bluuebunny/crossref_metadata_2025 huggingface dataset:
Accuracy of Three-Dimensional Soft Tissue Prediction in Orthognathic Cases Using Dolphin Three-Dimensional Software
Authors: Elshebiny Tarek , Morcos Sherif , Mohammad Abdulaziz , Quereshy Faisal , Valiathan Manish
Published: October 2018

Introduction:

Orthodontists and surgeons have been looking for more accurate methods to plan and predict surgical outcomes in patients with skeletal discrepancies.

Methods:

The sample consisted of 20 subjects from the surgical clinic of a graduate orthodontic program who had been treated with Le Fort I maxillary movement, bisagittal split osteotomy, with or without genioplasty. All subjects had to have preoperative (T0) and at least 6 months postoperative (T1) cone-beam computed tomographies that were imported to Dolphin three-dimensional (3D) software version 11.9 in digital imaging and communications in medicine format. Three-dimensional voxel-based superimposition on the cranial base was performed for T0 and T1 to accurately measure the skeletal surgical movements. A virtual orthognathic surgery was performed on T0 to mimic the actual skeletal osteotomies using the treatment simulation tool in Dolphin 3D. A prediction 3D soft tissue image (Tp) was generated based on the Dolphin virtual skeletal planning. The differences between Tp and T1 for all patients were measured using linear and angular measurements visualized by surface mapping.

Results:

Significant differences were found between Tp and T1 in Nasolabial angle, Soft tissue A point, and Subalar area.

Conclusions:

The soft tissue prediction accuracy after double jaw surgery using Dolphin 3D is limited in some areas, especially upper lip and base of the nose.
Initial evaluation of the efficacy and safety of in-hospital expandable hemostatic minisponge use in penetrating trauma
Authors: Warriner Zachary , Lam Lydia , Matsushima Kazuhide , Benjamin Elizabeth , Strumwasser Aaron , Demetriades Demetrios , Inaba Kenji
Published: October 2018

BACKGROUND

Hemorrhage remains the leading cause of preventable death after trauma. The XSTAT expandable minisponge hemostatic device was developed for the control of severe, life-threatening bleeding from junctional wounds not amenable to tourniquet application. This is an initial report of the clinical use of this novel method of hemorrhage control for civilian penetrating injury.

METHODS

A review of trauma admissions at a high-volume Level I trauma center was performed from July 2016 to November 2017. All patients sustaining penetrating trauma with active hemorrhage were evaluated for XSTAT use. Ten device deployments occurred during this time. Each deployment was reviewed in detail, capturing patient and injury data, efficacy of hemorrhage control, and evaluation of any potential device or treatment related complications.

RESULTS

Six thousand three hundred sixty-three trauma admissions were reviewed with 22.1% sustaining a penetrating mechanism of injury. XSTAT was deployed in 10 (0.7%) penetrating trauma admissions with a mean age of 38.3 (range, 16–59) years, systolic blood pressure (SBP) of 126.7 (range, 74–194) mm Hg, Glasgow Coma Scale (GCS) score of 14.5 (range, 13–15), and New Injury Severity Score (NISS) of 9.5 (range, 1–27). Eight patients had an identifiable arterial injury; the remainder had vein or soft tissue bleeding. Overall, half were junctional injuries. XSTAT was able to stop bleeding in nine of ten patients on the first deployment, with the remaining patient requiring one repeat injection. Dwell times ranged from 1 hour to 40 hours (median, 15 hours). There were no technical device failures or embolic complications. Retained sponges were identified in two patients on initial postremoval x-rays following wound exploration for definitive hemorrhage control and sponge removal. No patient died during the study period.

CONCLUSION

XSTAT use appears safe. It is rapid, reliable, and provides a high degree of hemorrhage control on first deployment. Sponge removal should always be followed by radiographic clearance. For patients with hemorrhage from cavitary wounds not amenable to tourniquet placement, this device was effective. Further study is warranted as XSTAT use becomes more widespread.

LEVEL OF EVIDENCE

Therapeutic study, level V.
Clinic Nonattendance Is a Risk Factor for Poor Kidney Transplant Outcomes
Authors: Richardson Cathy , Williams Aimee , McCready Jill , Khalil Khalid , Evison Felicity , Sharif Adnan
Published: October 2018

Background

The aim of this study was to analyze the impact of clinic nonattendance within the first year after kidney transplantation on graft-related outcomes.

Methods

Our retrospective analysis included all patients receiving their transplant (2007-2017) and receiving their long-term follow up at our center. Clinic nonattendance was extracted from electronic patient records and informatics systems, with highest clinic nonattenders stratified at the 75th percentile.

Results

Data were analyzed for 916 kidney allograft recipients, with median follow up 1168 days (interquartile range, 455-2073 days). Median number of missed transplant clinic visits in the first year was 5 (interquartile range, 3-7) and nonattenders were defined above the 75th percentile. Nonattenders versus attenders were more likely to be black, ABO-incompatible, repeat kidney transplant recipients but less likely to have pretransplantation diabetes. Nonattenders versus attenders had longer hospital stays after their transplant surgery in days (14.4 vs 12.2 respectively, P = 0.007), higher rate of delayed graft function (21.3% vs 12.8% respectively, P = 0.005), higher risk for 1-year rejection (12.5% vs 7.8% respectively, P = 0.044), worse 1-year estimated glomerular filtration rate in mL/min (47.0 vs 54.1, respectively, P = 0.002) and increased risk for death-censored graft loss by median follow (17.5% vs 12.0%, respectively, P = 0.013). In a Cox regression model, kidney transplant recipients defined as clinic nonattenders within the first postoperative year demonstrated a significantly increased rate of death-censored graft loss (hazard ratio, 1.983; 95% confidence interval, 1.061-3.707; P = 0.032).

Conclusions

Kidney transplant recipients in the top quartile for nonattendance require additional support and supervision to help attenuate long-term risks to their graft function and survival.
Proteins in the periplasmic space and outer membrane vesicles of Rhizobium etli CE3 grown in minimal medium are largely distinct and change with growth phase
Authors: Taboada Hermenegildo , Meneses Niurka , Dunn Michael F. , Vargas-Lagunas Carmen , Buchs Natasha , Castro-Mondragón Jaime A. , Heller Manfred , Encarnación Sergio
Published: October 2018

Rhizobium etli

CE3 grown in succinate-ammonium minimal medium (MM) excreted outer membrane vesicles (OMVs) with diameters of 40 to 100 nm. Proteins from the OMVs and the periplasmic space were isolated from 6 and 24 h cultures and identified by proteome analysis. A total of 770 proteins were identified: 73.8 and 21.3 % of these occurred only in the periplasm and OMVs, respectively, and only 4.9 % were found in both locations. The majority of proteins found in either location were present only at 6 or 24 h: in the periplasm and OMVs, only 24 and 9 % of proteins, respectively, were present at both sampling times, indicating a time-dependent differential sorting of proteins into the two compartments. The OMVs contained proteins with physiologically varied roles, including

Rhizobium

adhering proteins (Rap), polysaccharidases, polysaccharide export proteins, auto-aggregation and adherence proteins, glycosyl transferases, peptidoglycan binding and cross-linking enzymes, potential cell wall-modifying enzymes, porins, multidrug efflux RND family proteins, ABC transporter proteins and heat shock proteins. As expected, proteins with known periplasmic localizations (phosphatases, phosphodiesterases, pyrophosphatases) were found only in the periplasm, along with numerous proteins involved in amino acid and carbohydrate metabolism and transport. Nearly one-quarter of the proteins present in the OMVs were also found in our previous analysis of the

R. etli

total exproteome of MM-grown cells, indicating that these nanoparticles are an important mechanism for protein excretion in this species.
Genome-wide gene expression profiling reveals that cuticle alterations and P450 detoxification are associated with pyrethroid resistance in Anopheles arabiensis populations from Ethiopia
Authors: Simma Eba Alemayehu , Dermauw Wannes , Balabanidou Vasileia , Snoeck Simon , Bryon Astrid , Clark Richard M. , Yewhalaw Delenasaw , Vontas John , Duchateau Luc , Van Leeuwen Thomas
Published: October 2018

BACKGROUND

Vector control is the main intervention in malaria control and elimination strategies. However, the development of insecticide resistance is one of the major challenges for controlling malaria vectors. Anopheles arabiensis populations in Ethiopia showed resistance against both DDT and the pyrethroid deltamethrin. Although a L1014F target-site resistance mutation was present in the voltage gated sodium channel of investigated populations, the levels of resistance and biochemical studies indicated the presence of additional resistance mechanisms. In this study, we used genome-wide transcriptome profiling by RNAseq to assess differentially expressed genes between three deltamethrin and DDT resistant An. arabiensis field populations (Tolay, Asendabo, Chewaka) and two susceptible strains (Sekoru and Mozambique).

RESULTS

Both RNAseq analysis and RT-qPCR showed that a glutathione-S-transferase, gstd3, and a cytochrome P450 monooxygenase, cyp6p4, were significantly overexpressed in the group of resistant populations compared to the susceptible strains, suggesting that the enzymes they encode play a key role in metabolic resistance against deltamethrin or DDT. Furthermore, a gene ontology enrichment analysis showed that expression changes of cuticle related genes were strongly associated with insecticide resistance, although this did not translate in increased thickness of the procuticle.

CONCLUSION

Our transcriptome sequencing of deltamethrin/DDT resistant An. arabiensis populations from Ethiopia suggests non-target site resistance mechanisms and pave the way for further investigation of the role of cuticle composition in resistance.
Transient Replication in Specialized Cells Favors Conjugative Transfer of a Selfish DNA Element
Authors: Delavat François , Moritz Roxane , van der Meer Jan Roelof
Published: October 2018

Bacterial evolution is driven to a large extent by horizontal gene transfer (HGT) – the processes that distribute genetic material between species rather than by vertical descent. HGT is mostly mediated by an assortment of different selfish DNA elements, several of which have been characterized in great molecular detail. In contrast, very little is known on adaptive features optimizing horizontal fitness. By using single DNA molecule detection and time-lapse microscopy, we analyze here the fate of an integrative and conjugative element (ICE) in individual cells of the bacteriumPseudomonas putida. We uncover how the ICE excises and irregularly replicates, exclusively in a sub-set of specialized host cells. As postulated, ICE replication is dependent on its origin of transfer and its DNA relaxase. Rather than being required for ICE maintenance, however, we find that ICE replication serves more effective conjugation to recipient cells, providing selectable benefit to its horizontal transfer.
Dynamic Hh signaling can generate temporal information during tissue patterning
Authors: García-Morales Diana , Navarro Tomás , Iannini Antonella , Míguez David G. , Casares Fernando
Published: October 2018

The differentiation of tissues and organs requires that cells exchange information in space and time. Spatial information is often conveyed by morphogens, molecules that disperse across receiving cells generating signaling gradients. Cells translate such concentration gradients into space-dependent patterns of gene expression and cellular behavior [1, 2]. But could morphogen gradients also convey developmental time? Here, investigating the developmental role of Hh on a component of theDrosophilavisual system, the ocellar retina, we discovered that ocellar cells use the non-linear gradient of Hh as a temporal cue, collectively performing the biological equivalent of a mathematical logarithmic transformation. In this way, a morphogen diffusing from a non-moving source is decoded as a wave of differentiating photoreceptors that travels at constant speed throughout the retinal epithelium.
Bacterial Hsp90 mediates the degradation of aggregation-prone Hsp70-Hsp40 substrates preferentially by HslUV proteolysis
Authors: Fauvet Bruno , Finka Andrija , Castanié-Cornet Marie-Pierre , Cirinesi Anne-Marie , Genevaux Pierre , Quadroni Manfredo , Goloubinoff Pierre
Published: October 2018

Whereas in eukaryotic cells, the Hsp90s are profusely-studied molecular chaperones controlling protein homeostasis together with Hsp70s, in bacteria, the function of Hsp90 (HtpG) and its collaboration with Hsp70 (DnaK) remains unknown. To uncover physiological processes depending on HtpG and DnaK, we performed comparative quantitative proteomic analyses of insoluble and total protein fractions from unstressed wild typeE. coli, and from knockout mutantsΔdnaKdnaJ(ΔKJ),ΔhtpG(ΔG) andΔdnaKdnaJΔhtpG(ΔKJG) and compared their growth rates under heat-stress also withΔdnaKdnaJΔhslV. Whereas, expectedly, mutant ΔG showed no proteomic differences with wild-type, ΔKJ expressed more chaperones, proteases and ribosomes and dramatically less metabolic and respiratory enzymes. Unexpectedly, we found that ΔKJG showed higher levels of metabolic and respiratory enzymes and both ΔKJG andΔdnaKdnaJΔhslVgrew better at 37oC than ΔKJ. The results indicate that bacterial Hsp90 mediates the degradation of aggregation-prone Hsp70-Hsp40 substrates, preferably by the HslUV protease.

Significance statement:

The molecular chaperones Hsp70 and Hsp90 are among the most abundant and well-conserved proteins in all realms of life, forming together the core of the cellular proteostasis network. In eukaryotes, Hsp90 functions in collaboration with Hsp70; we studied this collaboration inE. coli, combining genetic studies with label-free quantitative proteomics in which both protein abundance and protein solubility were quantified. Bacteria lacking Hsp70 (DnaK) and its co-chaperone DnaJ (ΔdnaKdnaJ) grew slower and contained significantly less key metabolic and respiratory enzymes. Unexpectedly, an additional deletion of the Hsp90(htpG)gene partially restored the WT phenotype. Deletion of the HslV protease in the ΔdnaKdnaJ background also improved growth, suggesting that bacterial Hsp90 mediates the degradation of Hsp70 substrates, preferentially through HslV.

At 37oCΔdnaKdnaJ E. colimutants grow slower than wild type cells. Quantitative proteomics shows that compared to wild type cells,ΔdnaKdnaJcells grown at 30oC contain significantly less key metabolic and respiratory enzymes. Unexpectedly, deletion of theHtpGgene in the ΔdnaKdnaJbackground ameliorates growth at 37oC and partially restores the cellular levels of some metabolic and respiratory enzymes.
State-dependent changes in olfactory cortical networks via cholinergic modulation
Authors: Wilson Donald A. , Juventin Maxime , Ilina Maria , Pizzo Alessandro , Teixeira Catia
Published: October 2018

Activity in sensory cortical networks reflects both peripheral sensory input and intra‐ and inter-cortical network input. How sensory cortices balance these diverse inputs to provide relatively stable, accurate representations of the external world is not well understood. Furthermore, neuromodulation could alter the balance of these inputs in a state‐ and behavior-dependent manner. Here, we used optogenetic stimulation to directly assay the relative strength of bottom-up (olfactory bulb) and top-down (lateral entorhinal cortex) synaptic inputs to piriform cortex in freely moving rats. Optotrodes in the piriform cortex were used to test the relative strength of these two inputs, in separate animals, with extracellular, monosynaptic evoked potentials. The results suggest a rapid state-dependent shift in the balance of bottom-up and top-down inputs to PCX, with enhancement in the strength of lateral entorhinal cortex synaptic input and stability or depression of olfactory bulb synaptic input during slow-wave sleep compared to waking. The shift is in part due to a state-dependent change in cholinergic tone as assessed with fiber photometry of GCaMP6 fluorescence in basal forebrain ChAT+ neurons, and blockade of the state-dependent synaptic shift with cholinergic muscarinic receptor activation.
Glycerol phosphate acyltransferase 6 controls filamentous pathogen interactions and cell wall properties of the tomato and Nicotiana benthamiana leaf epidermis
Authors: Fawke Stuart , Torode Thomas A. , Gogleva Anna , Fich Eric A. , Sørensen Iben , Yunusov Temur , Rose Jocelyn K.C. , Schornack Sebastian
Published: October 2018

The leaf epidermal wall is covered by a cuticle, composed of cutin and waxes, which protects against dehydration and constitutes a barrier against pathogen attack. Cutin monomers are formed by the transfer of 16- or 18-carbon fatty acids to glycerol by glycerol-3-phosphate acyltransferase (GPAT) enzymes, which facilitates their transport to the plant surface. Here we address the dual functionality of pathogen-inducible Glycerol phosphate acyltransferase 6 (GPAT6) in controlling pathogen entry and dehydration in leaves. Silencing of Nicotiana benthamiana NbGPAT6a increased leaf susceptibility to the oomycetes Phytophthora infestans and P. palmivora, whereas stable overexpression of NbGPAT6a-GFP rendered leaves more resistant to infection. A loss-of-function mutation of the orthologous gene in tomato (Solanum lycopersicum), SlGPAT6, similarly resulted in increased susceptibility of leaves to Phytophthora infection concomitant with altered intracellular infection structure morphology. Conversely, Botrytis cinerea disease symptoms were reduced. Modulation of GPAT6 expression predominantly altered the outer cell wall of leaf epidermal cells. The impaired cell wall-cuticle continuum of tomato gpat6-a mutants resulted in increased water loss and these plants had fewer stomata. Our work highlights a hitherto unknown role for GPAT6-generated cutin monomers in controlling epidermal cell properties that are integral to leaf-microbe interactions and limit dehydration.
Structural Organization of a Type III-A CRISPR Effector Subcomplex Determined by X-ray Crystallography and Cryo-EM
Authors: Dorsey Bryan W. , Huang Lei , Mondragón Alfonso
Published: October 2018

Clustered regularly interspaced short palindromic repeats (CRISPR) and their associated Cas proteins provide an immune-like response in many prokaryotes against extraneous nucleic acids. CRISPR-Cas systems are classified into different classes and types. Class 1 CRISPR-Cas systems form multi-protein effector complexes that includes a guide RNA (crRNA) used to identify the target for destruction. Here we present crystal structures of Staphylococcus epidermidis Type III-A CRISPR subunits Csm2 and Csm3 and a 5.2 Å resolution single-particle cryo-electron microscopy (cryo-EM) reconstruction of an effector subcomplex including the crRNA. The structures help to clarify the quaternary architecture of Type III-A effector complexes, as well as to provide details on crRNA binding, target RNA binding and cleavage, and intermolecular interactions essential for effector complex assembly. The structures allow a better understanding of the organization of Type III-A CRISPR effector complexes as well as highlighting the overall similarities and differences with other Class 1 effector complexes.
Feeding behavior of Costa Rican velvet worms: food hiding, parental feeding investment and ontogenetic diet shift (Onychophora: Peripatidae)
Authors: Barquero-González José Pablo , Vega-Hidalgo Álvaro , Monge-Nájera Julián
Published: October 2018

We report, for the first time in onychophorans, food hiding, parental feeding investment and an ontogenetic diet shift two weeks after birth: from the parent’s adhesive used to capture prey, to the prey itself.
Transcriptome profiling of pathogen-specific CD4 T cells identifies T-cell-intrinsic caspase-1 as an important regulator of Th17 differentiation
Authors: Gao Yajing , Deason Krystin , Jain Aakanksha , Irizarry-Caro Ricardo A , Dozmorov Igor , Rauch Isabella , Wakeland Edward K , Pasare Chandrashekhar
Published: October 2018

One sentence summary

Our study revealed that DCs shape distinct pathogen-specific CD4 T cell transcriptome and from which, we discovered an unexpected role for T-cell-intrinsic caspase-1 in promoting Th17 differentiation.

Dendritic cells (DCs) are critical for priming and differentiation of pathogen-specific CD4 T cells. However, to what extent innate cues from DCs dictate transcriptional changes in T cells leading to effector heterogeneity remains elusive. Here we have used anin vitroapproach to prime naïve CD4 T cells by DCs stimulated with distinct pathogens. We have found that such pathogen-primed CD4 T cells express unique transcriptional profiles dictated by the nature of the priming pathogen. In contrast to cytokine-polarized Th17 cells that display signatures of terminal differentiation, pathogen-primed Th17 cells maintain a high degree of heterogeneity and plasticity. Further analysis identified caspase-1 as one of the genes upregulated only in pathogen-primed Th17 cells but not in cytokine-polarized Th17 cells. T-cell-intrinsic caspase-1, independent of its function in inflammasome, is critical for inducing optimal pathogen-driven Th17 responses. More importantly, T cells lacking caspase-1 fail to induce colitis following transfer into RAG-deficient mice, further demonstrating the importance of caspase-1 for the development of pathogenic Th17 cellsin vivo. This study underlines the importance of DC-mediated priming in identifying novel regulators of T cell differentiation.
Actomyosin-driven force patterning controls endocytosis at the immune synapse
Authors: Kumari Anita , Sáez Pablo J. , Maurin Mathieu , Lankar Danielle , San Roman Mabel , Voituriez Raphael , Hennig Katharina , Boura Vanessa F. , Karlsson Mikael C.I. , Balland Martial , Lennon Dumenil Ana-Maria , Pierobon Paolo
Published: October 2018

An important channel of cell-to-cell communication is direct contact. The immune synapse is a paradigmatic example of such type of interaction: it forms upon engagement of antigen receptors in lymphocytes by antigen-presenting cells and allows the local exchange of molecules [1]. Although [2], how forces organize and mechanics has been shown to play an important role in this process impact on synapse function is unknown. We found that mechanical forces are spatio-temporally patterned at the immune synapse: global contractile forces are observed at the synapse periphery and local point-like forces are detected at its centre. The global contractile forces result from a pulsatile centripetal actomyosin flow that leads to formation of F-actin protrusions from which the central point like forces emerge. Noticeably, these force-producing actin protrusions constitute the main site of antigen extraction and endocytosis. Accordingly, deletion of the myosin IIA gene leads to impaired B cell responses. The interplay between global and local forces governed by the actomyosin cytoskeleton therefore controls the endocytic function of the immune synapse and might constitute a more general mechanism in the physical regulation of cell-cell interactions.
Characterisation of deubiquitylating enzymes in the cellular response to high-LET ionising radiation and complex DNA damage
Authors: Carter Rachel J. , Nickson Catherine M. , Thompson James M. , Kacperek Andrzej , Hill Mark A. , Parsons Jason L.
Published: October 2018

Purpose

Ionising radiation, particular high linear energy transfer (LET) radiation, can induce complex DNA damage (CDD) where two or more DNA lesions are induced in close proximity which contributes significantly to the cell killing effects. However knowledge of the enzymes and mechanisms involved in co-ordinating the recognition and processing of CDD in cellular DNA are currently lacking.

Methods and Materials

An siRNA screen of deubiquitylation enzymes was conducted in HeLa cells irradiated with high-LET -particles or protons, versus low-LET protons and x-rays, and cell survival monitored by clonogenic assays. Candidates whose depletion led to decreased cell survival specifically in response to high-LET radiation were validated in both HeLa and oropharyngeal squamous cell carcinoma (UMSCC74A) cells, and the association with CDD repair was confirmed by using an enzyme modified neutral comet assay.

Results

Depletion of USP6 decreased cell survival specifically following high-LET α-particles and protons, but not by low-LET protons or x-rays. USP6 depletion caused cell cycle arrest and a deficiency in CDD repair mediated through instability of poly(ADP-ribose) polymerase-1 (PARP-1). This phenotype was mimicked using the PARP inhibitor olaparib.

Conclusion

USP6 controls cell survival in response to high-LET radiation by stabilising PARP-1 protein levels which is essential for CDD repair. We also describe synergy between CDD induced by high-LET protons and PARP inhibition in effective cancer cell killing.
Fair allocation of healthcare research funds by the European Union?
Authors: Kaló Zoltán , van den Akker Loek Hendrik Matheo , Vokó Zoltán , Csanádi Marcell , Pitter György János
Published: October 2018

This study aimed to investigate the distribution of European Union (EU) healthcare research grants across EU countries, and to study the effect of the potential influencing factors on grant allocation. We analysed publicly available data on healthcare research grants from the 7th Framework Programme and the Horizon 2020 Programme allocated to beneficiaries between 2007 and 2016. Grant allocation was analysed at the beneficiary-, country-, and country group-level (EU-15 versus newer Member States, defined as EU-13). The investigated country-level explanatory variables included GDP per capita, population size, overall disease burden, and healthcare research excellence. Grant amounts per 100,000 inhabitants was used as an outcome variable in the regression analyses.

Research funds were disproportionally allocated to EU-15 versus the EU-13, as 96.9% of total healthcare grants were assigned to EU-15 countries. At the beneficiary level, EU funding was positively influenced by participating in previous grants. The average grant amount per beneficiary was higher for EU-15 organizations. In univariate regression analyses at the country level, higher GDP per capita (p<0.001) and better medical research excellence (p<0.001) were associated with more EU funding, and a higher disease burden was associated with less EU funding (p=0.003). In the multiple regression analysis GDP per capita (p=0.002) and research excellence (p<0.001) had a significant positive association with EU funding. Population size had an inverted U-shaped relationship with EU funding for healthcare research, having the largest per capita funding in second and the third quartiles (p=0.03 and p=0.02).

The uneven allocation of healthcare research funds across EU countries was influenced by GDP per capita, medical research excellence and population size. Wealthier countries with an average population size and strong research excellence in healthcare had more EU funding for healthcare research. Higher disease burden apparently was not associated with more EU research funding.
ModelingEdarexpression reveals the hidden dynamics of tool signaling center patterning
Authors: Sadier Alexa , Twarogowska Monika , Steklikova Klara , Hayden Luke , Lambert Anne , Schneider Pascal , Laudet Vincent , Hovorakova Maria , Calvez Vincent , Pantalacci Sophie
Published: October 2018

The generation of patterns during development is generally viewed as a direct process. In the mouse jaw, however, the sequential patterning of molars initiates with abortive tooth signaling centers called MS and R2, thought to be vestiges of the lost rodent premolars. Moreover, the mature signaling center of the first molar (M1) is formed from the fusion of two signaling centers (R2 and early M1). Here, we report thatEdarexpression reveals the hidden dynamics of signalling centers patterning. First,Edarexpression evidenced a hidden two-step patterning process that we modelled with a single activator-inhibitor pair: the epithelium is initially broadly activated, then activation becomes restricted in space to give rise to the signalling centers. Second,Edarexpression unveils successive phases of pattern making and pattern erasing events, a phenomenon that we called a developmental palimpsest. MS is erased by a broad activation for the benefit of R2, which itself is erased before it recovers when the first molar signaling center forms. In the lower but not the upper jaw, the two neighboring signaling centers then fuse into a single elongated center. Our model recapitulated the erasure of the R2 signaling center by the wave of activation that precedes the formation of M1 signaling center, and predicted the surprising rescue of R2 in the context of anEdarmutant with reduced activation. It suggested that R2 was not intrinsically defective, but actively outcompeted by M1 formation. We confirmed this by cultivating R2 separately from the posterior tissue and showing it could then generate a tooth. Finally, by introducing chemotaxis as a secondary process of tooth germ maturation, we recapitulated the fusion of R2 and M1 in the lower jaw only, and the loss of fusion when Edar function is impaired in organ cultures. In conclusion, we have uncovered a highly indirect and dynamic nature of pattern formation in the molar field that could nevertheless be simulated with simple mathematical models. Our study argues for viewing embryonic patterns as dynamical objects rather than as fixed endpoints, where dynamics is essential to the outcome of the patterning process.
Universal antibiotic tolerance arising from antibiotic-triggered accumulation of redox metabolites
Authors: Zhu Kui , Chen Shang , Sysoeva Tatyana A. , You Lingchong
Published: October 2018

Pseudomonas aeruginosais an opportunistic pathogen that often infects open wounds or patients with cystic fibrosis. Once established,P. aeruginosainfections are notoriously difficult to eradicate. This difficulty is in part due to the ability ofP. aeruginosato tolerate antibiotic treatment at the individual-cell level or through collective behaviors. Here we describe a new mechanism by whichP. aeruginosatolerates antibiotic treatment by modulating its global cellular metabolism. In particular, treatment ofP. aeruginosawith sublethal concentrations of antibiotics covering all major classes promoted accumulation of the redox-sensitive phenazine - pyocyanin (PYO). PYO in turn conferred general tolerance against diverse antibiotics for bothP. aeruginosaand other Gram-negative and Gram-positive bacteria. We show that PYO promotes energy generation to enhance the activity of efflux pumps, leading to enhanced antibiotic tolerance. This property is shared by other redox-active phenazines produced byP. aeruginosa. Our discovery sheds new insights into the physiological functions of phenazines and has implications for designing effective antibiotic treatment protocols.

Author Summary

Antibiotic tolerance can facilitate the evolution of resistance, and here we describe a previously unknown mechanism of collective antibiotic tolerance inPseudomonas aeruginosa. In particular,P. aeruginosatreated with sublethal concentrations of antibiotics covering all major classes promotes accumulation of pyocyanin (PYO), an important virulence factor. In turn, PYO confers general tolerance against diverse antibiotics for bothP. aeruginosaand other bacteria. Our discovery is a perfect example of what Nietzsche once said:That which does not kill me makes me stronger.
Non-market strategies and Indonesian SMEs: casualties of decentralisation?
Authors: Sanusi Abdullah , Connell Julia
Published: October 2018

Purpose

The purpose of this paper is to examine the non-market strategies adopted by government-contracted small and medium enterprises (SMEs) in order to address the challenges they faced in the business of procurement. Although SMEs are important contributors to employment and the national economy, they demonstrated different levels of effectiveness depending on the management strategies they adopted.

Design/methodology/approach

Using case study methodology, data were gathered by conducting interviews with the owners/managers of Indonesian SMEs. Findings were analysed using the (ia)3framework developed to assist the understanding of non-market environments.

Findings

Findings indicated that a key characteristic of the Indonesian non-market environment was the influence of the government and Indonesian society. This led to differing degrees of dissatisfaction among SME owners and managers who reported that they had to work within a number of constraints for business survival, while simultaneously learning how to “play the games” demanded by the business and regulatory environment.

Research limitations/implications

Limitations relate to the number of empirical cases represented and the geographical area covered. Further research is recommended in order to provide the opportunity for research generalisation.

Practical implications

These findings illustrate the need for transparency and integrity in the procurement process in relation to Indonesian SMEs. It is proposed that SMEs in similar sectors may benefit from forming strategic alliances/industry clusters to support future knowledge sharing and promote their collective voice.

Originality/value

To date, studies on non-market strategies have largely focused on developed countries and large firms. Consequently, this paper goes some way towards bridging the gap in the non-market environment in developing countries concerning SMEs and potential strategies for adoption.
Benchmarking responsible management and non-financial reporting
Authors: Hilliard Ivan , Priede Tiziana
Published: October 2018

Purpose

The purpose of this paper is to present a model, which assesses the wide range of data offered in non-financial reports, and enables benchmarking of these data between different organizations.

Design/methodology/approach

This work uses aspects of fuzzy logic and qualitative comparative analysis to build fuzzy sets, which form the basis of the benchmarking tool.

Findings

The model presented permits the identification of both negative and positive aspects of an organization’s CSR actions, and shows where improvements can be made by highlighting the standards reached by others.

Originality/value

The model offers a benchmarking tool that allows analysis of non-financial reporting, something missing from the field of CSR until now. Additionally, it offers a new approach where data sets are constructed to measure environmental/social impact in function of each unit of economic value generated. This approach aligns social/environmental and economic performance, thereby emphasizing the interconnectivity of a company’s financial, social and environmental bottom lines.
Consumer participation in drug treatment: a systematic review
Authors: Goodhew Mark , Stein-Parbury Jane , Dawson Angela
Published: October 2018

Purpose

It is unclear how consumer participation (CP) can be optimised to transform drug and alcohol treatment services and improve health outcomes. The purpose of this paper is to present the findings of a systematic review examining the types and benefits of activities, and the factors that facilitate CP in drug treatment services.

Design/methodology/approach

A structured search of four databases was undertaken to identify peer reviewed primary research literature in English. Screened articles were appraised. A content analysis was applied to examine the types and outcomes of CP and the associated factors affecting the process. In total, 16 articles were included for review.

Findings

A range of CP activities were identified, and benefits included increased consumer satisfaction, and improved health service delivery. Factors that facilitated the process of CP included positive attitudes of both consumers and providers and employment of people with a lived experience of drug use. However, the lack of consumer and organisational capacity, negative attitudes of providers and power imbalances between consumers and providers constrained CP efforts.

Practical implications

To maximise the benefits of CP in drug and alcohol treatment services, negative attitudes about CP and power dynamics between consumers and health providers need to be addressed. This can be achieved by the strategic use of strengths-based interventions and consumer led education to enhance social capital.

Originality/value

This is the first known review to examine the benefits and facilitators of CP in drug treatment services.
“Never the first time on a patient”: the stakes of high-fidelity simulation for safety training
Authors: Cuvelier Lucie
Published: October 2018

Purpose

This paper aims to review the latest management developments across the globe and pinpoint practical implications from cutting-edge research and case studies.

Design/methodology/approach

This briefing is prepared by an independent writer who adds their own impartial comments and places the articles in context.

Findings

An operative approach is described that is designed to structure the debriefing along three axes.

Practical implications

The paper provides strategic insights and practical thinking that have influenced some of the world’s leading organizations.

Originality/value

The briefing saves busy executives and researchers hours of reading time by selecting only the very best, most pertinent information and presenting it in a condensed and easy-to-digest format.
Double-diffusive natural convection in an inclined enclosure with heat generation and Soret effect
Authors: Hasnaoui Safae , Amahmid Abdelkhalek , Raji Abdelghani , Beji Hassen , Hasnaoui Mohammed , Dahani Youssef , Benhamed Haykel
Published: October 2018

Purpose

The purpose of this paper is to study numerically thermosolutal natural convection within an inclined rectangular cavity in the presence of Soret effect and heat generation. The enclosure is heated and salted from its long sides with constant but different temperatures and concentrations. The study focuses on the effects of three main parameters which are, the Soret parameter (Sr = 0 and –0.5), the internal to external Rayleigh numbers ratio 0 ≤ R ≤ 80 and the cavity inclination γ, varied from 0° (vertical position) to 60°. The combined effects of these parameters on fluid flow and heat and mass transfer characteristics are examined for the external Rayleigh number RaE = 105, the Prandtl number Pr = 0.71, the buoyancy ratio N = 1, the Lewis number Le = 2 and the aspect ratio of the cavity A = 2.

Design/methodology/approach

A hybrid lattice Boltzmann-finite difference method (LBM-FD) was used to tackle the problem under consideration. The LBM with the simple relaxation time was used for the fluid flow in the presence of the gravity force, while the temperature and concentration equations were solved separately using an explicit finite-difference technique at the Boltzmann scale.

Findings

The monocellular nature of the flow, obtained for R = 0 is not destroyed by varying the cavity inclination and the Soret parameter but rather by the increase of the parameter R. The Soret parameter and the cavity inclination become perceptible at high values of R. The inclination γ = 60° leads to high mean temperatures compared to the other inclinations. The effect of R on mean concentration is amplified in the presence of Soret effect but limited in the absence of the latter. The negative Soret parameter combined with high internal heat generation and a relatively high inclination is important when the objective is to maintain the fluid at a high concentration of species. The presence of bicellular flow combined with the important elevation undergone by the fluid temperature, makes both the cold and hot walls playing a cooling role with the most important exchanges taking place at the upper part of these walls. The analysis of the mean mass transfer shows that the increase of the inclination may lead to an increase or a decrease of the mass transfer depending on the range of R, in the case of Sr = 0. However, for Sr = −0.5, it is observed that the increase of γ is generally accompanied by a reduction of the mass transfer.

Originality/value

To the best of the authors’ knowledge, the hybrid LBM-FD was not used before to study such a problem. Combined effect of R and inclination may be useful in charging the fluid with species when the objective is to maintain high concentrations in the medium.
Do brands compete or coexist? How persistence of brand loyalty segments the market
Authors: Sheth Jagdish , Koschmann Anthony
Published: October 2018

Purpose

This study aims to question the conventional wisdom that brands compete for customers, especially in mature industries such as soft drinks. Rather than engaging in price wars or promotion wars, brands coexist in the markets by focusing on their own brand loyal customers.

Design/methodology/approach

Consumer panel data of carbonated beverages are examined using Markov chains to measure switching between two brands: Coke and Pepsi. Switching rates are conducted for all Coke households (n = 10,474) and Pepsi households (n = 7,227). This is further examined with respect to heavy half (upper median) consumers of each brand who make up approximately 86 per cent of volume purchases.

Findings

Households that made a majority of their purchase volume in either Coke or Pepsi products stayed with their preferred brands in subsequent quarters: 85 to 97 per cent of households. These findings are validated at all levels of the brand architecture (family brands, product brands and modified brands), even though both brands engage in similar marketing mix tactics (advertising, price cuts, distribution, product offerings). Loyalty was even higher among the heavy user households.

Research limitations/implications

The research was conducted using two well-known brands in a mature industry. Services or non-mature markets may exhibit different loyalty patterns.

Originality/value

The study extends prior research on competition, loyalty and branded offerings to show that brand loyalty remains high despite marketing efforts to switch the brand buying behavior.
A Chinese legal intelligent auxiliary discretionary adviser based on GA-BP NNs
Authors: Zhang Ni , Pu Yi-fei , Yang Suiquan , Gao Jinkang , Wang Zhu , Zhou Ji-liu
Published: October 2018

Purpose

This paper aims to build a legal intelligent auxiliary discretionary system for predicting the penalty and damage compensation values. After extensively considering current the characteristics of the current Chinese legal system, a practical legal intelligent auxiliary discretionary system based on genetic algorithm-backpropagation (GA-BP) neural network (NN) is proposed herein.

Design/methodology/approach

An experiment is designed to analyze cases involving mental anguish compensation in medical disputes, and a Chinese legal intelligent auxiliary discretionary adviser system is built based on a GA-BP NN. Because BP neural networks perform well for nonlinear problems and GAs can improve their ability to find optimal values, and accelerate their convergence, a combined GA–BP algorithm is used. In addition, an ontology is used to reduce the semantic ambiguities and extract the implied semantic information.

Findings

We confirm that a case-based legal intelligent auxiliary discretionary adviser system based on a GA-BP NN and ontology techniques has good performance in prediction. By predicting the mental anguish compensation values, the legal intelligent auxiliary discretionary adviser system can help judges to handle cases more quickly and ordinary people to discover the suggested compensation or penalty. In contrast to BP NN or SVM, the result seems more close to the actual compensation rate.

Practical implications

Recently, smart court has been developed in China; the purpose of which is to build the legal advice system for improving judicial justice and reducing differences in sentencing. A practical legal advice system is an urgent requirement for the judiciary.

Originality/value

This paper presents a study of a case-based legal intelligent auxiliary discretionary adviser system based on a GA-BP NN and ontology techniques. The findings offer advice to optimize legal intelligent auxiliary discretionary adviser systems for mental anguish compensation in medical disputes.
The guanxi ties of managers in mainland China – a critical analysis based on gender
Authors: Aaltio Iiris , Huang Jiehua
Published: October 2018

Purpose

Inadequate social networks are often seen as an explanation of the under-representation of women in management. Networks contain culture-specific features, as in China where the term guanxi is used, defined as a shared common identification held by two or more individuals (Jacobs, 1979). In several studies, guanxi has been found to relate positively to success at work both for the individual and the organization, but little is known about it from gender and career perspectives. Referring especially to the earlier studies by Chow and Ng (2004), the purpose of this paper is to address the meaning of guanxi networks for top women IT managers in mainland China.

Design/methodology/approach

The authors collected data from 21 women managers in mainland China, using a questionnaire about the composition and structure of their core guanxi networks and face-to-face interviews which allowed ample opportunity to elaborate the participants’ responses to items included in the questionnaire and their perspectives to using guanxi in general. The authors used both data in an interpretive analysis.

Findings

It was found that: there is a significant effect of female-to-male dyads concerning power and work-related guanxi bases, such as influence; there is a significant effect of female-to-female dyads concerning questions of private life and crisis, and women IT managers have a relatively limited guanxi base. The findings of this paper support Ibarra’s (1993) suggestion that a common strategy for women is to use and develop a functionally differentiated network. Based on findings, the authors further suggest that in building a successful managerial career, women managers in China need to reflect their gender, be gender-sensitive in building up their networks and stay incorporated at the core networks in the organization whatever gender they represent. They also suggest that because networks are dependent on culturally bound definitions (like guanxi), even the guanxi practices may vary locally in different parts of China.

Research limitations/implications

Women managers are important role models for younger female candidates and the possibility to close connections with them is relevant. Because networks are dependent on culturally bound definitions (like guanxi), even the guanxi practices may vary locally in different parts of China. For further studies, the authors suggest to focus on the consequences of guanxi practice limitations to women managers’ careers, especially from the perspective of private life responsibilities and the possible problematic nature of power ties between the gender(s).

Originality/value

Even if working life is becoming more and more global, the local and culture-based nature of networking remains. This paper contributes on the extensive research on social networking practices in China, often described in terms of guanxi, which has seldom been investigated using critical gender perspective.