bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of a Multidisciplinary Care Coordination Program for Frequent Users of the Emergency Department
Authors: Flowers Angela , Shade Kate
Published: August 2019

Purpose of Study:

The purpose of this study was to evaluate the impact of a quality improvement multidisciplinary care coordination program designed to reduce frequent emergency department (ED) utilization and hospital admissions.

Primary Practice Setting:

The single hospital ED is part of a large, integrated, managed care delivery system in Northern California serving the city of Oakland, California.

Methodology and Sample:

A retrospective cohort study design was used to analyze a multidisciplinary care coordination program on 58 patients during January 2015 and August 2018. Patients were identified from a high-utilization report when they had 10 or more ED visits in a 6-month period, were 18 years of age or older, and members of the integrated delivery system's health plan. Data were collected at initiation and 6 months postintervention. The pre-/postanalysis consisted of descriptive statistics, Wilcoxon signed ranks test, and binary logistic regression.

Results:

There was a statistically significant pre-/postdifference of 7.7 ED visits (95% confidence interval [CI] = 4.44–10.97, p < .001). The program did not result in statistically significant reduced hospital admissions (95% CI =−1.24 to 1.45, p = .875). Prior frequent use, number of pre-ED visits, age, sex, complex medical history, and mental health disorder had a significant effect on frequent ED use (χ2[6] =17.62, p = .007, McFadden R
2 = .32]. Sex (odds ratio [OR] = 5.13, p = .070), prior frequent use (OR = 2.87, p = .252), and complex medical history (OR = 2.52, p = .412) had the greatest odds of ongoing frequent ED use.

Implications for Case Management Practice:

We demonstrated reductions in ED use among frequent users with a low-cost care management intervention. Our multidisciplinary care coordination program confirms the positive impact case management has on utilization and health outcomes. We established that a care coordination program can optimize the overall quality of care and control hospital costs incurred by this vulnerable population. The effectiveness of this program contributes to the advancement of case management efforts in undertaking the challenging health care issue of reducing repeated visits by frequent users, a practice that strains emergency medical services.
Delayed Admissions to the Pediatric Intensive Care Unit
Authors: Czolgosz Thomas , Cashen Katherine , Farooqi Ahmad , Kannikeswaran Nirupama
Published: August 2019

Objectives

Few studies have evaluated impact of emergency department (ED) management on delayed transfers to the pediatric intensive care unit (PICU). Our study objectives were to describe patient characteristics of PICU transfers less than or equal to 12 hours of admission and determine the reason for transfer.

Methods

We conducted a retrospective chart review of patients transferred to PICU less than or equal to 12 hours of admission. We extracted patient demographics, emergency severity index category, ED, floor and PICU length of stay (LOS), and PICU “significant” interventions. Charts were reviewed independently by the study principal investigator and a PICU attending who classified transfers as secondary to progression of disease or error in ED management. Furthermore, errors were classified as diagnostic, management, or disposition errors.

Results

A total of 164 patients met inclusion criteria. Most were male (86/164, 52.4%), with emergency severity index category 2 (116/164, 70.7%) and respiratory diagnosis (98/164, 59.8%). Most transfers (136/164, 82.9%) resulted from progression of illness. No significant interventions were performed in 48.8% (80/164) of patients. Of 164 transfers, 28 (17.1%) resulted from ED error, and half of these were management errors. Compared with disease progression, the ED error group had a significantly shorter median floor LOS {3.45 [interquartile range (IQR): 2.15, 7.56] vs 6.58 (IQR: 3.70, 9.20); P = 0.005}, more PICU interventions [1.5 (IQR: 0, 4) vs 0 (IQR: 0, 2); P = 0.006], and longer PICU LOS [2.50 (IQR: 1.09, 4.25) vs 1.36 (IQR: 0.80, 2.50); P = 0.013].

Conclusions

Most PICU transfers less than or equal to 12 hours after admission result from illness progression. Half of these do not require significant interventions. The PICU transfers after ED management error had significantly shorter floor LOS, longer PICU LOS, and more interventions.
Management of Pediatric Condyle Fractures
Authors: McGoldrick David M. , Parmar Paras , Williams Rhodri , Monaghan Andrew , McMillan Kevin
Published: August 2019

Introduction:

Mandibular condyle fractures are a common type of facial fracture in children. The authors aimed to examine the demographics, etiology, treatment, and outcomes of these fractures managed in a single pediatric trauma unit.

Materials and Methods:

A retrospective review was performed of patients presenting to a pediatric hospital between 2003 and 2016 with mandibular condyle fractures. Initial data was extracted from a dedicated trauma database. Included patient's medical records and imaging were then reviewed. Data on demographics, etiology, fracture type, and treatment were recorded. Univariate statistical analysis was performed.

Results:

Forty-four patients with 49 condyle fractures were included. The average age of patients was 11.4 years (range 3–15 years). A fall from a bicycle/scooter was the most common mechanism. Twenty-six fractures were isolated and 23 involved a further fracture of the mandibular arch. The condylar neck was the most common site of fracture (55%). There was no statistical significance between age (0–10 years, 10–16 years) and site of fracture or the presence of an associated arch fracture. The majority of isolated fractures (73%) were treated conservatively without inter-maxillary fixation. Thirty-nine patients attended the follow-up and the median follow-up period was 196 days (interquartile range 21–165 days). Two patients had a malocclusion at follow-up that required intervention.

Conclusion:

There was a broad range of presentations in our cohort. Conservative management in isolated fractures resulted in stable outcomes and this large case series supports the consensus that management of pediatric condyle fractures should be as conservative as possible.
Unexpected Total Zygomatic Arch Bone Resorption Induced by Reduction Malarplasty
Authors: Zhou Jing , Zheng Houbing , Qi Zuoliang , Jin Xiaolei
Published: August 2019

In this report, the authors introduce a rare complication after reduction malarplasty in 2 patients. One patient underwent temporal rhytidectomy and malar osteotomy. The other patient underwent zygoma grinding without osteotomy. Both patients presented malar depression and cheek ptosis after surgery and visited the clinic. Physical examination, cephalometric radiographs, and facial 3-dimensional computed tomography were conducted, which indicated total zygomatic arch bone resorption. After examining the possible causes of the complication, the authors concluded that preserving enough blood supply and performing adequate rigid fixation of the separated zygoma bone are key prevention for bone resorption. This is the first report of total zygomatic arch bone resorption after reduction malarplasty.
The development of competency frameworks in healthcare professions: a scoping review
Authors: Batt Alan M. , Tavares Walter , Williams Brett
Published: August 2019

Background

Competency frameworks serve various roles including outlining characteristics of a competent workforce, facilitating mobility, and analysing or assessing expertise. Given these roles and their relevance in the health professions, we sought to understand the methods and strategies used in the development of existing competency frameworks.

Methods

We applied the Arksey and O’Malley framework to undertake this scoping review. We searched six electronic databases (MEDLINE, CINAHL, PsycINFO, EMBASE, Scopus, and ERIC) and three grey literature sources (greylit.org, Trove and Google Scholar) using keywords related to competency frameworks. We screened studies for inclusion by title and abstract, and we included studies of any type that described the development of a competency framework in a healthcare profession. Two reviewers independently extracted data including study characteristics. Data synthesis was both quantitative and qualitative.

Results

Among 5,710 citations, we selected 190 for analysis. The majority of studies were conducted in medicine and nursing professions. Literature reviews and group techniques were conducted in 116 studies each (61%), and 85 (45%) outlined some form of stakeholder deliberation. We observed a significant degree of diversity in methodological strategies, inconsistent adherence to existing guidance on the selection of methods, who was involved, and based on the variation we observed in timeframes, combination, function, application and reporting of methods and strategies, there is no apparent gold standard or standardised approach to competency framework development.

Conclusions

We observed significant variation within the conduct and reporting of the competency framework development process. While some variation can be expected given the differences across and within professions, our results suggest there is some difficulty in determining whether methods were fit-for-purpose, and therefore in making determinations regarding the appropriateness of the development process. This uncertainty may unwillingly create and legitimise uncertain or artificial outcomes. There is a need for improved guidance in the process for developing and reporting competency frameworks.
An integrated analysis of myeloid cells identifies gaps in in vitro models of in vivo biology
Authors: Rajab Nadia , Angel Paul W , Deng Yidi , Gu Jennifer , Jameson Vanta , Kurowska-Stolarska Mariola , Milling Simon , Pacheco Chris M , Rutar Matt , Laslett Andrew L , Lê Cao Kim Anh , Choi Jarny , Wells Christine A
Published: August 2019

The Stemformatics myeloid atlas is an integrated transcriptome atlas of human macrophages and dendritic cells that systematically compares freshly isolated tissue-resident, cultured, and stem-cell derived myeloid cell types. We identified two broad classes of tissue-resident macrophages with lung, gut and tumour-associated macrophages most similar to monocytes. Microglia, Kupffer cells and synovial macrophages shared similar profiles with each other, and with cultured macrophages. Pluripotent stem cell-derived macrophages were not reminiscent of fetal-derived cells. Instead, they were characterized by atypical expression of collagen and a highly efferocytotic phenotype. Likewise, Flt3L-derived cord blood dendritic cells were distinct from conventional dendritic cell subsets isolated from primary tissues and lacked expression of key pattern recognition receptors. Myeloid subsets were reproducible across different experimental series, showing the resource is a robust reference for new data. External users can annotate and benchmark their own samples, including annotation of myeloid single cell data at www.stemformatics.org/atlas/myeloid/.
JNK-dependent intestinal barrier failure disrupts host-microbe homeostasis during tumorigenesis
Authors: Zhou Jun , Boutros Michael
Published: August 2019

In all animals, the intestinal epithelium forms a tight barrier to the environment. The epithelium regulates the absorption of nutrients, mounts immune responses and prevents systemic infections. Here, we investigate the consequences of tumorigenesis on the microbiome using a Drosophila intestinal tumor model. We show that upon loss-of BMP signaling, tumors lead to aberrant activation of JNK signaling, followed by intestinal barrier dysfunction and commensal imbalance. In turn, the dysbiotic microbiome triggers a regenerative response and stimulates tumor growth. We find that inhibiting JNK signaling or depletion of the microbiome restores barrier function of the intestinal epithelium, leading to a reestablishment of host-microbe homeostasis, and organismic lifespan extension. Our experiments identify a JNK-dependent feedback amplification loop between intestinal tumors and the microbiome. They also highlight the importance of controlling the activity level of JNK signaling to maintain epithelial barrier function and host-microbe homeostasis.
TALE and NF-Y co-occupancy marks enhancers of developmental control genes during zygotic genome activation in zebrafish
Authors: Stanney William , Ladam Franck , Donaldson Ian J. , Parsons Teagan J. , Maehr René , Bobola Nicoletta , Sagerström Charles G
Published: August 2019

Animal embryogenesis is initiated by maternal factors, but zygotic genome activation (ZGA) shifts control to the embryo at early blastula stages. ZGA is thought to be mediated by specialized maternally deposited transcription factors (TFs), but here we demonstrate that NF-Y and TALE – TFs with known later roles in embryogenesis – co-occupy unique genomic elements at zebrafish ZGA. We show that these elements are selectively associated with early-expressed genes involved in transcriptional regulation and possess enhancer activity in vivo. In contrast, we find that elements individually occupied by either NF-Y or TALE are associated with genes acting later in development – such that NF-Y controls a cilia gene expression program while TALE TFs control expression ofhoxgenes. We conclude that NF-Y and TALE have a shared role at ZGA, but separate roles later during development, demonstrating that combinations of known TFs can regulate subsets of key developmental genes at vertebrate ZGA.
Perinatal Inflammation Influences but Does Not Arrest Rapid Immune Development in Preterm Babies
Authors: Kamdar S. , Hutchinson R. , Laing A. , Stacey F. , Ansbro K. , Millar M.R. , Costeloe K. , Wade W.G. , Fleming P. , Gibbons D. L.
Published: August 2019

Infection and infection-related complications are important causes of death and morbidity following preterm birth. Despite this, there is limited understanding of the development of the immune system in those born prematurely and how it is influenced by perinatal factors. To investigate this, we prospectively and longitudinally followed a cohort of babies born before 32 weeks of gestation. We demonstrated that preterm babies, including those born extremely prematurely, were capable of rapidly acquiring adult levels of immune functionality; that immune maturation appeared to occur independently of the developing microbiome, which was highly heterogeneous across different infants; and that the biggest drivers of change in the trajectory of perinatal immune development was exposure to infection in utero or post-natally. Conspicuously, a unifying factor among infants who developed infection despite their growing immune potentials was an inability to mount adequate T cell CXCL8 responses. Because this defect was present at birth, it may predict those babies likely to have poor clinical outcomes.
A new twist on bacterial motility – two distinct type IV pili revealed by cryoEM
Authors: Neuhaus Alexander , Selvaraj Muniyandi , Salzer Ralf , Langer Julian D. , Kruse Kerstin , Sanders Kelly , Daum Bertram , Averhoff Beate , Gold Vicki A. M.
Published: August 2019

Many bacteria express flexible protein filaments on their surface that enable a variety of important cellular functions. Type IV pili are examples of such filaments and are comprised of a helical assembly of repeating pilin subunits. Type IV pili are involved in motility (twitching), surface adhesion, biofilm formation and DNA uptake (natural transformation). They are therefore powerful structures that enable bacterial proliferation and genetic adaptation, potentially leading to the development of pathogenicity and antibiotic resistance. They are also targets for drug development.

By a complement of experimental approaches, we show that the bacteriumThermus thermophilusproduces two different forms of type IV pilus. We have determined the structures of both and built atomic models. The structures answer key unresolved questions regarding the molecular architecture of type IV pili and identify a new type of pilin. We also delineate the roles of the two filaments in promoting twitching and natural transformation.
Precision of Tissue Patterning is Controlled by Dynamical Properties of Gene Regulatory Networks
Authors: Exelby Katherine , Herrera-Delgado Edgar , Perez Lorena Garcia , Perez-Carrasco Ruben , Sagner Andreas , Metzis Vicki , Sollich Peter , Briscoe James
Published: August 2019

During development, gene regulatory networks allocate cell fates by partitioning tissues into spatially organised domains of gene expression. How the sharp boundaries that delineate these gene expression patterns arise, despite the stochasticity associated with gene regulation, is poorly understood. We show, in the vertebrate neural tube, using perturbations of coding and regulatory regions, that the structure of the regulatory network contributes to boundary precision. This is achieved, not by reducing noise in individual genes, but by the configuration of the network modulating the ability of stochastic fluctuations to initiate gene expression changes. We use a computational screen to identify network properties that influence boundary precision, revealing two dynamical mechanisms by which small gene circuits attenuate the effect of noise in order to increase patterning precision. These results highlight design principles of gene regulatory networks that produce precise patterns of gene expression.
scribble abrogation induces tumor growth through JNK-Wnt pathways depending on cellular-microenvironment in Drosophila wing imaginal tissue
Authors: Yadav Amarish Kumar , Fatima Roshan , Srikrishna Saripella
Published: August 2019

scribble (scrib) is a cell-polarity determinant in Drosophila and human. Cell polarity plays a crucial role in the maintenance of tissue homeostasis and its disruption leads to neoplastic cancer progression. However, the underlying mechanisms by which loss of cell-polarity regulators drives cancer progression are poorly known. In this study, we have explored the tumor progression mechanisms upon scrib knockdown in Drosophila wing imaginal disc using UASRNAi-GAL4 approach. We have found that scrib knockdown in wing disc leads to tumor growth with disrupted actin cytoskeleton, loss of cell-polarity and elevated JNK signalling, resulting in absolute early pupal lethality. Further, scrib abrogated cells in a large area of the disc are capable of invading the surrounding wild type cells and inducing apoptosis along with compensatory proliferation through JNK-Wnt pathways. Moreover, JNK pathway upstream candidate hep (JNKK) knockdown in scrib abrogated cells rescues the cell polarity defects, actin cytoskeleton disruption and tumor growth, while constitutive hep activation further aggravates the tumor phenotype. Interestingly, generation of undead cells by apoptosis inhibition in these hep knockdown cells by p35 expression further leads to tumor development. Hence, we conclude that scrib knockdown in a large area of wing disc might have a ‘group-protection’ and ‘undead-cells’ microenvironment that modulates the action of JNK signalling resulting in tumor formation. Furthermore, JNK dependent activation of Wnt/Ca2+ signalling also supports the tumor growth and actin cytoskeleton disruption. Thus, our results importantly highlight the role of JNK signalling in tumor progression upon scrib loss of function depending on cellular-microenvironment.
Regenerative neurogenic response from glia requires insulin driven neuron-glia communication
Authors: Harrison Neale , Connolly Elizabeth , Gubieda Alicia Gascón , Yang Zidan , Altenhein Benjamin , Losada-Perez Maria , Moreira Marta , Hidalgo Alicia
Published: August 2019

Some animals can regenerate their central nervous system (CNS) after injury by inducing de novo neurogenesis: discovering the underlying mechanisms would help promote regeneration in the damaged human CNS. Glial cells could be the source of regenerative neurogenesis, but this is debated. The glia transmembrane protein Neuron-Glia antigen-2 (NG2) may have a key role in sensing injury-induced neuronal signals, however these have not been identified. Here, we used Drosophila genetics to search for functional neuronal partners of the NG2 homologue kon-tiki (kon), and identified Islet Antigen-2 (Ia-2), required in neurons for insulin secretion. Alterations in Ia-2 function induced neural stem cell fate, injury increased ia-2 expression and induced ectopic neural stem cells. Using genetic epistasis analysis and lineage tracing, we demonstrate that Ia-2 functions with Kon to regulate Drosophila insulin-like peptide 6 (Dilp-6) which in turn generates both more glial cells and neural stem cells from glia. Ectopic neural stem cells can divide, and limited de novo neurogenesis could be traced back to glial cells. Altogether, Ia-2 and Dilp-6 drive a neuron-glia relay that restores glia, and reprograms glia into neural stem cells for CNS regeneration.
Co-translational folding allows misfolding-prone proteins to circumvent deep kinetic traps
Authors: Bitran Amir , Jacobs William M. , Zhai Xiadi , Shakhnovich Eugene
Published: August 2019

Many large proteins suffer from slow or inefficient foldingin vitro. Here, we provide evidence that this problem can be alleviatedin vivoif proteins start folding co-translationally. Using an all-atom simulation-based algorithm, we compute the folding properties of various large protein domains as a function of nascent chain length, and find that for certain proteins, there exists a narrow window of lengths that confers both thermodynamic stability and fast folding kinetics. Beyond these lengths, folding is drastically slowed by non-native interactions involving C-terminal residues. Thus, co-translational folding is predicted to be beneficial because it allows proteins to take advantage of this optimal window of lengths and thus avoid kinetic traps. Interestingly, many of these proteins’ sequences contain conserved rare codons that may slow down synthesis at this optimal window, suggesting that synthesis rates may be evolutionarily tuned to optimize folding. Using kinetic modelling, we show that under certain conditions, such a slowdown indeed improves co-translational folding efficiency by giving these nascent chains more time to fold. In contrast, other proteins are predicted not to benefit from co-translational folding due to a lack of significant non-native interactions, and indeed these proteins’ sequences lack conserved C-terminal rare codons. Together, these results shed light on the factors that promote proper protein folding in the cell, and how biomolecular self-assembly may be optimized evolutionarily.

Significance Statement

Many proteins must adopt a specific structure in order to perform their functions, and failure to do so has been linked to disease. Although small proteins often fold rapidly and spontaneously to their native conformations, larger proteins are less likely to fold correctly due to the myriad incorrect arrangements they can adopt. Here, we show that this problem can be alleviated if proteins start folding while they are being translated, namely, built one amino acid at a time on the ribosome. This process of co-translational folding biases certain proteins away from misfolded states that tend to hinder spontaneous refolding. Signatures of unusually slow translation suggest that some of these proteins have evolved to fold co-translationally.
Ureteric Bud Cells Programmed from Embryonic Stem Cells Obtain Competence for Secondary Induction in the Kidney
Authors: Tan Zenglai , Rak-Raszewska Aleksandra , Skovorodkin Ilya , Vainio Seppo J.
Published: August 2019

Generation of kidney organoids from pluripotent stem cells (PSCs) is regarded as a potentially powerful way to study kidney development, disease, and regeneration. Direct differentiation of PSCs towards renal lineages is well studied, however, most of the studies relates to generation of nephron progenitor population from PSCs. Until now, differentiation of PSCs into ureteric bud (UB) progenitor cells demonstrates limited success. Here, we describe a simple, efficient and reproductive protocol to direct differentiation of mouse embryonic stem cells (mESCs) into UB progenitor cells. The mESC–derived UB cells were able to induce nephrogenesis when placed in the interaction with the primary metanephric mesenchyme (pMM). In generated kidney organoids, the embryonic pMM developed nephron structures and the mESC-derived UB cells formed network of collecting ducts, connected with the nephron tubules. Altogether, our studies established an uncomplicated and reproducible platform for kidney disease modelling, drug testing and regenerative medicine applications.
Acoustic contamination of electrophysiological brain signals during speech production and sound perception
Authors: Roussel Philémon , Godais Gaël Le , Bocquelet Florent , Palma Marie , Hongjie Jiang , Zhang Shaomin , Kahane Philippe , Chabardès Stéphan , Yvert Blaise
Published: August 2019

A current challenge of neurotechnologies is the development of speech brain-computer interfaces to restore communication in people unable to speak. To achieve a proof of concept of such system, neural activity of patients implanted for clinical reasons can be recorded while they speak. Using such simultaneously recorded audio and neural data, decoders can be built to predict speech features using features extracted from brain signals. A typical neural feature is the spectral power of field potentials in the high-gamma frequency band (between 70 and 200 Hz), a range that happens to overlap the fundamental frequency of speech. Here, we analyzed human electrocorticographic (ECoG) and intracortical recordings during speech production and perception as well as rat microelectrocorticographic (µ-ECoG) recordings during sound perception. We observed that electrophysiological signals, recorded with different recording setups, often contain spectrotemporal features highly correlated with those of the sound, especially within the high-gamma band. The characteristics of these correlated spectrotemporal features support a contamination of electrophysiological recordings by sound. In a recording showing high contamination, using neural features within the high-gamma frequency band dramatically increased the performance of linear decoding of acoustic speech features, while such improvement was very limited for another recording showing weak contamination. Further analysis and in vitro replication suggest that the contamination is caused by a mechanical action of the sound waves onto the cables and connectors along the recording chain, transforming sound vibrations into an undesired electrical noise that contaminates the biopotential measurements. This study does not question the existence of relevant physiological neural information underlying speech production or sound perception in the high-gamma frequency band, but alerts on the fact that care should be taken to evaluate and eliminate any possible acoustic contamination of neural signals in order to investigate the cortical dynamics of these processes.
Individuation of parts of a single object and multiple distinct objects relies on a common neural mechanism in inferior intraparietal sulcus
Authors: Wurm Moritz F. , Porter Katharine B. , Caramazza Alfonso
Published: August 2019

Object identification and enumeration rely on the ability to distinguish, or individuate, objects from the background. Does multiple object individuation operate only over bounded, separable objects or does it operate equally over connected features within a single object? While previous fMRI experiments suggest that connectedness affects the processing and enumeration of objects, recent behavioral and EEG studies demonstrated that parallel individuation occurs over both object parts and distinct objects. However, it is unclear whether individuation of object parts and distinct objects relies on a common or independent neural mechanisms. Using fMRI-based multivariate pattern analyses, we here demonstrate that activity patterns in inferior and superior intraparietal sulci (IPS) encode numerosity independently of whether the individuated items are connected parts of a single object or distinct objects. Lateral occipital cortex is more sensitive to perceptual aspects of the two stimulus types and the targets of the stimuli, suggesting a dissociation between ventral and dorsal areas in representing perceptual object properties and more general information about numerosity, respectively. Our results suggest that objecthood is not a necessary prerequisite for parallel individuation in IPS. Rather, our results point toward a common individuation mechanism that selects targets over a flexible object hierarchy, independently of whether the targets are distinct separable objects or parts of a single object.
Internalizing cooperative norms in group-structured populations
Authors: Akçay Erol , Van Cleve Jeremy
Published: August 2019

Social norms play a crucial role in human behavior, especially in maintaining cooperation within human social groups. Social norms might be self-enforcing or be enforced by the threat of punishment. In many cases, however, social norms are internalized and individuals have intrinsic motivations to observe norms. Here, we present a model for how intrinsic preferences to adhere to cooperative norms can evolve with and without external enforcement of compliance. Using the methodology of preference evolution, we model how cooperative norms coevolve with the intrinsic motivations to follow them. We model intrinsic motivations as being provided by guilt, a kind of internal “punishment” that individuals feel for falling short of cooperative norms, and show that the shape of this internal punishment function plays a crucial role in determining whether and how much internalization can evolve. We find that internal punishment functions that eventually level off with the deviation from the norm can support internalization without external punishment. In contrast, internal punishment functions that keep escalating with the deviation from the norm require external punishment, but yield stronger norms and more cooperation when external punishment is present. By showing how different preference mechanisms can enhance or limit norms that stabilize cooperation, these results provide insights into how our species might have evolved the norm psychology that helps us maintain such complex social and cultural institutions.
Autophagy controls lipid droplet formation by fine-tuning NCoR1 levels
Authors: Takahashi Shun-saku , Sou Yu-Shin , Saito Tetsuya , Kuma Akiko , Yabe Takayuki , Koike Masato , Terai Shuji , Mizushima Noboru , Waguri Satoshi , Komatsu Masaaki
Published: August 2019

Lipid droplets (LDs) are dynamic organelles that store neutral lipids during times of energy excess, such as following a meal. LDs serve as an energy reservoir during fasting and have a buffering capacity that prevents lipotoxicity. Autophagy and the autophagic machinery have been proposed to play a role in LD biogenesis but the underlying molecular mechanism remains unclear. Here, we show that when nuclear receptor co-repressor 1 (NCoR1), which inhibits the transactivation of nuclear receptors, accumulates due to autophagy suppression, LD biogenesis is blocked. Ablation of ATG7, a gene essential for autophagy, suppressed the expression of gene targets of liver X receptor α (LXRα), a nuclear receptor responsible for fatty acid and triglyceride synthesis in an NCoR1-dependent manner. LD biogenesis in response to fasting and after hepatectomy was hampered by the suppression of autophagy. These results indicate that autophagy controls physiological hepatosteatosis by fine-tuning NCoR1 protein levels.
Functional analysis of clinical BARD1 germline variants
Authors: Toh Ming Ren , Chong Siao Ting , Chan Sock Hoai , Low Chen Ee , Ishak Nur Diana Binte , Lim Jing Quan , Courtney Eliza , Ngeow Joanne
Published: August 2019

Germline pathogenic variants in BRCA1/2 account for one-third of familial breast cancers. The majority of BRCA1 function requires heterodimerization with BARD1. In contrast to BRCA1, BARD1 is a low-penetrance gene with an unclear clinical relevance, partly because of limited functional evidence. Using patient-derived lymphoblastoid cells, we functionally characterized two pathogenic variants (c.1833dupT, c.2099delG) and three variants of uncertain significance (VUSs) (c.73G>C, c.1217G>A, c.1918C>A). Three of these patients had breast cancers, whereas the remaining had colorectal cancers (n = 3). Both patients with pathogenic variants (c.1833dupT, c.2099delG) developed breast cancers with aggressive disease phenotypes such as triple-negative breast cancer and high cancer grades. As BARD1 encompasses multiple functional domains, including those of apoptosis and homologous recombination repair, we hypothesized that the function being impaired would correspond with the domain where the variant was located. Variants c.1918C>A, c.1833dupT, c.1217G>A, and c.2099delG, located within and proximal to apoptotic domains of ankyrin and BRCT, were associated with impaired apoptosis. Conversely, apoptosis function was preserved in c.73G>C, which was distant from the ankyrin domain. All variants displayed normal BRCA1 heterodimerization and RAD51 colocalization, consistent with their location being distal to BRCA1—and RAD51-binding domains. In view of deficient apoptosis, VUSs (c.1217G>A and c.1918C>A) may be pathogenic or likely pathogenic variants. In summary, functional analysis of BARD1 VUSs requires a combination of assays and, more importantly, the use of appropriate functional assays with consideration to the variant's location.
The pivotal role of sampling recurrent tumors in the precision care of patients with tumors of the central nervous system
Authors: Wong Derek , Shen Yaoqing , Levine Adrian B. , Pleasance Erin , Jones Martin , Mungall Karen , Thiessen Brian , Toyota Brian , Laskin Janessa , Jones Steven J.M. , Marra Marco A. , Yip Stephen
Published: August 2019

Effective management of brain and spine tumors relies on a multidisciplinary approach encompassing surgery, radiation, and systemic therapy. In the era of personalized oncology, the latter is complemented by various molecularly targeting agents. Precise identification of cellular targets for these drugs requires comprehensive profiling of the cancer genome coupled with an efficient analytic pipeline, leading to an informed decision on drug selection, prognosis, and confirmation of the original pathological diagnosis. Acquisition of optimal tumor tissue for such analysis is paramount and often presents logistical challenges in neurosurgery. Here, we describe the experience and results of the Personalized OncoGenomics (POG) program with a focus on tumors of the central nervous system (CNS). Patients with recurrent CNS tumors were consented and enrolled into the POG program prior to accrual of tumor and matched blood followed by whole-genome and transcriptome sequencing and processing through the POG bioinformatic pipeline. Sixteen patients were enrolled into POG. In each case, POG analyses identified genomic drivers including novel oncogenic fusions, aberrant pathways, and putative therapeutic targets. POG has highlighted that personalized oncology is truly a multidisciplinary field, one in which neurosurgeons must play a vital role if these programs are to succeed and benefit our patients.
Preparation of a DNA Standard for Quantitative Polymerase Chain Reaction (qPCR)
Authors: Lock Martin , Korn Michael , Wilson James , Sena-Esteves Miguel , Gao Guangping
Published: August 2019

Here we describe the preparation of quantitative polymerase chain reaction (qPCR) standards.
Direct Cyanine-dCTP Labeling of DNA for Microarrays
Authors: Rando Oliver
Published: August 2019

Similar to direct RNA labeling, direct DNA labeling with Cy-dCTP is the simplest and fastest method for labeling DNA. This is a standard Klenow labeling protocol in which Cy-dCTP is incorporated during the labeling reaction. After stopping the reaction, labeled nucleotide is separated from unreacted Cy-dCTP, and Cy3- and Cy5-labeled materials are combined for hybridization. This protocol is suitable for many applications, including detection of copy-number variation, nucleosome mapping, and other location analysis (e.g., chromatin immunoprecipitation [ChIP]-chip).
Indirect Labeling of DNA for Microarrays
Authors: Rando Oliver
Published: August 2019

As with RNA labeling protocols, the main difference between direct and indirect DNA labeling protocols is a trade-off of cost and time. Indirect labeling of DNA, described here, takes ∼2 h longer than direct labeling but is hundreds of dollars cheaper.
Ligation and Ligases
Authors: Green Michael R. , Sambrook Joseph
Published: August 2019

DNA ligases are used chiefly to create novel combinations of nucleic acid molecules and to attach them to vectors before molecular cloning. They are either of bacterial origin or bacteriophage encoded and have different properties, as discussed here.
Otherness and closeness: residential tourism and rural gentrification processes
Authors: di Campli Antonio
Published: August 2019

Purpose

This essay looks at how various forms of residential tourism or lifestyle migration, produced by people arriving from the cities and territories of the so-called Global North, have triggered complex processes of social-spatial modification in the landscapes and rural environments of Vilcabamba, Ecuador, a small Andean village of approximately 5,000 inhabitants in the southern part of the canton of Loja. The paper aims to discuss this issue.

Design/methodology/approach

Residential tourism in rural areas is a phenomenon that can be investigated by combining socio-economic studies with spatial analyses to define the specific characteristics of territories and environments affected by this phenomenon. In the case of Vilcabamba, the relationships and conflicts between imaginations, spaces, ecologies and desires have taken the form of a complex “implicit project”, a “palimpsest-project” intended as a set of territorial descriptions, interpretations and transformation actions triggered by a plot featuring migrant tourists, activists, eco-institutions, schools, artisans, intellectuals and artists. Though weakly connected to one another, these subjects nonetheless produce substantially coherent actions.

Findings

Two main hypotheses are given as: the first is that in particular rural contexts, such as the Andean area around Vilcabamba, dwelling practices and economies related to residential tourism have triggered processes through which these areas have progressively become peripheries to distant metropolitan territories and are reconfigured as sets of specialised places. The second hypothesis is that Vilcabamba and its rural surroundings can be viewed as a particular “contact zone” in which different types of residential tourists and local dwellers interact, together with different economies of tourism. In this case the reference is, on the one hand, to the logics and discourses of the so-called extractive tourism, a concept that describes the processes of “extracting” and converting local cultural characteristics, and “indigenousness”. To support these hypotheses, the result is the construction of a spatial representation of the ways in which specific practices of residential tourism are territorialised, and how they modify the meaning and functioning of rural spaces.

Originality/value

What is new in the paper is the attempt to define a spatial representation of transnational spaces trying to highlight relationships between extractive tourism and remittance urbanism.
Domestic demand-based economic globalization and inclusive growth
Authors: Zheng Jianghuai , Shen Chunmiao
Published: August 2019

Purpose

The purpose of this paper is to propose policy recommendations that resort to the domestic market to achieve inclusive growth from an open perspective.

Design/methodology/approach

How will economic globalization based on domestic demand affect economic growth and income distribution in an open and large country? With the aim of discussing the mechanism of the impact of expanding domestic demand on the inclusive growth from an open perspective, this paper incorporates the Global Value Chains vs National Value Chains (GVC-NVC) competition, which is triggered by foreign investments attracted by the domestic demand scale into an endogenous growth model with “Schumpeterian Innovation.”

Findings

Theoretical analysis indicates the following findings: although domestic demand-based economic globalization can promote transnational inclusive growth across countries, it is not conducive to national (domestic) inclusive growth; the impacting effect of domestic demand scale on inclusive growth across countries is subject to the moderating effect of the development maturity of the labor market; and the impacting effect of domestic demand scale on national inclusive growth is subject to the joint moderating effect of the development maturity of the labor market and labor skill structure.

Originality/value

First, this paper examines the impact of domestic demand-based economic globalization on the inclusiveness of economic growth from an open perspective, which deepens the existing theory of intra-product specialization and inclusive growth. Second, the paper puts the sequential production process into Schumpeterian growth model and reveals the mechanism that domestic demand affects inclusive growth. Third, the study finds that the enhancement of labor market efficiency, transfer payments to low-skilled labor and the creation of a fair competitive market environment will contribute to the globalization of a domestic demand-oriented economy, which provides a policy-making basis for government sectors.
Hide and seek: evasion and search as FDI motivation
Authors: Burmester Brent , Scott-Kennel Joanna
Published: August 2019

Purpose

The purpose of this paper is to argue for inclusion of evasive foreign direct investment (FDI) into search-based motivation typologies in international business.

Design/methodology/approach

Critically reassessing academic literature and using anecdotal evidence, the authors augment the theory of FDI motivation with the concept of evasion.

Findings

Evasive FDI is a firm-level response to denial-of-privilege by a state. Divergence of policy environments between home and host prompts relocation or international expansion of productive assets and often the affectation of ‘foreignness’ by the multinational enterprise (MNE). The role of responsibility evasion via FDI is understood in the research literature, mainly because of an emphasis on search-based motives and a failure to distinguish between escape and evasion. International business research is vulnerable to mis-identification of FDI motive which consequently distorts its strategic and policy implications.

Originality/value

The argument for inclusion of evasive FDI serves to augment the established, yet asymmetrically focussed typology of search FDI, demonstrating that evasion is conceptually and analytically distinguishable from search. Further, an augmented typology lends accuracy and insight to research into the reconfiguration strategies of MNEs and legitimation of the international business discipline itself, providing researchers with a more comprehensive account of FDI causation and offering new research paths.
Projectification in Iceland measured – a comparison of two methods
Authors: Ingason Helgi Thor , Fridgeirsson Thordur V. , Jonasson Haukur Ingi
Published: August 2019

Purpose

The purpose of this paper is to improve the methodology of assessing the importance of projects in a national economy. The subject of study is projectification in the Icelandic economy and to measure this, the share of project work in relation to the total work done in an organisation was used as an indicator. This is a time-consuming approach and it was decided to do an additional benchmark study, to verify the alleged importance of projects, and to investigate the usefulness of a benchmark study and establish whether the two approaches could complement each other.

Design/methodology/approach

Data were collected from 146 organisations in Iceland, regarding the share of project work relative to total work, as explained by Schoper et al. (2018). In addition, by participation in a large quarterly omnibus survey among people with high management positions in their respective companies in Iceland, more general data were collected. The methods and outcomes of both surveys were compared, and general conclusions are drawn.

Findings

The authors conclude that the two research approaches complement each other and could be applied in a systematic way to give a longitudinal view of the evolution of projectification in a society, where projectification is measured, traced over time and benchmarked. The first part is more complicated and expensive in execution, and could be done at longer intervals, whereas the second part takes less effort and can be used to monitor the evolution more regularly.

Originality/value

Two very different research approaches were applied to assess projectification. On the one hand, a detailed quantitative survey of the economic impact of projects. On the other hand, a general survey of a very large sample of managers. This combined approach to assess the level of projectification is new, and the authors hope that this will be of value in the context of developing efficient, reliable and practical methods to assess projectification of societies.
M&As in Africa – effects of law and governance
Authors: Lundqvist Alex , Liljeblom Eva , Löflund Anders , Maury Benjamin
Published: August 2019

Purpose

The cultural and legal differences between foreign acquirers and African target firms can be substantial. There is also a large variation in cultures and legal systems within Africa. However, there is limited research on merger and acquisition (M&A) performance by foreign firms in Africa. The purpose of this paper is to fill this gap by exploring the “spillover by law” hypothesis (Martynova and Renneboog, 2008) that focuses on the influence of the external environment on the governance and performance of foreign M&As in Africa.

Design/methodology/approach

The data set covers 415 M&A transactions by foreign firms in Africa during the period of 1999–2016. Dynamic data covering the country’s legal, cultural and political environment are collected from the World Bank, the Heritage Foundation and Transparency International.

Findings

The authors find that the legal environment significantly affects the returns of bidders on African firms. For complete acquisitions, bidder returns are significantly higher when the bidder’s country has higher shareholder protection and higher creditor protection compared with the target firm’s country. The results show that the effects are significant when there is a full control change (including a change in the target firm’s nationality) but not in the case of partial control transfers. The results are consistent with the “spillover by law” hypothesis.

Originality/value

The authors contribute to the literature on cross-border M&As by separately studying the valuation effects of full, majority and minority changes in control; by being the first study of the legal spillover effects in Africa; and by being the most extensive study of the legal determinants of the valuations of non-African acquirers of African firms.