suppression of H3/H4 exchange as measured by H3K56ac and new H3 deposition. These interactions are also crucial for the inhibition of spurious transcription from within coding regions. Together, our data indicate that Spt2 interacts with the periphery of the H3/H4 tetramer and promotes its recycling in the wake of RNA polymerase.
A YAP/TAZ-induced feedback mechanism regulates Hippo pathway homeostasis
Authors: Moroishi Toshiro , Park Hyun Woo , Qin Baodong , Chen Qian , Meng Zhipeng , Plouffe Steven W. , Taniguchi Koji , Yu Fa-Xing , Karin Michael , Pan Duojia , Guan Kun-Liang
Published: June 2015

YAP (Yes-associated protein) and TAZ (transcriptional coactivator with PDZ-binding motif) are major downstream effectors of the Hippo pathway that influences tissue homeostasis, organ size, and cancer development. Aberrant hyperactivation of YAP/TAZ causes tissue overgrowth and tumorigenesis, whereas their inactivation impairs tissue development and regeneration. Dynamic and precise control of YAP/TAZ activity is thus important to ensure proper physiological regulation and homeostasis of the cells. Here, we show that YAP/TAZ activation results in activation of their negative regulators, LATS1/2 (large tumor suppressor 1/2) kinases, to constitute a negative feedback loop of the Hippo pathway in both cultured cells and mouse tissues. YAP/TAZ in complex with the transcription factor TEAD (TEA domain family member) directly induce LATS2 expression. Furthermore, YAP/TAZ also stimulate the kinase activity of LATS1/2 through inducing NF2 (neurofibromin 2). This feedback regulation is responsible for the transient activation of YAP upon lysophosphatidic acid (LPA) stimulation and the inhibition of YAP-induced cell migration. Thus, this LATS-mediated feedback loop provides an efficient mechanism to establish the robustness and homeostasis of YAP/TAZ regulation.
Genome Sequencing of Arabidopsis abp1-5 Reveals Second-Site Mutations That May Affect Phenotypes
Authors: Enders Tara A. , Oh Sookyung , Yang Zhenbiao , Montgomery Beronda L. , Strader Lucia C.
Published: June 2015

Auxin regulates numerous aspects of plant growth and development. For many years, investigating roles for AUXIN BINDING PROTEIN1 (ABP1) in auxin response was impeded by the reported embryo lethality of mutants defective in ABP1. However, identification of a viable Arabidopsis thaliana TILLING mutant defective in the ABP1 auxin binding pocket (abp1-5) allowed inroads into understanding ABP1 function. During our own studies with abp1-5, we observed growth phenotypes segregating independently of the ABP1 lesion, leading us to sequence the genome of the abp1-5 line described previously. We found that the abp1-5 line we sequenced contains over 8000 single nucleotide polymorphisms in addition to the ABP1 mutation and that at least some of these mutations may originate from the Arabidopsis Wassilewskija accession. Furthermore, a phyB null allele in the abp1-5 background is likely causative for the long hypocotyl phenotype previously attributed to disrupted ABP1 function. Our findings complicate the interpretation of abp1-5 phenotypes for which no complementation test was conducted. Our findings on abp1-5 also provide a cautionary tale illustrating the need to use multiple alleles or complementation lines when attributing roles to a gene product.
MISTRAL: a transmission soft X-ray microscopy beamline for cryo nano-tomography of biological samples and magnetic domains imaging
Authors: Sorrentino Andrea , Nicolás Josep , Valcárcel Ricardo , Chichón Francisco Javier , Rosanes Marc , Avila Jose , Tkachuk Andrei , Irwin Jeff , Ferrer Salvador , Pereiro Eva
Published: June 2015

The performance of MISTRAL is reported, the soft X-ray transmission microscopy beamline at the ALBA light source (Barcelona, Spain) which is primarily dedicated to cryo soft X-ray tomography (cryo-SXT) for three-dimensional visualization of whole unstained cells at spatial resolutions down to 30 nm (half pitch). Short acquisition times allowing for high-throughput and correlative microscopy studies have promoted cryo-SXT as an emerging cellular imaging tool for structural cell biologists bridging the gap between optical and electron microscopy. In addition, the beamline offers the possibility of imaging magnetic domains in thin magnetic films that are illustrated here with an example.
Development of variable-magnification X-ray Bragg optics
Authors: Hirano Keiichi , Yamashita Yoshiki , Takahashi Yumiko , Sugiyama Hiroshi
Published: June 2015

A novel X-ray Bragg optics is proposed for variable-magnification of an X-ray beam. This X-ray Bragg optics is composed of two magnifiers in a crossed arrangement, and the magnification factor,M, is controlled through the azimuth angle of each magnifier. The basic properties of the X-ray optics such as the magnification factor, image transformation matrix and intrinsic acceptance angle are described based on the dynamical theory of X-ray diffraction. The feasibility of the variable-magnification X-ray Bragg optics was verified at the vertical-wiggler beamline BL-14B of the Photon Factory. For X-ray Bragg magnifiers, Si(220) crystals with an asymmetric angle of 14° were used. The magnification factor was calculated to be tunable between 0.1 and 10.0 at a wavelength of 0.112 nm. At various magnification factors (M≥ 1.0), X-ray images of a nylon mesh were observed with an air-cooled X-ray CCD camera. Image deformation caused by the optics could be corrected by using a 2 × 2 transformation matrix and bilinear interpolation method. Not only absorption-contrast but also edge-contrast due to Fresnel diffraction was observed in the magnified images.
Single-image phase retrieval using an edge illumination X-ray phase-contrast imaging setup
Authors: Diemoz Paul C. , Vittoria Fabio A. , Hagen Charlotte K. , Endrizzi Marco , Coan Paola , Brun Emmanuel , Wagner Ulrich H. , Rau Christoph , Robinson Ian K. , Bravin Alberto , Olivo Alessandro
Published: June 2015

A method is proposed which enables the retrieval of the thickness or of the projected electron density of a sample from a single input image acquired with an edge illumination phase-contrast imaging setup. The method assumes the case of a quasi-homogeneous sample,i.e.a sample with a constant ratio between the real and imaginary parts of its complex refractive index. Compared with current methods based on combining two edge illumination images acquired in different configurations of the setup, this new approach presents advantages in terms of simplicity of acquisition procedure and shorter data collection time, which are very important especially for applications such as computed tomography and dynamical imaging. Furthermore, the fact that phase information is directly extracted, instead of its derivative, can enable a simpler image interpretation and be beneficial for subsequent processing such as segmentation. The method is first theoretically derived and its conditions of applicability defined. Quantitative accuracy in the case of homogeneous objects as well as enhanced image quality for the imaging of complex biological samples are demonstrated through experiments at two synchrotron radiation facilities. The large range of applicability, the robustness against noise and the need for only one input image suggest a high potential for investigations in various research subjects.
Adalimumab markedly improves enthesitis in patients with psoriatic arthritis: Evaluation with a magnetic resonance imaging scoring system
Authors: Yanaba Koichi , Sadaoka Akari , Yonenaga Takenori , Saeki Hidehisa , Umezawa Yoshinori , Tojo Shinjiro , Ito Toshihiro , Kikuchi Sota , Fukuda Kunihiko , Nakagawa Hidemi
Published: June 2015

Psoriatic arthritis (PsA), a seronegative arthropathy, may often result in progressive joint damage without treatment, leading to disability and impaired quality of life. Early therapeutic intervention of PsA is therefore crucial before the development of irreversible joint damage. Because psoriatic skin lesions generally precede the onset of PsA, dermatologists occupy an important position in treating patients with early PsA. This study aimed to evaluate the efficacy of adalimumab in treating joint disease in patients with PsA, using the PsA magnetic resonance imaging scoring system (PsAMRIS). Five adult Japanese male patients with active PsA were treated with adalimumab. Magnetic resonance imaging was obtained at baseline and 8–32 weeks with 2–3 time points following adalimumab treatment and assessed using PsAMRIS. Adalimumab treatment markedly improved clinical symptoms and disease activities of joint disease, which was confirmed by the reduction of PsAMRIS scores in all patients. Bone marrow edema and periarticular inflammation, reflecting the presence of enthesitis, were dramatically improved at week 8, while improvement of synovitis and flexor tenosynovitis was observed later, at week 24 or 32. However, bone erosion was not improved by adalimumab treatment during the follow‐up period. These results indicate that adalimumab treatment is associated with dramatic improvement of enthesitis in patients with PsA, whereas bone erosion may be resistant to such treatment. PsAMRIS appears to be useful for the evaluation of treatment efficacy in PsA.
An integrated assessment model of seabird population dynamics: can individual heterogeneity in susceptibility to fishing explain abundance trends in Crozet wandering albatross?
Authors: Tuck Geoffrey N. , Thomson Robin B. , Barbraud Christophe , Delord Karine , Louzao Maite , Herrera Miguel , Weimerskirch Henri
Published: June 2015

Seabirds have been incidentally caught in distant‐water longline fleets operating in the Southern Ocean since at least the 1970s, and breeding numbers for some populations have shown marked trends of decline and recovery concomitant with longline fishing effort within their distributions. However, lacking is an understanding of how forms of among‐individual heterogeneity may interact with fisheries bycatch and influence population dynamics.

We develop a model that uses comprehensive data on the spatial and temporal distributions of fishing effort and seabird foraging to estimate temporal overlaps, fishery catchability and consequent bycatch. We apply a population model that is structured by age, sex, life stage and spatially to Crozet Island wandering albatross and explore how heterogeneity in susceptibility to capture may have influenced the population's demography over time.

A model where some birds were assumed to be more susceptible to fisheries bycatch was able to successfully replicate the observed trend in breeding pairs. Considerably poorer fits were found without this assumption. Results suggested that the more susceptible birds may have been removed from the population by the 1990s.

The model was also able to highlight areas, times and fleets prone to increased bycatch. Knowledge of these factors should assist fisheries and conservation management bodies to quantify and reduce seabird bycatch through spatial management and fleet‐specific mitigation efforts.

Synthesis and application. Many seabirds show complex life histories that make them highly susceptible to additional incidental mortality from fishing vessels. By applying a population model that integrates key aspects of seabird and fishery dynamics, we were able to explain the observed trends in the breeding population of Crozet wandering albatross and identify key areas and fleets where further mitigation may be required. In addition, the potential removal of a category of birds that shows increased susceptibility to capture has important implications for the conservation management of this population and other iconic species incidentally caught by large‐scale commercial fisheries.
Shining trinkets and unkempt gardens: on the materiality of care
Authors: van Hout Annemarie , Pols Jeannette , Willems Dick
Published: June 2015

The increasing use of telecare will profoundly change nursing care. How to understand these changes is, however, far from clear. This is because (i) studies on telecare seldom consider the situation it replaces, and (ii) current concepts and methods used to study the impact of telecare may not allow us to fully grasp these changes. We suggest that an analysis of the changing materiality of care practices is a suitable way to articulate and reflect on possible concerns. It allows us to compare care practices in the same terms before and after telecare has been introduced. To demonstrate this, we study the materiality of the classical care setting, the nursing house call, to map the situation before telecare is introduced. Building on science and technology studies, we apply four categories as heuristics to analyse materiality in care: signs, dis/enablers (or scripted things), tools and practical arrangements. We leave open the question of how material arrangements could or should be matters of concern in nursing care, and instead argue for studies that give insights into the everyday tinkering with the materiality of care that both nurses and patients need to engage in.
Off‐label and unlicenced medicine administration to paediatric emergency department patients
Authors: McD Taylor David , Joffe Paul , Taylor Simone E , Jones Alicia , Cheek John A , Craig Simon S , Graudins Andis , Dhir Reetika , Krieser David , Babl Franz E
Published: June 2015

Objective

To determine the prevalence and nature of off‐label and unlicenced (off‐label/unlicenced) medicine administration to paediatric ED patients.

Methods

We undertook a retrospective, observational study in six EDs (July 2011 to June 2012, inclusive). Patients, aged 0–17 years, who were administered a medicine in the ED were included. At each site, 50 eligible patients were randomly selected each month of the study period. An explicit review of each patient's records was undertaken. Medicines were classified as on or off‐label/unlicenced according to categories of use approved by the Therapeutic Goods Administration.

Results

There were 3343 patients enrolled (56.5% men, mean ± SD age 6.7 ± 5.4 years). Of the 6786 medicine doses administered, 2072 (30.5%, 95% CI 29.4–31.7%) were off‐label/unlicenced. The off‐label/unlicenced doses were administered to 1213 (36.3%, 95% CI 34.7–37.9%) patients. Patients administered an off‐label/unlicenced medicine were younger than those who were not (P < 0.01). Salbutamol, ondansetron, ipratropium, fentanyl and oxycodone were the medicines most commonly administered off‐label. In 910 (44.0%) cases, the dose/frequency was not approved; in 592 (28.6%), there was an unapproved indication for treatment; in 158 (7.6%), the medicine was administered via an unapproved route; in 154 (7.4%) the medicine was not approved for the weight or age; and in 74 (3.5%) an unlicenced product was administered. The remaining cases had combinations of reasons.

Conclusions

Off‐label/unlicenced medicine administration is common. A registry of commonly used off‐label medicines is recommended in which the safety and efficacy of their off‐label use have been demonstrated by published evidence.
Metaphor and the Anthropocene: Presenting Humans as a Geological Force
Authors: RICKARDS LAUREN A.
Published: June 2015

Intellectually as well as materially, the Anthropocene is a deeply cultural phenomenon. This includes its communicative form, which is a contested trope‐rich narrative, even within the sciences. In this essay I focus on the role of metaphor in Anthropocene thought and in particular, on the provocative, ambiguous, and potentially far‐reaching idea of humans as a geological force. By considering the different interpretations and meaning this metaphor encourages – including differences in what is meant by geological and force, both within and beyond stratigraphy and Earth System Science – we gain a stronger sense of the deeply allegorical and theological character of the Anthropocene story and the way it promises to reposition humans in the world.
Dietary risk scores of toddlers are associated with nutrient intakes and socio‐demographic factors, but not weight status
Authors: Bell Lucinda K. , Golley Rebecca K. , Magarey Anthea M.
Published: June 2015

Aim

To determine the convergent validity of the toddler dietary questionnaire (TDQ), previously shown to have good reliability and comparative validity, by assessing whetherTDQ‐derived dietary risk scores are associated with nutrient intakes, socio‐demographic characteristics and weight status.

Methods

Parents of 117Australian children aged 12–36 months completed a demographic questionnaire and the 19‐itemTDQthat assesses intake over the last 7 days of ‘core’ and ‘non‐core’ food‐groups, which is scored against a dietary risk criteria (0–100; higher score = higher risk). Nutrient intakes were established by applyingTDQfood‐group nutrient profiles to the amount consumed per week and tallying for all items. Energy and energy‐adjusted nutrient intakes across quartiles (Q1–Q4) of dietary risk scores were investigated using linear trend analysis for parametric data. Regression analysis was employed to determine the association between risk score, socio‐demographic characteristics and toddler body mass index (BMI) z‐score.

Results

Toddler risk scores (Q1 20.0 ± 2.7vs Q4 41.6 ± 5.6) were positively associated with energy, total fat, saturated fat, sugar and sodium intakes and negatively associated with protein, fibre, iron, magnesium and phosphorus intakes. Higher risk scores were associated with higher number of people per household (n = 115; β = 2.26 [0.13, 4.38],P= 0.037) and toddler age (n = 115, β = 4.03 [1.10, 6.96],P= 0.008) but notBMIz‐scores (n = 114; β = −0.00 [−0.04, 0.03],P= 0.845).

Conclusions

Dietary risk scores are associated with selected nutrient intakes and socio‐demographic characteristics in expected directions, but notBMIz‐scores, providing support for use of theTDQas a dietary screening tool. Longitudinal investigation of the influence of dietary risk on weight status is warranted.
Comprehensive sampling of an isolated dune system demonstrates clear patterns in soil fungal communities across a successional gradient
Authors: Roy‐Bolduc Alice , Bell Terrence H. , Boudreau Stéphane , Hijri Mohamed
Published: June 2015

Coastal sand dunes are extremely dynamic ecosystems, characterized by stark ecological succession gradients. Dune stabilization is mainly attributed to plant growth, but the establishment and survival of dune‐inhabiting vegetation is closely linked to soil microorganisms and to the ecological functions they fulfill. Fungi are particularly important in this context, as some interact intimately with plant roots, while others are critical to soil structure and nutrient availability.

Our study aimed to describe wholly fungal diversity and community composition in a secluded coastal dune ecosystem at eight different stages of succession. We comprehensively sampled a relic foredune plain, which is part of an archipelago in the Gulf of Saint Lawrence (Québec, Canada), by collecting soils from 80 sites and measuring soil characteristics. Soil fungal communities were characterized by pyrosequencing, followed by taxonomic classification and assignment of putative roles. Even though we did not observe clear patterns in diversity, we were able to detect distinct taxonomic and community composition signatures across succession stages, which seemed to translate into variations in fungal life strategies. Our results show that a taxonomically and functionally diverse fungal community exists at each dune succession stage, even in the barren foredunes.
Wild bird‐associated Campylobacter jejuni isolates are a consistent source of human disease, in Oxfordshire, United Kingdom
Authors: Cody Alison J. , McCarthy Noel D. , Bray James E. , Wimalarathna Helen M. L. , Colles Frances M. , Jansen van Rensburg Melissa J. , Dingle Kate E. , Waldenström Jonas , Maiden Martin C. J.
Published: June 2015

The contribution of wild birds as a source of human campylobacteriosis was investigated in Oxfordshire, United Kingdom (UK) over a 10 year period. The probable origin of human Campylobacter jejuni genotypes, as described by multilocus sequence typing, was estimated by comparison with reference populations of isolates from farm animals and five wild bird families, using the STRUCTURE algorithm. Wild bird‐attributed isolates accounted for between 476 (2.1%) and 543 (3.5%) cases annually. This proportion did not vary significantly by study year (P = 0.934) but varied seasonally, with wild bird‐attributed genotypes comprising a greater proportion of isolates during warmer compared with cooler months (P = 0.003). The highest proportion of wild bird‐attributed illness occurred in August (P < 0.001), with a significantly lower proportion in November (P = 0.018). Among genotypes attributed to specific groups of wild birds, seasonality was most apparent for Turdidae‐attributed isolates, which were absent during cooler, winter months. This study is consistent with some wild bird species representing a persistent source of campylobacteriosis, and contributing a distinctive seasonal pattern to disease burden. If Oxfordshire is representative of the UK as a whole in this respect, these data suggest that the national burden of wild bird‐attributed isolates could be in the order of 10 000 annually.
Inferring the evolutionary history of outcrossing populations through computing a multiallelic linkage–linkage disequilibrium map
Authors: Zhu Xuli , Xu Fang , Zhao Shu , Bo Wenhao , Jiang Libo , Pang Xiaoming , Wu Rongling
Published: June 2015

Linkage disequilibrium (LD), the non‐random association of alleles at different loci, has been used as an important parameter to study the genetic diversity and evolutionary history of natural populations. A joint analysis of LD with the linkage of the same marker pair has proven to gain more insight into the genetic signature of population diversification than LD analysis alone.

We develop a unifying framework for simultaneously estimating the linkage and LD across pairs of multiallelic markers. The framework has particular power to construct the LD map from any markers with an arbitrary number of alleles per locus. We provide an efficient strategy to manipulate disequilibrium parameters whose number increases exponentially with the number of alleles.

The model was tested through extensive simulation studies and validated by analysing a real marker data set from a population genetic research project of euphrates poplar, a desert tree, distributed in the north‐western China. For widespread undomesticated natural populations, compared with biallelic markers, multiallelic markers with a high level of polymorphism are more powerful to study their genetic structure and organization of an outcrossing population.

The model developed will potentially have an immediate implication for population and evolutionary genetic studies.
Auditory function following post‐dural puncture headache treated with epidural blood patch. A long‐term follow‐up
Authors: Darvish B. , Dahlgren G. , Irestedt L. , Magnuson A. , Möller C. , Gupta A.
Published: June 2015

Background

Epidural analgesia is commonly used for pain management during labor. Sometimes, accidental dural puncture (ADP) occurs causing severely debilitating headache, which may be associated with transient hearing loss. We investigated if auditory function may be impaired several years after ADP treated with epidural blood patch (EBP).

Methods

Sixty women (ADP group) without documented hearing disability, who received EBP following ADP during labor between the years 2005–2011 were investigated in 2013 for auditory function using the following tests: otoscopic examination, tympanometry, pure tone audiometry, and transient‐evoked otoacoustic emissions. Additionally, they responded to a questionnaire, the Speech, Spatial and Qualities (SSQ) of hearing, concerning perceived hearing impairment. The results were compared to a control group of 20 healthy, non‐pregnant women in the same age group.

Results

The audiometric test battery was performed 5.2 (1.9) years after delivery. No significant differences were found between the ADP and the control groups in tympanometry or otoacoustic emissions. Pure tone audiometry revealed a significant but small (< 5 dB) difference between the ADP and control groups (P < 0.05). The ability to hear speech in noise as measured by SSQ was significantly reduced in the ADP group compared to the control group (P < 0.05).

Conclusions

A minor hearing loss was detected in the ADP group compared to the control group in pure tone audiometry in some women and during speech‐in‐noise component several years after accidental dural puncture treated with an epidural blood patch. This small residual hearing loss has minor clinical significance.
Whole blood glutathione status and ICU morbidity in critically ill children
Authors: Fläring U. , Ekmark L. , Wernerman J. , Rooyackers O.
Published: June 2015

Background

A high reduced glutathione ratio is associated with high mortality in adult ICU patients. Whole blood glutathione status in critically ill children is less well characterized. In this study, whole blood glutathione status in pediatric intensive care (PICU) patients was determined and the relation between the redox status of whole blood glutathione and morbidity was investigated.

Methods

A prospective consecutive cohort of critically ill children (n = 146) admitted to the PICU of a tertiary university hospital, and a reference group of healthy children (n = 60) and healthy adults (n = 10) were included in the study. The concentrations of total and reduced whole blood were determined at admission and patient characteristics were recorded.

Results

A high fraction of reduced glutathione in the glutathione redox status was associated with longer dependency of mechanical ventilation and length of stay in the PICU (P = 0.02 and P = 0.03 respectively). In patients with a prolonged stay in the PICU (> 5 days), a more reduced state of glutathione was seen in patients who had more than two organ failures as compared to patients with one or two failing organs (P < 0.01 and P < 0.05), respectively. A positive correlation was also seen between numbers of organ failures and redox status of glutathione (r  = 0.45, P < 0.001).

Conclusion

A high reduced glutathione ratio was associated with longer PICU stay, duration of mechanical ventilation, and multiple organ failure.
Registration of randomized clinical trials – a challenge
Authors: Østervig R. M. , Sonne A. , Rasmussen L. S.
Published: June 2015

Background

Registration of interventional studies is necessary according to the Declaration of Helsinki but implementation has been a challenge for many journals. Acta Anaesthesiologica Scandinavica (Acta) requires registration for studies conducted after January 1st 2010. We aimed to assess the proportion of correctly registered randomized controlled trials (RCTs) published in Acta from 2009 to 2014.

Methods

We manually searched all Acta issues from 2009 to 2014 for RCTs. Information about timing of data collection and registration in trial registries was extracted. We classified RCTs as correctly registered when it could be verified that patient enrolment was started after registration in a trial registry.

Results

We identified 200 RCTs. Dates for patient enrolment were not specified in 51 (25.5%). The proportion of correctly registered trials increased significantly from 17.1% (19/111) for trials starting enrolment before 2010 to 63.2% after 2010 (24/38, P < 0.01). Most clinical trials were registered at clinicaltrials.gov.

Conclusion

Many published randomized controlled trials from Acta Anaesthesiologica Scandinavica were not adequately registered but the requirement of trial registration has resulted in a significant increase in the proportion of correctly registered trials.
Natural Killer Cells: Key Players in Endometriosis
Authors: Thiruchelvam Uma , Wingfield Mary , O'Farrelly Cliona
Published: June 2015

Endometriosis affects more than 10% of women, causing significant pain and morbidity. It is also a significant cause of infertility. The aetiology of the disease remains an enigma, and the mechanisms responsible for the associated infertility are unclear. A role for immune cells in endometriosis has been postulated, with attention directed towards natural killer (NK) cells and macrophages. NK cells kill tumours and infected cells but also have roles in tissue remodelling in several organs including the uterus and are key to successful pregnancy. Here, we explore evidence (from peer‐reviewed published articles) of phenotypic and functional abnormalities in NK cell subpopulations of women with endometriosis. It is clear that peripheral blood NK cells and peritoneal NK cells have reduced cytotoxic function in women with endometriosis. Uterine NK cells have a vital role in infertility, but very little research has been carried out in this area. We propose that abnormal u NK cell activity may contribute to the pathogenesis of endometriosis and its associated infertility and that future research should focus on this complex area.
A Simple Numerical Body Surface Mapping Parameter Signifies Successful Percutaneous Coronary Artery Intervention
Authors: Simonyi Gábor , Kirschner Róbert , Szűcs Endre , Préda István , Duray Gábor , Medvegy Nóra , Horvath Bálint , Medvegy Mihály
Published: June 2015

Background

In coronary artery disease (CAD), body surface potential mapping (BSPM) may reveal minor electrical potential changes appearing in the depolarization phase even if pathological changes are absent on the conventional 12‐lead ECG. We hypothesized that a simple BSPM parameter, Max/Min signifies successful percutaneous coronary intervention (PCI).

Methods

Ninety‐two adult Caucasian patients with stable CAD and positive exercise test underwent coronary angiography. Seventy patients (age, 59 ± 8; 46 males) were revascularized by PCI (left anterior descending [LAD] in 38, right [RCA] in 17 and left circumflex [LCX] coronary artery in 15). Control groups contained 22 patients (age, 60 ± 8; 14 males) without intervention and 35 healthy subjects (age, 58 ± 2; 15 males). Left ventricular ejection fraction (LVEF, transthoracic echocardiography) and Max/Min BSPM parameter (63‐lead Montreal system) were evaluated before and 4–40 days following coronary angiography. Max/Min was defined by the ratio of the highest maximum to the deepest minimum potential of all leads recorded by BSPM.

Results

Before PCI, Max/Min value of patients with LAD lesion (0.83 [0.74; 0.93]) was significantly lower while that with RCA lesion (1.63 [1.35; 1.99]) was significantly higher than that of healthy group (1.01 [0.970; 1.13]) (P < 0.05) and LVEF was significantly lower in LAD lesion (46.50% [43.00; 51.00]) than in the healthy group (55.00% [50.00; 58.75]) (P < 0.01). Max/Min value significantly increased from 0.83 [0.74; 0.93] to 0.92 [0.82; 0.99] (P < 0.01) following LAD PCI while significantly decreased from 1.63 [1.35; 1.98] to 1.35 [1.21; 1.43] (P < 0.01) post‐RCA PCI. It did not vary significantly, however, either following LCX PCI or without intervention. LVEF significantly increased (from 46.50% [43.00; 51.00] to 49.00% [46.00; 51.00]) only after LAD PCI.

Conclusion

Max/Min parameter is suitable to follow patients after LAD and RCA PCI.
Antibiotic consumption among a Swedish cohort of children born in 2006
Authors: Hellman Jenny , Grape Malin , Ternhag Anders
Published: June 2015

Aim

It is important to measure antibiotic consumption because it contributes to antimicrobial resistance. Our objective was to follow all children born in 2006 in Sweden and to analyse antibiotic consumption during each month of life for the first two years and thereafter for every year during their third to fifth years of life.

Methods

This was a register‐based, open‐cohort study where we used the Swedish Prescribed Drug Register, which covers the whole population, to identify the type and date of purchase of antibiotics for the children in the cohort.

Results

During the first one‐year follow‐up period, 101 555 children up to one year of age were living in Sweden, of which 50 135 were boys and 49 420 were girls. Children consumed the largest amount of antibiotics during their second year of life. In our cohort, 51% received antibiotics at some point during the second year and 24% received multiple treatments. The consumption then dropped with every year of life during the follow‐up.

Conclusion

This study suggests that actions against overprescribing of antibiotics to children should be targeted towards the second year of life in order to have the greatest effect on consumption.
Using isopropyl alcohol impregnated disinfection caps in the neonatal intensive care unit can cause isopropyl alcohol toxicity
Authors: Sauron Charlotte , Jouvet Philippe , Pinard Geneviève , Goudreault Danielle , Martin Brigitte , Rival Bastien , Moussa Ahmed
Published: June 2015

Aim

The safety of SwabCap alcohol impregnated disinfection caps was questioned in our unit because of malfunctions in luer access valves. We examined whether SwabCaps affected the integrity of two luer access valves and were associated with alcohol injected into the lines.

Methods

Our bench test study included seven circuits using SmartSite or CARESITE valves exposed to two environmental temperatures. Passive circuits consisted of a 96‐hour contact system using SwabCap without other interventions. Active circuits consisted of nine sham injections during a 24‐hour period, with the SwabCap replaced after each injection. The active control circuit used isopropyl alcohol impregnated pads to disinfect valves. Isopropyl alcohol was measured at the extremity of all active circuits by gas chromatography.

Results

The visual appearance of all SmartSite valves and 67% of the CARESITE valves was changed by SwabCap use. The mean isopropyl alcohol dosages were 52 mmol/L in the SmartSite and 8 mmol/L in the CARESITE at room temperature and 73 and 7 mmol/L, respectively, at 35°C. No alcohol was found in the control circuit.

Conclusion

The SwabCap altered the valves' appearance and allowed significant amounts of isopropyl alcohol to be injected. It should not be used for neonates without further research.
Efficacy and safety of anti‐TNF therapy in elderly patients with inflammatory bowel disease
Authors: Lobatón T. , Ferrante M. , Rutgeerts P. , Ballet V. , Van Assche G. , Vermeire S.
Published: June 2015

Background

The general increased life expectancy is reflected in the age of patients with inflammatory bowel disease (IBD). The knowledge about efficacy and safety of anti‐tumour necrosis factor (TNF) therapy in elderly is scarce and conflicting.

Aim

To assess the efficacy and safety of anti‐TNF therapy in elderly patients taking into account eventual comorbidity.

Methods

Observational and retrospective single‐centred study where 66 IBD patients initiating anti‐TNF treatment at age ≥65 years (cases: ≥65 anti‐TNF) were compared with 112 IBD patients initiating anti‐TNF <65 years (controls <65 anti‐TNF) and 61 anti‐TNF naïve IBD patients treated with immunosuppressants (IMS) and/or corticosteroids (CS) ≥65 years (controls ≥65 IMS/CS). Controls were matched to cases for IBD type, follow‐up, disease duration and anti‐TNF type. Comorbidity was assessed by using the Charlson Comorbidity Index (CCI). Both efficacy and safety of treatment were adjusted for comorbidity.

Results

The short‐term clinical response to anti‐TNF at 10 weeks was significantly lower in cases: ≥65 anti‐TNF (68% vs. 89%; P < 0.001), whereas at ≥6 months, differences were not significant (79.5% vs. 82.8%; P = 0.639). The risk for any severe adverse events was higher in cases: ≥65 anti‐TNF than in controls <65 anti‐TNF (RR = 4.7; P < 0.001) or controls ≥65 IMS/CS (RR = 3.09; P = 0.0008). Age older than 65 and CCI > 0 were independent risk factors for malignancy and mortality regardless of the medication.

Conclusion

Elderly patients treated with anti‐TNF have a lower rate of short‐term clinical response and a higher rate of severe adverse events than the younger patients under the same treatment.
Moral Philosophy, Moral Expertise, and the Argument from Disagreement
Authors: Cross Ben
Published: June 2015

Several recent articles have weighed in on the question of whether moral philosophers can be counted as moral experts. One argument denying this has been rejected by both sides of the debate. According to this argument, the extent of disagreement in modern moral philosophy prevents moral philosophers from being classified as moral experts. Call this the Argument From Disagreement (AD). In this article, I defend a version of AD. Insofar as practical issues in moral philosophy are characterized by disagreement between moral philosophers who are more or less equally well credentialed on the issue, non‐philosophers have no good reasons to defer to their views.
Fear of Childbirth and Preference for Cesarean Delivery Among Young American Women Before Childbirth: A Survey Study
Authors: Stoll Kathrin , Edmonds Joyce Katherine , Hall Wendy A.
Published: June 2015

Background

Fear of birth and mode of delivery preferences are similar among pregnant and nonpregnant women, suggesting that attitudes toward birth are formed in young adulthood or earlier. Understanding why some young women fear birth and prefer obstetric interventions can inform public health initiatives aimed at reducing fear and promoting birth as a normal life event.

Methods

We conducted an online survey with 752 American nulliparous young women to assess their preferences and attitudes toward childbirth. We identified explanatory variables associated with reported fear of childbirth and cesarean delivery (CD) preferences.

Results

A preference for CD was reported by 14 percent of young women and 27 percent had scores indicating elevated fear of birth. Fear of birth increased the likelihood of cesarean preference (adjusted relative risk (ARR) 3.84 [95% CI 2.49–5.95]) as did a family history of CD (ARR 1.65 [95% CI 1.13–2.42]). The likelihood of reporting elevated childbirth fear was increased among young women who reported concerns about the physical changes pregnancy and birth have on women's bodies (ARR 2.04 [95% CI 1.50–2.78]). Young women who reported a high degree of confidence in their knowledge about childbirth were significantly less likely to report childbirth fear (ARR 0.61 [95% CI 0.42–0.87]). Access to childbirth information was also associated with a decreased likelihood of fear of birth (ARR 0.75 [95% CI 0.59–0.95]).

Conclusions

Young women reporting high levels of childbirth fear are nearly four times more likely to prefer a CD. Specific fears, such as worries over the influence of pregnancy and birth on the female body, need to be addressed before pregnancy.
Brefeldin A exerts differential effects on anaplastic lymphoma kinase positive anaplastic large cell lymphoma and classical Hodgkin lymphoma cell lines
Authors: Toda Takashi , Watanabe Mariko , Kawato Junji , Kadin Marshall E. , Higashihara Masaaki , Kunisada Takao , Umezawa Kazuo , Horie Ryouichi
Published: June 2015

To obtain further insights into the biological differences of anaplastic lymphoma kinase positive anaplastic large cell lymphoma (ALK+ ALCL) and classical Hodgkin lymphoma (HL), we screened microbial culture filtrates to search for compounds that would exert a significantly greater effect on the viability of ALK+ ALCL cell lines compared to HL cell lines and identified Brefeldin A (BFA) as a suitable candidate. BFA inhibited phosphorylation of ALK and its downstream molecule, signal transducer and activator of transcription 3 (STAT3), one of the central pathways for the survival of ALK+ ALCL cells. In HL cell lines BFA did not affect CD30 expression or constitutive nuclear factor (NF)‐κB activity, both of which are critical for HL cell survival. BFA induced disruption of the Golgi apparatus in ALK+ ALCL cell lines, which was accompanied by a decrease in active ADP‐ribosylation factor 1 (ARF1), whereas BFA had no significant effect on these parameters in HL cell lines. These results add extra insights into the biological distinction between ALK+ ALCL and HL cells and highlight the Golgi apparatus as a target for the treatment of ALK+ ALCL.