bluuebunny/crossref_metadata_2025 huggingface dataset:
tRNAnalysis: A flexible pre-processing and next-generation sequencing data analysis pipeline for transfer RNA
Authors: James-Bott Anna , Cribbs Adam P.
Published: June 2019

Many tools have been developed to analyse small RNA sequencing data, however it remains a challenging task to accurately process reads aligning to small RNA due to their short-read length. Most pipelines have been developed with miRNA analysis in mind and there are currently very few workflows focused on the analysis of transfer RNAs. Moreover, these workflows suffer from being low throughput, difficult to install and lack sufficient visualisation to make the output interpretable. To address these issues, we have built a comprehensive and customisable small RNA-seq data analysis pipeline, with emphasis on the analysis of tRNAs. The pipeline takes as an input a fastq file of small RNA sequencing reads and performs successive steps of mapping and alignment to transposable elements, gene transcripts, miRNAs, snRNAs, rRNA and tRNAs. Subsequent steps are then performed to generate summary statistics on reads of tRNA origin, which are then visualised in a html report. Unlike other low-throughput analysis tools currently available, our high-throughput method allows for the simultaneous analysis of multiple samples and scales with the number of input files. tRNAnalysis is command line runnable and is implemented predominantly using Python and R. The source code is available at https://github.com/Acribbs/tRNAnalysis.
Essential gene networks in acute myeloid leukemia identified using a microRNA-knockout CRISPR library screen
Authors: Gabra Martino , Pastrello Chiara , Machado Nicole , Chow Jonathan Tak-Sum , Kotlyar Max , Tokar Tomas , Jurisica Igor , Salmena Leonardo
Published: June 2019

MicroRNAs (miRNA) are small RNAs that function as key modulators of gene expression. Due to their promiscuity of binding, a single miRNA may regulate several genes and hence, multiple pathways simultaneously. In addition, the 3’-UTR of mRNA can be recognized by several miRNA for suppression or degradation. We built a microRNA-only Knock-out (miRKo) CRISPR/Cas-9 library to identify essential miRNA in Acute Myeloid Leukemia (AML) using OCI-AML2, OCI-AML3 and U937 cell lines as in vitro models. 10 miRNA were identified to be essential in our screen among all three cell lines: miR-19b-1, -19b-2, 29b-2, -302a, -3678, -3713, -3910-1, -4447, -4718 and -6795. By using weighted degrees of association, we identified pathway hubs that uniquely affect all 3 cell lines by integrating miRNA:mRNA networks using mirDIP and pathway analysis using pathDIP. Through the miRKo screen, network membership analyses and biological anticorrelation scoring through patient data analysis, we identified RRP2CA, RPS6KB-1, CREB1, RPM1A, MAPK10, MAP3K2, ITCH, FBX-W7, NR3C1 and XIAP as likely targets of the essential miRNA in AML; and signal transduction, apoptosis, TGF-beta signalling and MAPK signalling as candidate essential pathways in AML.
Mesenchymal stem cells suppress leukemia via macrophage-mediated functional restoration of bone marrow microenvironment
Authors: Xia Chengxiang , Wang Tongjie , Cheng Hui , Dong Yong , Weng Qitong , Sun Guohuan , Zhou Peiqing , Wang Kaitao , Liu Xiaofei , Geng Yang , Ma Shihui , Hao Sha , Xu Ling , Guan Yuxian , Du Juan , Du Xin , Li Yangqiu , Zhu Xiaofan , Shi Yufang , Xu Sheng , Wang Demin , Cheng Tao , Wang Jinyong
Published: June 2019

Bone marrow (BM) mesenchymal stem cells (MSCs) are critical components of the BM microenvironment and play an essential role in supporting hematopoiesis. Dysfunction of MSCs is associated with the impaired BM microenvironment that promotes leukemia development. However, whether and how restoration of the impaired BM microenvironment can inhibit leukemia development remain unknown. Using an established leukemia model and the RNA-seq analysis, we discovered functional degeneration of MSCs during leukemia progression. Importantly, intra-BM instead of systemic transfusion of donor healthy MSCs restored the BM microenvironment, thus systemically altering cytokine expression patterns, improving normal hematopoiesis, reducing tumor burden, and ultimately prolonging survival of the leukemia-bearing mice. Donor MSC treatment restored the function of host MSCs and reprogrammed host macrophages to fulfill tissue-repair function. Transfusion of MSC-reprogrammed macrophages largely recapitulated the therapeutic effects of MSCs. Further, we found that donor MSCs reprogrammed macrophages to reduce leukemia burden through autocrine of IL-6. Taken together, our study reveals that donor MSCs reprogram host macrophages to restore the BM microenvironment and inhibit leukemia development, thus offering rationales for local MSC administration as a potentially effective therapy for leukemia.

Key Points

Key Point 1: Intra-BM transfusion of MSCs restores the BM microenvironment, improves thrombopoiesis, and suppresses MDS/MPN initiated by Nras mutation.

Key Point 2: Donor MSCs reprogram macrophages to restore the BM microenvironment, improve thrombopoiesis, and suppress leukemia.
Auditory attention alterations in migraine: a behavioral and MEG/EEG study
Authors: Masson Rémy , Lévêque Yohana , Demarquay Geneviève , ElShafei Hesham , Fornoni Lesly , Lecaignard Françoise , Morlet Dominique , Bidet-Caulet Aurélie , Caclin Anne
Published: June 2019

Abstract

Objectives

To evaluate alterations of top-down and/or bottom-up attention in migraine and their cortical underpinnings.

Methods

19 migraineurs between attacks and 19 matched control participants performed a task evaluating jointly top-down and bottom-up attention, using visually-cued target sounds and unexpected task-irrelevant distracting sounds. Behavioral responses and MEG/EEG were recorded. Event-related potentials and fields (ERPs/ERFs) were processed and source reconstruction was applied to ERFs.

Results

At the behavioral level, neither top-down nor bottom-up attentional processes appeared to be altered in migraine. However, migraineurs presented heightened evoked responses following distracting sounds (orienting component of the N1 and Re-Orienting Negativity, RON) and following target sounds (orienting component of the N1), concomitant to an increased recruitment of the right temporo-parietal junction. They also displayed an increased effect of the cue informational value on target processing resulting in the elicitation of a negative difference (Nd).

Conclusions

Migraineurs appear to display increased bottom-up orienting response to all incoming sounds, and an enhanced recruitment of top-down attention.

Significance

The interictal state in migraine is characterized by an exacerbation of the orienting response to attended and unattended sounds. These attentional alterations might participate to the peculiar vulnerability of the migraine brain to all incoming stimuli.

Highlights

Migraineurs performed as well as healthy participants in an attention task.

However, EEG markers of both bottom-up and top-down attention are increased.

Migraine is also associated with a facilitated recruitment of the right temporo-parietal junction.
Integration of a FT expression cassette into CRISPR/Cas9 construct enables fast generation and easy identification of transgene-free mutants in Arabidopsis
Authors: Cheng Yuxin , Zhang Na , Hussain Saddam , Ahmed Sajjad , Yang Wenting , Wang Shucai
Published: June 2019

The CRISPR/Cas9 genome editing technique has been widely used to generate transgene-free mutants in different plant species. Several different methods including fluorescence marker-assisted visual screen of transgene-free mutants and programmed self-elimination of CRISPR/Cas9 construct have been use to increase the efficiency of genome edited transgene-free mutants isolation, but the overall time length required to obtain transgene-free mutants has remained unchanged in these methods. We report here a method for fast generation and easy identification of transgene-free mutants in Arabidopsis. By generating and using a single FT expression cassette-containing CRISPR/Cas9 construct, we targeted two sites of the AITR1 gene. We obtained many early bolting plants in T1 generation, and found that about two thirds of these plants have detectable mutations. We then analyzed T2 generations of two representative lines of genome edited early bolting T1 plants, and identified plants without early bolting phenotype, i.e., transgene-free plants, for both lines. Further more, homologues aitr1 mutants were successful obtained for both lines from these transgene-free plants. Taken together, these results suggest that the method described here enables fast generation, and at the mean time, easy identification of transgene-free mutants in plants.
Neurodegeneration exposes firing rate dependent effects on oscillation dynamics in computational neural networks
Authors: Gabrieli D. , Schumm Samantha N. , Parvesse B. , Meaney D.F.
Published: June 2019

Traumatic brain injury (TBI) can lead to neurodegeneration in the injured circuitry, either through primary structural damage to the neuron or secondary effects that disrupt key cellular processes. Moreover, traumatic injuries can preferentially impact subpopulations of neurons, but the functional network effects of these targeted degeneration profiles remain unclear. Although isolating the consequences of complex injury dynamics and long-term recovery of the circuit can be difficult to control experimentally, computational networks can be a powerful tool to analyze the consequences of injury. Here, we use the Izhikevich spiking neuron model to create networks representative of cortical tissue. After an initial settling period with spike-timing-dependent plasticity (STDP), networks developed rhythmic oscillations similar to those seenin vivo. As neurons were sequentially removed from the network, population activity rate and oscillation dynamics were significantly reduced. In a successive period of network restructuring with STDP, network activity levels were returned to baseline for some injury levels and oscillation dynamics significantly improved. We next explored the role that specific neurons have in the creation and termination of oscillation dynamics. We determined that oscillations initiate from activation of low firing rate neurons with limited structural inputs. To terminate oscillations, high activity excitatory neurons with strong input connectivity activate downstream inhibitory circuitry. Finally, we confirm the excitatory neuron population role through targeted neurodegeneration. These results suggest targeted neurodegeneration can play a key role in the oscillation dynamics after injury.

Author Summary

In this study, we study the impact of neuronal degeneration – a process that commonly occurs after traumatic injury and neurodegenerative disease – on the neuronal dynamics in a cortical network. We create computational models of neural networks and include spike timing plasticity to alter the synaptic strength among connections as networks remodel after simulated injury. We find that spike-timing dependent plasticity helps recover the neural dynamics of an injured microcircuit, but it frequently cannot recover the original oscillation dynamics in an uninjured network. In addition, we find that selectively injuring excitatory neurons with the highest firing rate reduced the neuronal oscillations in a circuit much more than either random deletion or the removing neurons with the lowest firing rate. In all, these data suggest (a) plasticity reduces the consequences of neurodegeneration and (b) losing the most active neurons in the network has the most adverse effect on neural oscillations.
Dedifferentiation by adenovirus E1A due to inactivation of Hippo pathway effectors YAP and TAZ
Authors: Zemke Nathan R. , Gou Dawei , Berk Arnold J.
Published: June 2019

Adenovirus transformed cells have a dedifferentiated phenotype. Eliminating E1A in transformed human embryonic kidney cells derepressed ∼2600 genes, generating a gene expression profile closely resembling mesenchymal stem cells (MSCs). This was associated with a dramatic change in cell morphology from one with scant cytoplasm and a globular nucleus to one with increased cytoplasm, extensive actin stress fibers, and actomyosin-dependent flattening against the substratum. E1A-induced hypoacetylation at histone H3 Lys27 and Lys18 (H3K27/18) was reversed. Most of the increase in H3K27/18ac was in enhancers near TEAD transcription factors bound by Hippo signaling-regulated coactivators YAP and TAZ. E1A causes YAP/TAZ cytoplasmic sequestration. After eliminating E1A, YAP/TAZ were transported into nuclei, where they associated with poised enhancers with DNA-bound TEAD4 and H3K4me1. This activation of YAP/TAZ required RHO family GTPase signaling and caused histone acetylation by p300/CBP, chromatin remodeling, and cohesin loading to establish MSC-associated enhancers and then superenhancers. Consistent results were also observed in primary rat embryo kidney cells, human fibroblasts, and human respiratory tract epithelial cells. These results together with earlier studies suggest that YAP/TAZ function in a developmental checkpoint controlled by signaling from the actin cytoskeleton that prevents differentiation of a progenitor cell until it is in the correct cellular and tissue environment.
Phase separation of Polycomb-repressive complex 1 is governed by a charged disordered region of CBX2
Authors: Plys Aaron J. , Davis Christopher P. , Kim Jongmin , Rizki Gizem , Keenen Madeline M. , Marr Sharon K. , Kingston Robert E.
Published: June 2019

Mammalian development requires effective mechanisms to repress genes whose expression would generate inappropriately specified cells. The Polycomb-repressive complex 1 (PRC1) family complexes are central to maintaining this repression. These include a set of canonical PRC1 complexes, each of which contains four core proteins, including one from the CBX family. These complexes have been shown previously to reside in membraneless organelles called Polycomb bodies, leading to speculation that canonical PRC1 might be found in a separate phase from the rest of the nucleus. We show here that reconstituted PRC1 readily phase-separates into droplets in vitro at low concentrations and physiological salt conditions. This behavior is driven by the CBX2 subunit. Point mutations in an internal domain of Cbx2 eliminate phase separation. These same point mutations eliminate the formation of puncta in cells and have been shown previously to eliminate nucleosome compaction in vitro and generate axial patterning defects in mice. Thus, the domain of CBX2 that is important for phase separation is the same domain shown previously to be important for chromatin compaction and proper development, raising the possibility of a mechanistic or evolutionary link between these activities.
Are CRM systems ready for AI integration?
Authors: Chatterjee Sheshadri , Ghosh Soumya Kanti , Chaudhuri Ranjan , Nguyen Bang
Published: June 2019

Purpose

The purpose of this paper is to develop a conceptual framework to check if an organization is ready to adopt an AI-integrated CRM system. The study also analyzes different situations which can provide a comprehensive check list in the form of indicators that could provide a signal indicating whether the organization is ready to adopt an AI-integrated CRM system by capturing actionable and appropriate data.

Design/methodology/approach

The paper is a general review, and appropriate literature has been used to support the conceptual framework.

Findings

The key findings of this study are the different indicators that make up the conceptual framework. This framework can help organizations to check at a glance whether they are ready to adopt AI-integrated CRM system in their organizations. Specifically, it has been identified that different approaches are needed to tackle various types of customer data so that those may be made fit and actionable for appropriate utilization of AI algorithms to facilitate business success of an organization.

Practical implications

The paper has elaborately discussed the different approaches to be undertaken to calibrate and reorient the various kinds of actionable data and the contemplated challenges one would face in doing so. This would help the practitioners that how the data so captured can be made fit for action and utilization toward application of AI technologies integrated with existing CRM system in an organization.

Originality/value

This study is claimed to be a unique study to provide a conceptual framework which could help arranging and rearranging of captured data by an organization for making the data fit and ready for use with the help of AI technologies. This successful integration of AI with CRM system can help organizations toward taking quick and automated decision-making without much intervention of human beings.
Impact of advent of electronic information resources on performance of library users
Authors: Bhat Nazir Ahmad
Published: June 2019

Purpose

The purpose of this study is to assess the impact of advent of electronic information resources on “academic and carrier related core aspects of user performance”.

Design/methodology/approach

Seven sampled agricultural universities across northern India were surveyed personally by the investigator for collecting data about the questions under investigation through a structured questionnaire. The response of the users for each statement under investigation was collected with simple “Yes”/“No” option. The investigator also resorted to the telephonic and e-mail communication to collect prompt response and had a personal interaction with respondents to substantiate the collected responses and remove any ambiguity thereof.

Findings

It is found that the majority of respondents are of the opinion that due to advent of e-resources the users’ interest in studies has enhanced (62.90 per cent) and that the e-resources have played a significant role in timely completion/submission of their study related assignments (74.30 per cent). It is also evident that a good proportion of respondents agree that the advent of e-resources has laid a positive impact on performance of users in “academic examinations” (50.80 per cent), “competitive examinations” (52.80 per cent), and the “interviews” (46.18 per cent) they face. Statistically, it is also verified that the performance of users with respect to five aspects investigated in this study is significantly associated with advent of e-resources (p < 0.01), whereas it does not show any association with one aspect i.e. “timely completion of an academic degree”.

Research limitations/implications

The findings are based on mere opinion of users and need to be verified by devising a well-articulated methodology for verification of the user performance related facts both in print and electronic eras, independent of the users’ opinion.

Practical implications

The findings of this study shall prompt the budget allocating authorities of the libraries to reformulate their fund allocation policies. Findings of this study shall act as logical basis to enhance budget for improving the volume of e-resources. These also emphasize the fact that a provision of recurring fund needs to be created for facilitating single window based anytime anywhere access to the available e-information base, which may include annual subscription charges for availing (i) proxy software services for remote access and (ii) federated search engine for single window searching.

Originality/value

This is first work of its nature in northern Indian agricultural libraries. The findings will be useful for the authorities to decide about the degree of importance the libraries need to endorse with the procurement of information resources in electronic form. The study will really inspire the researchers and librarians to conduct similar studies in other specific domains of knowledge and come out with significant findings and suggestions.
Critical engagement in international business: creating meaning for a broad constituency
Authors: Cairns George M.
Published: June 2019

Purpose

The purpose of this paper is to present a personal reflection on the nature of international business (IB) as a field of both academic study and business practice and, specifically, a domain of political action and societal impact.

Design/methodology/approach

The author summarizes what he consider to be his personal contributions to the field of IB over the 15 years of Critical Perspectives on International Business’s existence, to underpin a set of critically reflective questions on the nature of IB, and to inform a brief ‘manifesto’ for how the author envisages a meaningful future for IB research.

Findings

The argumentation of this paper is directed at supporting IB research and activity that is underpinned by an Aristotelian phronetic perspective – thinking to inform action for the good of society at large.

Originality/value

This paper presents an original perspective from the author, one that appreciates the multitude of perspectives, values and beliefs of the full range of stakeholders who might impact or be impacted by IB activity.
Corporate engagement in humanitarian action
Authors: Hotho Jasper , Girschik Verena
Published: June 2019

Purpose

The purpose of this paper is to open up new lines of research into the engagement of corporations during humanitarian crises. The paper provides an introduction to core concepts in the delivery of humanitarian assistance, as well as a comprehensive overview of when, why, how, and to what effect corporations engage in humanitarian action.

Design/methodology/approach

Building on extant literature and policy reports, the paper synthesizes concepts and insights to map the interdisciplinary field of research on corporate engagement in humanitarian action.

Findings

The paper systematically reviews and describes different dimensions of corporate engagement for delivering humanitarian action and explains key complications that inspire new research questions. In particular, the paper highlights challenges associated with getting corporations to engage in humanitarian action; challenges associated with ensuring effective corporate engagement; and challenges associated with ensuring ethical engagement.

Originality/value

By raising new questions about corporate engagement in humanitarian action, this paper develops an original and positive research agenda for international business, management research, and related fields.
Evaluation of an infused alcohol and drug prevention programme
Authors: Orsini Muhsin Michael , Wyrick David L. , Hansen William B. , O’Sullivan Rita G. , Hallfors Denise , Steckler Allan B. , Ridenour Ty A.
Published: June 2019

Purpose

Alcohol, tobacco, marijuana and other drugs use typically increases in prevalence and frequency during middle and late adolescence. School health instruction often focusses on providing facts and rarely provides tools for addressing the psychosocial risk factors needed to prevent substance use. The purpose of this paper is to report about the effectiveness of a prevention programme delivered in US high school health classes. The intervention augments typical instruction by providing teachers with activities that can be infused in their daily teaching.

Design/methodology/approach

In total, 26 schools were randomly assigned to receive the intervention or serve as controls. Pupils were pretested near the beginning of the school year, posttest near the end of the school year and administered a final test near the beginning of the following school year. Teachers in treatment schools were provided with activities designed to target psychosocial variables known to mediate substance use onset and self-initiated cessation. These include normative beliefs, intentionality, lifestyle incongruence, beliefs about consequences of use, peer pressure resistance skills, decision-making skills, goal setting skills and stress management skills.

Findings

Hierarchical modelling analytic strategies revealed the intervention to have definable positive impacts on alcohol and cigarette use. Moreover, the intervention had strongest effects on alcohol and cigarette use among pupils who were identified at pretest as being lower-than-average risk.

Originality/value

This research provides support for providing teachers with a strategy for preventing alcohol, tobacco and other drugs that can be used in a flexible manner to augment the instruction they are already mandated to provide.
Tacit knowledge in unstructured decision process
Authors: Lucena Fábio de Oliveira , Popadiuk Silvio
Published: June 2019

Purpose

This paper aims to identify the expressions and flows of tacit knowledge in the unstructured decision process. In this type of process, decision-makers use not only the explicit knowledge but also aspects such as intuition, experience and other forms of tacit knowledge. The research developed a qualitative approach, through a study of multiple cases, and applied semi-structured interviews to ten executives. The analysis of data was carried out according to Flores (1994) interpretative analysis of text technique. Results indicated that there was the insertion of tacit knowledge in all unstructured decision-making routines. It was also detected the need to explicitly add the routine of evaluation to the Mintzberg et al.’s (1976) model as elements of tacit knowledge were also identified at this stage of the decision-making process.

Design/methodology/approach

The research has taken a qualitative approach, through a study of multiple cases, applying semi-structured interviews to ten executives. The analysis of data was carried out according to technique for interpretative analysis of the text.

Findings

Results indicated that there was tacit knowledge in all unstructured decision-making routines. Also detected was the need to explicitly add the routine of evaluation to the model.

Research limitations/implications

It was unable to perform psychological studies to investigate the deepest cognitive and emotional aspects of managers, and it does not address, in depth, some issues that are related to tacit knowledge in decisions and that would be considered relevant.

Practical implications

Although this research was unable to dissect the composition of tacit knowledge in unstructured decision process, a better understanding of the aspects that make up the knowledge in question has been developed, providing some decision-making guidelines to managers.

Social implications

The language between communications actors can share decision-making rules to assist in the production and process of arguments necessary for the debate, evaluation and attribution of institutionally recurrent decisions.

Originality/value

The original contribution is present in a detailed description of the expressions of flows of tacit knowledge in unstructured decision-making processes, based on the model of Mintzberg et al. (1976). From the influence of tacit knowledge, it was found that the model in question needs to consider the relevance of the evaluation phase, as a stage equivalent to the other described by Mintzberg et al. (1976). These aspects have been better explained in the introduction and conclusion. Participant observation was not possible because the decision had already been taken by the informant at the moment of the interviews.
Conceptualizing and qualifying disruptive business models
Authors: Schiavi Giovana Sordi , Behr Ariel , Marcolin Carla Bonato
Published: June 2019

Purpose

This paper aims to elaborate a set of characteristics that conceptualize and qualify a disruptive business model.

Design/methodology/approach

The literature on disruptive business models will be analyzed using the latent semantic analysis (LSA) technique, complemented by content analysis, to obtain a more precise qualification and conceptualization regarding disruptive business models.

Findings

The results found described concepts already described in the theory. However, such findings, highlighted by the LSA, bring new perspectives to the analysis of the disruptive business models, little discussed in the literature and which reveal important considerations to be made on this subject.

Research limitations/implications

It should be noted, about the technique used, a limitation on the choice of the number of singular values. For this to be a problem in the open literature, the authors tried to work not just with the cost-benefit ratio given the addition of each new dimension in the analysis, as well as a criterion of saturation of the terms presented.

Practical implications

The presentation of this set of characteristics can be used as a validation tool to identify if a business is or is not a disruptive business model by managers.

Originality/value

The originality of this paper is the achievement of a consolidated set of characteristics that conceptualize and qualify the disruptive business models by conducting an in-depth analysis of the literature on disruptive business models through the LSA technique, considering the difficulty of obtaining precise concepts on this subject in the literature.
Big money, corruption, and black markets
Authors: Custis Tyler , Hoben Meghan , Larsen Payton
Published: June 2019

Purpose

The purpose of this paper is to explore why the stagnant version of amateurism that is being used by the National Collegiate Athletic Association (NCAA) and its member institutions to limit student–athlete compensation is creating labor law and antitrust violations, and ultimately contributing to a black market in college athletics.

Design/methodology/approach

The qualitative portion of the examination uses a review of historic and recent cases regarding labor law and antitrust violations and applies them to the college athletic industry. Furthermore, the quantitative portion creates a scaled revenue sharing calculation utilizing financial reports from university athletic departments and corresponding professional revenue-sharing agreements to discern an approximate value of a student–athlete’s participation.

Findings

The authors find that the current structure of the NCAA and regulatory framework perpetuate injustice for those who lack a voice in the system. Furthermore, the research shows a wage disparity of millions of dollars creating a lack of free market and black-market tensions to reach free market equilibrium.

Social implications

This research creates reasoning to restructure the NCAA system to adjust for modern commercialization and profits of the industry.

Originality/value

This paper highlights the legal and regulatory abuses by the NCAA, and demonstrates how the compensation gap created by these legal violations is creating a strain on free market flow ultimately leading to a black-market effect in the industry.
Racial discrimination in Britain, 1969–2017: a meta‐analysis of field experiments on racial discrimination in the British labour market
Authors: Heath Anthony F. , Di Stasio Valentina
Published: June 2019

Field experiments represent the gold standard for determining whether discrimination occurs. Britain has a long and distinguished history of field experiments of racial discrimination in the labour market, with pioneering studies dating back to 1967 and 1969. This article reviews all the published reports of these and subsequent British field experiments of racial discrimination in the labour market, including new results from a 2016/17 field experiment. The article finds enduring contours of racial discrimination in Britain. Firstly, there is an enduring pattern of modest discrimination against white minorities of European heritage in contrast to much greater risks of discrimination faced by the main non‐white groups, suggesting a strong racial component to discrimination. Secondly, while there is some uncertainty about the magnitude of the risks facing applicants with Chinese and Indian names, the black Caribbean, black African and Pakistani groups all face substantial and very similar risks of discrimination. Thirdly, there is no significant diminution in risks of discrimination over time either for Caribbeans or for South Asians as a whole. These results are broadly in line with those from the ethnic penalties literature, suggesting that discrimination is likely to be a major factor explaining the disproportionately and enduringly high unemployment rates of ethnic minorities.
How should we deal with unexpected results from randomised trials?
Authors: Chien Patrick
Published: June 2019

Deputy Editor‐in‐Chief, Dr Patrick Chien, discusses the latest thinking in women's health and highlights articles from this issue in an audio podcast available at: https://soundcloud.com/bjog/july-editorial-2019
The Geography of Real Property Information and Investment: Firm Location, Asset Location and Institutional Ownership
Authors: Ling David C. , Wang Chongyu , Zhou Tingyu
Published: June 2019

Using a sample of Real Estate Investment Trusts (REITs), we show that institutional investors exploit location‐based information asymmetries by overweighting firms headquartered locally and those with greater economic interests in the investor's home metropolitan statistical area (MSA). This asset allocation strategy is associated with superior portfolio performance. In a difference‐in‐difference‐in‐differences analysis of investor headquarters relocations, we find that investors tend to increase their ownership of REITs that have property holdings in the market to which the investor relocates. Our findings highlight the importance of understanding the relation between information advantages and the geography of firm's operations, as well as the implications on ownership patterns and portfolio construction.
Total RNA Analysis of Bacterial Community Structural and Functional Shifts Throughout Vertebrate Decomposition
Authors: Burcham Zachary M. , Cowick Caitlyn A. , Baugher Courtney N. , Pechal Jennifer L. , Schmidt Carl J. , Rosch Jason W. , Benbow M. Eric , Jordan Heather R.
Published: June 2019

Multiple methods have been proposed to provide accurate time since death estimations, and recently, the discovery of bacterial community turnover during decomposition has shown itself to have predictable patterns that may prove useful. In this study, we demonstrate the use of metatranscriptomics from the postmortem microbiome to simultaneously obtain community structure and functional data across postmortem intervals (PMIs). We found that bacterial succession patterns reveal similar trends as detected through DNA analysis, such as increasing Clostridiaceae as decomposition occurs, strengthening the reliability of total RNA community analyses. We also provide one of the first analyses of RNA transcripts to characterize bacterial metabolic pathways during decomposition. We found distinct pathways, such as amino acid metabolism, to be strongly up‐regulated with increasing PMIs. Elucidating the metabolic activity of postmortem microbial communities provides the first steps to discovering postmortem functional biomarkers since functional redundancy across bacteria may reduce host individual microbiome variability.
Tangential excision debulking with vertical sections prior to Mohs micrographic surgery
Authors: Tucker Simon C , Vinciullo Carl
Published: June 2019

The tangential excision technique for removal of skin tumours has been previously described for truncal superficial BCCs but never before as an option for debulking prior to Mohs micrographic surgery (MMS). Tangential excision debulking with vertical sections represents an alternative to traditional curettage debulking and offers many advantages, most notably a far better tissue specimen for histopathological analysis.
Challenges facing the introduction of SMART patrols in a game reserve, western Tanzania
Authors: Wilfred Paulo , Kayeye Heri , Magige Flora John , Kisingo Alex , Nahonyo Cuthbert L.
Published: June 2019

The spatial monitoring and reporting tool (SMART) is being implemented in Tanzania's protected areas to help improve the efficiency of ranger patrols. Unfortunately, there has been no attempt to understand users' perspectives regarding site‐specific factors likely to affect its use. In this study, we investigated the perspectives of staff in Ugalla Game Reserve, a protected area in western Tanzania, to understand the challenges that affect the use of SMART in the reserve. The main challenges included a lack of motivation to use SMART, limited knowledge of SMART among game scouts, insufficient ranger capacity, difficulty collecting data during night patrols, limited resources for patrolling, and difficulty accessing some remote sections of Ugalla. The presence of trophy hunting company patrol teams has led Ugalla rangers to concentrate their effort in less‐patrolled areas. We recommend introducing incentives to encourage game rangers to use SMART alongside improving patrol coverage in wet seasons. Advanced and regular refresher trainings in SMART should be conducted to enhance data collection. Furthermore, game scouts should be trained and equipped to participate effectively in the SMART process. Although SMART is now becoming increasingly popular in Tanzania, understanding local factors that influence its implementation will be important to improve uptake.
Nationwide epidemiology of early‐onset sepsis in Israel 2010‐2015, time to re‐evaluate empiric treatment
Authors: Glikman Daniel , Curiel Nitzan , Glatman‐Freedman Aharona , Megged Orli , Youngster Ilan , Marom Ronella , Lavie Karen , Smolkin Tatiana , Troitzky Mara , Stein Michal ,   the EOS Israeli study group
Published: June 2019

Aim

Early‐onset neonatal sepsis (EOS) may lead to significant morbidity and mortality, yet the recommended antimicrobials have not changed for many years. We aimed to optimise EOS treatment by examining EOS pathogens, resistance rates and resistance risk factors.

Methods

A retrospective, nationwide cohort study analysing 2010‐2015 EOS data in Israel.

Results

The 21 participating centres constitute 92% of the total birth cohort (around 180 000 live births/year). Of 549 EOS neonates (0.57/1000 live births), 306 (56%) and 243 (44%) were full‐term and preterm, respectively (0.35 vs. 2.94 per/1000 live births). Gram‐negative pathogens predominated, especially in preterms. Escherichia coli and Streptococcus agalactiae were most common pathogens (0.2 and 0.19 per 1000 live births, respectively). In 277 Gram‐negatives, 16%, 14%, 8% and 3% were gentamicin‐resistant, extended‐spectrum beta‐lactamase (ESBL)‐positive, gentamicin‐resistant and ESBL‐positive, and amikacin‐resistant, respectively; preterms had higher resistance rates. No risk factors for antimicrobial resistance were identified. Mortality was reported in 21% of Gram‐negative EOS versus 7% of Gram‐positive EOS [OR 3.4 (95% CI 1.8‐6.2), p < 0.01].

Conclusion

In this nationwide study, EOS was caused predominantly by Gram‐negatives, with high gentamicin resistance and ESBL phenotype rates, without identifiable resistance risk factors. As EOS is life‐threatening, modification of empiric therapy for amikacin‐based regimens should be considered, mainly in preterms.
Rifaximin reduces the incidence of spontaneous bacterial peritonitis, variceal bleeding and all‐cause admissions in patients on the liver transplant waiting list
Authors: Salehi Shayon , Tranah Thomas H. , Lim Samuel , Heaton Nigel , Heneghan Michael , Aluvihare Varuna , Patel Vishal C. , Shawcross Debbie L.
Published: June 2019

Background

Rifaximin reduces the risk of overt hepatic encephalopathy (HE) and is associated with significant reductions in hospitalisations and 30‐day readmissions.

Aim

To examine the outcomes of patients listed for liver transplantation with a diagnosis of HE on rifaximin compared to those naïve to the drug.

Methods

Patient records of those listed for liver transplantation over a 2‐year period were retrospectively reviewed. Patients were included if they had at least two episodes of overt HE resulting in hospitalisation or were encephalopathic at the time of assessment.

Results

Of the 622 patients listed for transplantation, 101 had HE. Sixty‐six patients were treated with rifaximin and 35 were naïve at listing. The use of concurrent lactulose was not significantly different between groups. Median MELD score was similar (15 [14‐16)] rifaximin‐treated and 16 [14‐18] rifaximin‐naïve). Patients on the waiting list treated with rifaximin had reduced all‐cause admissions, episodes of spontaneous bacterial peritonitis and variceal bleeding. Mean length of stay was 9 days (95% CI 6‐12) in the rifaximin‐treated group vs 14 (95% CI 7‐21) in the rifaximin‐naïve group. Multivariate regression analysis demonstrated that rifaximin was independently associated with an increase in average days to readmission (adjusted effect estimate 71, 95% CI 3‐140 days) and reduced likelihood of requirement for prioritisation on the waiting list (odds ratio 0.29; 95% CI 0.89‐0.93).

Conclusion

Rifaximin prescribed for HE in patients listed for liver transplantation improved outcomes with significant reduction in admissions related to spontaneous bacterial peritonitis, ascites and variceal bleeding.
Efficacy and safety of a bortezomib and reduced‐intensity cytarabine‐based protocol, TMC ALLR1, for relapsed childhood ALL in India
Authors: Roy Prakriti , Islam Rubina , Saha Debparna , Gogoi Manash , Kumar Mishra Deepak , Arora Neeraj , Parihar Mayur , Krishnan Shekhar , Saha Vaskar
Published: June 2019

The feasibility of bortezomib (BZB) in induction and reduced cytarabine doses in intensification was evaluated in children with relapsed acute lymphoblastic leukaemia (rALL) at a single centre in India. Of 55 children with rALL, 23 received supportive care and 7 refused treatment, with a median survival of 2 (interquartile range 1–6) months. Twenty‐two (88%) of 25 children who were treated achieved second remission and 9 (69%) of 13 had end‐of‐induction minimal residual disease of <10−4. The lower cytarabine dose was associated with decreased hospitalisation. One‐year event‐free and overall survival for the treated group was 74·7% (95% confidence interval 52–88) and 79·6% (58–91) respectively.
Planning for the future: Exploring the experiences of older carers of adult children with a learning disability
Authors: Deville Jane , Davies Helen , Kane Ros , Nelson David , Mansfield Paul
Published: June 2019

Accessible summary

There are a large number of adults with learning disabilities who live with and are cared for by their parents.

There is a need for interventions to support older carers with their caring role and to plan for a time when they can no longer continue caring.

This research looked at a local support service in England that aimed to support carers over 55 who had an adult child with a learning disability living at home.

Twelve carers were interviewed individually.

The study highlights the unmet needs of older family carers and shows the value of support from a carer perspective.

Background

There are a significant number of adults with a learning disability who live with and are cared for by their parents. There is a pressing need for interventions to support older parent carers with their role and to plan for a time when they can no longer continue caring. This article reports on the experiences of older parent carers who have been in receipt of an intervention to support future planning, in a rural part of England, delivered to older carers of their adult children with learning disabilities.

Methods

Semi‐structured carer interviews (n = 12) were conducted and analysed thematically.

Results

Four themes were identified (a) emotional needs of carer, (b) future planning, (c) accessing other services and resources and (d) links to adult care services. Carers welcomed the flexibility of the intervention and its focus on support for them, relieving their sense of isolation.

Conclusions

The research highlights the unmet needs of older family carers and shows the value of tailored support from a carer perspective. The findings have implications for national social care provision delivered to carers of adult children with learning disabilities in rural areas.
Monitoring of cancer patients via next‐generation sequencing of patient‐derived circulating tumor cells and tumor DNA
Authors: Onidani Kaoru , Shoji Hirokazu , Kakizaki Takahiko , Yoshimoto Seiichi , Okaya Shinobu , Miura Nami , Sekikawa Shoichi , Furuta Koh , Lim Chwee Teck , Shibahara Takahiko , Boku Narikazu , Kato Ken , Honda Kazufumi
Published: June 2019

Liquid biopsy of circulating tumor cells (CTC) and circulating tumor DNA (ctDNA) is gaining attention as a method for real‐time monitoring in cancer patients. Conventional methods based upon epithelial cell adhesion molecule (EpCAM) expression have a risk of missing the most aggressive CTC subpopulations due to epithelial‐mesenchymal transition and may, thus, underestimate the total number of actual CTC present in the bloodstream. Techniques utilizing a label‐free inertial microfluidics approach (LFIMA) enable efficient capture of CTC without the need for EpCAM expression. In this study, we optimized a method for analyzing genetic alterations using next‐generation sequencing (NGS) of extracted ctDNA and CTC enriched using an LFIMA as a first‐phase examination of 30 patients with head and neck cancer, esophageal cancer, gastric cancer and colorectal cancer (CRC). Seven patients with advanced CRC were enrolled in the second‐phase examination to monitor the emergence of alterations occurring during treatment with epidermal growth factor receptor (EGFR)‐specific antibodies. Using LFIMA, we effectively captured CTC (median number of CTC, 14.5 cells/mL) from several types of cancer and detected missense mutations via NGS of CTC and ctDNA. We also detected time‐dependent genetic alterations that appeared during anti–EGFR therapy in CTC and ctDNA from CRC patients. The results of NGS analyses indicated that alterations in the genomic profile revealed by the liquid biopsy could be expanded by using a combination of assays with CTC and ctDNA. The study was registered with the University Hospital Medical Information Network Clinical Trials Registry (ID: UMIN000014095).
Clinical characteristics and depression score response after parathyroidectomy in primary hyperparathyroidism
Authors: Kearns Ann E. , Espiritu Rachel P. , Vickers Douglass Kristin , Thapa Prabin , Wermers Robert A.
Published: June 2019

Objective

Several studies indicate that patients with primary hyperparathyroidism (PHPT) undergoing parathyroid surgery have improvement in mood and neuropsychological functioning. The current analysis aims to examine the relationship between biochemical and clinical variables and the improvement in depression scores and in specific symptoms, after parathyroidectomy.

Design

A prospective observational case‐control study at a referral centre.

Patients

Patients with PHPT undergoing parathyroidectomy (n = 88) or thyroid surgery (n = 85).

Measurements

The Patient Health Questionnaire‐9 (PHQ‐9) was utilized to obtain depression scores at enrolment and 12 months after surgery. The changes in PHQ‐9 were analysed and correlated with baseline clinical and biochemical parameters.

Results

At enrolment, there was no difference between the groups in the number with a depression diagnosis (PHPT 34.1%, thyroid surgery, 35.5%, P = 0.86). However, baseline PHQ‐9 scores were significantly higher in PHPT (median 7.5, range 0‐27) than thyroid surgery patients (median 3.0, range 0‐18, P < 0.0001). Following surgery, all PHQ‐9 scores, total and symptom group (cognitive, somatic) improved and were no longer different between PHPT (total PHQ‐9 median 2, range 0‐16) and thyroid (median 1, range 0‐14, P = 0.31) groups. Baseline parathyroid hormone level, but not calcium, had a weak relationship with change in PHQ‐9 score after parathyroid surgery (P = 0.003). Baseline PHQ‐9 score was correlated with change in PHQ‐9 score at 12 months after parathyroid surgery (P < 0.001).

Conclusions

Depression scores improve in both somatic and cognitive domains after parathyroidectomy for PHPT and baseline severity of depression predicts the response.