bluuebunny/crossref_metadata_2025 huggingface dataset:
The NDV-3A vaccine protects mice from multidrug resistantCandida aurisinfection
Authors: Singh Shakti , Uppuluri Priya , Alqarihi Abdullah , Elhassan Hana , French Samuel , Lockhart Shawn R. , Chiller Tom , Edwards John E. , Ibrahim Ashraf S.
Published: November 2018

Candida aurisis an emerging, multi-drug resistant, health care-associated fungal pathogen. Its predominant prevalence in hospitals and nursing homes indicates its ability to adhere to and colonize the skin, or persist in an environment outside the host - a trait unique from otherCandidaspecies. Besides being associated globally with life-threatening disseminated infections,C. aurisalso poses significant clinical challenges due to its ability to adhere to polymeric surfaces and form highly drug-resistant biofilms. Here, we performed bioinformatic studies to identify the presence of adhesin proteins inC. auris, with sequence as well as 3-D structural homologies to the major adhesin/invasin ofC. albicans, Als3. Anti-Als3p antibodies generated by vaccinating mice with NDV-3A (a vaccine based on the N-terminus of Als3 protein formulated with alum) recognizedC. auris in vitro, blocked its ability to form biofilms and enhanced macrophage-mediated killing of the fungus. Furthermore, NDV-3A vaccination induced significant levels ofC. auriscross-reactive humoral and cellular immune responses, and protected immunosuppressed mice from lethalC. aurisdisseminated infection, compared to the control alum-vaccinated mice. Finally, NDV-3A potentiated the protective efficacy of the antifungal drug micafungin, againstC. auriscandidemia. Identification of Als3-like adhesins inC. aurismakes it a target for immunotherapeutic strategies using NDV-3A, a vaccine with known efficacy against otherCandidaspecies and safety as well as efficacy in clinical trials. Considering thatC. auriscan be resistant to almost all classes of antifungal drugs, such an approach has profound clinical relevance.

Author Summary

Candida aurishas emerged as a major health concern to hospitalized patients and nursing home subjects.C. aurisstrains display multidrug resistance to current antifungal therapy and cause lethal infections. We have determined thatC. aurisharbors homologs ofC. albicansAls cell surface proteins. TheC. albicansNDV-3A vaccine, harboring the N-terminus of Als3p formulated with alum, generates cross-reactive antibodies againstC. aurisclinical isolates and protects neutropenic mice from hematogenously disseminatedC. aurisinfection. Importantly, the NDV-3A vaccine displays an additive protective effect in neutropenic mice when combined with micafungin. Due to its proven safety and efficacy in humans againstC. albicansinfection, our studies support the expedited testing of the NDV-3A vaccine againstC. aurisin future clinical trials.
Plastic multicellular development ofMyxococcus xanthus: genotype-environment interactions in a physical gradient
Authors: Rivera-Yoshida Natsuko , Arzola Alejandro V. , Arias Del Angel Juan A. , Franci Alessio , Travisano Michael , Escalante Ana E. , Benítez Mariana
Published: November 2018

In order to investigate the contribution of the physical environment to variation in multicellular development ofMyxococcus xanthus, phenotypes developed by different genotypes in a gradient of substrate stiffness conditions were quantitatively characterized. Statistical analysis showed that plastic phenotypes result from the genotype, the substrate conditions and the interaction between them. Also, phenotypes were expressed with scale- and trait-specificity. Overall, the presented information highlights the constructive role of the physical context in the development of microbial multicellularity, with both ecological and evolutionary implications.
Neuron-astrocyte metabolic coupling during neuronal stimulation protects against fatty acid toxicity
Authors: Ioannou Maria S. , Jackson Jesse , Sheu Shu-Hsein , Chang Chi-Lun , Weigel Aubrey V. , Liu Hiu , Pasolli H. Amalia , Xu C. Shan , Pang Song , Hess Harald F. , Lippincott-Schwartz Jennifer , Liu Zhe
Published: November 2018

Metabolic coordination between neurons and astrocytes is critical for the health of the brain. However, neuron-astrocyte coupling of lipid metabolism, particularly in response to neural activity, remains largely uncharacterized. Here, we demonstrate that toxic, peroxidated fatty acids (FAs) produced in hyperactive neurons are transferred to astrocytic lipid droplets by lipoprotein particles. Astrocytes consume the FAs stored in lipid droplets via mitochondrial β-oxidation in response to neuronal activity and turn on a detoxification gene expression program. Together, our findings reveal that FA metabolism between neurons and astrocytes is coupled in an activity-dependent manner to protect neurons from FA toxicity. This coordinated mechanism for metabolizing FAs could underlie both homeostasis and a variety of disease states of the brain.
duphold: scalalable, depth-based annotation and curation of high-confidence structural variant calls
Authors: Pedersen Brent S. , Quinlan Aaron R.
Published: November 2018

Most structural variant detection tools use clusters of discordant read-pair and split-read alignments to identify variants, yet do not integrate depth of sequence coverage as an additional means to support or refute putative events. Here, we present duphold, as a new method to efficiently annotate structural variant calls with sequence depth information that can add (or remove) confidence to SV predicted to affect copy number. It indicates not only the change in depth across the event, but also the presence of a rapid change in depth relative to the regions surrounding the breakpoints. It uses a unique algorithm that allows the run time to be nearly independent of the number of variants. This performance is important for large, jointly-called projects with many samples, each of which must be evaluated at thousands of sites. We show that filtering on duphold annotations can greatly improve the specificity of deletion calls and that its annotations match visual inspection. Duphold can annotate structural variant predictions made from both short-read and long-read data. It is available under the MIT license at: https://github.com/brentp/duphold.
Bayesian computation through cortical latent dynamics
Authors: Sohn Hansem , Narain Devika , Meirhaeghe Nicolas , Jazayeri Mehrdad
Published: November 2018

Statistical regularities in the environment create prior beliefs that we rely on to optimize our behavior when sensory information is uncertain. Bayesian theory formalizes how prior beliefs can be leveraged, and has had a major impact on models of perception 1, sensorimotor function 2,3, and cognition 4. However, it is not known how recurrent interactions among neurons mediate Bayesian integration. Using a time interval reproduction task in monkeys, we found that prior statistics warp the underlying structure of population activity in the frontal cortex allowing the mapping of sensory inputs to motor outputs to be biased in accordance with Bayesian inference. Analysis of neural network models performing the task revealed that this warping was mediated by a low-dimensional curved manifold, and allowed us to further probe the potential causal underpinnings of this computational strategy. These results uncover a simple and general principle whereby prior beliefs exert their influence on behavior by sculpting cortical latent dynamics.
Distance-based Protein Folding Powered by Deep Learning
Authors: Xu Jinbo
Published: November 2018

Direct coupling analysis (DCA) for protein folding has made very good progress, but it is not effective for proteins that lack many sequence homologs, even coupled with time-consuming folding simulation. We show that we can accurately predict the distance matrix of a protein by deep learning, even for proteins with ∼60 sequence homologs. Using only the geometric constraints given by the resulting distance matrix we may construct 3D models without involving any folding simulation. Our method successfully folded 21 of the 37 CASP12 hard targets with a median family size of 58 effective sequence homologs within 4 hours on a Linux computer of 20 CPUs. In contrast, DCA cannot fold any of these hard targets in the absence of folding simulation, and the best CASP12 group folded only 11 of them by integrating DCA-predicted contacts into complex, fragment-based folding simulation. Rigorous experimental validation in CASP13 shows that our distance-based folding server successfully folded 17 of 32 hard targets (with a median family size of 36 sequence homologs) and obtained 70% precision on top L/5 long-range predicted contacts. Latest experimental validation in CAMEO shows that our server predicted correct fold for two membrane proteins of new fold while all the other servers failed. These results imply that it is now feasible to predict correct fold for proteins lack of similar structures in PDB on a personal computer without folding simulation.

Significance

Accurate description of protein structure and function is a fundamental step towards understanding biological life and highly relevant in the development of therapeutics. Although greatly improved, experimental protein structure determination is still low-throughput and costly, especially for membrane proteins. As such, computational structure prediction is often resorted. Predicting the structure of a protein with a new fold (i.e., without similar structures in PDB) is very challenging and usually needs a large amount of computing power. This paper shows that by using a powerful deep learning technique, even with only a personal computer we can predict new folds much more accurately than ever before. This method also works well on membrane protein folding.
Viable and efficient electroporation-based genetic manipulation of unstimulated human T cells
Authors: Aksoy Pinar , Aksoy Bülent Arman , Czech Eric , Hammerbacher Jeff
Published: November 2018

Electroporation is the most feasible non-viral material delivery system for manipulating human T cells given its time- and cost-effectiveness. However, efficient delivery requires electroporation settings to be optimized for different devices, cellular states, and materials to be delivered. Here, we used electroporation to either induce exogenous gene expression in human primary T cells by plasmids or in vitro transcribed (IVT) mRNA and also target endogenous genes by Cas9 ribonucleoproteins (RNPs). We characterized the electroporation conditions both for activated and unstimulated human T cells. Although naive cells are non-dividing and therefore their genetic manipulation is harder compared to activated T cells, we developed the technical ability to manipulate both naive and memory cells within the unstimulated T cell population by IVT mRNA and Cas9 RNP electroporation. Here, we outline the best practices for achieving highly-efficient genetic manipulation in primary T cells without causing significant cytotoxicity to the cells. Because there is increasing evidence for “less-differentiated” T cells to have better anti-tumor activity for immunotherapy, manipulating naive T cells with high efficiency is also of high importance to clinical applications and to study the biology of these cells.
Early detonation by sprouted mossy fibers enables aberrant dentate network activity
Authors: Hendricks William D. , Westbrook Gary L. , Schnell Eric
Published: November 2018

In temporal lobe epilepsy, sprouting of hippocampal mossy fiber axons onto dentate granule cell dendrites creates a recurrent excitatory network. However, unlike mossy fibers projecting to CA3, sprouted mossy fiber synapses depress upon repetitive activation. Thus, despite their proximal location, large presynaptic terminals, and ability to excite target neurons, the impact of sprouted mossy fiber synapses on hippocampal hyperexcitability is unclear. We find that despite their short-term depression, single episodes of sprouted mossy fiber activation in hippocampal slices initiated bursts of recurrent polysynaptic excitation. Consistent with a contribution to network hyperexcitability, optogenetic activation of sprouted mossy fibers reliably triggered action potential firing in postsynaptic dentate granule cells after single light pulses. This pattern resulted in a shift in network recruitment dynamics to an “early detonation” mode and an increased probability of release compared to mossy fiber synapses in CA3. A lack of tonic adenosine-mediated inhibition contributed to the higher probability of glutamate release thus facilitating reverberant circuit activity.

Significance Statement

Sprouted mossy fibers are one of the hallmark histopathological findings in temporal lobe epilepsy. These fibers form recurrent excitatory synapses onto other dentate granule cells that display profound short-term depression. Here, however, we show that although these sprouted mossy fibers weaken substantially during repetitive activation, their initial high probability of glutamate release can activate reverberant network activity. Furthermore, we find that a lack of tonic adenosine inhibition enables this high probability of release and, consequently, recurrent network activity.
Rapid Brain Responses to Familiar vs. Unfamiliar Music – an EEG and Pupillometry study
Authors: Jagiello Robert , Pomper Ulrich , Yoneya Makoto , Zhao Sijia , Chait Maria
Published: November 2018

Human listeners exhibit marked sensitivity to familiar music – perhaps most readily revealed by popular “name that tune” games, in which listeners often succeed in recognizing a familiar song based on extremely brief presentation. In this work we used electro-encephalography (EEG) and pupillometry to reveal the temporal signatures of the brain processes that allow differentiation between familiar and unfamiliar music. Participants (N=10) passively listened to snippets (750 ms) of familiar and, acoustically matched, unfamiliar songs, presented in random order. A group of control participants (N=12), which were unfamiliar with all of the songs, was also used. In the main group we reveal a rapid differentiation between snippets from familiar and unfamiliar songs: Pupil responses showed greater dilation rate to familiar music from 100-300 ms post stimulus onset. Brain responses measured with EEG showed a differentiation between familiar and unfamiliar music from 350 ms post onset but, notably, in the opposite direction to that seen with pupillometry: Unfamiliar snippets were associated with greater responses than familiar snippets. Possible underlying mechanisms are discussed.
Expanding the CITE-seq tool-kit: Detection of proteins, transcriptomes, clonotypes and CRISPR perturbations with multiplexing, in a single assay
Authors: Mimitou Eleni , Cheng Anthony , Montalbano Antonino , Hao Stephanie , Stoeckius Marlon , Legut Mateusz , Roush Timothy , Herrera Alberto , Papalexi Efthymia , Ouyang Zhengquing , Satija Rahul , Sanjana Neville E. , Koralov Sergei B , Smibert Peter
Published: November 2018

Rapid technological progress in the recent years has allowed the high-throughput interrogation of different types of biomolecules from single cells. Combining several of these readouts into integrated multi-omic assays is essential to comprehensively understand and model cellular processes. Here, we report the development of Expanded CRISPR-compatible Cellular Indexing of Transcriptomes and Epitopes by sequencing (ECCITE-seq) for the high-throughput characterization of at least five modalities of information from each single cell: transcriptome, immune receptor clonotypes, surface markers, sample identity and sgRNAs. We demonstrate the use of ECCITE-seq to directly and efficiently capture sgRNA molecules and measure their effects on gene expression and protein levels, opening the possibility of performing high throughput single cell CRISPR screens with multimodal readout using existing libraries and commonly used vectors. Finally, by utilizing the combined phenotyping of clonotype and cell surface markers in immune cells, we apply ECCITE to study a lymphoma sample to discriminate cells and define molecular signatures of malignant cells within a heterogeneous population.
SLIC-CAGE: high-resolution transcription start site mapping using nanogram-levels of total RNA
Authors: Cvetesic Nevena , Leitch Harry G. , Borkowska Malgorzata , Müller Ferenc , Carninci Piero , Hajkova Petra , Lenhard Boris
Published: November 2018

Cap analysis of gene expression (CAGE) is a methodology for genome-wide quantitative mapping of mRNA 5′ ends to precisely capture transcription start sites at a single nucleotide resolution. In combination with high-throughput sequencing, CAGE has revolutionized our understanding of the rules of transcription initiation, led to discovery of new core promoter sequence features, and discovered transcription initiation at enhancers genome-wide. The biggest limitation of CAGE is that even the most recently improved version (nAnT-iCAGE) still requires large amounts of total cellular RNA (5 µg), preventing its application to scarce biological samples such as those from early embryonic development or rare cell types. Here, we present SLIC-CAGE, a Super-Low Input Carrier-CAGE approach to capture 5′ ends of RNA polymerase II transcripts from as little as 5–10 ng of total RNA. This dramatic increase in sensitivity is achieved by specially designed, selectively degradable carrier RNA. We demonstrate the ability of SLIC-CAGE to generate data for genome-wide promoterome with 1000-fold less material than required by existing CAGE methods, by generating a complex, high-quality library from mouse embryonic day 11.5 primordial germ cells.
The use of environmental performance indicators in “the greenest city in Europe”
Authors: Alpenberg Jan , Wnuk-Pel Tomasz , Adamsson Philip , Petersson Johannes
Published: November 2018

Purpose

The purpose of this paper is to examine why and how municipal managers and CEOs for municipally owned companies use the environmental performance indicators.

Design/methodology/approach

A case study approach as a research design was used. In total, 18 semi-structured interviews were conducted among managers for administrative departments and municipal company CEOs.

Findings

This study found that the environmental performance indicators are used by department managers mainly for resource allocation, control and for teaching the employees. The CEOs of the municipal companies use the environmental indicators for communicating with external stakeholders and see the indicators primarily as marketing tools. The main reason why the environmental performance indicators are used in the municipality can be the strong demand from the local politicians to push the “green agenda,” and therefore the managers have to comply.

Research limitations/implications

As in any case study, generalizations from the research should be made with care, but since this is only one municipality, further research is needed to find additional evidence.

Practical implications

The findings of this study have a number of implications for future practice, and it is worth mentioning that clear guidelines for how the information could be made more useful for managers at the managerial level in Växjö municipality (VM) are requested for both the municipal managers and the CEOs.

Social implications

Overall, this study strengthens the idea that environmental performance indicators could be used to a larger extent for communicating with external stakeholders both for municipal departments and companies.

Originality/value

The research adds to the literature by examining different patterns of using environmental performance indicators in a unique setting – in VM, which is called “the greenest city in Europe” and is one of the “pioneers” in environmental work and extensively uses performance indicators.
The impact of knowledge management on knowledge worker productivity
Authors: Kianto Aino , Shujahat Muhammad , Hussain Saddam , Nawaz Faisal , Ali Murad
Published: November 2018

Purpose

The productivity of knowledge workers is crucial not only for organizational innovation and competitiveness but also for sustainable development. In the context of knowledge-intensive firms, implementation of knowledge management is likely to increase knowledge worker productivity. Therefore, the purpose of this paper is to examine the influence of knowledge management on knowledge worker productivity.

Design/methodology/approach

A research framework on the effects of knowledge management processes on knowledge worker productivity is established and empirically tested with data from 336 knowledge workers at five mobile network operator companies in Pakistan.

Findings

The results indicate that knowledge creation and knowledge utilization impact knowledge worker productivity positively and statistically significantly. However, knowledge sharing does not have statistically significant impact on knowledge worker productivity. Demographic factors (gender, managerial position and formal education level) do not moderate the relationship between knowledge management and knowledge worker productivity statistically significantly.

Research limitations/implications

The key limitations are the cross-sectional nature of the data and the geographic limitation to telecom companies in Pakistan.

Practical implications

Irrespective of gender, education and managerial position, implementation of knowledge management can increase knowledge worker productivity. Therefore, knowledge management practices should be implemented to enhance the knowledge worker productivity via fostering the knowledge worker’s engagement in and propensity to knowledge management processes.

Originality/value

This study is among the first to examine the likely influence of knowledge management on the productivity of knowledge workers conclusively while controlling for three individual demographic factors. This study also addresses the effectiveness of knowledge management in the little-explored cultural context of Pakistan.
Adaptive mobile Web server framework for Mist computing in the Internet of Things
Authors: Liyanage Mohan , Chang Chii , Srirama Satish Narayana
Published: November 2018

Purpose

The distant data centre-centric Internet of Things (IoT) systems face the latency issue especially in the real-time-based applications, such as augmented reality, traffic analytics and ambient assisted living. Recently, Fog computing models have been introduced to overcome the latency issue by using the proximity-based computational resources, such as the computers co-located with the cellular base station, grid router devices or computers in local business. However, the increasing users of Fog computing servers cause bottleneck issues and consequently the latency issue arises again. This paper aims to introduce the utilisation of Mist computing (Mist) model, which exploits the computational and networking resources from the devices at the very edge of the IoT networks.

Design/methodology/approach

This paper proposes a service-oriented mobile-embedded Platform as a Service (mePaaS) framework that allows the mobile device to provide a flexible platform for proximal users to offload their computational or networking program to mePaaS-based Mist computing node.

Findings

The prototype has been tested and performance has been evaluated on the real-world devices. The evaluation results have shown the promising nature of mePaaS.

Originality/value

The proposed framework supports resource-aware autonomous service configuration that can manage the availability of the functions provided by the Mist node based on the dynamically changing hardware resource availability. In addition, the framework also supports task distribution among a group of Mist nodes.
Efficiency and ranking of sustainability index of India using DEA-TOPSIS
Authors: Mehta Kiran , Sharma Renuka , Vyas Vishal
Published: November 2018

Purpose

This study aims to assign efficiency score and then ranking the Indian companies known for best practices to control carbon-emission in the environment. It is destined to benchmark one company for best performance on the basis of selected alternatives among its peer group companies.

Design/methodology/approach

The present study has used a hybrid model by applying data envelopment analysis (DEA)-technique for order performance by similarity to ideal solution (TOPSIS) to measure the efficiency and ranking of various decision units on the basis of specified variables.

Findings

The findings of DEA have given the best alternative or best decision-making unit (DMU) among the set of 25 DMUs considered for empirical testing. The DEA technique is used with TOPSIS, which is another popular multi-criteria decision model. The integrated DEA-TOPSIS model has helped to compute the efficiency score of all 25 DMUs of study and also provide a unique rank to each of the efficient unit identified with the help of DEA technique.

Practical implications

The findings of the study have provided Benchmark Company amongst the companies following best practices for saving energy and having best operating profits too. This benchmark business unit can be studied extensively by peer group companies to compare various parameters affecting their efficiency and profits both.

Social implications

The findings of the study will promote the socially responsible practices by corporate citizens and adopt the practices to reduce their carbon footprints. It will also suggest to socially responsible investors to select the benchmark and most efficient companies for investment purpose.

Originality/value

The study is original in terms of measuring efficiency and ranking of companies known for best practices for controlling their carbon footprints and suggesting a benchmark company to its peer group. Also, the integrated approach of using DEA-TOPSIS for such type of studies also makes it distinctive from earlier work done in the related field.
Self-initiated expatriates in the local organizations of developing countries
Authors: Kumar Rajiv , Chhokar Jagdeep
Published: November 2018

Purpose

The purpose of this paper is to report three main findings. First, the paper reports why local organizations in developing countries would demand self-initiated expatriates (SIEs); second, the paper reports why SIEs accept employment with such organizations; and third, the paper reports the factors that seem to govern the role allocation to SIEs.

Design/methodology/approach

The authors used semi-structured interviews to elicit and collect data. The authors followed the procedures of grounded theory for data analysis.

Findings

Local organizations in developing countries seem increasingly willing to employ SIEs. Emergence of hitherto nonexistent businesses, rapid expansion, global ambition and organizational maturity seem to drive the demand for SIEs. Industrial decline elsewhere, attractiveness of emerging economies, challenging role, prior experience within similar countries and non-working spouse are factors that enable the SIEs’ acceptance of employment with such organizations. Required boundary spanning and repatriation status determine the role allocation for SIEs.

Research limitations/implications

The findings may be idiosyncratic as they result from a qualitative research design. External validity could, therefore, be low.

Practical implications

Managers can benefit by comprehending the factors motivating SIEs to work for local organizations in developing countries. SIEs can benefit by understanding why such organizations need them, and the roles they are likely to get therein.

Originality/value

Unlike the typical SIEs studied in literature, the authors theorize about SIEs who move from developed countries to work in developing countries and occupy senior positions. Additionally, unlike a typical SIE study, the authors gathered the perspectives of both SIEs and organizations. Lastly, the paper is about an emerging trend: SIEs’ employment in the local organizations of developing countries.
How nation-level background governance conditions shape the economic payoffs of corporate environmental performance
Authors: Sandhu Sukhbir , Orlitzky Marc , Louche Céline
Published: November 2018

Purpose

Companies develop and implement environmental initiatives in particular national governance and institutional contexts. The purpose of this paper is to study how the background governance conditions of legal systems, economic policies and national culture enable or impede the relationship between corporate environmental performance (CEP) and lagged corporate financial performance (CFP).

Design/methodology/approach

This is an empirical study of 427 MNCs headquartered in 22 different countries. The authors merged data from the SiRi database (generally known as SustainAnalytics now), which contains ratings of stakeholder relations for 427 large corporations with publicly available data from Datastream.

Findings

Drawing on the new institutionalism in economics and sociology, the authors show that common-law systems and high economic freedom in a company’s home country tend to strengthen the CEP-CFP link. In addition, the home-country cultural variables of uncertainty avoidance, long-term orientation, and (to a lesser extent) masculinity may impede the deployment of CEP for maximum financial gain at the organizational level. The macrolevel analysis starts to move the field toward an understanding of the particular national governance configurations that provide the most supportive conditions for any CEP-CFP links.

Originality/value

One of the central questions in the field of organizations and the natural environment is about the background conditions that may incentivize and reward firms to be more environmentally responsive. The paper addresses this issue through a nation-level investigation of the background governance conditions that may help or hinder the relationship between CEP and CFP.
Promoting gender equality in a challenging environment
Authors: Kemper Lena Elisabeth , Bader Anna Katharina , Froese Fabian Jintae
Published: November 2018

Purpose

Gender diversity and equality vary tremendously among countries. This is a particular challenge for foreign subsidiaries, when the level of gender diversity and equality differs between the home and host country. Various indicators such as a low-gender pay gap or a high ratio of females in managerial positions suggest that Scandinavia is ahead in terms of gender diversity and equality, whereas those indicators suggest that the level in Japan is currently lower. The purpose of this paper is to investigate how executives leading Scandinavian subsidiaries operating in Japan perceive this situation, and whether and what kind of actions they take to initiate change.

Design/methodology/approach

This study is based on a qualitative analysis of 20 in-depth interviews with executives of Scandinavian subsidiaries in Japan.

Findings

Findings reveal that executives of Scandinavian subsidiaries respond to the major differences in gender equality between Scandinavia and Japan with three strategies of change: resistance and rigid change, compromise and moderate change, and adaptation and maintaining status quo. Moreover, the findings indicate that the strategy of change varies depending on individual differences of the executives, e.g., nationality, and organizational differences, e.g., subsidiary size.

Research limitations/implications

Due to the small sample size, the generalizability of the findings is limited. Given the paucity of research on this topic, this approach provides first insights for building a basis for future studies.

Originality/value

This study contributes to the scarce literature on gender diversity and equality in multinational enterprises by identifying strategies of how gender equality can be fostered in a non-Western context from a top executive perspective.
Symbolic action methods: how systemic team consultation can help to strengthen the self‐concept of teams and foster team cohesion
Authors: Schweitzer Jochen , Drews Antonia
Published: November 2018

This article describes a workshop format including three symbolic action methods, i.e. the ‘who is who sculpture’, the ‘walking through a team’s history’ technique and the ‘speech chorus’ for use in systemic team consultation. The described action methods are suited for work with large teams and small organisations. They help team members to quickly understand their internal diversity and develop a joint sense of the team’s history, hence strengthening the team’s self‐concept and fostering team cohesion. Teams are thereby enabled to find ways out of experienced states of collective depression or anxiety. If combined with large group approaches such as appreciative inquiry or open space (Owen, 2000), such a workshop can help teams and organisations to move from their present situation towards a shared vision for a desired future. The workshop and its methods have been carried out and evaluated in many systemic therapy teams and small clinical and welfare organisations in Germany, China and the UK, as well as at conference workshops in the US and Russia.

Practitioner points

Three Tools to “make teams and small organizations swing”

Integrated into a one‐day‐ workshop fostering systemic organizational self reflection

Conducted in Germany, China, Russia, the US and the UK
Educational assortative mating: a micro‐educational approach
Authors: Andrade Stefan B. , Thomsen Jens‐Peter
Published: November 2018

This article presents a new way of analysing educational assortative mating patterns, using a detailed ‘micro‐educational’ classification capturing both hierarchical and horizontal forms of educational differentiation. Taking advantage of rich Danish population data, we apply log‐linear models that include four ways of measuring educational homogamy patterns: (a) by returns to education, (b) by macro‐education (five aggregated levels), (c) by field of study (16 categories), and (d) by a disaggregated micro‐educational classification, combining levels and fields of study (54 groups). Our results show declines in educational homogamy from 1984 to 2013, but the odds ratios of being educationally homogamous at the university college and university levels remain of substantial magnitude, by both the macro‐ and micro‐educational measures. The micro‐educational classification outperforms all other measures in explaining the associations in the homogamy tables. The income measure (‘returns to education’) does a particularly poor job of explaining homogamy patterns from 1984 to 2013.
The collective/affective practice of cancer survivorship
Authors: Broom Alex , Kenny Katherine , Kirby Emma , Lwin Zarnie
Published: November 2018

Whether within an atmosphere of hope, or amidst relations of fear, the emotions of cancer are unavoidably collectively produced. Yet persistent individualistic paradigms continue to obscure how the emotions of cancer operate relationally – between bodies, subjects, discourses, and practices – and are intertwined with circulating beliefs, cultural desires, and various forms of normativity. Drawing on interviews with 80 people living with cancer in Australia, this paper illustrates why recognition of the collective enterprise of survivorship – and the collective production of emotion, more generally – is important in light of persistent, culturally dominant conceptions of the individual patient as the primary ‘afflicted’, ‘feeling’, and ‘treated’ subject. Building on previous work on affective relations and moral framings, we posit that the collective affects of survivorship inflect what people living with cancer can, and should, feel. We highlight how such things as hope, resignation, optimism, and dread are ‘products’ of the collective affects of cancer, with implications for how survivorship is lived, felt, and done.
Shortage of energy intake rather than protein intake is associated with sarcopenia in elderly patients with type 2 diabetes: A cross‐sectional study of the KAMOGAWA‐DM cohort
Authors: Okamura Takuro , Miki Akane , Hashimoto Yoshitaka , Kaji Ayumi , Sakai Ryosuke , Osaka Takafumi , Hamaguchi Masahide , Yamazaki Masahiro , Fukui Michiaki
Published: November 2018

Background

Energy intake is important for the maintenance of muscle mass. The relationship between energy intake and sarcopenia in elderly patients with type 2 diabetes (T2D) has been unclear.

Methods

Using a brief‐type self‐administered diet history questionnaire we assessed habitual food and nutrient intake of patients with T2D aged ≥65 years, all of whom were Japanese and physically active, taking part in the KAMOGAWA‐DM cohort study. Patients' body composition was evaluated by bioimpedance analysis. Sarcopenia was defined as having both a grip strength of <26 kg for men and <18 kg for women and a skeletal muscle mass index of <7.0 kg/m2 for men and <5.7 kg/m2 for women. Logistic regression analyses were used to investigate the effect of energy intake on the presence of sarcopenia in this cross‐sectional study of 391 patients (205 men, 186 women).

Results

Fifty‐five patients (14.1%) were diagnosed as having sarcopenia. Energy intake was significantly lower in patients with sarcopenia than without sarcopenia (mean  ±  SD [n = 366] 1498.8 ± 389.4 vs 1786.2 ± 706.7 kcal/d, respectively; P = 0.016). After adjusting for age, sex, exercise, smoking status, HbA1c, and body mass index, patients' energy intake (per 100 kcal) was negatively associated with the presence of sarcopenia (odds ratio 0.86; 95% confidence interval 0.78‐0.95; P = 0.001).

Conclusion

Energy intake was negatively associated with the presence of sarcopenia in elderly patients with T2D.
Owners and Tenants: The Commonwealth Housing Commission and Post‐War Housing, 1943–1949
Authors: Macintyre Stuart
Published: November 2018

This article takes as its point of departure early research by the economic historian David Merrett on owner‐occupiers and tenants. In the light of his subsequent explanation of the growth of sources of finance for house purchasers after 1945, it investigates the post‐war housing program of the Commonwealth government with its emphasis on planning, co‐ordination and public provision. Within the larger context of post‐war reconstruction, it argues that the failure of the public housing program provided the stimulus for the spread of owner‐occupation. The failure is explained as the outcome of economic constraints and the shrinking political capacity of post‐war reconstruction.
Complex and monosomal karyotype are distinct cytogenetic entities with an adverse prognostic impact in paediatric acute myeloid leukaemia. A NOPHO‐DBH‐AML study
Authors: Bager Ninna , Juul‐Dam Kristian L. , Sandahl Julie D. , Abrahamsson Jonas , Beverloo Berna , de Bont Eveline S. J. M. , Ha Shau‐Yin , Jahnukainen Kirsi , Jónsson Ólafur G. , Kaspers Gertjan L. , Kovalova Zhanna , Lausen Birgitte , De Moerloose Barbara , Noren‐Nyström Ulrika , Palle Josefine , Saks Kadri , Zeller Bernward , Kjeldsen Eigil , Hasle Henrik
Published: November 2018

Data on occurrence, genetic characteristics and prognostic impact of complex and monosomal karyotype (CK/MK) in children with acute myeloid leukaemia (AML) are scarce. We studied CK and MK in a large unselected cohort of childhood AML patients diagnosed and treated according to Nordic Society for Paediatric Haematology and Oncology (NOPHO)‐AML protocols 1993–2015. In total, 800 patients with de novo AML were included. CK was found in 122 (15%) and MK in 41 (5%) patients. CK and MK patients were young (median age 2·1 and 3·3 years, respectively) and frequently had FAB M7 morphology (24% and 22%, respectively). Refractory disease was more common in MK patients (15% vs. 4%) and stem cell transplantation in first complete remission was more frequent (32% vs. 19%) compared with non‐CK/non‐MK patients. CK showed no association with refractory disease but was an independent predictor of an inferior event‐free survival (EFS; hazard ratio [HR] 1·43, P = 0·03) and overall survival (OS; HR 1·48, P = 0·01). MK was associated with a poor EFS (HR 1·57, P = 0·03) but did not show an inferior OS compared to non‐MK patients (HR 1·14, P = 0·62). In a large paediatric cohort, we characterized AML with non‐recurrent abnormal karyotype and unravelled the adverse impact of CK and MK on prognosis.
Diagnosis of Hodgkin lymphoma in the modern era
Authors: Wang Hao‐Wei , Balakrishna Jayalakshmi P. , Pittaluga Stefania , Jaffe Elaine S.
Published: November 2018

The Hodgkin lymphomas are a family of unique lymphoma subtypes, in which the nature of the neoplastic cell was enigmatic for many years. Much of the mystery has been solved, with all forms now considered to be of B‐cell origin, in most cases of germinal centre derivation. Today we recognize Hodgkin lymphoma as an eponym that encompasses multiple entities. One of the unifying themes is the major contribution from the tumour microenvironment. Both the character of the neoplastic cells and the nature of the immune environment are critical to accurate diagnosis. Moreover, an understanding of the molecular alterations that characterize both the neoplastic cells and their microenvironment have led to therapeutic advances, targeting both neoplastic and reactive components. Other conditions may foster a similar inflammatory milieu and lead to lymphoproliferations that mimic the Hodgkin lymphomas. In this review we provide an update on the diagnostic features of the various subtypes and include additional information relevant for prognostic evaluation and investigation of potential therapeutic targets. Additionally, we also discuss those conditions that often cause confusion in diagnosis and need to be distinguished from the Hodgkin lymphomas.
A novel complete blood count‐based score to screen for myelodysplastic syndrome in cytopenic patients
Authors: Boutault Robin , Peterlin Pierre , Boubaya Marouane , Sockel Katja , Chevallier Patrice , Garnier Alice , Guillaume Thierry , Le Bourgeois Amandine , Debord Camille , Godon Catherine , Le Bris Yannick , Theisen Olivier , Kroschinsky Frank , Moreau Philippe , Béné Marie C. , Platzbecker Uwe , Eveillard Marion
Published: November 2018

The diagnosis of myelodysplastic syndromes (MDS) is often challenging, time‐ and resource‐consuming. A thorough analysis of complete blood count (CBC) parameters could, however, help to screen for MDS among other causes of cytopenia. To test this hypothesis, 109 newly‐diagnosed MDS patients and 399 cytopenic patients older than 50 years with confirmed absence of MDS were enrolled in a prospective study. Multiparametric analysis highlighted three CBC parameters that were significantly different between the two cohorts: mean corpuscular volume, absolute neutrophil count and median neutrophil complexity and width of dispersion of the events measured (Ne‐WX), which were used to define an MDS‐CBC score. This score enables the prediction of MDS with 86% sensitivity and 88% specificity. The MDS‐CBC score excluded MDS in 89% of cytopenic controls. Moreover, high score values at MDS diagnosis significantly correlated with decreased event‐free (P = 0·02) and overall survival (P = 0·01). The power of this score was confirmed in an independent validation cohort (MDS n = 34, cytopenic controls n = 28). The MDS‐CBC score is an easy and fast tool to exclude or suspect MDS in unselected patients with cytopenia of unknown reasons at the time of analysis, by prompting blood smear examination. It may thus improve allocation of further MDS‐specific work‐up in patients with cytopenia at the time of CBC assessment.
Clinical outcomes in chronic lymphocytic leukaemia associated with expression of CD5, a negative regulator of B‐cell receptor signalling
Authors: Friedman Daphne R. , Guadalupe Eross , Volkheimer Alicia , Moore Joseph O. , Weinberg J. Brice
Published: November 2018

Chronic lymphocytic leukaemia (CLL) is characterized by expression of CD5 on clonal B cells, and is partly driven by activated B‐cell receptor (BCR) signalling. While CD5 is known to be a negative regulator of BCR signalling, it is unknown if variability in CD5 expression exists among patients and whether CLL cell CD5 expression affects CLL clinical outcomes. We assessed the extent to which CD5 expression is correlated with clinical outcomes, and whether this information adds to currently used prognostic markers. We evaluated CD5 expression from 1275 blood samples, established prognostic markers and time to event data from 423 CLL patients followed at the Duke University and Durham VA Medical Centers. CD5 median fluorescence intensity (MFI) was largely stable over time in individual patients, but ranged between 0·5 and 760 in the entire cohort. Lower CD5 MFI was significantly associated with a shorter time to first therapy. CD5 MFI, combined with established clinical and molecular prognostic markers, significantly improved risk‐stratification. CD5 may affect disease outcomes by suppressing signalling through the BCR. Thus, a strategy to modulate CLL cell CD5 expression or function could be a therapeutic approach in CLL.
The role of transplantation in Hodgkin lymphoma
Authors: Broccoli Alessandro , Zinzani Pier Luigi
Published: November 2018

Autologous stem cell transplantation is the standard salvage strategy for young and fit patients with Hodgkin lymphoma failing induction therapy, and is effective in nearly 50% of cases. The quality of response at transplantation is the most relevant prognostic aspect, as patients in complete response can obtain better outcomes. Therefore, first‐line salvage treatments applied before transplantation need to produce high quality responses without excessive myelotoxicity and without affecting peripheral blood stem cell mobilisation. In this sense, the incorporation of new agents active in Hodgkin lymphoma, such as brentuximab vedotin and anti‐programmed death 1 antibodies, in conventional regimens, may help to enhance complete remission rates. Working on conditioning regimen and applying a post‐autologous consolidation treatment (for example with brentuximab vedotin) are two ways for improving transplant outcomes, particularly in patients displaying high‐risk features for early relapse or progression. Allogeneic transplantation maintains its curative potential also in the era of new drugs, although its most correct timing and the most suitable sequence of post‐autologous salvage treatments still remain to be determined.
Cytokine release syndrome and neurotoxicity afterCD19 chimeric antigen receptor‐modified (CAR‐) T cell therapy
Authors: Hay Kevin A.
Published: November 2018

Chimeric antigen receptor‐modified (CAR)‐T cells have demonstrated impressive results in the treatment of haematological malignancies. However, cytokine release syndrome (CRS) and neurotoxicity are common toxicities which are potentially life‐threatening in severe cases. Risk factors forCRSand neurotoxicity identified so far include disease burden, lymphodepletion intensity andCAR‐T cell dose administered. Risk‐adapted dosing, with lowerCAR‐T cell doses administered to B‐cell acute lymphoblastic leukaemia patients with high marrow blast counts, has been successful at decreasing severeCRSrates in this population. Intervention with therapies, such as tocilizumab and corticosteroids, have been effective at ameliorating toxicity, enablingCAR‐T cells to be administered safely to many patients without significantly compromising efficacy. Deeper understanding of the pathophysiology of underlyingCRSand neurotoxicity will enable the development of novel approaches to reduce toxicity and improve outcomes.