bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of a simple method for differential delivery of volatile anaesthetics to the spinal cord of the rabbit
Authors: Zhang Peng , Li Yao , Xu Ting
Published: September 2019

Emulsified volatile anaesthetics can be easily injected into the circulation and eliminated from blood to lungs. Taking advantage of this unique pharmacokinetics, we aimed to develop a less trauma model for preferential delivery of volatile anaesthetics to the spinal cord with an intact CNS and circulatory system in the rabbit. Sixteen New Zealand White rabbits were randomly assigned to the isoflurane and sevoflurane group. A catheter for delivering emulsified isoflurane (8mg/kg/h) or sevoflurane (12mg/kg/h) to the spinal cord was placed into the descending aorta in all rabbits. The concentration and partial pressure of isoflurane and sevoflurane in the jugular and femoral vein were measured. Our results showed that the partial pressure of isoflurane was 3.91±1.11 mmHg in the jugular vein and 12.61±1.60 mmHg (1.0MAC) in the femoral vein. The partial pressure of sevoflurane was 3.89±1.00 mmHg in the jugular vein and 19.92±1.84mmHg (1.0MAC) in the femoral vein. There was significant difference regarding the partial pressure of isoflurane and sevoflurane between jugular and femoral veins in two groups (both P<0.001). In conclusion, a simple method has been successfully developed to selectively deliver isoflurane and sevoflurane to the spinal cord in the rabbit. Before acting on the brain, 69% isoflurane and 81% sevoflurane were removed from body via lungs. This method can be used to investigate the pharmacological properties of volatile anesthetics.
Knowledge discovery with Bayesian Rule Learning for actionable biomedicine
Authors: Balasubramanian Jeya Balaji , Kip Kevin E. , Reis Steven E. , Gopalakrishnan Vanathi
Published: September 2019

Biomarker discovery is critical for both biomedical research and for clinical diagnostic, prognostic, and therapeutic decision-making. They help improve our understanding of the underlying physiological processes within an individual. Discovery of biomarkers from complex biomedical datasets is done using data mining algorithms. Hundreds of thousands of biomarkers have been discovered and reported in literature but only a few dozen have been found to be clinically useful. This discrepancy is because statistical significance is not clinical relevance. Statistical significance only accounts for the correctness of the learned associations. Clinical relevance, in addition to statistical significance, also accounts for clinical utility such as cost-effectiveness, non-invasiveness, efficacy, and safety of the proposed biomarkers. We need models that are statistically significant and clinically relevant, all the while keeping it interpretable. Interpretable classifiers are more actionable in medicine because they offer human-readable explanations for their predictions. Traditional data mining methods cannot account for clinical relevance. We formulate this as a knowledge discovery problem. In computer science, knowledge discovery in databases is “a non-trivial process of the extraction of valid, novel, potentially useful, and ultimately understandable patterns in data”. Bayesian Rule Learning (BRL) finds an optimal Bayesian network to explain the training data and translates that into an interpretable rule model. In this paper, we extend BRL for knowledge discovery (BRL-KD) to enable BRL to incorporate a clinical utility function to learn models that are clinically more relevant. We demonstrate this using a real-world dataset to predict cardiovascular disease outcome. We evaluate predictive performance with the area under the receiver operating characteristic curve (AUROC) and clinical utility with the cost of the model. We show that BRL-KD successfully generates a set of models offering different trade-offs between AUROC and cost. Based on the clinical standard, a model with an acceptable trade-off can then be chosen.
Multiscale mechanical model for cell division orientation in developing biological systems
Authors: Leggio B. , Laussu J. , Faure E. , Lemaire P. , Godin C.
Published: September 2019

Developing biological structures are highly complex systems, within which shape dynamics at different places is tightly coordinated. One key process at play during development is the regulation of cell division orientation. In this work, through a reformulation of cell division in terms of its energetic cost, we propose that oriented cell division is one mechanism by which cells can read and react to mechanical forces propagating in a tissue even in the absence of interphase cellular elongation in the direction of these forces. This view reproduces standard geometric division long-axis rules as a special case of a more general behaviour, in which systematic deviations from these rules can emerge. We show that states of anisotropic tension in multicellular systems can be the cause of these deviations, as often experimentally found in living tissues. Our results provide a unifying view on the different intracellular mechanisms at play in orienting cell division: they are processes which minimize energy loss, reflecting a trade-off between local and long-range mechanical signals. The consequences of this competition are explored in simulated tissues and confirmed in vivo during both the development of the pupal epithelium of dorsal thorax in D. melanogaster and the epidermal morphogenesis of ascidian embryos.

Author summary

In this work we reformulate the process of cell division orientation in development as a mechanical-energy optimization. We show that classical rules for division orientation naturally emerge when a cell minimizes the work performed against its local environment. Moreover, when multicellular stress profiles are taken into account, observed systematic violations of these rules are explained in correlation with states of anisotropic tension within the tissue. We confirm our findings experimentally on developing systems imaged with cellular resolution. Our results provide a new paradigm to understand cell division in multicellular contexts and contribute to building a physical view of biological phenomena.
A hybrid stochastic-deterministic mechanochemical model of cell polarization
Authors: Copos Calina , Mogilner Alex
Published: September 2019

Polarization is a crucial component in cell differentiation, development, and motility and its details are not yet well understood. At the onset of cell locomotion, cells break symmetry to form a well-defined cell front and rear. This polarity establishment varies across cell types: inDictyostelium discoideumcells, it is mediated by biochemical signaling pathways and can function in the absence of a cytoskeleton, while in keratocytes it is tightly connected to cytoskeletal dynamics and mechanics. Theoretical models that have been developed to understand the onset of polarization have explored either signaling or mechanical pathways, yet few have explored mechanochemical mechanisms. However, many motile cells rely on both signaling modules and actin cytoskeleton to break symmetry and achieve a stable polarized state. We propose a general mechanochemical polarization model based on the coupling between a stochastic model for the segregation of signaling molecules and a simplified mechanical model for actin cytoskeleton network competition. We find that local linear coupling between minimally nonlinear signaling and cytoskeletal systems, separately not supporting stable polarization, yields a robustly polarized cell state.
TAK1 Regulates Endothelial Integrity Through Stabilization of Junctions via GSK3β and FoxO1
Authors: Regmi Sushil C. , Soni Dheeraj , Wang Dong-Mei , Vogel Stephen M. , Malik Asrar B. , Tiruppathi Chinnaswamy
Published: September 2019

TLR4 signaling in endothelial cells (ECs) induces vascular injury by disrupting the endothelial junctional barrier. However, it is not known whether TLR4 signaling can also promote endothelial barrier repair after vascular injury. Here we addressed the role of TAK1 activation downstream of TLR4 in the mechanism of vascular integrity. In inducible EC-restricted TAK1 knockout (TAK1iΔEC) mice, the endothelial barrier was compromised. Blocking TAK1 activity caused spontaneous loss of the endothelial barrier. Importantly, TAK1 inactivated GSK3β via AKT to prevent β-catenin downregulation. We observed in ECs of GSK3βiΔEC mice an increase in β-catenin transfer to the nucleus to form a complex with transcription factor FoxO1, thus repressing the expression of the tight junction protein claudin-5 and causing vascular leak. Strikingly, in TAK1iΔEC mice, FoxO1 expression was dramatically increased while expression of AKT was suppressed, and in vivo inhibition of FoxO1 prevented sepsis-induced lung vascular leak in GSK3βiΔEC and TAK1iΔEC mice. Further, EC-restricted deletion of FoxO1 in mice suppressed sepsis-induced lung vascular leak and mortality. Our findings point to the potential of targeting the TAK1-AKT-GSK3β-FoxO1 axis as a therapeutic approach to treat uncontrolled lung vascular leak in sepsis.
Myt1 kinase promotes mitotic cell cycle exit inDrosophilaintestinal progenitor cells
Authors: Willms Reegan J. , Zeng Jie , Campbell Shelagh D.
Published: September 2019

Inhibitory phosphorylation of Cdk1 is a well-established mechanism for gating mitotic entry during development. However, failure to inhibit Cdk1 in adult organs causes ectopic cell division and tissue dysplasia, indicating that Cdk1 inhibition is also required for cell cycle exit. Two types of progenitor cells populate the adultDrosophilamidgut: intestinal stem cells (ISCs) and post-mitotic enteroblasts (EBs). ISCs are the only mitotic cells under homeostatic conditions, dividing asymmetrically to produce quiescent EB daughter cells. We show here that Myt1, the membrane associated Cdk1 inhibitory kinase, is required for EB quiescence and subsequent differentiation. Loss of Myt1 disrupts EB cell cycle dynamics, promoting Cyclin A-dependent mitosis and accumulation of smaller progenitor-like cells that fail to differentiate. Thus, Myt1 inhibition of Cyclin A/Cdk1 functions as a mechanism for coupling cell cycle arrest with terminal cell differentiation in this developmental context.
Stochastic delays suppress noise in a genetic circuit with negative feedback
Authors: Smith Madeline , Singh Abhyudai
Published: October 2019

We consider a mechanistic stochastic model of an autoregulatory genetic circuit with time delays. More specifically, a protein is expressed in random bursts from its corresponding gene. The synthesized protein is initially inactive and becomes active after a time delay. Rather than considering a deterministic delay, a key aspect of this work is to incorporate stochastic time delays, where delay is an independent and identically distributed random variable. The active protein inhibits its own production creating a negative feedback loop. Our analysis reveals that for an exponentially-distributed time delay, the noise in the protein levels decreases to the Poisson limit with increasing mean time delay. Interesting, for a gamma-distributed time delay contrasting noise behaviors emerge based on the negative feedback strength. At low feedback strengths the protein noise levels monotonically decreases to the Poisson limit with increasing average delay. At intermediate feedback strengths, the noise levels first increase to reach a maximum, and then decease back to the Poisson limit with increasing average delay. Finally, for strong feedbacks the protein noise levels monotonically increase with the average delay. For each of these scenarios we provide approximate analytical formulas for the protein mean and noises levels, and validate these results by performing exact Monte Carlo simulations. In conclusion, our results uncover a counter intuitive feature where inclusion of stochastic delays in a negative feedback circuit can play a beneficial role in buffering deleterious fluctuations in the level of a protein.
Oxidation shuts down an auto-inhibitory mechanism of von Willebrand factor
Authors: Tsai Rachel , Interlandi Gianluca
Published: October 2019

The blood protein von Willebrand factor (VWF) is a key link between inflammation and pathological thrombus formation. In particular, oxidation of methionine residues in specific domains of VWF due to the release of oxidants in inflammatory conditions has been linked to an increased platelet-binding activity. However, the atomistic details how methionine oxidation activates VWF have not been elucidated to date. Yet understanding the activation mechanism of VWF under oxidizing conditions can lead to the development of novel therapeutics that target VWF selectively under inflammatory conditions in order to reduce its thrombotic activity while maintaining its haemostatic function. In this manuscript, we used a combination of a dynamic flow assay and molecular dynamics (MD) simulations to investigate how methionine oxidation removes an auto-inhibitory mechanism of VWF. Results from the dynamic flow assay revealed that oxidation does not directly activate the A1 domain, which is the domain in VWF that contains the binding site to the platelet surface receptor glycoprotein Ibα(GpIbα), but rather removes the inhibitory function of the neighboring A2 and A3 domains. Furthermore, the MD simulations combined with free energy perturbation calculations suggested that methionine oxidation may destabilize the binding interface between the A1 and A2 domains leading to unmasking of the GpIbα-binding site in the A1 domain.
eIF5a reduction via decreased Klf5 leads to cell senescence by mitochondrial fission in VSMCs
Authors: Ma Dong , Zheng Bin , Liu He-liang , Zhao Yong-bo , Liu Xiao , Zhang Xin-hua , Li Qiang , Shi Wei-bo , Suzuki Toru , Wen Jin-kun
Published: October 2019

Though dysregulation of mitochondrial dynamics has been linked to cellular senescence, which contributes to advanced age-related disorders, it is unclear how Klf5, an essential transcriptional factor of cardiovascular remodeling, mediates the link between mitochondrial dynamics and vascular smooth muscle cell (VSMC) senescence. Here we show that Klf5 downregulation in VSMCs is correlated with rupture of abdominal aortic aneurysm (AAA), an age-related vascular disease. Mice lacking Klf5 in VSMCs exacerbate vascular senescence and progression of Ang II-induced AAA by facilitating ROS formation. Klf5 knockdown enhances, while Klf5 overexpression suppresses mitochondrial fission. Mechanistically, Klf5 activates eIF5a transcription through binding to the promoter of eIF5a, which in turn preserves mitochondrial integrity by interacting with Mfn1. Accordingly, decreased expression of eIF5a elicited by Klf5 downregulation leads to mitochondrial fission and excessive ROS production. Inhibition of mitochondrial fission decreases ROS production and VSMC senescence. Our studies provide a potential therapeutic target for age-related vascular disorders.
Calcium Phosphate-Mediated Transfection of Eukaryotic Cells with Plasmid DNAs
Authors: Kumar Priti , Nagarajan Arvindhan , Uchil Pradeep D.
Published: October 2019

This protocol describes a calcium phosphate-mediated transfection method for use with plasmid DNAs and adherent cells. At the end of the protocol is an alternative method for high-efficiency generation of stable transfectants.
Study on the particle stratification and penetration of a swing vibrating screen by using DEM
Authors: Ning Shuigen , Xiao Jianzhang , Wang Guifeng , Huang Pengcheng
Published: October 2019

Purpose

As for vibrating screen, the separation of granular materials is a very complicated process, particularly the screening with a swing trace. To study the characteristics of stratification and penetration in the swing vibrating screen, a three-dimensional numerical model was developed to simulate the screening process.

Design/methodology/approach

The discrete element method (DEM) was used to perform the numerical simulation, and the kinetic model of the swing screening was established. The regions of stratification and penetration were defined, and the mathematical functions relating fine particle ratio of stratification and penetration to time were presented using the least squares method.

Findings

The results show that the low value of frequency (5 and 10 Hz) has a limited effect on the stratification, while the obvious effect can be found at high frequency. A low frequencies or small swing angles may enhance the particle penetration. By studying the vibration parameters affecting the stratification and penetration rate, it is found that the frequency has more influence than the swing angle.

Originality/value

The higher screening efficiency and processing capacity can be further obtained for the swing vibrating screen by comparing with the linear vibrating screen. These results reveal the fundamental characteristics of particle motion in the swing screening, which will provide reliable guidance for studying the design optimization of vibrating screen.
Habiba Community: brand management for a family business
Authors: Hamed Sara
Published: October 2019

Learning outcomes

Marketing and brand management examples used in classes usually revolve around publicly traded corporations. Students are expected to learn how to deal with branding problems that can arise in new types of organizations as family businesses.

Case overview/synopsis

The case study discusses a brand identity and brand management problem facing the Founder of Habiba Community, Maged El Said. Habiba Community is an initiative focusing on sustainability and giving back to community. Many foundations were established under Habiba Community, such as its beach lodge, organic farm and learning center. The beach lodge and organic farm were more familiar to tourists and visitors than the other established foundations. The organic farm produced many organic products sold nationally and internationally. The founder was now faced with the challenge of whether to create one brand identity for Habiba Community as a whole or to go for separate brand identities for each of its foundations.

Complexity academic level

This case study is developed for students of the bachelor level in marketing and design studies. The case difficulty is regarded as intermediate as it includes new trends and ideas from the field of marketing and branding (as eco-branding and family business branding) and new trends in the tourism service industry (as voluntourism). Courses in which this case study can be used are integrated marketing communication, corporate identity, services marketing and brand management under marketing and graphic design studies. The case study is not designed for earlier courses in marketing and design, as students need to have basic knowledge in marketing and branding beforehand.

Supplementary materials

Teaching Notes are available for educators only. Please contact your library to gain login details or email support@emeraldinsight.com to request teaching notes.

Subject code

CSS 8: Marketing
The effect of task conflict on outsourcers’ long-term orientation toward suppliers: the moderating role of formal control and Chinese guanxi
Authors: Li Shuting , Haney Mark H. , Lee Gukseong , Kang Mingu , Ko Changsuk
Published: October 2019

Purpose

This paper aims to investigate the antecedents of manufacturing firms’ long-term orientation towards their suppliers in the context of outsourcing relationships in China.

Design/methodology/approach

Based on survey data collected from 224 manufacturing firms in China, this study examines the hypothesized relationships.

Findings

The results show that task conflict has a negative effect on long-term orientation, both Chinese guanxi and formal control are useful governance mechanisms to enhance long-term orientation, and the negative effect of task conflict on the long-term orientation weakens as Chinese guanxi between a manufacturer and its supplier increases.

Originality/value

This study contributes to a better understanding of conflict management in outsourcing relationships in China.
A dimensional analysis of psychological empowerment on engagement
Authors: Joo Baek-Kyoo (Brian) , Bozer Gil , Ready Kathryn J.
Published: October 2019

Purpose

The purpose of this paper is to examine the effects of learning organization culture (LOC), learning goal orientation (LGO) and psychological empowerment (PsyEmp) on employee engagement, focusing on the mediating role of each dimension of PsyEmp (meaning, competence, self-determination and impact).

Design/methodology/approach

Individual perceptions of 329 employees in 9 South Korean for-profit companies were obtained by a cross-sectional survey. Construct validity of each measurement model was examined using confirmatory factor analysis, and the hypothesized structural model was tested by structural equation modeling. Bootstrap analyses were used for testing mediation effects of PsyEmp.

Findings

The authors found that PsyEmp had a significant effect on job engagement, and that LOC and LGO significantly predicted the level of PsyEmp and engagement. The four dimensions of PsyEmp partially mediated the relationship between the two predictors (i.e. LOC and LGO) and job engagement. LGO had a stronger effect than LOC on both PsyEmp and job engagement.

Practical implications

Employees who are high in LGO and perceive that an organization provides opportunities for continuous learning with supportive leadership are more likely to experience improved meaning in their work, competence in their knowledge and skills, and foster self-determination with respect to their personal impact on their work and organization. These important facets of PsyEmp that promote employee engagement should be considered by human resource and OD professionals when recommending workplace changes to improve organizational effectiveness and sustainability.

Originality/value

This study complements the trend to use employee engagement as a proxy for understanding both individual and organizational performance by investigating the relationships among LOC, goal orientation, empowerment and engagement.
A tale of scale: Plot but not neighbourhood tree diversity increases leaf litter ant diversity
Authors: Skarbek Carl J. , Noack Merle , Bruelheide Helge , Härdtle Werner , von Oheimb Goddert , Scholten Thomas , Seitz Steffen , Staab Michael
Published: September 2019

Diversity of producers (e.g. plants) usually increases the diversity of associated organisms, but the scale (i.e. the spatial area of plant diversity considered) at which plant diversity acts on other taxa has rarely been studied. Most evidence for cross‐taxon diversity relations come from above‐ground consumers that directly interact with plants.

Experimental tests of plant diversity effects on elusive organisms inhabiting the leaf litter layer, which are important for nutrient cycling and decomposition, are rare.

Using a large tree diversity experiment, we tested whether tree diversity at the larger plot (i.e. community) or the smaller neighbourhood scale relates to the abundance, species richness, functional and phylogenetic diversity of leaf litter ants, which are dominant organisms in brown food webs.

Contrary to our expectations of scale‐independent positive tree diversity effects, ant diversity increased only with plot but not neighbourhood tree diversity. While the exact causal mechanisms are unclear, nest relocation or small‐scale competition among ants may explain the stronger tree diversity effects at the plot scale.

Our results indicate that even for small and less mobile organisms in the leaf litter, effects of tree diversity are stronger at relatively larger scales. The finding emphasizes the importance of diverse forest stands, in which mixing of tree species is not restricted to small patches, for supporting arthropod diversity in the leaf litter.
Is salvage logging effectively dampening bark beetle outbreaks and preserving forest carbon stocks?
Authors: Dobor Laura , Hlásny Tomáš , Rammer Werner , Zimová Soňa , Barka Ivan , Seidl Rupert
Published: September 2019

Salvage logging is one of most frequently applied management responses to forest disturbances world‐wide. As forest disturbances are increasing, so too is the application of salvage logging, yet its effects on ecosystems remains incompletely understood. In the Norway spruce (Picea abies (L.) Karst.) forests of Europe, salvaging of windfelled trees is inter alia applied to reduce the risk of bark beetle outbreaks (mainly Ips typographus L.). By preventing further disturbances, salvage logging can conserve live tree carbon (C) in forest landscapes. At the same time salvage logging reduces C stocks in detrital pools via the extraction of disturbed trees, its net effect thus remains unclear.

We used the forest landscape model iLand to explore the effect of a wide range of salvaging intensities on (a) subsequent bark beetle outbreaks, and (b) landscape‐scale forest C stocks in a Norway spruce‐dominated production forest in Slovakia under past and future climatic conditions.

Climate change resulted in a two‐ to three‐fold increase in bark beetle disturbances throughout the 21st century in our simulations. We found that removing >95% of disturbed trees can effectively buffer the effect of increasing disturbances, dampening bark beetle infestations and increasing live tree C. Total ecosystem C followed a U‐shaped pattern over salvaging intensity, with highest values in no salvage and 100% salvage scenarios.

However, realistic rates of salvaging (<95% of disturbed trees detected and removed) had no significant effect on bark beetle dynamics and live tree C, and reduced the total ecosystem C stored in the landscape. Furthermore, the effect of reduced bark beetle disturbance under intensive salvaging was partly offset by increased wind disturbance.

Synthesis and applications. Clearing disturbed areas to prevent future disturbances from bark beetles and conserve live tree carbon should only be applied where very high salvaging rates are feasible (i.e. small and concentrated disturbances). Considering that changing disturbance regimes make high‐intensity salvaging increasingly challenging, alternative disturbance management approaches need to be developed.
Testing urban drivers of riparian woody vegetation composition in a precipitation‐limited system
Authors: Solins Joanna P. , Cadenasso Mary L.
Published: September 2019

In precipitation‐limited regions, where water availability is a key driver of vegetation patterns, altered hydrology in urban areas may have a particularly strong effect on riparian plant communities. Urban water inputs can create perennial flows in formerly intermittent streams, potentially providing a water subsidy to riparian plants during dry seasons. However, during rainy seasons, increased storm flow magnitudes in urban areas can cause stream channel incision and associated lowered water tables. Channel incision may reduce riparian soil moisture throughout the year and limit the effect of dry‐season stream flow.

We investigated whether channel incision and dry‐season stream flow were related to the composition of riparian vegetation communities along small streams in Sacramento, California, United States, and whether these two factors interacted. Sacramento has a Mediterranean climate with a long summer dry season. We sampled the riparian woody plant community along 66 stream reaches that created a gradient of channel incision severity across sites with and without dry‐season flow.

The riparian vegetation community was more strongly related to channel incision than dry‐season flow. The two factors did interact in relation to the overall community composition based on multivariate analyses, but we did not detect interactions in univariate generalized linear mixed models predicting specific components of the woody vegetation community, with the exception of large native oak trees. We found that wetland‐associated species and non‐native species both became less prevalent with increasing channel incision. Conversely, native upland oak trees became more prevalent with increasing incision, although large oak trees only showed this pattern along flowing streams. Wetland‐associated seedlings were almost exclusively found along flowing streams.

Synthesis. Our findings suggest that channel incision is a key driver of riparian woody vegetation composition. Although the effects of dry‐season flow were less pronounced, urban water subsidies may be essential for the establishment of wetland‐associated trees along historically intermittent streams. Varied hydrological conditions in precipitation‐limited cities are associated with divergent assemblages of woody species in riparian zones.
Genome‐resolved metagenomics and metatranscriptomics reveal niche differentiation in functionally redundant microbial communities at deep‐sea hydrothermal vents
Authors: Galambos David , Anderson Rika E. , Reveillaud Julie , Huber Julie A.
Published: October 2019

The structure and function of microbial communities inhabiting the subseafloor near hydrothermal systems are influenced by fluid geochemistry, geologic setting and fluid flux between vent sites, as well as biological interactions. Here, we used genome‐resolved metagenomics and metatranscriptomics to examine patterns of gene abundance and expression and assess potential niche differentiation in microbial communities in venting fluids from hydrothermal vent sites at the Mid‐Cayman Rise. We observed similar patterns in gene and transcript abundance between two geochemically distinct vent fields at the community level but found that each vent site harbours a distinct microbial community with differing transcript abundances for individual microbial populations. Through an analysis of metabolic pathways in 64 metagenome‐assembled genomes (MAGs), we show that MAG transcript abundance can be tied to differences in metabolic pathways and to potential metabolic interactions between microbial populations, allowing for niche‐partitioning and divergence in both population distribution and activity. Our results illustrate that most microbial populations have a restricted distribution within the seafloor, and that the activity of those microbial populations is tied to both genome content and abiotic factors.
Communitas and the commons: The open access movement and the dynamics of restructuration in scholarly publishing
Authors: BELL KIRSTEN
Published: October 2019

In this article, the author reflects on the open access movement as a social and political phenomenon via the lens of Turner’s work on liminality and communitas. Moving beyond the neo‐liberalization frame, which is the primary way that the transformations in open access have been conceptualized to date, she argues that they are better understood as a product of the hybridizing relationship between structure and anti‐structure. This perspective allows us to make sense of the open access movement’s seemingly paradoxical qualities, which, the author suggests, point to cultural processes still very much in the subjunctive mood.
Where next for understanding race/ethnic inequalities in severe mental illness? Structural, interpersonal and institutional racism
Authors: Nazroo James Y. , Bhui Kamaldeep S. , Rhodes James
Published: September 2019

In this article we use the example of race/ethnic inequalities in severe mental illness to demonstrate the utility of a novel integrative approach to theorising the role of racism in generating inequality. Ethnic minority people in the UK are at much greater risk than White British people of being diagnosed with a severe – psychosis related – mental illness, and this is particularly the case for those with Black Caribbean or Black African origins. There is entrenched dispute about how we might understand the drivers of this inequality. To address this dispute we build on, and to a certain extent refine, established approaches to theorising structural and institutional racism, and integrate this within a theoretical framework that also incorporates racist/discriminatory interactions (interpersonal racism). We argue that this provides a conceptually robust and thorough analysis of the role of inter‐related dimensions of racism in shaping risks of severe mental illness, access to care, and policy and practice responses. This analysis carries implications for a broader, but integrated, understanding of the fundamental drives of race/ethnic inequalities in health and for an anti‐racism public health agenda.
Asymptomatic azygos vein overflow in a young patient with primary mediastinal seminoma
Authors: Di Liello Raimondo , Sparano Francesca , Iacovino Maria Lucia , Viscardi Giuseppe , Della Corte Carminia Maria , Ronchi Andrea , Sabetta Rosa Laura , Fasano Morena , Vicidomini Giovanni , Reginelli Alfonso , Ciardiello Fortunato , Morgillo Floriana
Published: October 2019

The azygos system is the most important pathway for decompression of the superior vena cava (SVC) when a blood flow obstruction to the right atrium is present. Thoracic and mediastinal malignancies, mainly lung cancers, are responsible for 60%–85% of superior vena cava syndrome (SVCS) cases. An uncommon origin of SVCS is primary malignant mediastinal germ cell tumor (PMMGCT) which represent 1%–4% of all mediastinal tumors and can be divided into two broad groups: seminomas and nonseminomatous germ cell tumors (NSGCTs). Primary mediastinal seminomas clinical presentation is often nonspecific, even if the majority of patients present with superior vena cava involvement. Here, we present the radiologic features of asymptomatic azygos system overflow in a patient with primary mediastinal seminoma.
Increased Sensitivity of Focused Cardiac Ultrasound for Pulmonary Embolism in Emergency Department Patients With Abnormal Vital Signs
Authors: Daley James I. , Dwyer Kristin H. , Grunwald Zachary , Shaw Daniel L. , Stone Michael B. , Schick Alexandra , Vrablik Michael , Kennedy Hall M. , Hall Jane , Liteplo Andrew S. , Haney Rachel M. , Hun Nancy , Liu Rachel , Moore Chris L.
Published: September 2019

Background

Focused cardiac ultrasound (FOCUS) is insensitive for pulmonary embolism (PE). Theoretically, when a clot is large enough to cause vital sign abnormalities, it is more likely to show signs of right ventricular dysfunction on FOCUS, although this has not been well quantified. A rapid bedside test that could quickly and reliably exclude PE in patients with abnormal vital signs could be of high utility in emergency department (ED) patients. We hypothesized that in patients with tachycardia or hypotension, the sensitivity of FOCUS for PE would increase substantially.

Methods

We performed a prospective observational multicenter cohort study involving a convenience sample of patients from six urban academic EDs. Patients suspected to have PE with tachycardia (heart rate [HR] ≥ 100 beats/min) or hypotension (systolic blood pressure [sBP] < 90 mm Hg) underwent FOCUS before computed tomography angiography (CTA). FOCUS included assessment for right ventricular dilation, McConnell's sign, septal flattening, tricuspid regurgitation, and tricuspid annular plane systolic excursion. If any of these were abnormal, FOCUS was considered positive, while if all were normal, FOCUS was considered negative. We a priori planned a subgroup analysis of all patients with a HR ≥ 110 beats/min (regardless of their sBP). We then determined the diagnostic test characteristics of FOCUS for PE in the entire patient population and in the predefined subgroup, based on CTA as the criterion standard. Inter‐rater reliability of FOCUS was determined by blinded review of images by an emergency physician with fellowship training in ultrasound.

Results

A total of 143 subjects were assessed for enrollment and 136 were enrolled; four were excluded because they were non–English‐speaking and three because of inability to obtain any FOCUS windows. The mean (±SD) age of enrolled subjects was 56 (±7) years, mean (±SD) HR was 114 (±12) beats/min, and 37 (27.2%) subjects were diagnosed with PE on CTA. In all subjects, FOCUS was 92% (95% confidence interval [CI] = 78% to 98%) sensitive and 64% specific (95% CI = 53% to 73%) for PE. In the subgroup of 98 subjects with a HR ≥ 110 beats/min, FOCUS was 100% sensitive (95% CI = 88% to 100%) and 63% specific (95% CI = 51% to 74%) for PE. There was substantial interobserver agreement for FOCUS (κ = 1.0, 95% CI = 0.31 to 1.0).

Conclusions

A negative FOCUS examination may significantly lower the likelihood of the diagnosis of PE in most patients who are suspected of PE and have abnormal vital signs. This was especially true in those patients with a HR ≥ 110 beats/min. Our results suggest that FOCUS can be an important tool in the initial evaluation of ED patients with suspected PE and abnormal vital signs.
Mortality of seabirds migrating across the tropical Atlantic in relation to oceanographic processes
Authors: Tavares D. C. , Moura J. F. , Merico A. , Siciliano S.
Published: September 2019

Large‐scale climatic processes such as the El Niño‐Southern Oscillation (ENSO) can have severe effects on the survival of seabirds in their breeding regions. However, there is a fundamental lack of understanding about how environmental factors are related to the mortality of these organisms in non‐breeding areas of the tropics. We investigate here the direct and indirect effects of ENSO and oceanographic variables on the mortality of three migratory seabird species targeted by conservation programmes focused on human impacts: the Atlantic yellow‐nosed albatross Thalassarche chlororhynchos, the Magellanic penguin Spheniscus magellanicus and the Manx shearwater Puffinus puffinus in a non‐breeding area in Brazil, tropical Atlantic. We find that the intensification of ENSO increases the mortality of Manx shearwaters by enhancing the local storm activity. The mortality of Atlantic yellow‐nosed albatrosses and Magellanic penguins is also related to a local increase in storm activity but regardless of the ENSO signature. Increased mortality of Magellanic penguins is observed when biological productivity falls below the annual average (1.7 mg m−3). Adverse climatic conditions are highly deleterious for migratory seabirds and single storm episodes can cause massive deaths, thus exacerbating population declines. We argue that conservation and management strategies for migratory seabirds studied here should not only focus on direct human impacts but should also consider mitigating the effects of climate variability.
Adult neurogenesis in the mammalian dentate gyrus
Authors: Abbott Louise C. , Nigussie Fikru
Published: October 2019

Earlier observations in neuroscience suggested that no new neurons form in the mature central nervous system. Evidence now indicates that new neurons do form in the adult mammalian brain. Two regions of the mature mammalian brain generate new neurons: (a) the border of the lateral ventricles of the brain (subventricular zone) and (b) the subgranular zone (SGZ) of the dentate gyrus of the hippocampus. This review focuses only on new neuron formation in the dentate gyrus of the hippocampus. During normal prenatal and early postnatal development, neural stem cells (NSCs) give rise to differentiated neurons. NSCs persist in the dentate gyrus SGZ, undergoing cell division, with some daughter cells differentiating into functional neurons that participate in learning and memory and general cognition through integration into pre‐existing neural networks. Axons, which emanate from neurons in the entorhinal cortex, synapse with dendrites of the granule cells (small neurons) of the dentate gyrus. Axons from granule cells synapse with pyramidal cells in the hippocampal CA3 region, which send axons to synapse with CA1 hippocampal pyramidal cells that send their axons out of the hippocampus proper. Adult neurogenesis includes proliferation, differentiation, migration, the death of some newly formed cells and final integration of surviving cells into neural networks. We summarise these processes in adult mammalian hippocampal neurogenesis and discuss the roles of major signalling molecules that influence neurogenesis, including neurotransmitters and some hormones. The recent controversy raised concerning whether or not adult neurogenesis occurs in humans also is discussed.
Potential use of stem cells for fertility preservation
Authors: Gauthier‐Fisher A. , Kauffman A. , Librach C. L.
Published: September 2019

Background

Infertility and gonadal dysfunction can result from gonadotoxic therapies, environmental exposures, aging, or genetic conditions. In men, non‐obstructive azoospermia (NOA) results from defects in the spermatogenic process that can be attributed to spermatogonial stem cells (SSC) or their niche, or both. While assisted reproductive technologies and sperm banking can enable fertility preservation (FP) in men of reproductive age who are at risk for infertility, FP for pre‐pubertal patients remains experimental. Therapeutic options for NOA are limited. The rapid advance of stem cell research and of gene editing technologies could enable new FP options for these patients. Induced pluripotent stem cells (iPSC), SSC, and testicular niche cells, as well as mesenchymal stromal cells (aka medicinal signaling cells, MSCs), have been investigated for their potential use in male FP strategies.

Objective

Here, we review the benefits and challenges for three types of stem cell‐based approaches under investigation for male FP, focusing on the role that promising sources of MSC derived from human umbilical cord, specifically human umbilical cord perivascular cells (HUCPVC), could fulfill. These approaches are as follows: 1. isolation and ex vivo expansion of autologous SSC for in vivo transplantation or in vitro spermatogenesis; 2. in vitro differentiation toward germ cell and testicular somatic cell lineages using autologous SSC, or stem cells such iPSC or MSC; and 3. protection or regeneration of the spermatogenic niche after gonadotoxic insults in vivo.

Conclusion

Our studies suggest that HUCPVC are promising sources of cells that could be utilized in multiple aspects of male FP strategies.
Triage of low‐grade squamous intraepithelial lesions using human papillomavirus messenger ribonucleic acid tests—A prospective population‐based register study
Authors: Reinholdt Kristian , Juul Kirsten E. , Dehlendorff Christian , Munk Christian , Kjær Susanne K. , Thomsen Louise T.
Published: September 2019

Introduction

The optimal clinical management of women diagnosed with low‐grade squamous intraepithelial lesions (LSIL) during cervical cancer screening remains unclear. In this prospective cohort study, we compared the clinical performance of two human papillomavirus (HPV) mRNA tests for triage of women with LSIL in Denmark.

Material and methods

In a nationwide pathology register, we identified women aged 23‐65 years with LSIL during 2008‐2012. We included women tested for HPV mRNA with the PreTect HPV Proofer test for five high‐risk HPV types (n = 2176) or the Aptima assay for 14 high‐risk HPV types (n = 426). Subsequent histological diagnoses of cervical intraepithelial neoplasia grades 2, 3 or cancer (CIN2+) were identified in the register. We calculated the sensitivity and specificity for CIN2+ at 18 and 36 months of follow up, and the cumulative incidence of CIN2+ among women testing positive and negative, overall and by age (23‐29, 30‐39, 40‐65 years).

Results

The proportion of women with a positive mRNA test at baseline was higher in women tested with Aptima (66.7%) than in women tested with Proofer (42.8%). After 18 months, Aptima had higher sensitivity for CIN2+ than Proofer (98% [95% CI 94% to 100%] vs 85% [95% CI 82% to 88%]), whereas Proofer showed higher specificity than Aptima (67% [95% CI 64% to 70%]) vs (40% [95% CI 33% to 46%]). Aptima had particularly low specificity in women aged <40 years (23‐29: 19% [95% CI 5% to 36%]; 30‐39: 10% [95% CI 0% to 33%]). The 36‐month cumulative incidence of CIN2+ was higher in Proofer positive (54.3% [95% CI 50.9% to 57.8%]) than in Aptima positive women (37.6% [95% CI 31.2% to 44.8%]). In women with a negative mRNA test, the 36‐month cumulative incidences of CIN2+ were 13.1% (95% CI 10.8% to 15.8%) and 5.9% (95% CI 1.7% to 19.0%) for Proofer and Aptima, respectively.

Conclusions

In women with LSIL, Aptima had high sensitivity for CIN2+, but low specificity, especially in women aged <40 years. The Proofer test may be useful to limit immediate colposcopy referrals in younger women with LSIL, but given its low sensitivity and negative predictive value, Proofer negative women must be followed with repeat cytology.
Review on long‐term non‐renal complications of childhood nephrotic syndrome
Authors: Lee Jiwon M. , Kronbichler Andreas , Shin Jae Il , Oh Jun
Published: September 2019

Background

Nephrotic syndrome (NS) is the most common glomerular childhood disease. A body of literature has described the long‐term renal prognosis of childhood‐onset idiopathic NS. However, the nonrenal outcomes have not been studied as much.

Aim

We aimed to discuss the long‐term non‐renal outcomes of childhood NS, highlighting studies with a follow‐up period of more than 10 years.

Results

We reviewed the literature and found that a number of immunosuppressive agents have stopped inflammation, stabilised the podocyte cytoskeleton and reduce proteinuria. However, prolonged treatment has frequently been associated with a high risk of renal and non‐renal complications in patients with a complicated disease course, defined as frequent relapses or steroid dependency. Non‐renal complications may include impaired longitudinal growth and pubertal development, undesirable fertility outcomes, ocular complications, bone mineral diseases and potential malignancies.

Conclusion

This review discusses and summarises the non‐renal outcomes of idiopathic childhood NS.
Adjusting for time‐varying confounders in survival analysis using structural nested cumulative survival time models
Authors: Seaman Shaun , Dukes Oliver , Keogh Ruth , Vansteelandt Stijn
Published: September 2019

Accounting for time‐varying confounding when assessing the causal effects of time‐varying exposures on survival time is challenging. Standard survival methods that incorporate time‐varying confounders as covariates generally yield biased effect estimates. Estimators using weighting by inverse probability of exposure can be unstable when confounders are highly predictive of exposure or the exposure is continuous. Structural nested accelerated failure time models (AFTMs) require artificial recensoring, which can cause estimation difficulties. Here, we introduce the structural nested cumulative survival time model (SNCSTM). This model assumes that intervening to set exposure at time to zero has an additive effect on the subsequent conditional hazard given exposure and confounder histories when all subsequent exposures have already been set to zero. We show how to fit it using standard software for generalized linear models and describe two more efficient, double robust, closed‐form estimators. All three estimators avoid the artificial recensoring of AFTMs and the instability of estimators that use weighting by the inverse probability of exposure. We examine the performance of our estimators using a simulation study and illustrate their use on data from the UK Cystic Fibrosis Registry. The SNCSTM is compared with a recently proposed structural nested cumulative failure time model, and several advantages of the former are identified.