bluuebunny/crossref_metadata_2025 huggingface dataset:
Gut microbiota and host defense in critical illness
Authors: Jacobs Max C. , Haak Bastiaan W. , Hugenholtz Floor , Wiersinga W. Joost
Published: May 2017

Purpose of review

The review aims to discuss emerging evidence in the field of microbiome-dependent roles in host defense during critical illness with a focus on lung, kidney, and brain inflammation.

Recent findings

The gut microbiota of critical ill patients is characterized by lower diversity, lower abundances of key commensal genera, and in some cases overgrowth by one bacterial genera, a state otherwise known as dysbiosis. Increasing evidence suggests that microbiota-derived components can reach the circulatory system from the gut and modulate immune homeostasis. Dysbiosis might have greater consequences for the critically ill than previously imagined and could contribute to poor outcome. Preclinical studies suggest that impaired communication across the gut – organ axes is associated with brain, lung – and kidney failure.

In health, a diverse microbiome might enhance host defense, while during critical illness, the dysbiotic microbiome might contribute to comorbidity and organ dysfunction. Future research should be aimed at further establishing the causes and consequences of dysbiosis seen in the critically ill, which will provide perspective for developing new strategies of intervention.
Estrogen Receptor, Progesterone Receptor, and Human Epidermal Growth Factor Receptor-2 Testing in Breast Cancer: Assessing the Value of Repeated Centralized Testing in Excision Specimens
Authors: Hariri Nosaibah , Hasteh Farnaz , Walavalkar Vighnesh , Roma Andres A. , Fadare Oluwole
Published: May 2017

At some tertiary breast care centers, where many patients are referred from other institutions, it is routine to repeat testing for estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2/neu) in excision specimens if these tests were performed on the preceding biopsy at the referring facility. The goal of this study is to assess the value of this practice. We documented results from ER, PR, and HER2 testing in 541 consecutive invasive breast cancers excised over a 2.5-year period and analyzed the subset (n=153) for which testing was performed on the excision specimen solely due to the fact that testing on the preceding biopsy was performed at an outside institution. The rates and directions of biopsy-to-excision change were as follows: ER [1.3% (2/153), 100% from (+) to (−)]; PR [4% (6/153), 83% from (+) to (−)]; HER2/neu assessed by immunohistochemistry [21% (29/137)]; HER2/neu assessed by fluorescence in situ hybridization [3.3% (2/61); 50% from amplified to nonamplified and 50% vice versa]. There were no ER(−) and PR(−) biopsy cases that became ER and/or PR(+) in the excision. By coordinate analysis for the hormone receptors [ie, ER and/or PR(+) being indicative of “hormone receptor” (HR) positivity], there were no cases that changed from HR(+) in the biopsy to HR(−) in the excision (or vice versa), which suggests that repeat testing for ER and PR in this setting is of limited value. In an analysis that incorporated both immunohistochemistry and in situ fluorescence hybridization results, there were 2 cases with a clinically significant biopsy-to-excision change in HER2/neu status in which that change was detected primarily because the excision was retested. These findings provide baseline data for formulating policies on whether repeat testing should routinely be performed in the described scenario.
Mantle Cell Lymphoma With Hodgkin and Reed-Sternberg Cells: Review With Illustrative Case
Authors: Kramer Steven , Uppal Guldeep , Wang Zi-Xuan , Gong Jerald Z.
Published: May 2017

Non-Hodgkin lymphoma may occasionally contain large transformed cells resembling Hodgkin and Reed-Sternberg cells (HRS cells). We report a 63-year-old man with HRS cells in a recurrent mantle cell lymphoma (MCL). The patient initially presented with orbital MCL and recurred after 8 years with widespread involvement. The HRS cells were present in the recurrent disease but not in the initial orbital lesions, suggesting a transformed event after a prolonged disease course. Morphologically, the HRS cells were single cells and small clusters among the MCL cells and were frequently accompanied by histiocytes but without eosinophils or other inflammatory cells. The HRS cells showed a phenotype of classic Hodgkin lymphoma (cHL). The HRS cells were clonally related to the MCL, which was demonstrated by the presence of identical t(11;14) that resulted in productive cyclin D1 expression in both cell types. Review of the literature identified 7 additional MCL cases that showed a spectrum of clinical and pathologic features ranging from scattered HRS cells to true composite MCL and cHL. The HRS cells were clonally related to MCL in 4 cases (including the current case) and unrelated in 2 cases. These findings suggest MCL with HRS cells is a heterogeneous group that may represent a spectrum of transformation at the various stages. Proof of clonal relationship between HRS cells and MCL is useful to distinguish these cases from true composite MCL and cHL.
NordiQC Assessments of SOX10 Immunoassays
Authors: Røge Rasmus , Nielsen Søren , Bzorek Michael , Vyberg Mogens
Published: May 2017

This paper is number 1 in a series developed through a partnership between ISIMM and NordiQC for the purpose of reporting research assessing the performance characteristics of immunoassays in an external proficiency testing program.
Use of Smooth Muscle Myosin Heavy Chain as an Effective Marker of Follicular Dendritic Cells
Authors: Ioannidis Ioannis , Laurini Javier A.
Published: May 2017

Smooth muscle myosin heavy chain (SMMHC) is a major structural component of the contractile apparatus in smooth muscle cells. Even though it is considered a relatively specific marker for terminal smooth muscle cell differentiation, expression in other cell types such as follicular dendritic cells (FDCs) has rarely been reported. To determine whether SMMHC represents an effective FDC marker in lymphoid tissues, we compared the immunohistochemical results for SMMHC with those of the traditional FDC markers podoplanin (D2-40) and CD21. Paraffin sections of 44 lymphoid tissues were analyzed, including 31 cases of follicular hyperplasia, 6 cases of follicular lymphoma, 2 cases of peripheral T-cell lymphoma, 3 cases of diffuse large B-cell lymphoma arising in follicular lymphoma, 1 case of nodular sclerosis classical Hodgkin lymphoma, and 1 case of small lymphocytic lymphoma. There was no statistically significant difference between the number of SMMHC-positive and D2-40-positive or CD21+ lymph nodes (P>0.05). The extent and intensity of SMMHC-positive FDCs were similar to those of D2-40-positive FDCs (P=0.127 and 0.733, respectively), but significantly lower compared with those of CD21+ cells (P=0.009 and 0.00002, respectively). However, in contrast to CD21 which was also positive in some germinal center B cells, SMMHC expression was restricted to FDCs. Our results indicate that SMMHC is an excellent marker for FDCs and can be particularly helpful in demonstrating the underlying architecture in lymphoid processes.
Paired Comparison of PD-L1 Expression on Cytologic and Histologic Specimens From Malignancies in the Lung Assessed With PD-L1 IHC 28-8pharmDx and PD-L1 IHC 22C3pharmDx
Authors: Skov Birgit G. , Skov Torsten
Published: May 2017

Background:

Programmed cell death ligand-1 (PD-L1) expression is a predictive biomarker for anti-PD-1 immunotherapy in non–small cell lung cancer. Different immunohistochemistry (IHC) assays have been developed on histologic material with different cutoffs for positivity. More than one third of the patients are diagnosed on cytology alone. We hypothesized that cytologic cell block material is suitable for PD-L1 analysis.

Materials and Methods:

Eighty-six paired samples of malignancies from the lung where cytologic cell block and histologic material were available from the same lesion were stained with PD-L1 IHC 28-8pharmDx and PD-L1 IHC 22C3pharmDx. Scorings of like material (cytology or histology) stained with different assays were analyzed in order to evaluate the analytical agreement between assays. Scoring of different materials stained with like assays were analyzed in order to evaluate the agreement between cytology and histology.

Results:

A high degree of agreement was found between 28-8pharmDx and 22C3pharmDx, whether applied to histologic or cytologic cell blocks, with Pearson R
2 of 0.95. The Pearson R
2 between 2 rounds of assessment of the same assay on the same type of material was also 0.95. The agreement between histologic and cytologic specimens was high with Pearson R
2 0.87 to 0.89 and overall agreement between 85% and 95%. There was no bias toward lower prevalence of positivity with cytology than with histology. Disagreement was related to heterogeneity of the histologic tumor sample.

Conclusion:

PD-L1 assessment is feasible on cytologic material with the tested assays using cutoffs for positivity similar to those used on histologic material.
Use of Elderly Donors in Liver Transplantation
Authors: Ghinolfi Davide , Lai Quirino , Pezzati Daniele , De Simone Paolo , Rreka Erion , Filipponi Franco
Published: May 2017

Objective:

To evaluate the use of elderly donors in liver transplantation (LT) and identify risk factors associated with a worse outcome.

Summary Background Data:

Use of livers from very old donors could expand the donor pool but is not universally implemented.

Methods:

This is a retrospective, single-center medical record review. From January 2001 to December 2014, 1354 LTs were performed. After exclusion of donors <18 years, ABO-incompatible LT, re-LT and UNOS 1 status patients, LT recipients were stratified into 2 groups based on donor age: 18–69 (n=692) vs. ≥70 years (n=515) then matched using a propensity score approach. Two groups were finally matched (young group = 448 cases; old group = 515 cases).

Results:

The median (interquartile range [IQR]) follow-up was 5.0 (2.0–8.4) years. Comparing the 2 identified groups, no differences were observed regarding early retransplants (1.8 vs. 2.9; P = 0.3), HCV-related death (7.6 vs. 8.7%; P = 0.6), vascular (5.8 vs. 5.0%; P = 0.7), and biliary complications (16.5 vs. 18.6%; P = 0.4). On multivariate analysis, independent risk factors for graft loss were: HCV-positive recipient (HR = 2.1; 95% CI = 1.6–2.7; P < 0.001), donor age (HR = 1.0; 95% CI = 1.0–1.0; P < 0.001), cold ischemia time (HR = 1.0; 95% CI = 1.0–1.0; P = 0.042), and donor history of diabetes mellitus (HR = 1.48; 95% CI = 1.03–2.13; P = 0.036).

Conclusions:

Use of elderly donors is not associated per se with an increased risk of vascular and biliary complications. In the presence of cold ischemia time and diabetes mellitus, appropriate donor-to-recipient matching is warranted.
RAS Mutation Clinical Risk Score to Predict Survival After Resection of Colorectal Liver Metastases
Authors: Brudvik Kristoffer W. , Jones Robert P. , Giuliante Felice , Shindoh Junichi , Passot Guillaume , Chung Michael H. , Song Juhee , Li Liang , Dagenborg Vegar J. , Fretland Åsmund A. , Røsok Bård , De Rose Agostino M. , Ardito Francesco , Edwin Bjørn , Panettieri Elena , Larocca Luigi M. , Yamashita Suguru , Conrad Claudius , Aloia Thomas A. , Poston Graeme J. , Bjørnbeth Bjørn A. , Vauthey Jean-Nicolas
Published: May 2017

Objective:

To determine the impact of RAS mutation status on the traditional clinical score (t-CS) to predict survival after resection of colorectal liver metastases (CLM).

Background:

The t-CS relies on the following factors: primary tumor nodal status, disease-free interval, number and size of CLM, and carcinoembryonic antigen level. We hypothesized that the addition of RAS mutation status could create a modified clinical score (m-CS) that would outperform the t-CS.

Methods:

Patients who underwent resection of CLM from 2005 through 2013 and had RAS mutation status and t-CS factors available were included. Multivariate analysis was used to identify prognostic factors to include in the m-CS. Log-rank survival analyses were used to compare the t-CS and the m-CS. The m-CS was validated in an international multicenter cohort of 608 patients.

Results:

A total of 564 patients were eligible for analysis. RAS mutation was detected in 205 (36.3%) of patients. On multivariate analysis, RAS mutation was associated with poor overall survival, as were positive primary tumor lymph node status and diameter of the largest liver metastasis >50 mm. Each factor was assigned 1 point to produce a m-CS. The m-CS accurately stratified patients by overall and recurrence-free survival in both the initial patient series and validation cohort, whereas the t-CS did not.

Conclusions:

Modifying the t-CS by replacing disease-free interval, number of metastases, and CEA level with RAS mutation status produced an m-CS that outperformed the t-CS. The m-CS is therefore a simple validated tool that predicts survival after resection of CLM.
Marek's disease virus infection of phagocytes: a de novo in vitro infection model
Authors: Chakraborty Pankaj , Vervelde Lonneke , Dalziel Robert G , Wasson Peter S , Nair Venugopal , Dutia Bernadette M , Kaiser Pete
Published: May 2017

Marek’s disease virus (MDV) is an alphaherpesvirus that induces T-cell lymphomas in chickens. Natural infections in vivo are caused by the inhalation of infected poultry house dust and it is presumed that MDV infection is initiated in the macrophages from where the infection is passed to B cells and activated T cells. Virus can be detected in B and T cells and macrophages in vivo, and both B and T cells can be infected in vitro. However, attempts to infect macrophages in vitro have not been successful. The aim of this study was to develop a model for infecting phagocytes [macrophages and dendritic cells (DCs)] with MDV in vitro and to characterize the infected cells. Chicken bone marrow cells were cultured with chicken CSF-1 or chicken IL-4 and chicken CSF-2 for 4 days to produce macrophages and DCs, respectively, and then co-cultured with FACS-sorted chicken embryo fibroblasts (CEFs) infected with recombinant MDV expressing EGFP. Infected phagocytes were identified and sorted by FACS using EGFP expression and phagocyte-specific mAbs. Detection of MDV-specific transcripts of ICP4 (immediate early), pp38 (early), gB (late) and Meq by RT-PCR provided evidence for MDV replication in the infected phagocytes. Time-lapse confocal microscopy was also used to demonstrate MDV spread in these cells. Subsequent co-culture of infected macrophages with CEFs suggests that productive virus infection may occur in these cell types. This is the first report of in vitro infection of phagocytic cells by MDV.
Excess Mortality Related to Chikungunya Epidemics in the Context of Co-circulation of Other Arboviruses in Brazil
Authors: Freitas André R. R. , Cavalcanti Luciano P. G. , von Zuben Andrea P. B. , Donalisio M. Rita
Published: May 2017

Chikungunya is an emerging arbovirus that reached the Western Hemisphere at the end of 2013. Studies conducted in Indie Ocean and India suggest that many of deaths associated with chikungunya cannot be recognized by passive surveillance system. The occurrence of these deaths can be inferred by an increase in the overall mortality observed during chikungunya epidemics. To evaluate the mortality associated with chikungunya epidemics in Brazil, we studied monthly mortality by age group comparing the pre-chikungunya period with the chikungunya epidemic period in the most affected states of Brazil. We obtained official data from National System of Notifiable Diseases (SINAN) and Mortality Information System (SIM), both maintained by the Ministry of Health. It was possible to identify a significant increase in all-cause mortality rate during chikungunya epidemics, there was no similar mortality in previous years, even during dengue epidemics. We estimated an excess of 4,842 deaths in Pernambuco during the chikungunya epidemics (51.4/100,000 inhabitants), the most affected age groups were the elderly and under 1 year of age, the same pattern occurred in all states. Further studies at other sites are needed to confirm the association between increased mortality and chikungunya epidemics. If these findings are confirmed, it will be necessary to revise guidelines to recognize the real mortality associated with chikungunya and to improve therapeutic approaches and protective measures in the most vulnerable groups.
Genome-wide analysis of the association of transposable elements with gene regulation suggests thatAluelements have the largest overall regulatory impact
Authors: Zeng Lu , Pederson Stephen M. , Cao Danfeng , Qu Zhipeng , Hu Zhiqiang , Adelson David L. , Wei Chaochun
Published: May 2017

Nearly half of the human genome is made up of transposable elements (TEs) and there is evidence that TEs are involved in gene regulation. Here, we have integrated publicly available genomic, epigenetic and transcriptomic data to investigate this in a genome-wide manner. A bootstrapping statistical method was applied to minimize the confounder effects from different repeat types. Our results show that although most TE classes are primarily associated with reduced gene expression,Aluelements are associated with up regulated gene expression. Furthermore,Aluelements had the highest probability of any TE class of contributing to regulatory regions of any type defined by chromatin state. This suggests a general model where clade specific SINEs may contribute more to gene regulation than ancient/ancestral TEs. Finally, non-coding regions were found to have a high probability of TE content within regulatory sequences, most notably in repressors. Our exhaustive analysis has extended and updated our understanding of TEs in terms of their global impact on gene regulation, and suggests that the most recently derived types of TEs,i.e.clade or species specific SINES, have the greatest overall impact on gene regulation.
Software Application Profile: mrrobust - a tool for performing two-sample summary Mendelian randomization analyses
Authors: Spiller Wesley , Davies Neil M. , Palmer Tom M.
Published: May 2017

Motivation

In recent years Mendelian randomization analysis using summary data from genome-wide association studies has become a popular approach for investigating causal relationships in epidemiology. The mrrobust Stata package implements several of the recently developed methods.

Implementation

mrrobust is freely available as a Stata package.

General Features

The package includes inverse variance weighted estimation, as well as a range of median and MR-Egger estimation methods. Using mrrobust, plots can be constructed visualising each estimate either individually or simultaneously. The package also provides statistics such aswhich are useful in assessing attenuation bias in causal estimates.

Availability

The software is freely available from GitHub [https://raw.github.com/remlapmot/mrrobust/master/].
Detailed analyses of stall force generation inMycoplasma mobilegliding
Authors: Mizutani Masaki , Tulum Isil , Kinosita Yoshiaki , Nishizaka Takayuki , Miyata Makoto
Published: May 2017

Mycoplasma mobileis a bacterium that uses a unique mechanism to glide on solid surfaces at a velocity of up to 4.5 µm/s. Its gliding machinery comprises hundreds of units that generate the force for gliding based on the energy derived from ATP; the units catch and pull on sialylated oligosaccharides fixed to solid surfaces. In the present study, we measured the stall force of wild-type and mutant strains ofM. mobilecarrying a bead manipulated using optical tweezers. The strains that had been enhanced for binding exhibited weaker stall forces than the wild-type strain, indicating that stall force is related to force generation rather than to binding. The stall force of the wild-type strain decreased linearly from 113 to 19 pN following the addition of 0–0.5 mM free sialyllactose (a sialylated oligosaccharide), with a decrease in the number of working units. Following the addition of 0.5 mM sialyllactose, the cells carrying a bead loaded using optical tweezers exhibited stepwise movements with force increments. The force increments ranged from 1 to 2 pN. Considering the 70-nm step size, this small unit force may be explained by the large gear ratio involved in theM. mobilegliding machinery.

SIGNIFICANCE

Mycoplasmais a genus of bacteria that parasitizes animals. Dozens ofMycoplasmaspecies glide over the tissues of their hosts during infection. The gliding machinery ofMycoplasma mobile, the fastest species, includes intracellular motors and hundreds of legs on the cell surface. In the present study, we precisely measured force generation using a highly focused laser beam arrangement (referred to as optical tweezers) under various conditions. The measurements obtained in this study suggest that the rapid gliding exhibited byM. mobilearises from the large gear ratio of its gliding machinery.
Sequential eviction of crowded nucleoprotein complexes by the RecBCD molecular motor
Authors: Terakawa Tsuyoshi , Redding Sy , Silverstein Timothy D. , Greene Eric C.
Published: May 2017

In physiological settings, all nucleic acids motor proteins must travel along substrates that are crowded with other proteins. However, the physical basis for how motor proteins behave in these highly crowded environments remains unknown. Here we use real–time single molecule imaging, kinetic Monte Carlo simulations, and Molecular dynamics simulations to determine how the ATP-dependent translocase RecBCD travels along DNA occupied by tandem arrays of high affinity DNA–binding proteins. We demonstrate that RecBCD forces each protein into its nearest adjacent neighbor, causing rapid disruption of the underlying protein–nucleic acid interface. This mechanism is not simply the same way that RecBCD disrupts isolated nucleoprotein complexes on otherwise naked DNA. Instead, molecular crowding itself completely alters the mechanism by which RecBCD removes tightly bound protein obstacles from DNA.

Significance statement

Chromosomes are crowded places, and any nucleic acid motor proteins that act upon DNA must function within these crowded environments. How crowded environments affect motor protein behaviors remains largely unexplored. Here, we use single molecule fluorescence microscopy visualize the ATP-dependent motor protein RecBCD as it travels along crowded DNA molecules bearing long tandem arrays of DNA-binding proteins. Our findings show that RecBCD can push through highly crowded protein arrays while evicting the proteins from DNA. Molecular dynamics simulations suggest that RecBCD forces the proteins into once another, causing rapid disruption of the protein-DNA interface. These findings may provide insights into how other types of motor proteins travel along crowded nucleic acids.
Nanoscale imaging approaches to quantifying the electrical properties of pathogenic bacteria
Authors: Berthelot Ryan , Neethirajan Suresh
Published: May 2017

Biofilms are natural, resilient films formed when microorganisms adhere to a surface and form a complex three-dimensional structure that allows them to persist in a wide variety of environments. Readily forming in hospitals and on medical equipment, biofilms are frequent causes of infections and their subsequent complications. Due to the complexity of these structures, systematically studying individual bacterial cells and their interactions with their surrounding environment will provide a deeper understanding of the processes occurring within the biofilm as whole versus bulk population based methods that do not differentiate individual cells or species. Methods based on atomic force microscopy (AFM) are particularly suited to the study of individual cells, but are underutilized for the study of bacterial electrical properties. The ability of electrical currents to impair bacterial attachment is well documented, but to utilize electrical current as an effective antibacterial treatment, it is important to understand the electrical properties of bacteria. Therefore, we used AFM, Kelvin probe force microscopy, and ResiScope to measure the surface potential and conductance ofPsuedomonas aeruginosaand methicillin resistanceStaphylococcus aureus(MRSA) on gold and stainless steel. This is the first study to directly measure the electrical resistance of single bacterial cells using ResiScope. Our goal was to develop a framework for measuring biological molecules using conductive atomic force microscopy. We found that the average resistance forP. aeruginosawas 135.4±25.04 GΩ, while MRSA had an average of 173.4±16.28 GΩ. Using KPFM, the surface potential of MRSA shifted from −0.304 V to 0.153 V and from −0.280 V to 0.172 V forP. aeruginosaon gold versus stainless steel substrates, respectively. In an attempt to identify a potential charge carrier, peptidoglycan was also measured with the ResiScope module and shown to have a resistance of 105 GΩ.
The nuclear matrix protein CIZ1 facilitates localization of Xist RNA to the inactive X-chromosome territory
Authors: Ridings-Figueroa Rebeca , Stewart Emma R. , Nesterova Tatyana B. , Coker Heather , Pintacuda Greta , Godwin Jonathan , Wilson Rose , Haslam Aidan , Lilley Fred , Ruigrok Renate , Bageghni Sumia A. , Albadrani Ghadeer , Mansfield William , Roulson Jo-An , Brockdorff Neil , Ainscough Justin F.X. , Coverley Dawn
Published: May 2017

The nuclear matrix protein Cip1-interacting zinc finger protein 1 (CIZ1) promotes DNA replication in association with cyclins and has been linked to adult and pediatric cancers. Here we show that CIZ1 is highly enriched on the inactive X chromosome (Xi) in mouse and human female cells and is retained by interaction with the RNA-dependent nuclear matrix. CIZ1 is recruited to Xi in response to expression of X inactive-specific transcript (Xist) RNA during the earliest stages of X inactivation in embryonic stem cells and is dependent on the C-terminal nuclear matrix anchor domain of CIZ1 and the E repeats of Xist. CIZ1-null mice, although viable, display fully penetrant female-specific lymphoproliferative disorder. Interestingly, in mouse embryonic fibroblast cells derived from CIZ1-null embryos, Xist RNA localization is disrupted, being highly dispersed through the nucleoplasm rather than focal. Focal localization is reinstated following re-expression of CIZ1. Focal localization of Xist RNA is also disrupted in activated B and T cells isolated from CIZ1-null animals, suggesting a possible explanation for female-specific lymphoproliferative disorder. Together, these findings suggest that CIZ1 has an essential role in anchoring Xist to the nuclear matrix in specific somatic lineages.
Single-cell DNA sequencing reveals a late-dissemination model in metastatic colorectal cancer
Authors: Leung Marco L. , Davis Alexander , Gao Ruli , Casasent Anna , Wang Yong , Sei Emi , Vilar Eduardo , Maru Dipen , Kopetz Scott , Navin Nicholas E.
Published: May 2017

Metastasis is a complex biological process that has been difficult to delineate in human colorectal cancer (CRC) patients. A major obstacle in understanding metastatic lineages is the extensive intra-tumor heterogeneity at the primary and metastatic tumor sites. To address this problem, we developed a highly multiplexed single-cell DNA sequencing approach to trace the metastatic lineages of two CRC patients with matched liver metastases. Single-cell copy number or mutational profiling was performed, in addition to bulk exome and targeted deep-sequencing. In the first patient, we observed monoclonal seeding, in which a single clone evolved a large number of mutations prior to migrating to the liver to establish the metastatic tumor. In the second patient, we observed polyclonal seeding, in which two independent clones seeded the metastatic liver tumor after having diverged at different time points from the primary tumor lineage. The single-cell data also revealed an unexpected independent tumor lineage that did not metastasize, and early progenitor clones with the “first hit” mutation in APC that subsequently gave rise to both the primary and metastatic tumors. Collectively, these data reveal a late-dissemination model of metastasis in two CRC patients and provide an unprecedented view of metastasis at single-cell genomic resolution.
In situelectrochemical high-energy X-ray diffraction using a capillary working electrode cell geometry
Authors: Young Matthias J. , Bedford Nicholas M. , Jiang Naisheng , Lin Deqing , Dai Liming
Published: May 2017

The ability to generate new electrochemically active materials for energy generation and storage with improved properties will likely be derived from an understanding of atomic-scale structure/function relationships during electrochemical events. Here, the design and implementation of a new capillary electrochemical cell designed specifically forin situhigh-energy X-ray diffraction measurements is described. By increasing the amount of electrochemically active material in the X-ray path while implementing low-Zcell materials with anisotropic scattering profiles, an order of magnitude enhancement in diffracted X-ray signal over traditional cell geometries for multiple electrochemically active materials is demonstrated. This signal improvement is crucial for high-energy X-ray diffraction measurements and subsequent Fourier transformation into atomic pair distribution functions for atomic-scale structural analysis. As an example, clear structural changes in LiCoO2under reductive and oxidative conditions using the capillary cell are demonstrated, which agree with prior studies. Accurate modeling of the LiCoO2diffraction data using reverse Monte Carlo simulations further verifies accurate background subtraction and strong signal from the electrochemically active material, enabled by the capillary working electrode geometry.
A method to stabilize the incident X-ray energy for anomalous diffraction measurements
Authors: Wang Wenjia , Yang Xiaoyun , Chang Guangcai , An Pengfei , Cha Kewen , Dong Yuhui , Liu Peng
Published: May 2017

A method to calibrate and stabilize the incident X-ray energy for anomalous diffraction data collection is provided and has been successfully used at the single-crystal diffraction beamline 1W2B at the Beijing Synchrotron Radiation Facilities. Employing a feedback loop to control the movement of the double-crystal monochromator, this new method enables the incident X-ray energy to be kept within a 0.2 eV range at the inflection point of the absorption edge.
Improving the turnover intention of tourist hotel employees
Authors: Chen Tso-Jen , Wu Chi-Min
Published: May 2017

Purpose

This study aims to explore the high turnover intention issue in Taiwan’s tourist hotel industry. Due to a lack of empirical research regarding front-line employees’ psychological contract breach perceptions in tourism literature, this study develops an integrated model to examine the causal relationship among transformational leadership behaviors, leader–member exchange (LMX), psychological contract breach and turnover intentions.

Design/methodology/approach

Data from the 226 frontline employees in Taiwan’s tourist hotel industry were employed to examine the proposed hypotheses by using a series of structural equation modeling analyses.

Findings

Statistic results revealed that transformational leadership behaviors influence LMX and LMX in turn influences psychological contract breach, which consequently leads to lower turnover intention.

Practical implication

The results of this study suggest that hospitality organizations should recruit individuals who have the potential to exhibit transformational leadership skills, along with designing leadership training programs for middle- and high-level managers.

Originality/value

This study provides hospitality organization leaders with the necessary information to formulate a beneficial relationship with their front-line employees, which, in turn, weakens their perception of psychological contract breaches and reduces their willingness to leave the organization.
UK company law and precarious employment contracts
Authors: Ndzi Ernestine
Published: May 2017

Purpose

This paper aim to examine the implication of section 172(1)(b) on employment rights, particularly on workers on precarious employment contracts. The aim of the paper is to analyse whether company directors have any liability for potential abuse of worker on precarious employment contracts. The paper examine the advantage of companies recruiting staff on precarious employment contracts and the effect of such contract on the worker.

Design/methodology/approach

The paper reviews case law, statutory provisions and academic opinions on precarious employment contracts and its advantages and disadvantages to the company and the worker. The paper critically reviews the impact of Section 172(1)(b) of the Companies Act 2006 on precarious employment contract workers.

Findings

The paper argues that companies benefit more from precarious employment contracts than workers do. The Companies Act 2006 is silent on whether directors should factor the interest of precarious employment worker when making company decision, thereby leaving these workers in a vulnerable position and at the mercy of the employers.

Originality/value

The paper offers a different argument about why the use of precarious employment contracts is on the rise in the UK. It highlights the silence of the Companies Act 2006 as a driver for the increase in the use of precarious employment contracts in the UK.
Intertemporal risk-return relationship in BRIC equity markets after the US financial crisis
Authors: Singh Amanjot , Singh Manjit
Published: May 2017

Purpose

This paper aims to attempt to capture the intertemporal/time-varying risk–return relationship in the Brazil, Russia, India and China (BRIC) equity markets after the global financial crisis (2007-2009), i.e. during a relative calm period. There has been a significant increase in advanced economies’ equity allocations to the emerging markets ever since the financial crisis. So, the present study is an attempt to account for the said relationship, thereby justifying investments made by the international investors.

Methodology

The study uses non-linear models comprising asymmetric component generalised autoregressive conditional heteroskedastic model in mean (CGARCH-M) (1,1) model, generalised impulse response functions under vector autoregressive framework and Markov regime switching in mean and standard deviation model. The span of data ranges from 1 July 2009 to 31 December 2014.

Findings

The ACGARCH-M (1,1) model reports a positive and significant risk-return relationship in the Russian and Chinese equity markets only. There is leverage and volatility feedback effect in the Russian market because falling returns further increase conditional variance making the investors to expect a risk premium in the expected returns. The impulse responses indicate that for all of the BRIC markets, the ex-ante returns respond positively to a shock in the long-term risk component, whereas the response is negative to a shock in the short-term risk component. Finally, the Markov regime switching model confirms the existence of two regimes in all of the BRIC markets, namely, Bull and Bear regimes. Both the regimes exhibit negative relationship between risk and return.

Practical implications

It is an imperative task to comprehend the relationship shared between risk and returns for an investor. The investors in the emerging economies should understand the risk-return dynamics well ahead of time so that the returns justify the investments made under riskier environment.

Originality/value

The present study contributes to the literature in three senses. First, the data relate to a period especially after the global financial crisis (2007-2009). Second, the study has used a relatively newer version of GARCH based model [ACGARCH-M (1,1) model], generalised impulse response functions and Markov regime switching model to account for the relationship between risk and return. Finally, the study provides an insightful understanding of the risk–return relationship in the most promising emerging markets group “BRIC nations”, making the study first of its kind in all the perspectives.
The role of employer brand equity in employee attraction and retention: a unified framework
Authors: Alshathry Sultan , Clarke Marilyn , Goodman Steve
Published: May 2017

Purpose

The purpose of this paper is to present a conceptual framework for employer brand equity (EBE) that combines both perspectives of employer brand customers into a unified framework for employee attraction and retention.

Design/methodology/approach

This paper extends previous conceptual work on EBE by identifying the role of EBE antecedents in internal and external employer branding. In addition, it recognizes the interactive nature of employer-employee relationship.

Findings

The framework incorporates employee experience with the employer, which relates to the interaction between employee and employer and recognizes the internal and external perspectives simultaneously. Further, the unified framework helps to develop a four-cell typology for the strategic management of an employer brand.

Originality/value

Existing research has failed to integrate the two perspectives of employment customers in a clear model and, thus, offered limited applicability to an employment setting. The EBE framework goes beyond existing models by providing a conceptualization that aims to reflect the employer-brand relationship from the perspective of existing and potential employees. Further, it provides theoretical and empirical rationale for a set of propositions that can empirically be examined in future research.
Gossip: a channel for the development of personal reputation
Authors: Zinko Robert , Tuchtan Charles , Hunt James , Meurs James , Furner Christopher , Prati L. Melita
Published: May 2017

Purpose

The purpose of this study is to empirically test the extent to which gossip plays a role in individual reputation development in the context of contemporary organizations. This study answers the continuous calls to integrate theory across fields by exploring the theoretical links between these two constructs.

Design/methodology/approach

This study provides a conceptual analysis and general review of the literature on gossip and reputation. The relationship between these two constructs is investigated through a two-study package (lab and field) yielding convergent results.

Findings

The findings of this study are that gossip contributes to organizational identity in that it reinforces the social norms of groups and that gossip serves as an important enabler of reputational development. This study provides empirical evidence that gossip serves a more significant role in the development of personal reputation than more formal methods of communication.

Practical implications

As organizations and individuals attempt to develop and capitalize on the effects of individuals’ reputations, this study provides practical insights into the knowledge that needs to be built regarding the method by which this development can occur. This study points to the practical value of gossip in the creation of personal reputation.

Originality/value

The theoretical framework in this study highlights the centrality of gossip as a primary enabler of reputation development in contemporary organizations. Reputation theory is advanced by studying a segment of the construct that has, until now, been excluded from consideration in this field.
Modeling human factors influencing herding during evacuation
Authors: Zafar Muzna , Zia Kashif , Saini Dinesh Kumar , Muhammad Arshad , Ferscha Alois
Published: May 2017

Purpose

It has been witnessed that many incidents of crowd evacuation have resulted in catastrophic results, claiming lives of hundreds of people. Most of these incidents were a result of localized herding that eventually turned into global panic. Many crowd evacuation models have been proposed with different aspects of interests. The purpose of this paper is to attempt to bring together many of these aspects to study evacuation dynamics.

Design/methodology/approach

The proposed agent-based model, in a hypothetical physical environment, uses perception maps for routing decisions which are constructed from agents’ personal observations of the surroundings as well as information gathered through distant communication. Communication is governed by a trust model which measures the authenticity of the information being shared. Agents are of two types; emotional and rational. The trust model is combined with a game-theoretic model to resolve conflict of agents’ own type with that of types of agents in the neighborhood.

Findings

Evacuation dynamics in different environmental and exit strategies are evaluated on the basis of reduced herding and evacuation time. Using this integrated information sharing model, agents gain an overall view of the environment, sufficient to select the optimal path towards exits with respect to reduced herding and evacuation time.

Originality/value

The proposed model has been formulated and established using an agent-based simulation integrating important modeling aspects. The paper helps in understanding the interplay between technological and humanistic aspects in smart and pervasive environments.
A framework for unsupervised change detection in activity recognition
Authors: Bashir Sulaimon Adebayo , Petrovski Andrei , Doolan Daniel
Published: May 2017

Purpose

This purpose of this paper is to develop a change detection technique for activity recognition model. The approach aims to detect changes in the initial accuracy of the model after training and when the model is deployed for recognizing new unseen activities without access to the ground truth. The changes between the two sessions may occur because of differences in sensor placement, orientation and user characteristics such as age and gender. However, many of the existing approaches for model adaptation in activity recognition are blind methods because they continuously adapt the recognition model without explicit detection of changes in the model performance.

Design/methodology/approach

The approach determines the variation between reference activity data belonging to different classes and newly classified unseen data. If there is coherency between the data, it means the model is correctly classifying the instances; otherwise, a significant variation indicates wrong instances are being classified to different classes. Thus, the approach is formulated as a two-level architectural framework comprising of the off-line phase and the online phase. The off-line phase extracts of Shewart Chart change parameters from the training data set. The online phase performs classification of new samples and the detection of the changes in each class of activity present in the data set by using the change parameters computed earlier.

Findings

The approach is evaluated using a real activity-recognition data set. The results show that there are consistent detections that correlate with the error rate of the model.

Originality/value

The developed approach does not use ground truth to detect classifier performance degradation. Rather, it uses a data discrimination method and a base classifier to detect the changes by using the parameters computed from the reference data of each class to discriminate outliers in the new data being classified to the same class. The approach is the first, to the best of the authors’ knowledge, that addresses the problem of detecting within-user and cross-user variations that lead to concept drift in activity recognition. The approach is also the first to use statistical process control method for change detection in activity recognition, with a robust integrated framework that seamlessly detects variations in the underlying model performance.
Workplace bullying in the Australian health context: a systematic review
Authors: Chadwick Sharlene , Travaglia Joanne
Published: May 2017

Purpose

During the past decade, there has been increased attention into bullying behaviours in workplaces. Research to date has varied in design, the definition of what constitutes bullying behaviour, as well as the methods used to collect data and measure bullying incidence and prevalence. Nonetheless, studies demonstrate that bullying is a significant issue, which warrants an increased research focus to develop greater understanding of the concept, its effects and implications in, and for, the workplace. The purpose of this paper is to focus on capturing a range of international and Australian literature regarding workplace bullying behaviours in a health context from a management perspective. As a result, this paper identified the gaps in the literature when expanded specifically to an Australian health context.

Design/methodology/approach

The purpose of this review is to summarise the existing literature, both internationally and in Australia which examines workplace bullying behaviours in a health context from a management perspective. This describes the review of the literature on workplace bullying in a health context undertaken from January to April 2014. The “Preferred Reporting Systematic Reviews and Meta-Analyses” method was used to structure the review, which covered a wide range of literature from databases including MEDLINE, Embase, CINAHL and InformIT, as well as reports, and grey literature.

Findings

The review included 62 studies that met the inclusion criteria and reported either: factors contributing to workplace bullying, at least one significant example of workplace bullying behaviour or the impact of workplace bullying behaviours in a health context.

Originality/value

There is limited data on workplace bullying behaviours in an Australian health context. The literature supports there is value in future research to develop consistent definitions, policies, procedures and frameworks, which could help to prevent or address workplace bullying behaviours based on work being undertaken internationally.
The link between UHC reforms and health system governance: lessons from Asia
Authors: Hort Krishna , Jayasuriya Rohan , Dayal Prarthna
Published: May 2017

Purpose

The purpose of this paper is to examine how and to what extent the design and implementation of universal health coverage (UHC) reforms have been influenced by the governance arrangements of health systems in low- and middle-income countries (LMIC); and how governments in these countries have or have not responded to the challenges of governance for UHC.

Design/methodology/approach

Comparative case study analysis of three Asian countries with substantial experience of UHC reforms (Thailand, Vietnam and China) was undertaken using data from published studies and grey literature. Studies included were those which described the modifications and adaptations that occurred during design and implementation of the UHC programme, the actors and institutions involved and how these changes related to the governance of the health system.

Findings

Each country adapted the design of their UHC programmes to accommodate their specific institutional arrangements, and then made further modifications in response to issues arising during implementation. The authors found that these modifications were often related to the impacts on governance of the institutional changes inherent in UHC reforms. Governments varied in their response to these governance impacts, with Thailand prepared to adopt new governance modes (which the authors termed as an “adaptive” response), while China and Vietnam have tended to persist with traditional hierarchical governance modes (“reactive” responses).

Originality/value

This study addresses a gap in current knowledge on UHC reform, and finds evidence of a complex interaction between substantive health sector reform and governance reform in the LMIC context in Asia, confirming recent similar observations on health reforms in high-income countries.