bluuebunny/crossref_metadata_2025 huggingface dataset:
Confounder selection via penalized credible regions
Authors: Wilson Ander , Reich Brian J.
Published: August 2014

When estimating the effect of an exposure or treatment on an outcome it is important to select the proper subset of confounding variables to include in the model. Including too many covariates increases mean square error on the effect of interest while not including confounding variables biases the exposure effect estimate. We propose a decision‐theoretic approach to confounder selection and effect estimation. We first estimate the full standard Bayesian regression model and then post‐process the posterior distribution with a loss function that penalizes models omitting important confounders. Our method can be fit easily with existing software and in many situations without the use of Markov chain Monte Carlo methods, resulting in computation on the order of the least squares solution. We prove that the proposed estimator has attractive asymptotic properties. In a simulation study we show that our method outperforms existing methods. We demonstrate our method by estimating the effect of fine particulate matter (PM) exposure on birth weight in Mecklenburg County, North Carolina.
How can weight‐loss app designers' best engage and support users? A qualitative investigation
Authors: Tang Jason , Abraham Charles , Stamp Elena , Greaves Colin
Published: August 2014

Objectives

This study explored young adults' experiences of using e‐health internetbased computer or mobile phone applications (apps) and what they valued about those apps.

Design and methods

A qualitative design was used. Semi‐structured interviews were conducted with a community sample of 19 young adults who had used a publicly available phone or internet‐based application. Transcripts were analysed using thematic analysis.

Results

Participants valued an attractive user interface. Structure, ease of use, personalised features and accessibility (including dual phone‐computer access) were all important to participants and users indicated that continued use depended on these design features. Many believed that a focus on calorie counting was too limiting. Some users mentioned behaviour change strategies and known behaviour change techniques utilised by apps including; self‐monitoring, goal setting and behavioural feedback. Only a few users reported positive changes in physical activity levels.

Conclusions

Use of particular design features and application of evidence‐based behaviour change techniques could optimise continued use and the effectiveness of internet/smart phone interventions.

Statement of contribution

What is already known on this subject?

E‐health is increasingly used to deliver weight loss/control programs.

Most e‐health programs have not been founded on evidence‐based designs and it is unclear what features and functions users find useful or not so useful.

What does this study add?

Weight loss app users valued structure, ease of use, personalised features and accessibility.

Goal setting and feedback on calorie intake/energy balance were the most widely used behaviour change techniques.

Designers should consider an extensive food database, a food scanner, and provision of diaries.
Patient‐reported outcomes of dental implant therapy in a large randomly selected sample
Authors: Derks Jan , Håkansson Jan , Wennström Jan L. , Klinge Björn , Berglundh Tord
Published: August 2014

Background

In addition to traditional clinical parameters, the need to include patient‐reported assessments into dental implant research has been emphasized.

Aim

The aim of this study was to evaluate patient‐reported outcomes following implant‐supported restorative therapy in a randomly selected patient sample.

Material and Methods

Four thousand seven hundred and sixteen patients were randomly selected from the data register of the Swedish Social Insurance Agency. A questionnaire containing 10 questions related to implant‐supported restorative therapy was mailed to each of the individuals about 6 years after therapy. Associations between questionnaire data, and (i) patient‐related, (ii) clinician‐related and (iii) therapy‐related variables were identified by multivariate analyses.

Results

Three thousand eight hundred and twenty‐seven patients (81%) responded to the questionnaire. It was demonstrated that the overall satisfaction among patients was high. Older patients presented with an overall more positive perception of the results of the therapy than younger patients and males were more frequently satisfied in terms of esthetics than females. While clinical setting did not influence results, patients treated by specialist dentists as opposed to general practitioners reported a higher frequency of esthetic satisfaction and improved chewing ability. In addition, patients who had received extensive implant‐supported reconstructions, in contrast to those with small reconstructive units, reported more frequently on improved chewing ability and self‐confidence but also to a larger extent on implant‐related complications.

Conclusion

It is suggested that patient‐perceived outcomes of implant‐supported restorative therapy are related to (i) age and gender of the patient, (ii) the extent of restorative therapy and (iii) the clinician performing the treatment.
A qualitative investigation of obese women's experiences of effective and ineffective social support for weight management
Authors: Zwickert K. , Rieger E.
Published: August 2014

An obese individual's social context influences the extent to which they engage in weight control behaviors. Although the available literature acknowledges the importance of social support for weight management, detailed analyses of obese individuals' experiences of social support for weight loss and/or weight loss maintenance have not been undertaken. Using a qualitative approach, this study presents 22 Australian obese women's perspectives of the availability and effectiveness of social support for weight control. Three superordinate categories, namely, ineffective support, effective support and personal barriers to accessing support, and 12 subcategories were identified. Participants reported minimal access to quality support for weight management, while also suggesting ways in which obese women themselves may hamper significant others' provision of effective support. The results support the investigation of interventions designed to enhance the skills of significant others in assisting obese individuals with weight management.
Colchicine levels in chronic kidney diseases and kidney transplant recipients using tacrolimus
Authors: Amanova Anara , Kendi Celebi Zeynep , Bakar Filiz , Caglayan Mehmet G. , Keven Kenan
Published: August 2014

Background

Tacrolimus is a CYP3A4 inhibitor and can alter colchicine metabolism. In this study, we aimed to evaluate plasma colchicine levels in different stages of kidney disease as well as in kidney transplant (KTx) recipients using tacrolimus.

Method

This study included six familial Mediterranean fever (FMF) patients with normal glomerular filtration rate (GFR) as controls, three patients with low GFR, six FMF patients on hemodialysis (HD), and six FMF patients who were KTx recipients using tacrolimus. After a three‐d washout period, plasma colchicine levels were measured at 0 (pre‐dose), one, two, four, eight, and 24 h post‐dose of 1 mg oral colchicine. Area under the curve 0–24 h (AUC0–24) and maximum concentration (Cmax) were evaluated and compared between the groups.

Results

Colchicine AUC0–24 was six‐fold higher in HD (p < 0.001) and three‐fold higher in KTx recipients (p < 0.001) when compared to the control. The low GFR group had mildly higher AUC0–24 than the control group. Cmax levels were also higher in HD (p = 0.011) and KTx recipient (p = 0.06) groups and mildly elevated in low GFR patients in comparison with controls.

Conclusion

Colchicine AUC0–24 and Cmax were significantly increased in HD patients and KTx recipients using tacrolimus. Therefore, dose adjustments are needed to avoid toxicity in both circumstances.
Pre‐existing anti‐HLA antibodies negatively impact survival of pediatric aplastic anemia patients undergoing HSCT
Authors: Zhu Hua , He Jun , Cai Junchao , Yuan Xiaoni , Jiang Hua , Luo Changying , Wang Jianmin , Luo Chengjuan , Pan Zhijuan , Terasaki Paul I. , Ding Lixia , Chen Jing
Published: August 2014

Graft failure and survival are the major problems for patients with aplastic anemia undergoing hematopoietic stem cell transplantation (HSCT). Previous studies showed that anti‐HLA antibodies negatively impact engraftment in HSCT. This retrospective study of 51 pediatric patients with acquired aplastic anemia who underwent allogeneic HSCT at a single institution between 2006 and 2012 investigated the influence of anti‐HLA antibodies on the outcome of HSCT. Serum samples collected before HSCT were tested for the presence of anti‐HLA antibodies. Pre‐existing anti‐HLA antibodies were detected in 54.9% (28/51) of patients, among whom 39.2% (20/51) had anti‐HLA class I antibodies. Anti‐HLA antibodies were associated with worse five‐yr survival (78.6% vs. 100%, p = 0.021) and higher treatment‐related mortality (21.4% vs. 0%, p = 0.028) compared with antibody‐negative patients. Anti‐HLA class I antibody‐positive patients had poorer five‐yr survival (75.0%) than anti‐HLA class I&II antibody‐positive and antibody‐negative patients (87.5% and 100.0%, respectively, p = 0.039). Presence of anti‐HLA class I antibodies (p = 0.024) and older age (10 yr or more; p = 0.027) significantly increased the risk of post‐HSCT mortality. Pre‐existing anti‐HLA antibodies negatively affect the outcome of HSCT in pediatric patients with aplastic anemia. Routine testing for anti‐HLA antibodies concurrent with efficient treatment should be conducted prior to HSCT.
Role of BRAF molecular analysis in the management of papillary thyroid carcinoma: analysis of cytological and histological samples
Authors: Capelli L. , Marfisi C. , Puccetti M. , Saragoni L. , De Paola F. , Zaccaroni A. , Chiadini E. , Gagliardi L. , Ferretti G. , Zoli W. , Ulivi P.
Published: August 2014

Background

Although fine needle aspiration (FNA) is the standard diagnostic test for the characterization of a suspicious thyroid nodule, in some cases cytological evaluation is inconclusive. The aim of this study was to determine the role of BRAF mutation in aiding diagnosis and to verify whether archival cytological samples could be suitable for molecular analysis.

Methods

Eighty‐five patients with suspicious (Thy4) or follicular (Thy3) lesions on cytology were resubmitted to a second FNA for BRAF mutation analysis. Of these, 56 subsequently underwent surgery. The usefulness of archival samples for molecular analysis was also studied in a second cohort of 42 patients with a confirmed diagnosis of papillary thyroid carcinoma for whom both archived paraffin‐embedded histological samples and cytological smears were available. A further 15 patients with paired fresh FNA and archived cytological and histological samples were recruited.

Results

BRAF mutation was found in the fresh FNA samples from 10 of 56 patients who had surgery with previous inconclusive cytology (4/45, 9%, Thy3 and 6/11, 55%, Thy4). The BRAF test showed a specificity and positive predictive value of 100% (26/26 and 10/10, respectively), sensitivity of 33% (10/30) and negative predictive value of 57% (26/46). There was absolute concordance between the BRAF results obtained with 42 histological and cytological archived samples. BRAF analysis on 15 archived cytological samples showed absolute concordance with histology, whereas there was one false negative on the matched fresh FNA.

Conclusion

BRAF analysis is a highly specific test that can facilitate cytological diagnosis in some cases and can also be performed on archived cytological samples.
Competing uses for China's straw: the economic and carbon abatement potential of biochar
Authors: Clare Abbie , Shackley Simon , Joseph Stephen , Hammond James , Pan Genxing , Bloom Anthony
Published: August 2014

China is under pressure to improve its agricultural productivity to keep up with the demands of a growing population with increasingly resource‐intensive diets. This productivity improvement must occur against a backdrop of carbon intensity reduction targets, and a highly fragmented, nutrient‐inefficient farming system. Moreover, the Chinese government increasingly recognizes the need to rationalize the management of the 800 million tonnes of agricultural crop straw that China produces each year, up to 40% of which is burned in‐field as a waste. Biochar produced from these residues and applied to land could contribute to China's agricultural productivity, resource use efficiency and carbon reduction goals. However competing uses for China's straw residues are rapidly emerging, particularly from bioenergy generation. Therefore it is important to understand the relative economic viability and carbon abatement potential of directing agricultural residues to biochar rather than bioenergy. Using cost‐benefit analysis (CBA) and life‐cycle analysis (LCA), this paper therefore compares the economic viability and carbon abatement potential of biochar production via pyrolysis, with that of bioenergy production via briquetting and gasification. Straw reincorporation and in‐field straw burning are used as baseline scenarios. We find that briquetting straw for heat energy is the most cost‐effective carbon abatement technology, requiring a subsidy of $7 MgCO2e−1 abated. However China's current bioelectricity subsidy scheme makes gasification (NPV $12.6 million) more financially attractive for investors than both briquetting (NPV $7.34 million), and pyrolysis ($−1.84 million). The direct carbon abatement potential of pyrolysis (1.06 MgCO2e per odt straw) is also lower than that of briquetting (1.35 MgCO2e per odt straw) and gasification (1.16 MgCO2e per odt straw). However indirect carbon abatement processes arising from biochar application could significantly improve the carbon abatement potential of the pyrolysis scenario. Likewise, increasing the agronomic value of biochar is essential for the pyrolysis scenario to compete as an economically viable, cost‐effective mitigation technology.
Biosecurity: securing circulations from the microbe to the macrocosm
Authors: Barker Kezia
Published: August 2014

Biosecurity poses the problem of how to live with and manage the complex, contingent and emergent circulations of life. This excess of circulating life manifests in a host of different circumstances: from the biopolitical attempt to sort ‘good’ from ‘bad’ circulations disrupted by a zoonotic virus making use of air transportation networks; to fluid microbial topologies that challenge the bounded individual body; from a biosurveillance network signal prompting anticipatory governance responses; to the intersection of financial and microbial geographies in the risky practices of industrial agribusiness. The ‘shock of the real’ from these eventful and everyday occurrences not only illuminates empirical connections between circulating bodies, microbes, knowledges, electronic signals, seeds, capital, food and anxiety, but also highlights that the complexity of securing processes that are elaborating new forms of life cannot be fully captured through any one theoretical lens. In this review article I consider the burgeoning field of biosecurity studies through attention to these differing concepts of circulation, and suggest neglected circulations for future research.
Immunohistochemical panel for the diagnosis of Hirschsprung's disease using antibodies to MAP2, calretinin, GLUT1 and S100
Authors: Bachmann Leonhard , Besendörfer Manuel , Carbon Roman , Lux Philipp , Agaimy Abbas , Hartmann Arndt , Rau Tilman T
Published: August 2014

Aims

The diagnosis of Hirschsprung's disease is currently based on the identification of aganglionosis and the presence of an increase in acetylcholinesterase‐positive hypertrophic nerve fibres in the large bowel submucosa. However, acetylcholinesterase staining is laborious and requires a skilled technician. The aim of this study was to identify a method for diagnosing Hirschsprung's disease reliably using an immunohistochemical panel of recently proposed markers.

Methods and results

Sixty‐nine specimens from 37 patients were evaluated. MAP2 and calretinin antibodies were shown to stain ganglia reliably in the submucosal and myenteric plexuses of normal tissue. By contrast, reduced staining of ganglia was observed in patients with Hirschsprung's disease. Staining for GLUT1 and S100 was used to evaluate the number and thickness of nerve fibres. Gain of GLUT1 and S100 expression was in contrast to the loss of calretinin and MAP2. Hypertrophic submucosal nerve fibres in Hirschsprung's disease develop a perineurium with a ring‐like GLUT1 staining pattern similar in size and intensity to that observed in deeper subserosal tissue.

Conclusions

The diagnosis of Hirschsprung's disease using immunohistochemical panels could be as accurate as with conventional frozen section techniques. In particular, the use of a combination of markers for ganglia and hypertrophic nerve fibres highlighting a prominent perineurium in Hirschsprung's disease could be an alternative method.
Primary cutaneous anaplastic large cell lymphomas with 6p25.3 rearrangement exhibit particular histological features
Authors: Onaindia Arantza , Montes‐Moreno Santiago , Rodríguez‐Pinilla Socorro M , Batlle Ana , González de Villambrosía Sonia , Rodríguez Antonio M , Alegre Víctor , Bermúdez Glenda M , González‐Vela Carmen , Piris Miguel A
Published: August 2014

Aims

CD30‐positive primary cutaneous lymphoproliferative disorders include several entities with differing clinical presentation but overlapping histological features, including lymphomatoid papulosis and primary cutaneous anaplastic large cell lymphoma (C‐ALCL). DUSP22–IRF4 locus translocation is present in 20–57% of C‐ALCLs, and has also been described in a series of 11 lymphomatoid papulosis patients, where it was associated with a particular biphasic histological pattern, including pagetoid reticulosis‐type epidermal infiltration. We aimed to study whether the presence of this translocation may define distinctive histological features in C‐ALCL.

Methods and results

We collected three cases of C‐ALCL with histological features similar to those described in the new variant of lymphomatoid papulosis with 6p25.3 rearrangement. We studied their histological features and immunophenotype, using a panel of antibodies against CD30, TCR‐βF1, TCR‐γ, CD4, CD8, CD20, Ki‐67 and ALK. FISH analyses were performed using an IRF4–DUSP22 break‐apart probe for the study of the 6p25.3 rearrangement. FISH results were positive in the three cases, which all showed distinctive histological and immunohistochemical features: a diffuse dermal infiltrate of atypical medium‐to‐large cells, and marked epidermotrophism with small, atypical intra‐epidermal lymphocytes.

Conclusions

Our findings suggest that the presence of 6p25.3 rearrangement might be related to this particular biphasic pattern.
Transcription activator‐like effector nuclease (TALEN)‐mediated female‐specific sterility in the silkworm, Bombyx mori
Authors: Xu J. , Wang Y. , Li Z. , Ling L. , Zeng B. , James A. A. , Tan A. , Huang Y.
Published: August 2014

Engineering sex‐specific sterility is critical for developing transgene‐based sterile insect technology. Targeted genome engineering achieved by customized zinc‐finger nuclease, transcription activator‐like effector nuclease (TALEN) or clustered, regularly interspaced, short palindromic repeats/Cas9 systems has been exploited extensively in a variety of model organisms; however, screening mutated individuals without a detectable phenotype is still challenging. In addition, genetically recessive mutations only detectable in homozygotes make the experiments time‐consuming. In the present study, we model a novel genetic system in the silkworm, Bombyx mori, that results in female‐specific sterility by combining transgenesis with TALEN technologies. This system induces sex‐specific sterility at a high efficiency by targeting the female‐specific exon of the B. mori doublesex (Bmdsx) gene, which has sex‐specific splicing isoforms regulating somatic sexual development. Transgenic animals co‐expressing TALEN left and right arms targeting the female‐specific Bmdsx exon resulted in somatic mutations and female mutants lost fecundity because of lack of egg storage and abnormal external genitalia. The wild‐type sexual dimorphism of abdominal segment was not evident in mutant females. In contrast, there were no deleterious effects in mutant male moths. The current somatic TALEN technologies provide a promising approach for future insect functional genetics, thus providing the basis for the development of attractive genetic alternatives for insect population management.
Innate immune regulation by STAT‐mediated transcriptional mechanisms
Authors: Li Haiyan S. , Watowich Stephanie S.
Published: August 2014

The term innate immunity typically refers to a quick but non‐specific host defense response against invading pathogens. The innate immune system comprises particular immune cell populations, epithelial barriers, and numerous secretory mediators including cytokines, chemokines, and defense peptides. Innate immune cells are also now recognized to play important contributing roles in cancer and pathological inflammatory conditions. Innate immunity relies on rapid signal transduction elicited upon pathogen recognition via pattern recognition receptors (PRRs) and cell:cell communication conducted by soluble mediators, including cytokines. A majority of cytokines involved in innate immune signaling use a molecular cascade encompassing receptor‐associated Jak protein tyrosine kinases and STAT (signal transducer and activator of transcription) transcriptional regulators. Here, we focus on roles for STAT proteins in three major innate immune subsets: neutrophils, macrophages, and dendritic cells (DCs). While knowledge in this area is only now emerging, understanding the molecular regulation of these cell types is necessary for developing new approaches to treat human disorders such as inflammatory conditions, autoimmunity, and cancer.
Complex interactions of transcription factors in mediating cytokine biology in T cells
Authors: Li Peng , Spolski Rosanne , Liao Wei , Leonard Warren J.
Published: August 2014

T‐helper (Th) cells play critical roles within the mammalian immune system, and the differentiation of naive CD4+ T cells into distinct T‐helper subsets is critical for normal immunoregulation and host defense. These carefully regulated differentiation processes are controlled by networks of cytokines, transcription factors, and epigenetic modifications, resulting in the generation of multiple CD4+ T‐cell subsets, including Th1, Th2, Th9, Th17, Treg, and Tfh cells. In this review, we discuss the roles of transcription factors in determining the specific type of differentiation and in particular the role of interleukin‐2 (IL‐2) in promoting or inhibiting Th differentiation. In addition to discussing master regulators and subset‐specific transcription factors for distinct T‐helper cell populations, we focus on signal transducer and activator of transcription (STAT) proteins and on the cooperative action of interferon regulatory factor 4 (IRF4) with activator protein 1 (AP‐1) family proteins and STAT3 in the assembly of complexes that broadly influence T‐cell differentiation.
Orchestration of plasma cell differentiation by Bach2 and its gene regulatory network
Authors: Igarashi Kazuhiko , Ochiai Kyoko , Itoh‐Nakadai Ari , Muto Akihiko
Published: August 2014

Bach2 is a basic region‐leucine zipper (bZip) transcription factor that forms heterodimers with small Maf oncoproteins and binds to target genes, thus repressing their expression. Bach2 is required for class switch recombination (CSR) and somatic hypermutation (SHM) of immunoglobulin genes in activated B cells. Bach2 represses the expression of Prdm1 encoding Blimp‐1 repressor and thereby inhibits terminal differentiation of B cells to plasma cells. This causes a delay in the induction of Prdm1, thereby securing a time window for the expression of Aicda encoding activation‐induced cytidine deaminase (AID) required for both CSR and SHM. Based on the characteristics of a gene regulatory network (GRN) involving Bach2 and Prdm1 and its dynamics, a ‘delay‐driven diversity’ model was introduced to explain the responses of activated B cells. Bach2 is also required for the proper differentiation and function of peripheral T cells. In the absence of Bach2, CD4+ T cells show increased differentiation to effector cells producing higher levels of Th2‐related cytokines, such as IL‐4 and IL‐10, and a reduction in the generation of regulatory T cells. Bach2 represses many genes in T cells, including Prdm1, suggesting that the Bach2‐Prdm1 pathway is also important in maintaining the homeostasis of T cells. Furthermore, Bach2 is essential for the function of alveolar macrophages. Therefore, Bach2 orchestrates both acquired and innate immunity at multiple points. Its connection with disease is also reviewed in this report.
Staying innate: transcription factor maintenance of innate lymphoid cell identity
Authors: Di Santo James P.
Published: August 2014

Innate and adaptive lymphocytes are characterized by phenotypic and functional characteristics that result from genomic rearrangements (in the case of antigen‐specific B and T cells) coupled with selective gene expression patterns that are generated in a context‐dependent fashion. Cell‐intrinsic expression of transcription factors (TFs) play a critical role in the regulation of gene expression that establish the distinct lymphoid subsets but also have been proposed to play an ongoing role in the maintenance of lineage‐associated transcriptional signatures that comprise lymphocyte identity. This is the case for CD19+ B cells that require Pax5 expression throughout their lifespan, as well as for diverse T‐helper subsets that have specialized immune functions. Innate lymphoid cells (ILCs) comprise diverse effectors cells that differentiate under TF control and have critical roles in the early stages of immune responses. In this review, ILC development is reviewed and the requirement for persistent TF expression in the maintenance of transcriptional signatures that define ILC identity is explored.
ID'ing innate and innate‐like lymphoid cells
Authors: Verykokakis Mihalis , Zook Erin C. , Kee Barbara L.
Published: August 2014

The immune system can be divided into innate and adaptive components that differ in their rate and mode of cellular activation, with innate immune cells being the first responders to invading pathogens. Recent advances in the identification and characterization of innate lymphoid cells have revealed reiterative developmental programs that result in cells with effector fates that parallel those of adaptive lymphoid cells and are tailored to effectively eliminate a broad spectrum of pathogenic challenges. However, activation of these cells can also be associated with pathologies such as autoimmune disease. One major distinction between innate and adaptive immune system cells is the constitutive expression of ID proteins in the former and inducible expression in the latter. ID proteins function as antagonists of the E protein transcription factors that play critical roles in lymphoid specification as well as B‐ and T‐lymphocyte development. In this review, we examine the transcriptional mechanisms controlling the development of innate lymphocytes, including natural killer cells and the recently identified innate lymphoid cells (ILC1, ILC2, and ILC3), and innate‐like lymphocytes, including natural killer T cells, with an emphasis on the known requirements for the ID proteins.
Deciphering the epigenetic code of T lymphocytes
Authors: Allan Rhys S. , Nutt Stephen L.
Published: August 2014

The multiple lineages and differentiation states that constitute the T‐cell compartment all derive from a common thymic precursor. These distinct transcriptional states are maintained both in time and after multiple rounds of cell division by the concerted actions of a small set of lineage‐defining transcription factors that act in conjunction with a suite of chromatin‐modifying enzymes to activate, repress, and fine‐tune gene expression. These chromatin modifications collectively provide an epigenetic code that allows the stable and heritable maintenance of the T‐cell phenotype. Recently, it has become apparent that the epigenetic code represents a therapeutic target for a variety of immune cell disorders, including lymphoma and acute and chronic inflammatory diseases. Here, we review the recent advances in epigenetic regulation of gene expression, particularly as it relates to the T‐cell differentiation and function.
Mi‐2/NuRD chromatin remodeling complexes regulate B and T‐lymphocyte development and function
Authors: Dege Carissa , Hagman James
Published: August 2014

Mi‐2/nucleosomal remodeling and deacetylase (NuRD) complexes are important epigenetic regulators of chromatin structure and gene expression. Mi‐2/NuRD complexes are an assemblage of proteins that combine key epigenetic regulators necessary for (i) histone deacetylation and demethylation, (ii) binding to methylated DNA, (iii) mobilization of nucleosomes, and (iv) recruitment of additional regulatory proteins. Depending on their context in chromatin, Mi‐2/NuRD complexes either activate or repress gene transcription. In this regard, they are important regulators of hematopoiesis and lymphopoiesis. Mi‐2/NuRD complexes maintain pools of hematopoietic stem cells. Specifically, components of these complexes control multiple stages of B‐cell development by regulating B‐cell specific transcription. With one set of components, they inhibit terminal differentiation of germinal center B cells into plasma B cells. They also mediate gene repression together with Blimp‐1 during plasma cell differentiation. In cooperation with Ikaros, Mi‐2/NuRD complexes also play important roles in T‐cell development, including CD4 versus CD8 fate decisions and peripheral T‐cell responses. Dysregulation of NuRD during lymphopoiesis promotes leukemogenesis. Here, we review general properties of Mi‐2/NuRD complexes and focus on their functions in gene regulation and development of lymphocytes.
Incisional negative pressure wound therapy after hemiarthroplasty for femoral neck fractures – reduction of wound complications
Authors: Pauser Johannes , Nordmeyer Matthias , Biber Roland , Jantsch Jonathan , Kopschina Carsten , Bail Hermann J , Brem Matthias H
Published: August 2014

The aim of the study was to evaluate the use of incisional negative pressure wound therapy (iNPWT) in wound healing after femoral neck fracture (FNF) treated with hip hemiarthroplasty (HA) and its influence on postoperative seromas, wound secretion, as well as time and material consumption for dressing changes. The study is a prospective randomised evaluation of iNPWT in patients with large surgical wounds after FNF. Patients were randomised either to be treated by iNPWT (group A) or a standard wound dressing (group B). Follow‐up included ultrasound measurements of seroma volumes on postoperative days 5 and 10, duration of wound secretion, and time and material spent for wound dressing changes. For comparison of the means, we used the t‐test for independent samples, P > 0·05 was considered significant. There were 21 patients randomised in this study. Group A (11 patients, 81·6 ± 5·2 years of age) developed a seroma of 0·257 ± 0·75 cm3 after 5 days and had a secretion of 0·9 ± 1·0 days, and the total time for dressing changes was 14·8 ± 3·9 minutes, whereas group B (ten patients, 82·6 ± 8·6 years of age) developed a seroma of 3·995 ± 5·01 cm3 after 5 days and had a secretion of 4·3 ± 2·45 days, and the total time for dressing changes was 42·9 ± 11·0 minutes. All mentioned differences were significant. iNPWT has been used on many different types of traumatic and non‐traumatic wounds. This prospective, randomised study has demonstrated decreased development of postoperative seromas, reduction of total wound secretion days and reduction of needed time for dressing changes.
Large Strain Response and Fatigue‐Resistant Behavior in Ternary Bi0.5Na0.5TiO3–BaTiO3–Bi(Zn0.5Ti0.5)O3 Solid Solutions
Authors: Li Yan , Wang Feifei , Ye Xiang , Xie Yiqun , Tang Yanxue , Sun Dazhi , Shi Wangzhou , Zhao Xiangyong , Luo Haosu
Published: August 2014

A ternary solid solution (1 − x)(0.88Bi0.5Na0.5TiO3–0.12BaTiO3)‐xBi(Zn0.5Ti0.5)O3 (BNBZT, BNBZTx) was designed and fabricated using the traditional solid‐state reaction method. The temperature and composition dependence of dielectric, ferroelectric, piezoelectric, and fatigue properties were systematically investigated and a schematic phase diagram was proposed. The substitution with Bi(Zn0.5Ti0.5)O3 was found to shift the phase transition (ferroelectric tetragonal to relaxor pseudocubic phase) to lower temperatures. At a critical composition x of 0.05, large electric‐field‐induced strain response with normalized strain Smax/Emax as high as 526 pm/V was obtained under a moderate field of 4 kV/mm around room temperature. The strain exhibited good temperature stability within the temperature range of 25°C–120°C. In addition, excellent fatigue‐resistant behavior was observed in the proposed BNBZT solid solution after 106 bipolar cycles. These give the BNBZT system great potential as environmental friendly solid‐state actuator.
Mothering, fathering, and the regulation of negative and positive emotions in high‐functioning preschoolers with autism spectrum disorder
Authors: Hirschler‐Guttenberg Yael , Golan Ofer , Ostfeld‐Etzion Sharon , Feldman Ruth
Published: August 2014

Background

Children with autism spectrum disorder (ASD) exhibit difficulties in regulating emotions and authors have called to study the specific processes underpinning emotion regulation (ER) in ASD. Yet, little observational research examined the strategies preschoolers with ASD use to regulate negative and positive emotions in the presence of their mothers and fathers.

Methods

Forty preschoolers with ASD and 40 matched typically developing children and their mothers and fathers participated. Families were visited twice for identical battery of paradigms with mother or father. Parent–child interactions were coded for parent and child behaviors and children engaged in ER paradigms eliciting negative (fear) and positive (joy) emotions with each parent. ER paradigms were microcoded for negative and positive emotionality, ER strategies, and parent regulation facilitation.

Results

During free play, mothers' and fathers' sensitivity and warm discipline were comparable across groups; however, children with ASD displayed lower positive engagement and higher withdrawal. During ER paradigms, children with ASD expressed less positive emotionality overall and more negative emotionality during fear with father. Children with ASD used more simple self‐regulatory strategies, particularly during fear, but expressed comparable levels of assistance seeking behavior toward mother and father in negative and positive contexts. Parents of children with ASD used less complex regulation facilitation strategies, including cognitive reappraisal and emotional reframing, and employed simple tactics, such as physical comforting to manage fear and social gaze to maintain joy.

Conclusion

Findings describe general and parent‐ and emotion‐specific processes of child ER and parent regulation facilitation in preschoolers with ASD. Results underscore the ability of such children to seek parental assistance during moments of high arousal and the parents' sensitive adaptation to their children's needs. Reduced positive emotionality, rather than increased negative reactivity and self‐regulatory efforts, emerges as the consistent element associated with ER processes in this group.
Primary Care Availability and Emergency Department Use by Older Adults: A Population‐Based Analysis
Authors: Hunold Katherine M. , Richmond Natalie L. , Waller Anna E. , Cutchin Malcolm P. , Voss Paul R. , Platts‐Mills Timothy F.
Published: August 2014

Objectives

To assess the relationship between the number of primary care providers (PCPs) in an area and emergency department (ED) visits by older adults.

Design

Population‐based cross‐sectional observational study.

Setting

Nonfederal EDs in North Carolina in 2010.

Participants

All older adults (n = 640,086) presenting to a nonfederal ED in North Carolina in 2010.

Measurements

The primary outcome was the number of ED visits by older adults in each ZIP code per 100 adults aged 65 and older living in that ZIP code. A secondary outcome was the number of ED visits not resulting in hospital admission per 100 older adults. The primary predictor variable was the number of PCPs per 100 older residents for each ZIP code. Covariates included those representing healthcare need (Medicare hospitalizations, nursing home beds), predisposing factors for healthcare use (race, education, population density of older adults), and enabling factors (distance to the nearest ED).

Results

In a multivariable regression model corrected for spatial clustering, ZIP code characteristics associated with ED visits included more hospitalizations by Medicare beneficiaries, more nursing home beds, and closer proximity to an ED. Number of PCPs per 100 older adult residents in each ZIP code was not associated with ED use, and the 95% confidence limit indicates at most a small effect of PCP availability on ED use.

Conclusion

These findings suggest that primary care availability has at most a limited effect on ED use by older adults in North Carolina.
The rtA181S mutation of hepatitis B virus primarily confers resistance to adefovir dipivoxil
Authors: Liu Y. , Li X. , Xin S. , Xu Z. , Chen R. , Yang J. , Liu L. , Wong V. W.‐S. , Yang D. , Chan H. L.‐Y. , Xu D.
Published: August 2014

The study aimed to clarify clinical significance of hepatitis B virus (HBV) rtA181S mutation in Chinese HBV‐infected patients. A total of 18 419 patients with chronic HBV infection from Beijing 302 Hospital were investigated. HBV complete reverse transcriptase region of polymerase was screened by direct sequencing, and the results were verified by clonal sequencing. Replication‐competent mutant and wild‐type HBV genomic amplicons were constructed and transfected into the HepG2 cells and cultured in the presence or absence of serially diluted nucleos(t)ide analogues. Intracellular HBV replicative intermediates were quantitated for calculating the 50% effective concentration of the drug (EC50). The rtA181S was detected in 98 patients with 12 kinds of mutational patterns. Genotype C and genotype B HBV infection occupied 91.8% and 8.2% in rtA181S‐positive patients, in contrast to 84.6% and 15.4% in rtA181S‐negative patients (P < 0.01). All rtA181S‐positive patients had received nucleos(t)ide analogues. rtA181S was detected in multiple patients with virologic breakthrough. Phenotypic analysis of patient‐derived viral strains showed that rtA181S, rtA181S+N236T, rtN236T and rtA181V strains had 68.5%, 49.9%, 71.4% and 66.2% of natural replication capacity of wild‐type strain, and 3.7‐fold, 9.8‐fold, 7.9‐fold and 5.6‐fold increased EC50 to adefovir dipivoxil (ADV). The rtA181S strain remained susceptible to lamivudine, entecavir and tenofovir, and ADV susceptibility was restored after the mutation was eliminated through site‐directed mutagenesis. Rescue therapy with entecavir or combination therapy was effective in rtA181S‐related ADV‐refractory patients. The rtA181S mutation confers moderate resistance to ADV. It could be induced by either lamivudine or ADV and contribute ADV treatment failure.
The Effects of Paraphrasing Interventions on Problem‐Solving Accuracy for Children at Risk for Math Disabilities
Authors: Moran Amber S. , Swanson H. Lee , Gerber Michael M. , Fung Wenson
Published: August 2014

The purpose of this study was to examine effectiveness of paraphrasing interventions on mathematics word problem‐solving accuracy in third grade children (N = 72) at risk for mathematics disabilities (MD). Three instructional conditions directed students’ attention through paraphrasing, via writing, to different propositions within word problems. Students were randomly assigned to one of four intervention conditions: paraphrase question propositions (restate), paraphrase relevant propositions (relevant) and paraphrase all propositions (complete) or an untreated control. A mixed ANCOVA indicated that paraphrasing relevant and complete propositions significantly increased posttest accuracy when compared to the control and restate condition. Results from the study provide support for the effectiveness of paraphrasing interventions that directs students to restate/paraphrase propositions of mathematics word problems relative to the control condition.
Fe‐bearing phases in a ureilite fragment from the asteroid 2008 TC3 (= Almahata Sitta meteorites): A combined Mössbauer spectroscopy and X‐ray diffraction study
Authors: Gismelseed Abbasher M. , Abdu Yassir A. , Shaddad Muawia H. , Verma Harish C. , Jenniskens Peter
Published: August 2014

The iron‐bearing phases in a ureilite fragment (AS#051) from the Almahata Sitta meteorite are studied using Mössbauer spectroscopy, X‐ray diffraction (XRD), and electron microprobe analysis (EMPA). AS#051 has a typical ureilite texture of medium‐ to coarse‐grained silicates (olivine, orthopyroxene, and pigeonite) with minor opaques (Fe‐Ni metal, troilite, and graphite). The silicate compositions, determined by EMPA, are homogeneous: olivine (Fo90.2), orthopyroxene (En86.3Fs8.6Wo5.1), and pigeonite (En81.6Fs8.9Wo9.5), and are similar to those of magnesian ureilites. The modal abundance of mineral phases was determined by Rietveld refinement of the powder XRD data. The Mössbauer spectra at 295 K and 78 K are composed of two sharp well‐defined paramagnetic doublets superimposed on a well‐resolved magnetic sextet and other weak absorption features. The two paramagnetic doublets are assigned to olivine and pyroxene (orthopyroxene and pigeonite), and the ferromagnetic sextet to kamacite (magnetic hyperfine field ≈ 33.2 T), in agreement with the XRD characterization. The Mössbauer results also show the presence of small amounts of troilite (FeS) and cohenite ([Fe,Ni,Co]3C). Using the Mössbauer data, the relative abundance of each Fe‐bearing phase is determined and compared with the results obtained by XRD.
Itching for Answers: How Histamine Relaxes Lymphatic Vessels
Authors: Scallan Joshua P. , Davis Michael J.
Published: August 2014

In the current issue of Microcirculation, studies by Kurtz et al. [12] and Nizamutdinova et al. [18] together provide new evidence supporting a role for histamine as an endothelial‐derived molecule that inhibits lymphatic muscle contraction. In particular, Nizamutdinova et al. show that the effects of flow‐induced shear stress on lymphatic endothelium are mediated by both nitric oxide and histamine, since only blockade of both prevents contraction strength and frequency from being altered by flow. Separately, Kurtz et al. used confocal microscopy to determine a preferential expression of histamine receptors on the lymphatic endothelium and demonstrated that histamine applied to spontaneously contracting collecting lymphatics inhibits contractions. Previous studies disagreed on whether histamine stimulates or inhibits lymphatic contractions, but also used differing concentrations, species, and preparations. Together these new reports shed light on how histamine acts within the lymphatic vasculature, but also raise important questions about the cell type on which histamine exerts its effects and the signaling pathways involved. This editorial briefly discusses the contribution of each study and its relevance to lymphatic biology.
ADAM10 correlates with uveal melanoma metastasis and promotes in vitro invasion
Authors: Gangemi Rosaria , Amaro Adriana , Gino Alice , Barisione Gaia , Fabbi Marina , Pfeffer Ulrich , Brizzolara Antonella , Queirolo Paola , Salvi Sandra , Boccardo Simona , Gualco Marina , Spagnolo Francesco , Jager Martine J. , Mosci Carlo , Rossello Armando , Ferrini Silvano
Published: August 2014

Uveal melanoma (UM) is a rare ocular tumor that may lead to deadly metastases in 50% of patients. A disintegrin and metalloproteinase (ADAM)10, ADAM17, and the HGF‐receptor c‐Met support invasiveness in different tumors. Here, we report that high ADAM10, MET, and, to a lesser extent, ADAM17 gene expression correlates with poor progression‐free survival in UM patients (hazard ratio 2.7, 2.6, and 1.9, respectively). About 60% of primary UM expresses c‐Met and/or ADAM10 proteins. Four UM cell lines display high levels of ADAM10 and ADAM17, which constitutively cleave c‐Met, inducing the release of soluble c‐Met. ADAM10/17 pharmacological inhibition or gene silencing reduces c‐Met shedding, but has limited impact on surface c‐Met, which is overexpressed. Importantly, ADAM10 silencing inhibits UM cell invasion driven by FCS or HGF, while ADAM17 silencing has a limited effect. Altogether our data indicate that ADAM10 has a pro‐invasive role and may contribute to UM progression.
Structure and development of ‘witches' broom’ galls in reproductive organs of Byrsonima sericea (Malpighiaceae) and their effects on host plants
Authors: Guimarães A. L. A. , Neufeld P. M. , Santiago‐Fernandes L. D. R. , Vieira A. C. M.
Published: August 2014

Galls are anomalies in plant development of parasitic origin that affect the cellular differentiation or growth and represent a remarkable plant–parasite interaction. Byrsonima sericea DC. (Malpighiaceae) is a super host of several different types of gall in both vegetative and reproductive organs. The existence of galls in reproductive organs and their effects on the host plant are seldom described in the literature. In this paper, we present a novel study of galls in plants of the Neotropical region: the ‘witches' broom’ galls developed in floral structures of B. sericea. The unaffected inflorescences are characterised by a single indeterminate main axis with spirally arranged flower buds. The flower buds developed five unaffected brownish hairy sepals and five pairs of elliptical yellow elaiophores, five yellow fringed petals, 10 stamens and a pistil with superior tricarpellar and trilocular ovary. The affected inflorescences showed changes in architecture, with branches arising from the main axis and flower buds. The flower buds exhibited several morphological and anatomical changes. The sepals, petals and carpels converted into leaf‐like structures after differentiation. Stamens exhibited degeneration of the sporogenous tissue and structures containing hyphae and spores. The gynoecium did not develop, forming a central meristematic region, from which emerges the new inflorescence. In this work, we discuss the several changes in development of reproductive structures caused by witches' broom galls and their effects on reproductive success of the host plants.