bluuebunny/crossref_metadata_2025 huggingface dataset:
Chaperone-mediated autophagy degrades mutant p53
Authors: Vakifahmetoglu-Norberg Helin , Kim Minsu , Xia Hong-guang , Iwanicki Marcin P. , Ofengeim Dimitry , Coloff Jonathan L. , Pan Lifeng , Ince Tan A. , Kroemer Guido , Brugge Joan S. , Yuan Junying
Published: August 2013

Missense mutations in the gene TP53, which encodes p53, one of the most important tumor suppressors, are common in human cancers. Accumulated mutant p53 proteins are known to actively contribute to tumor development and metastasis. Thus, promoting the removal of mutant p53 proteins in cancer cells may have therapeutic significance. Here we investigated the mechanisms that govern the turnover of mutant p53 in nonproliferating tumor cells using a combination of pharmacological and genetic approaches. We show that suppression of macroautophagy by multiple means promotes the degradation of mutant p53 through chaperone-mediated autophagy in a lysosome-dependent fashion. In addition, depletion of mutant p53 expression due to macroautophagy inhibition sensitizes the death of dormant cancer cells under nonproliferating conditions. Taken together, our results delineate a novel strategy for killing tumor cells that depend on mutant p53 expression by the activation of chaperone-mediated autophagy and potential pharmacological means to reduce the levels of accumulated mutant p53 without the restriction of mutant p53 conformation in quiescent tumor cells.
Drosophila Gtsf1 is an essential component of the Piwi-mediated transcriptional silencing complex
Authors: Dönertas Derya , Sienski Grzegorz , Brennecke Julius
Published: August 2013

The PIWI-interacting RNA (piRNA) pathway is a small RNA silencing system that keeps selfish genetic elements such as transposons under control in animal gonads. Several lines of evidence indicate that nuclear PIWI family proteins guide transcriptional silencing of their targets, yet the composition of the underlying silencing complex is unknown. Here we demonstrate that the double CHHC zinc finger protein gametocyte-specific factor 1 (Gtsf1) is an essential factor for Piwi-mediated transcriptional repression in Drosophila. Cells lacking Gtsf1 contain nuclear Piwi loaded with piRNAs, yet Piwi's silencing capacity is ablated. Gtsf1 interacts directly with a small subpool of nuclear Piwi, and loss of Gtsf1 phenocopies loss of Piwi in terms of deregulation of transposons, loss of H3K9 trimethylation (H3K9me3) marks at euchromatic transposon insertions, and deregulation of genes in proximity to repressed transposons. We propose that only a small fraction of nuclear Piwi is actively engaged in target silencing and that Gtsf1 is an essential component of the underlying Piwi-centered silencing complex.
DmGTSF1 is necessary for Piwi–piRISC-mediated transcriptional transposon silencing in the Drosophila ovary
Authors: Ohtani Hitoshi , Iwasaki Yuka W. , Shibuya Aoi , Siomi Haruhiko , Siomi Mikiko C. , Saito Kuniaki
Published: August 2013

The Piwi–piRNA (PIWI-interacting RNA) complex (Piwi–piRISC) in Drosophila ovarian somatic cells represses transposons transcriptionally to maintain genome integrity; however, the underlying mechanisms remain obscure. Here, we reveal that DmGTSF1, a Drosophila homolog of gametocyte-specific factor 1 (GTSF1) (which is required for transposon silencing in mouse testes), is necessary for Piwi–piRISC to repress target transposons and neighboring genes. DmGTSF1 depletion affected neither piRNA biogenesis nor nuclear import of Piwi–piRISC. DmGTSF1 mutations caused derepression of transposons and loss of ovary follicle layers, resulting in female infertility. We suggest that DmGTSF1, a nuclear Piwi interactor, is an integral factor in Piwi–piRISC-mediated transcriptional silencing.
Enhancement of microhomology-mediated genomic rearrangements by transient loss of mouse Bloom syndrome helicase
Authors: Yamanishi Ayako , Yusa Kosuke , Horie Kyoji , Tokunaga Masahiro , Kusano Kohji , Kokubu Chikara , Takeda Junji
Published: August 2013

Bloom syndrome, an autosomal recessive disorder of the BLM gene, confers predisposition to a broad spectrum of early-onset cancers in multiple tissue types. Loss of genomic integrity is a primary hallmark of such human malignancies, but many studies using disease-affected specimens are limited in that they are retrospective and devoid of an appropriate experimental control. To overcome this, we devised an experimental system to recapitulate the early molecular events in genetically engineered mouse embryonic stem cells, in which cells undergoing loss of heterozygosity (LOH) can be enriched after inducible down-regulation of Blm expression, with or without site-directed DNA double-strand break (DSB) induction. Transient loss of BLM increased the rate of LOH, whose breakpoints were distributed along the chromosome. Combined with site-directed DSB induction, loss of BLM synergistically increased the rate of LOH and concentrated the breakpoints around the targeted chromosomal region. We characterized the LOH events using specifically tailored genomic tools, such as high-resolution array comparative genomic hybridization and high-density single nucleotide polymorphism genotyping, revealing that the combination of BLM suppression and DSB induction enhanced genomic rearrangements, including deletions and insertions, whose breakpoints were clustered in genomic inverted repeats and associated with junctional microhomologies. Our experimental approach successfully uncovered the detailed molecular mechanisms of as-yet-uncharacterized loss of heterozygosities and reveals the significant contribution of microhomology-mediated genomic rearrangements, which could be widely applicable to the early steps of cancer formation in general.
DNA methylation contributes to natural human variation
Authors: Heyn Holger , Moran Sebastian , Hernando-Herraez Irene , Sayols Sergi , Gomez Antonio , Sandoval Juan , Monk Dave , Hata Kenichiro , Marques-Bonet Tomas , Wang Liewei , Esteller Manel
Published: August 2013

DNA methylation patterns are important for establishing cell, tissue, and organism phenotypes, but little is known about their contribution to natural human variation. To determine their contribution to variability, we have generated genome-scale DNA methylation profiles of three human populations (Caucasian-American, African-American, and Han Chinese-American) and examined the differentially methylated CpG sites. The distinctly methylated genes identified suggest an influence of DNA methylation on phenotype differences, such as susceptibility to certain diseases and pathogens, and response to drugs and environmental agents. DNA methylation differences can be partially traced back to genetic variation, suggesting that differentially methylated CpG sites serve as evolutionarily established mediators between the genetic code and phenotypic variability. Notably, one-third of the DNA methylation differences were not associated with any genetic variation, suggesting that variation in population-specific sites takes place at the genetic and epigenetic levels, highlighting the contribution of epigenetic modification to natural human variation.
Molecular cocrystals of 5-(4-bromophenyl)-1,3,4-thiadiazol-2-amine: hydrogen bonding in the structures of the 1:1 adduct with 2-(naphthalen-2-yloxy)acetic acid and the salt with 3,5-dinitrobenzoic acid
Authors: Smith Graham , Lynch Daniel E.
Published: August 2013

The crystal structures of the anhydrous products from the interaction of 5-(4-bromophenyl)-1,3,4-thiadiazol-2-amine with 2-(naphthalen-2-yloxy)acetic acid,viz.the 1:1 adduct C8H6BrN3S·C12H10O3, (I), and with 3,5-dinitrobenzoic acid,viz.the salt 2-amino-5-(4-bromophenyl)-1,2,4-thiadiazol-3-ium 3,5-dinitrobenzoate, C8H7BrN3S+·C7H3N2O6−, (II), have been determined. In adduct (I), a heterodimer is formed through a cyclic hydrogen-bonding motif [graph setR22(8)], involving carboxylic acid–heteroatom O—H...N and amine–carboxylic acid N—H...O interactions. The heterodimers are essentially planar, with a thiadiazole-to-naphthalene ring dihedral angle of 15.9 (2)° and an intramolecular thiadiazole-to-benzene ring angle of 4.7 (2)°. An amine–heteroatom N—H...N hydrogen bond between the heterodimers generates a one-dimensional chain structure extending down [001]. Also present are weak benzene–benzene and naphthalene–naphthalene π–π stacking interactions down thebaxis [minimum ring-centroid separation = 3.936 (3) Å]. With salt (II), the cation–anion association is also through a cyclicR22(8) motif but involving duplex N—H...Ocarboxylatehydrogen bonds, giving a heterodimer that is close to planar [dihedral angles between the thiadiazole ring and the two benzene rings = 5.00 (16) (intra) and 7.23 (15)° (inter)]. A secondary centrosymmetric cyclic R_{4}^{2}(8) N—H...Ocarboxylatehydrogen-bonding association involving the second amino H atom generates a heterotetramer. Also present in the crystal structure are weak π–π interactions between thiadiazolium rings [minimum ring-centroid separation = 3.9466 (18) Å], as well as a short Br...Onitrointeraction [3.314 (4) Å]. The two structures reported here now provide a total of three crystallographically characterized examples of cocrystalline products from the interaction of 5-(4-bromophenyl)-1,3,4-thiadiazol-2-amine with carboxylic acids, of which only one involves proton transfer.
(N,N-Diethyldithiocarbamato)[tris(3,5-dimethylpyrazol-1-yl)hydroborato]copper(II): a new copper(II) dithiocarbamate compound with the classic TpMe2scorpionate
Authors: Cañada Louise Marie C. , Yap Glenn P. A. , Lim Patrick John Y.
Published: August 2013

The title complex, [Cu(C5H10NS2)(C15H22BN6)] or (TpMe2)Cu(S2CNEt2), incorporating the classic TpMe2scorpionate, is relevant to blue copper protein models and to Cu extraction from waste treatment and mine-tailing leachate. The IR and UV–Vis spectra are consistent with the crystal structure.
Social reporting by Islamic banks: does social justice matter?
Authors: Kamla Rania , G. Rammal Hussain
Published: August 2013

Purpose

– This study examines social reporting by Islamic banks with special emphasis on themes related to social justice. By using critical theory and “immanent critique”, the study attempts to explain and delineate reasons for disclosures and silences in Islamic banks ' annual reports and web sitesvis-à-vissocial justice.

Design/methodology/approach

– The approach taken was a content analysis of annual reports and web sites of 19 Islamic banks.

Findings

– Islamic banks ' disclosures emphasise their religious character through claims that they adhere to Sharia ' s teachings. Their disclosures, however, lack specific or detailed information regarding schemes or initiativesvis-à-vispoverty eradication or enhancing social justice.

Research limitations/implications

– Limitations associated with content analysis of annual reports and internet web sites apply. This study focuses on Islamic banks ' social roles. Further studies of banks ' social roles in society in general are of interest.

Practical implications

– Drawing attention of Islamic banks and other stakeholders to the gap between the rhetorical religious and ethical claims of Islamic banks and their activities (as depicted through their disclosures) opens up the possibility of a positive change in Islamic banks ' actual social roles.

Originality/value

– The study fills a gap in both social accounting and Islamic accounting literatures with its emphasis on social justice and poverty eradication. The study contributes to the very scarce literature linking religion (especially Islam), critical theory, social accounting and Islamic accounting. It goes beyond previous research in Islamic accounting literature by exposing contradictions in the Islamic banking industry ' s rhetoric regarding their social role in society.
Methodological problems of sampling young homeless people in four European societies with different levels of service provision and definitions of homelessness
Authors: Smith Joan
Published: August 2013

Purpose

This article aims to describe methodological issues in relation to the definition of homelessness and the drawing of samples of young homeless people in four European countries. The purposes of the research project were, first, to make a comparison of different homeless situations facing young people in these four countries, and second, to introduce early intervention and action planning methodologies developed in the UK and The Netherlands to other countries in the study – Portugal (a family welfare society) and the Czech Republic (an ex‐communist regime redeveloping its welfare policies).

Design/methodology/approach

After extensive discussions and key worker interviews with local agencies, 54 homeless young people were interviewed in each country. Each sample was intended to be purposive in that it should recruit homeless young men and women from those born in that country from the dominant (white) ethnic group, born in that country from minority ethnic groups, and young people not born in that country. A major issue was how to define homelessness in order to be able to recruit across the spectrum of homeless youth.

Findings

The purposive samples recruited in the four countries reflected the availability of services in those countries and levels of family support. Whilst young homeless people in The Netherlands and the UK were mostly living in supported housing, in Portugal they were living as “hidden homeless” and in the Czech Republic on the streets or in squats.

Research limitations/implications

The methodological difficulties encountered during the project are themselves a useful lesson learnt, for the creation of trans‐national understanding and politicy.

Practical implications

Nevertheless, despite the very different circumstances of limited services in Portugal and the Czech Republic, it appeared that both early intervention methods and key working approaches could be applied broadly across the EU.

Originality/value

Transnational studies of youth homelessness are rare and therefore produce particularly useful insights for research, policy and practice.
Bridging situated learning theory to the resource‐based view of project management
Authors: Jugdev Kam , Mathur Gita
Published: August 2013

Purpose

This paper aims to present a high‐level conceptual framework to strengthen the conceptual bridge between project management and workplace learning by applying situated learning theory to project management practice to guide shared learning within and between projects.

Design/methodology/approach

The paper bridges situated learning theory from the workplace learning literature and the resource‐based view (RBV) of project management from the strategic management literature, using them as lenses to view two learning mechanisms in the project management domain, project reviews and communities of practices.

Findings

The paper finds that situated learning theory can be applied to project management to highlight processes that enable capability development through shared project learning.

Research limitations/implications

This paper is conceptual in nature and intended to make a case for empirical research that draws on workplace learning literature which is useful to project management as there remains the challenge of leveraging these perspectives for project management practice.

Practical implications

The paper believes that situated learning theory offers insights that can be leveraged to make project management environments more effective through improved intra‐project and inter‐project shared learning.

Originality/value

This paper presents a high‐level conceptual framework to bridge situated learning theory to the RBV of project management. The paper finds that situated learning theory is well suited to contribute to an understanding of shared learning in projects and justifies future research.
Winterbourne View Hospital: a glimpse of the legacy
Authors: Flynn Margaret , Citarella Vic
Published: August 2013

Purpose

This paper concerns the fall‐out from a TV programme which exposed the arbitrariness of cruelty at a private hospital that purported to provide assessment, treatment and rehabilitation to adults with learning disabilities, autism and mental health problems. The paper seeks to address the issues involved.

Design/methodology/approach

It describes the principal findings of a Serious Case Review which was commissioned after the TV broadcast, and outlines some of the activities designed to reduce the likelihood of such abuses recurring.

Findings

From policy, commissioning, regulation, management, service design and practice perspectives, events at Winterbourne View Hospital highlight a gulf between professionals, professionals and their organisations, and leadership shortcomings.

Originality/value

The English government responded promptly and encouragingly to the wretched circumstances of patients at Winterbourne View Hospital with a “Timetable of Actions”. The Serious Case Review which was commissioned after the TV broadcast contributed to the growing scepticism of “out of sight, out of mind” placements. It covered wide‐ranging territory.
“An unnoticing environment”: deficiencies and remedies – services for adults with learning disabilities
Authors: Green Sheree Louise
Published: August 2013

Purpose

This article aims to outline simple measures which, by making better use of existing legislation and provision, could change the day‐to‐day experience of individuals with learning disabilities currently in long stay hospitals, whilst phased local provision is being sourced for them. The proposals will also promote the safety and dignity of the minority of patients who ultimately cannot be settled successfully within their own community. Further, these measures may help ensure that any individual undergoing assessment and treatment at such a unit, for whatever period, and for whatever reason, will receive care in an environment where abuse cannot go unnoticed or unchecked.

Design/methodology/approach

The paper provides a review of the potential to use current legislation and provision to better effect, highlighted by case studies.

Findings

Commissioners contracting with providers could include measures to promote the safety and protection of adults with learning disabilities from abuse at little or no cost to the commissioning authority.

Originality/value

This is an original piece of work – developed from a short opinion/comment piece (750 words) originally prepared for the benefit of mental health lawyers in the Law Society Gazette. It is primarily of value, however, to social workers, care providers, adult safeguarding teams, advocacy services and commissioners of services.
A series of tsunamis are underway: leaders must learn how to surf the waves
Authors: Vilstrup Hansgaard Jeppe , Mikkelsen Kenneth
Published: August 2013

Purpose

The purpose of this paper is to discuss the rapid changes occurring in the business world, fundamentally shifting the way we work, connect, and collaborate in the modern workplace.

Design/methodology/approach

The authors discuss problems connected with the matrix organization.

Findings

In today's world, organizations are collapsing and failing in every direction. With few exceptions, the business models that organizations use to manage processes and people date from the industrial era. They were invented for mass‐production of inputs into outputs and the underlying thinking was elitist and hierarchical. Throughout the twentieth century, managers have adjusted the models but they have not changed fundamentally.

Originality/value

The paper shows that if attention is not paid to planning for and resolving these issues, there is a strong probability that entire organizations will be wiped out by this interrelated series of tsunamis in the near future.
UK media: managing turbulence and uncertainty
Authors: Oliver John
Published: August 2013

Purpose

Businesses increasingly find themselves competing in highly dynamic markets, making visibility of the future limited and the strategic way forward ambiguous. The purpose of this paper is to present the findings from a survey of UK media executives and identify their outlook for the industry, and an evaluation of their usage and satisfaction with the tools that they use to manage their businesses.

Design/methodology/approach

The survey sampled 24 UK media executives who had responsibility for strategy and other functional areas of their business.

Findings

The survey found four strong themes amongst media executives. These were related to the launch of new products and services, seeking innovation through collaborative partnerships, leveraging their brand and content through new platforms, and uncertainty regarding the future direction of the industry.

Practical implications

The paper will provide media executives with a better understanding of the management tools at their disposal and how these can be used to improve performance in a number of key areas. Non‐media executives will be able to draw on the paper's findings to see how other firms are managing turbulent and uncertain market conditions.

Originality/value

This is the first survey of the UK media industry in terms of examining the strategic tools that are being used to manage media firms through turbulence and uncertainty.
The end of the strategy world as we know it?
Authors: Bell Gareth
Published: August 2013

Purpose

The purpose of this paper is to provide an interview with Rita Gunther McGrath, Columbia Business School Professor, and author of The End of Competitive Advantage: How to Keep Your Strategy Moving as Fast as Your Business.

Design/methodology/approach

The paper takes the form of an interview.

Findings

In the following interview, Rita Gunther McGrath discusses the demise of traditional strategy practices, proposing a more flexible approach in response to the volatile environment in which we live.

Originality/value

McGrath signals the end of sustainable competitive advantage, suggesting that businesses must organize for the “waves of transient advantage” that are now commonplace.
Beyond Generalised Trust: Norms of Reciprocity as an Alternative Form of Social Capital in an Assimilationist Integration Regime
Authors: Gundelach Birte , Traunmüller Richard
Published: August 2013

Scholars have recently stressed two important avenues for the study of cultural diversity and social capital: the role of political integration regimes as well as alternative indicators to generalised trust. This article addresses both. Focusing on Germany, it provides the first study of the relationship between cultural diversity and social capital in a country implementing an ‘assimilationist’ model of integration. As a further innovation, the article contrasts social trust with an alternative, yet often neglected form of social capital, namely norms of reciprocity. Results based on data from the German Socio-Economic Panel (GSOEP) and using multi-level analyses of 97 German regions suggest a negative relationship between cultural diversity and social trust in Germany. Assimilationist policies have not (yet) led to efficient integration of minority groups and a value convergence that could bridge cultural divides. Nevertheless, cultural diversity does not erode the commitment to norms of reciprocity, which may therefore be regarded as an alternative foundation of social cohesion in culturally diverse societies.
The Problem of Pluralist Authority
Authors: Muñiz-Fraticelli Víctor M.
Published: August 2013

This article presents a reconstruction of political pluralism derived from Joseph Raz's explanation of the authority of law. It argues that Harold Laski's critique of state authority, while claiming to be pluralistic, leaves little room for the exercise of authority by associations themselves. The authority of an association may be justified if it facilitates its members' compliance with reasons that apply to them, especially reasons that are particular to the members' association. This results in the recognition of two types of authority in the state: first-order authority, which the state has by virtue of being an association of citizens; and second-order authority, which it has by virtue of providing the institutional context in which other associations can exercise their authority more effectively. The resulting image of the state may better acknowledge the variety of authoritative claims made by the various associations that effectively hold the allegiance of individuals.
‘I Can See it in the Nightclub’: Dance, Capoeira and Male Bodies
Authors: Stephens Neil , Delamont Sara
Published: August 2013

This paper reports an ethnographic study of how Brazilians teaching capoeira in the UK use dance as a discursive and embodied pedagogic strategy both to change men's bodies and also to gauge the success of their instructional work. The theoretical framework is drawn from Herzfeld's neglected study of the poetics of manhood in Crete which is revisited in the light of his subsequent analysis of the embodiment of ethnographic practice. Ethnographic research is used to show how British men learning capoeira are enculturated into a different, Brazilian, embodiment in which dance is masculine, and dancing is one way to display a social self-regard. Discourse about performance helps to define the appropriateness of the social self-regard that the capoeira students acquire and display.
Chemical Properties of a Polysaccharide Purified From Solid‐State Fermentation of Auricularia Auricular and its Biological Activity as a Hypolipidemic Agent
Authors: Zeng Feng , Zhao Chao , Pang Jie , Lin Zhanxi , Huang Yifan , Liu Bin
Published: August 2013

A water‐soluble crude polysaccharide was extracted by hot water from Auricularia auricular mycelium grown under solid‐state fermentation (SSF). The crude polysaccharide was purified by DEAE Sephadex A‐50 and Sephadex G‐200 chromatography. Fourier transform infrared spectroscopy and nuclear magnetic resonance (1H NMR) spectroscopy were used to investigate the structure of the purified A. auricular polysaccharide (AAP‐I) and revealed that it is α‐glycosidically linked. After 14 and 28 days of AAP‐I orally administered, the AAP‐I significantly decreased the levels of total cholesterol, triglyceride, and low‐density lipoprotein cholesterol in mice in which hyperlipidemia had been induced by a high fat diet (P < 0.05). The results revealed that AAP‐I from SSF of A. auricular mycelium possesses potent hypolipidemic properties. The polysaccharide may be useful as a functional food additive and a hypolipidemic agent.
Ultrasound measurement of subglottic diameter and an empirical formula for proper endotracheal tube fitting in children
Authors: KIM E. J. , KIM S. Y. , KIM W. O. , KIM H. , KIL H. K.
Published: August 2013

Background

The appropriate endotracheal tube (ETT) size is commonly determined using age‐based formula; ETT size determination based on ultrasound (US) measurement of subglottic diameter (SD), the narrowest portion of the paediatric upper airway, may provide a better method for accurate fit. We aimed to validate ETT size determination using US measures of SD before intubation to establish an empirical formula for ETT fitting based on SD and biographic parameters.

Methods

We included 215 children aged 1–72 months undergoing general anaesthesia. US was performed on the anterior neck to measure SD during mask ventilation under anaesthesia. Endotracheal intubation was performed with a cuffed ETT selected by age‐based recommendation; the transverse outer diameter (OD) of the ETT within the trachea at the subglottis level (OD‐ETT at SD) was measured.

Results

The OD‐ETT at SD was correlated with the actual OD‐ETT outside the trachea (R2 = 0.635), showing the validity of ultrasonographic measurement; moreover, the US‐measured SD revealed strong correlation with the actual OD‐ETT (R2 = 0.834). US‐measured SD and biographic data (age, height and weight) showed little correlation in children less than 12 months but good correlation (age, height) in children older than 12 months (P < 0.01).

Conclusions

US‐measured OD‐ETT at SD was in good agreement with the actual OD‐ETT, suggesting that US‐measured SD helps in choosing the appropriate ETT diameter for children. In children older than 12 months, the equation ‘OD (mm) = 0.01 × age (months) + 0.02 × height (cm) + 3.3’ may help select the appropriate ETT.
About the role and underlying mechanisms of cofactors in anaphylaxis
Authors: Wölbing F. , Fischer J. , Köberle M. , Kaesler S. , Biedermann T.
Published: August 2013

Anaphylaxis is the systemic and most severe presentation of type I allergy. A number of conditions were identified that modulate the onset of anaphylaxis such as co‐ or augmentation factors, which significantly lower the allergen dose necessary for triggering anaphylaxis. Next to physical exercise or alcohol consumption, co‐administration of nonsteroidal anti‐inflammatory drugs (NSAID) or concomitant infectious diseases are well‐documented cofactors of anaphylaxis. Registries for anaphylaxis document a role for cofactors in about 30% of anaphylactic reactions. Some disease entities such as ‘wheat‐dependent exercise‐induced anaphylaxis’ (WDEIA) are explicitly characterized by elicitation of anaphylaxis only in the presence of at least one such cofactor. Using WDEIA as a model disease, studies demonstrated that exercise increases skin prick test reactivity to and bioavailability of the allergen. Additional data indicate that alcohol consumption and NSAID administration display similar effects. Modulation of the cellular activation threshold is another mechanism underlying cofactor‐induced anaphylaxis, most likely also functional when infectious diseases orchestrate elicitation of anaphylaxis. Cofactors are increasingly accepted to play a fundamental role in eliciting anaphylaxis. Consequently, to improve patient management modalities, a better understanding of the underlying mechanisms is warranted. This review aims to update clinicians and clinical scientists on recent developments.
Outcomes of cholecystectomy for treatment of acute cholecystitis in octogenarians
Authors: Nikfarjam Mehrdad , Yeo David , Perini Marcos , Fink Michael A. , Muralidharan Vijayaragavan , Starkey Graham , Jones Robert M. , Christophi Christopher
Published: August 2013

Background

The independent influence of advanced age on outcomes in contemporary series treated by early cholecystectomy is undetermined.

Methods

Elderly patients, aged 80 years and older, with histology proven acute cholecystitis treated by cholecystectomy on initial presentation between 2005 and 2011 were compared to all others.

Results

In total, 411 patients had histologically proven acute cholecystitis, of whom 71 (17%) were aged 80 years and older. Elderly patients were more likely to have ischaemic heart disease, underlying diabetes and chronic renal failure. There was greater conversion from laparoscopic to open surgery in the elderly (21% versus 7%; P = 0.001). Elderly patients were more likely to have gangrenous cholecystitis (44% versus 31%; P = 0.033) and common bile duct stones (27% versus 17%; P = 0.048). Elderly patients had more complications (31% versus 13%; P < 0.001), a higher mortality rate (4% versus 1%; P = 0.038) and a longer median post‐operative length of stay (7 days versus 3 days; P < 0.001). Age ≥ 80 (P = 0.004) was an independent risk factors for complications.

Conclusion

Age 80 years and older is independently associated with increased morbidity following cholecystectomy for treatment acute cholecystitis at initial presentation.
How Do Teachers Talk About Economic Inequality? The Complexity of Teaching at a Socioeconomically Integrated Elementary School
Authors: White Elizabeth S. , Mistry Rashmita S. , Chow Kirby A.
Published: August 2013

This study examined elementary school teachers’ experiences at a socioeconomically integrated school. Specifically we focused on the ways that teachers address privilege and promote friendships among economically diverse students and the challenges they face in doing so. Open‐ended interviews were conducted with teachers (N = 25) in prekindergarten through sixth grades. Results indicated that while socioeconomic status (SES) was the most frequently mentioned domain of student difference, teachers were unsure about how to effectively address SES in the classroom. Some teachers reported working (unsuccessfully) to mask SES differences among students, though this became increasingly difficult in the upper elementary grades. Additionally, teachers described challenges associated with having an economically heterogeneous student body including parents’ differential power and involvement at the school and the lack of geographic proximity among students. Findings highlight the need for clear and specific classroom‐ and school‐based strategies to better address SES differences among students in socioeconomically integrated school settings. Implications for teacher practice are discussed.
Every Heart Beats True, for the Red, White, and Blue: National Identity Predicts Voter Support
Authors: Ma Debbie S. , Devos Thierry
Published: August 2013

In two studies conducted during the 2012 U.S. presidential election, we sought to determine whether the relative ascription of the American identity to Barack Obama and Mitt Romney was distinct from attitudinal responses and from associations about racial categories. We also tested the degree to which these associations accounted for voter support. In both studies, participants completed a series of Implicit Association Tests and reported their intention to vote for and their willingness to support these candidates. In contrast to implicit associations about racial categories (Black vs. White), Obama was implicitly seen as more American and elicited a more favorable implicit evaluation than Romney (Study 1). At the same time, these effects were reduced when candidates were categorized based on their racial (rather than personal) identity (Study 2). Implicit associations about the candidates (but not racial categories) accounted for intention to vote for them and relative willingness to support them over and above the effect of political orientation (Studies 1 & 2). These findings suggest that the implicit ascription of a national identity is an important facet of presidential elections.
Participation, interaction and social presence: An exploratory study of collaboration in online peer review groups
Authors: Zhao Huahui , Sullivan Kirk P. H. , Mellenius Ingmarie
Published: August 2013

A key reason for using asynchronous computer conferencing in instruction is its potential for supporting collaborative learning. However, few studies have examined collaboration in computer conferencing. This study examined collaboration in six peer review groups within an asynchronous computer conferencing. Eighteen tertiary students participated in the study. Content analyses of discussion protocols were performed in terms of participation, interaction, and social presence.

The results indicate that collaboration does not occur automatically in asynchronous computer conference. Collaboration requires participation because no collaboration occurred in the two groups with low student participation; however, participation does not lead to collaboration, evidenced by student postings receiving no peer responses. Collaboration requires interaction but does not end with interaction, substantiated by different levels of collaboration across different interactional patterns. Social presence helps to realise collaboration through establishing a warm and collegial learning community to encourage participate and interaction, exemplified by the contrast of the group with the highest level of social presence and the group with the lowest level of social presence. A model of understanding and assessing collaboration in online learning is recommended, consisting of participation, interaction and social presence.
Innovations in Practice: pilot evaluation of the supported discharge service (SDS): clinical outcomes and service use
Authors: Ougrin Dennis , Zundel Toby , Corrigall Richard , Padmore Jane , Loh Cheryl
Published: August 2013

Background

The Supported Discharge Service (SDS) is a model of enhanced care in the community for adolescents after inpatient discharge.

Methods

This study comprised the first 20 patients referred to SDS, largely those with delayed discharges. Service use and clinical outcomes were collected and predictors of total contact time were investigated.

Results

Significant improvements had been made with SDS. Higher baseline Strengths and Difficulties Questionnaire (SDQ) conduct scores were associated with less contact time.

Conclusions

SDS is a feasible model of care. Adolescents with conduct problems may benefit from engagement strategies. Further rigorous evaluation of the model is required.
Interobserver concordance of Ki67 labeling index in breast cancer: Japan Breast Cancer Research Group Ki67 Ring Study
Authors: Mikami Yoshiki , Ueno Takayuki , Yoshimura Kenichi , Tsuda Hitoshi , Kurosumi Masafumi , Masuda Shinobu , Horii Rie , Toi Masakazu , Sasano Hironobu
Published: August 2013

The standardized assessment of Ki67 labeling index (LI) is of clinical importance to identify patients with primary breast cancer who could benefit from chemotherapy. In this study, we evaluated the interobserver concordance of Ki67 LI assessment. Six surgical pathologists participated and all the slides were prepared from archival breast cancer tissues fixed in 10% buffered formalin for 24 h and stained with MIB‐1. Three independent studies were conducted. In the first study, 30 stained slides were assessed using two different methods: the scoring system, with a positive rate scored from 1 (0–9%) to 10 (90–100%) by visual estimate; and the counting method, with approximately 1000 cells counted in hot spots. In the second study, 20 tumors with Ki67 LI 5–25% were assessed, and in the third study, 15 printed photographs of stained slides were assessed to avoid variations by selecting different fields. In study 1, the counting system (intraclass correlation coefficient [ICC], 0.66 [95% confidence interval 0.52–0.78]) demonstrated a better correlation than the scoring system (ICC, 0.57 [0.42–0.72]). In study 2, the assessment for Ki67 LI of 5–25% demonstrated a correlation (ICC, 0.68 [0.50–0.81]) similar to that of study 1 (unrestricted range of Ki67 LI). In study 3, the assessment of Ki67 LI by counting yielded a good concordance (ICC, 0.94 [0.88–0.97]). In conclusion, there was better concordance with the counting system, and concordance was high when the assessed field was predetermined, indicating that the selection of the evaluation area is critical for obtaining reproducible Ki67 LI in breast cancer.
Identification of small molecule inhibitors of p27Kip1 ubiquitination by high‐throughput screening
Authors: Ooi Li‐Ching , Watanabe Nobumoto , Futamura Yushi , Sulaiman Shaida Fariza , Darah Ibrahim , Osada Hiroyuki
Published: August 2013

Dysregulation of p27Kip1 due to proteolysis that involves the ubiquitin ligase (SCF) complex with S‐phase kinase‐associated protein 2 (Skp2) as the substrate‐recognition component (SCFSkp2) frequently results in tumorigenesis. In this report, we developed a high‐throughput screening system to identify small‐molecule inhibitors of p27Kip1 degradation. This system was established by tagging Skp2 with fluorescent monomeric Azami Green (mAG) and CDK subunit 1 (Cks1) (mAGSkp2–Cks1) to bind to p27Kip1 phosphopeptides. We identified two compounds that inhibited the interaction between mAGSkp2–Cks1 and p27Kip1: linichlorin A and gentian violet. Further studies have shown that the compounds inhibit the ubiquitination of p27Kip1 in vitro as well as p27Kip1 degradation in HeLa cells. Notably, both compounds exhibited preferential antiproliferative activity against HeLa and tsFT210 cells compared with NIH3T3 cells and delayed the G1 phase progression in tsFT210 cells. Our approach indicates a potential strategy for restoring p27Kip1 levels in human cancers.
Decreased Readmissions and Improved Quality of Care With the Use of an Inexpensive Checklist in Heart Failure
Authors: Basoor Abhijeet , Doshi Nitin C. , Cotant John F. , Saleh Tarek , Todorov Mina , Choksi Nishit , Patel Kiritkumar C. , DeGregorio Michele , Mehta Rajendra H. , Halabi Abdul R.
Published: August 2013

Providing effective discharge instructions, appropriate dose uptitration, education regarding heart failure (HF) monitoring, and strict follow‐up have all been shown to decrease readmissions for HF but are all underutilized. The authors developed and evaluated the impact of a quality‐improvement HF checklist as a tool to remind physicians to improve quality of care in HF patients. The checklist was used in randomly selected patients admitted with a primary diagnosis of acute decompensated HF. It included documentation regarding medications and dose uptitration, relevant counseling, and follow‐up instructions at discharge. The checklist was used in 48 patients, and this checklist group was compared with 48 patients as a randomly selected control group. Higher proportions of patients were taking angiotensin‐converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) in the checklist group compared with the control group (40 of 48 vs 23 of 48, P<.001). Compared with the controls, the rate of dose uptitration for β‐blockers and/or ACE inhibitors/ARBs was more common in the checklist group (4 of 48 vs 21 of 48, P<.001). Both 30‐day (19% to 6%) and 6‐month (42% to 23%) readmissions were lower in the checklist group. The use of an HF checklist was associated with better quality of care and decreased readmission rates for patients admitted with HF.
Preload Reserve Is Restored in Patients With Decompensated Chronic Heart Failure Who Respond to Treatment
Authors: Squara Pierre , Estagnasie Philippe , Belliard Olivier , Squara Fabien , Dib Jean Claude
Published: August 2013

The authors designed this prospective study to show the relationship between preload reserve and treatment effectiveness of chronic heart failure (CHF). Fifty patients, aged 77±24 years, with decompensated CHF (B‐type brain natriuretic peptide [BNP] >1000 pg/mL) were included. Preload reserve was assessed by the changes in contraction indices during a passive leg raise (PLR). Contraction indices were assessed noninvasively using Bioreactance technology. After 4 days of optimized therapy, the same variables were reassessed and treatment‐induced differences were calculated. Treatment effectiveness was assessed by the 4‐day changes in BNP, body weight, and thoracic fluid content. The authors then compared treatment‐induced changes in preload reserve with treatment effectiveness. Therapy was associated with an overall decrease in heart rate, blood pressure, and cardiac power index (CPi) and with an increase in all preload reserve indices. Treatment effectiveness correlated well with changes in preload reserve. The best correlation was found between treatment‐induced changes in BNP and in PLR‐induced changes of CPi (R=0.63, P<.001). The PLR‐induced changes in CPi increased from 21±48 to 51±48 in BNP responders and decreased from 34±34 to 5±19 mW/m2 in BNP nonresponders (P<.0001). Hence, effective treatment, as indexed by a decrease in BNP, restores the preload reserve in patients with decompensated CHF.
Thiamine Supplementation for the Treatment of Heart Failure: A Review of the Literature
Authors: DiNicolantonio James J. , Niazi Asfandyar K. , Lavie Carl J. , O'Keefe James H. , Ventura Hector O.
Published: August 2013

A systematic review of the literature was performed by searching Pubmed and EMBASE databases using the terms “thiamine,” “vitamin B1,” “heart failure,” “systolic dysfunction,” “ventricular dysfunction,” “cardiomyopathy,” “ventricular failure,” and “systolic failure.” Relevant trials and articles were evaluated pertaining to thiamine deficiency in patients with heart failure (HF) and references were searched for further inclusion of articles. A total of 20 articles were reviewed and summarized in detail. While more research is needed to fully elucidate the clinical thiamine deficiency in HF patients, recent evidence has indicated that supplementing with thiamine in HF patients has the potential to improve left ventricular ejection fraction. Thiamine deficiency appears to be not uncommon in patients with HF, and supplementation with thiamine has been shown to improve cardiac function, urine output, weight loss, and signs and symptoms of HF. Therefore, this simple therapy should be tested in large‐scale randomized clinical trial to further determine the effects of thiamine in HF patients.
A kinetic compartment model for evaluating salivary gland scintigraphies
Authors: Afzelius Pia , Fuglsang Stefan
Published: August 2013

Purpose

The semi‐quantitative analysis of salivary gland scintigraphy with 99mTc‐pertechnetate has been used to evaluate salivary gland function. However, no objective parameters distinguishing abnormal from normal functions have been established thus far. We propose using a simple kinetic model applied to the four major salivary glands. This kinetic model is based on a two‐compartment model and the assumption of first‐order kinetics to characterize normal salivary gland function and other selected parameters to evaluate the normal function of salivary glands.

Methods

Thirty patients referred for 99mTc‐pertechnetate thyroid scintigraphy were studied. Dynamic imaging of the head in a fixed anterior projection was performed after an intravenous bolus injection of 150 MBq 99mTc‐pertechnetate using a gamma scintillation camera. After 30 min, lemon juice was orally administered through a syringe. Time activity curves were generated for each of the four major salivary glands (i.e. the right and left submandibular and right and left parotid glands). Excretion fractions (the fraction of mobilizable radioactivity after administering lemon juice) and the gland activity‐to‐thyroid activity ratio were calculated. The data were fitted to both a one‐ and two‐phase uptake model.

Results

The median uptake slope and maximal activity were significantly higher in the parotid glands than the submandibular glands (P<0·0001). The gland‐to‐thyroid ratio was higher in the parotid glands than the submandibular glands (P<0·0001), and the ejection fractions were higher in the parotid glands (P<0·0001). No difference was found in functional contributions of the parotid and submandibular glands.

Conclusions

Tracer accumulation can be represented by a one‐phase simple uptake model. The background regions that have been previously recommended in the literature are acceptable.
Liver allocation: urgency of need or prospect of success? Ethical considerations
Authors: Bobbert Monika , Ganten Tom M.
Published: August 2013

In German legislation and in Eurotransplant's practice of liver allocation, urgency of need is considered as the primary distribution criterion. However, at a certain stage, the “sickest‐first” principle is regarded as counterproductive as the performance status of these patients receiving an organ is on average critical and mortality and morbidity after liver transplantation increase. Within the medical transplant community, the criterion of prospect for success is highly accepted. As clinicians having a certain scope in decision‐making as “gatekeepers” in regard to which patient gets on the waiting list and at which stage a patient is defined as “not transplantable” and as transplantation centers aspire good success rates, the goal of high prospect for success might become more weighty than intended by legislation and professional guidelines. From an ethical point of view, it is submitted a so‐called mediatory approach in between the two extremes “sickest‐first” and “fittest‐first.” Beyond that, it is argued for further development of a prognostic score for post‐operative outcome after liver transplantation – as long as questions of social justice are borne in mind – to support “objective” decision‐making.