bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of Healthcare Use and Clinical Outcomes of Alvimopan in Patients Undergoing Bowel Resection: A Propensity Score-Matched Analysis
Authors: Steele Scott R. , Brady Justin T. , Cao Zhun , Baumer Dorothy L. , Robinson Scott B. , Yang H. Keri , Delaney Conor P.
Published: October 2018

BACKGROUND:

Postoperative ileus is a significant complication after bowel resection surgeries. Alvimopan is the only US Food and Drug Administration–approved therapy for accelerating the return of bowel function after large- and small-bowel resection.

OBJECTIVE:

The purpose of this study was to estimate the healthcare use and in-hospital morbidities associated with on-label use of alvimopan in patients undergoing bowel resection surgeries.

DESIGN:

A retrospective observational propensity-matched cohort study was conducted using a large hospital administrative database.

SETTING:

The study included inpatient postsurgical patients.

PATIENTS:

Patients aged ≥18 years undergoing a primary large or small segmental bowel resection with discharge dates between January 2010 and December 2014 were included.

INTERVENTIONS:

Patients receiving 2 to 15 doses of alvimopan were defined as the treatment cohort, and those without any alvimopan use were included as control subjects.

MAIN OUTCOME MEASURES:

The primary outcome was postoperative length of stay. Secondary outcomes included postoperative in-hospital morbidities, inpatient mortality, intensive care unit length of stay, discharge disposition, and 30-day readmission.

RESULTS:

Each propensity-score matched cohort included 18,559 patients. The mean (±SD) postoperative length of stay was 4.62 ± 2.45 days in alvimopan-treated patients compared with 5.24 ± 3.35 days in control subjects (p< 0.001). Alvimopan-treated patients had lower rates of postoperative GI complication (12.15% vs 16.50%;p< 0.001). The rates of urinary tract infections; other postoperative infections; and cardiovascular, pulmonary, thromboembolic, and cerebrovascular events were also lower compared with the control subjects.

LIMITATIONS:

The study was limited by its inability to generalize to the US population, because the database included a convenience sample of hospital discharges. The identification of patients undergoing bowel resection and their clinical conditions relied on the accuracy and completeness of International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis and procedure coding. There may be a confounding effect by the use of enhanced recovery pathways associated with the use of alvimopan.

CONCLUSIONS:

The use of alvimopan was associated with a reduction of 0.62 days in postsurgery length of stay and lower rates of postoperative GI complications, infections, and other in-hospital morbidities. SeeVideo Abstractat http://links.lww.com/DCR/A703.
Impact of Disgust on Intentions to Undergo Colorectal Surgery
Authors: Turner Megan C. , O’Brien Julia D. , Kahn Rachel M. , Mantyh Christopher R. , Migaly John , Ariely Dan
Published: October 2018

BACKGROUND:

Surgeons present patients with complex information at the perioperative appointment. Emotions likely play a role in surgical decision-making, and disgust is an emotion of revulsion at a stimulus that can lead to avoidance.

OBJECTIVE:

The purpose of this study was to determine the impact of disgust on intention to undergo surgical resection for colorectal cancer and recall of perioperative instructions.

DESIGN:

This was a cross-sectional observational study conducted online using hypothetical scenarios with nonpatient subjects.

SETTINGS:

The study was conducted using Amazon’s Mechanical Turk.

PATIENTS:

Survey respondents were living in the United States.

MAIN OUTCOME MEASURES:

Surgery intention and recall of perioperative instructions were measured.

RESULTS:

A total of 319 participants met the inclusion criteria. Participants in the experimental condition, who were provided with detailed information and pictures about stoma care, had significantly lower surgery intentions (mean ± SD, 4.60 ± 1.15) compared with the control condition with no stoma prompt (mean ± SD, 5.14 ± 0.91; p = 0.05) and significantly lower recall for preoperative instructions (mean ± SD, 13.75 ± 2.38) compared with the control condition (mean ± SD, 14.36 ± 2.19; p = 0.03). Those within the experimental conditions also reported significantly higher state levels of disgust (mean ± SD, 4.08 ± 1.74) compared with a control condition (mean ± SD, 2.35 ± 1.38; p < 0.001). State-level disgust was found to fully mediate the relationship between condition and recall (b = –0.31) and to partially mediate the effect of condition on surgery intentions (b = 0.17).

LIMITATIONS:

It is unknown whether these results will replicate with patients and the impact of competing emotions in clinical settings.

CONCLUSIONS:

Intentions to undergo colorectal surgery and recall of preoperative instructions are diminished in patients who experience disgust when presented with stoma information. Surgeons and care teams must account for this as they perform perioperative counseling to minimize interference with recall of important perioperative information. See Video Abstract at http://links.lww.com/DCR/A776.
PHOTODYNAMIC THERAPY–INDUCED ACUTE EXUDATIVE MACULOPATHY
Authors: Manayath George Joseph , Ranjan Ratnesh , Vidhate Swapnil , Narendran Venkatapathy
Published: October 2018

Purpose:

To describe the incidence, clinical features, and long-term outcomes of photodynamic therapy (PDT)-induced acute exudative maculopathy (PAEM) in patients who underwent PDT for various indications.

Methods:

This retrospective observational case series included all cases who developed massive serofibrinous macular exudation within a week after PDT. Medical records of patients with post-PDT exudative events were reviewed for relevant data and imaging abstraction including optical coherence tomography and indocyanine green angiography features and were subjected to analysis.

Results:

The incidence rate of PAEM was 4.52%, being noted in 8 eyes (out of 177 PDT sessions in 155 eyes) with a mean age of 70.25 ± 6.65 years. Pre-PDT factors commonly associated with PAEM included age ≥65 years (87.5%), clinical diagnosis of polypoidal choroidal vasculopathy (75%), spot size ≥3,500 µm (100%), best-corrected visual acuity of 20/40 or better (87.5%), low-fluence PDT (87.5%), and the first exposure to PDT (75%). Photodynamic therapy–induced acute exudative maculopathy was noted at a mean interval of 2.9 ± 1.7 days (2–7 days) after PDT. Photodynamic therapy–induced acute exudative maculopathy resulted in significant decrease in mean best-corrected visual acuity from logMAR 0.29 ± 0.21 (approximate Snellen equivalent 20/39) to logMAR 0.91 ± 0.37 (approximate Snellen equivalent 20/163) [P = 0.0018], and significant increase in mean central macular thickness from 228.1 ± 71.8 µm to 481.4 ± 154.8 µm (P = 0.0029). Photodynamic therapy–induced acute exudative maculopathy resolved to baseline or even better tomographic status at a mean interval of 4.6 ± 1.2 weeks, resulting in complete visual recovery compared with baseline. During mean follow-up of 77.8 ± 46.4 weeks after PDT, no activity was noted for a mean duration of 26.3 ± 42.5 weeks after resolution. At final visit, mean best-corrected visual acuity and central macular thickness was logMAR 0.49 ± 0.28 (approximate Snellen equivalent 20/62) and 153.6 ± 40.0 µm, respectively, with underlying pathology being stable in 50% of the eyes.

Conclusion:

Photodynamic therapy–induced acute exudative maculopathy is an uncommon complication with self-resolving course and favorable prognosis. Patients undergoing PDT should be warned of the possibility of PAEM. The factors frequently associated with PAEM include elderly age (>65 years), clinical diagnosis of polypoidal choroidal vasculopathy, larger spot size (≥3,500 µm), pre-PDT best-corrected visual acuity of 20/40 or better, low-fluence PDT, and the first exposure to PDT.
Socket Reconstruction With Bleomycin, Gentamicin, and Gelatin Sponges Following Eyelid-Sparing Orbital Exenteration for a Colobomatous Macrocyst in an Infant
Authors: Michelson Sarah J. , Ciongoli Marina R. , Elner Victor M. , Kahana Alon
Published: October 2018

Microphthalmia is defined by a globe axial length greater than or equal to 2 standard deviations below the age-adjusted mean and can occur as part of a broader syndrome. The presence of a colobomatous cyst with microphthalmia signifies failure of the embryonic neuroectodermal fissure to close appropriately during development of the globe, creating a protuberant globular appendage that inhibits normal growth and development of the eye itself. Cystic reaccumulation of fluid is common after aspiration or surgical removal. Here, the authors describe a case of a young boy with a colobomatous cyst who underwent eyelid-sparing orbital exenteration followed by reconstruction with absorbable gelatin sponge (Gelfoam, Pfizer, Inc.) and the chemotherapeutic agent bleomycin to promote scarring, achieving the equivalent of a biointegrated implant and facilitating satisfactory placement of an ocular prosthesis. A 2-year follow-up MRI revealed adequate volume in the posterior orbit.
Motivation to Care: A Qualitative Study on Iranian Nurses
Authors: ASADI Neda , MEMARIAN Robabeh , VANAKI Zohreh
Published: October 2018

Background:

The performance of nurses, which is rooted in personal motivation, determines the quality of care. Therefore, it is important that nurses are motivated to provide high-quality care.

Purpose:

The purpose of this study was to explore the factors that affect caring motivation from the perspectives of nurses in Iran.

Methods:

This was a qualitative study. Seventeen nurses were interviewed using a semistructured, in-depth interview method. The interviews were recorded, transcribed verbatim, and analyzed using content analysis.

Results:

Data analysis led to the identification of the two themes of (a) self-valuation and (b) providing beneficial care.

Conclusions/Implications for Practice:

The findings of this study increase scholarly understanding of the caring motivations of nurses. These motivations may be used in related programs by senior nursing managers to improve the quality of nursing care.
Yellow Means Caution: Correlations Between Liver Injury and Mortality with the Use of VA-ECMO
Authors: Masha Luke , Peerbhai Shareez , Boone David , Shobayo Fisayomi , Ghotra Aman , Akkanti Bindu , Zhao Yelin , Banjac Igor , Gregoric Igor D. , Kar Biswajit
Published: October 2018

Abnormalities in markers of liver injury after venoarterial extracorporeal membrane oxygenation (VA-ECMO) initiation are of unclear distribution and clinical significance. This study included all consecutive adult patients from a single institution who underwent VA-ECMO cannulation between May 2012 and September 2016 and had liver function panels drawn during their admission (n = 223). Data points include: age, sex, body mass index, diagnosis, duration of ECMO cannulation, duration of hospitalization, pre-ECMO cardiac arrest, central nervous system (CNS) injury, the presence of chronic kidney disease or acute renal failure, renal replacement therapy utilization, lactate levels, duration of pre-ECMO intubation, admission and peak bilirubin/aspartate aminotransferase (AST)/alanine aminotransferase (ALT)/alkaline phosphatase (ALP) levels, and time to peak bilirubin/AST/ALT/ALP in relation to cannulation. Multivariate Poisson regression analyses were performed to determine associations with mortality. In-hospital mortality was 66%. Serum bilirubin elevation appeared to significantly correlate continuously with mortality. Other markers of liver injury were not significant in final multivariate models. As a univariate factor, no patient survived with a total serum bilirubin greater than 30 mg/dl, and specificity for 90% mortality was crossed at 11 mg/dl. Mortality was also significantly associated with the presence of CNS injury and elevation of lactic acid levels. Postcannulation liver injury is significantly associated with increased mortality and total serum bilirubin appears to be a biomarker of considerable clinical significance.
New autoinflammatory diseases
Authors: Poli M. Cecilia
Published: October 2018

Purpose of review

Advances in sequencing techniques and systematic cohort-analysis of patients with autoinflammatory phenotypes have enabled a burst in the recognition of new autoinflammatory diseases and contributed to the description of the mechanisms involved in autoinflammation. This review focuses on new genetic and mechanistic discoveries that have broadened the definition of autoinflammatory diseases in the context of the established landscape, providing new therapeutic opportunities and avenues for further discoveries.

Recent findings

Mechanistic insights of inflammatory diseases open opportunities for new targeted therapies. Advances in high-throughput screening of small-molecule inhibitors accelerate the discovery of new and more specific therapeutic options. Recent evidence establishes IL-18 as a driver of macrophage activation, emerging as a new biomarker and therapeutic target. Finally, the identification of escape of nonsense-mediated decay as the genetic mechanism resulting in a monogenic immune-dysregulatory disease, unveils a possibility for future discoveries.

Recent mechanistic findings in autoinflammatory diseases as well as the identification of specific biomarkers and discovery of new diseases, continue to pave the way for ever more specific targeted approaches. These therapies are not only applicable to monogenic autoinflammatory syndromes but also for other diseases in which the same pathways are dysregulated.
Fast and Easy-to-Perform BRAF Testing in Melanoma Samples: An Accessible Tool for Pathologists With no Experience in Molecular Analyses
Authors: Barel Fanny , Uguen Arnaud
Published: October 2018

BRAFV600 mutation testing is mandatory for treatment choices in patients with advanced melanomas. Besides molecular methods, VE-1 immunohistochemistry has paved the way for BRAF mutation detection by every pathologist, but it only detects BRAFV600E mutant protein, and additional DNA-based molecular analyses are often delegated to molecular genetics laboratories to detect mutations other than BRAFV600E. In this technical article, we present a new diagnostic device that is easy to implement in surgical pathology laboratories, even for pathologists lacking any experience in molecular analyses, to diagnose most of the BRAF mutations encountered in melanoma. The implementation of this fast (<2 h per analysis) and fully automated new real-time polymerase chain reaction diagnostic device, in pathology laboratories, could help to reduce the turnaround times for molecular results, to allow rapid subsequent therapeutic choices in patients with advanced melanomas and other cancers.
Reconstruction of Major Dehiscence After Bilateral Cleft Lip Repair
Authors: Lim Elva , Pai Betty C.J. , Getachew Daniel , Jung Soyeon , Lo Lun-Jou
Published: October 2018

Repair of complete bilateral cleft lip with protruding premaxilla is challenging, and postoperative dehiscence was common. Re-repair is usually suggested for the dehisced lip, but other methods might be needed in unique situations. Evaluation was performed to check the presence of prolabial skin, wound scarring, and the position of premaxilla. Reconstruction plan was made to restore the anatomical components as possible and to repair under minimal tension. Two patients with major dehiscence were reported. In the first case, separation from the columella base and tissue destruction in central lip were noted. Repeated complete dehiscence on one side was reported in the second case before he was referred to our center. The premaxilla was protruding in both cases. Abbe flap was performed as delayed procedure in the first case. Reposition of the premaxilla in conjunction with lip repair was required in the second case. In both cases, adequate muscle approximation plus subcutaneous retention sutures were used to cope with the tension, and satisfactory healing was achieved. It is concluded that additional methods could be required for the reconstruction of major dehiscence after bilateral cleft lip repair. Careful planning and surgical execution ensured successful outcome.
Objectifying Micrognathia Using Three-Dimensional Photogrammetric Analysis
Authors: Basart Hanneke , Suttie Michael , Ibrahim Amel , Ferretti Patrizia , van der Horst Chantal M.A.M. , Hennekam Raoul C. , Hammond Peter
Published: October 2018

Background:

Micrognathia occurs isolated and as part of entities like Robin sequence (RS). An objective measurement of mandible size and growth is needed to determine the degree of micrognathia and enable a comparison of treatment outcomes. A pilot study was conducted to investigate the usability of 3-dimensional (3D) facial photogrammetry, a fast, noninvasive method, to estimate mandible size and growth in a small cohort of newborns and infants.

Methods:

Exterior mandibular volume was estimated using a tetrahedron defined by 4 facial landmarks. Twelve patients with RS with different etiologies were selected and photogrammetric images were obtained prospectively in 3 patients with RS in whom mandibular growth in the first year of life was determined. We used 3 tetrahedra defined by 6 landmarks on mandibular computed tomography (CT) scans to estimate an interior mandibular volume, which we compared to the exterior mandibular volume in 10 patients.

Results:

The exterior mandibular volume using 3D photography could be determined in all patients. Signature heat maps allowed visualization of facial dysmorphism in 3D; signature graphs demonstrated similarities of facial dysmorphism in patients with the same etiology and differences from those with other diagnoses and from controls. The correlation between interior (3D photogrammetry) and exterior mandibular volumes (CT imaging) was 0.8789.

Conclusion:

The 3D facial photogrammetry delineates the general facial characteristics in patients with different syndromes involving micrognathia, and can objectively estimate mandibular volume and growth, with excellent correlation with bony measurement. It has been concluded that 3D facial photogrammetry could be a clinically effective instrument for delineating and quantifying micrognathia.
Instruments to evaluate complexity in end-of-life care
Authors: Martin-Rosello Maria Luisa , Sanz-Amores Maria Reyes , Salvador-Comino Maria Rosa
Published: October 2018

Purpose of review

The growing number of patients with terminal and chronic conditions and co-morbidities constitutes a challenge for any healthcare system, to provide effective and efficient patient-centred care at the end of life. Resources are limited, and complexity is rising within patients’ situations and healthcare professionals interventions. This review presents the state of art of the role of complexity in specialist palliative care provision.

Recent findings

Although studies related to complexity in palliative care are still limited, interesting reviews on complexity frameworks in co-morbidity conditions and palliative care are growing more present in current literature. They identify multidimensional issues, resource utilisation, and the relationship between them as fundamental aspects of complexity constructs, helping to define and understand complexity, and to therefore design validated tools to support healthcare professionals identifying the most complex patients, such as Hui's criteria, PALCOM, INTERMED, and IDC-Pal which is presented in this review.

There is an urgent need to guarantee quality and equity of care for all the patients eligible for palliative care, from those who need a palliative care approach to those needing specialist intensive palliative care. Implementing complexity theory into practice is paramount. In this review, complexity science, complexity frameworks, as well as tools evaluating complexity in palliative care are described.
The fallacy of inscrutability
Authors: Kroll Joshua A.
Published: October 2018

Contrary to the criticism that mysterious, unaccountable black-box software systems threaten to make the logic of critical decisions inscrutable, we argue that algorithms are fundamentally understandable pieces of technology. Software systems are designed to interact with the world in a controlled way and built or operated for a specific purpose, subject to choices and assumptions. Traditional power structures can and do turn systems into opaque black boxes, but technologies can always be understood at a higher level, intensionally in terms of their designs and operational goals and extensionally in terms of their inputs, outputs and outcomes. The mechanisms of a system's operation can always be examined and explained, but a focus on machinery obscures the key issue of power dynamics. While structural inscrutability frustrates users and oversight entities, system creators and operators always determine that the technologies they deploy are fit for certain uses, making no system wholly inscrutable. We investigate the contours of inscrutability and opacity, the way they arise from power dynamics surrounding software systems, and the value of proposed remedies from disparate disciplines, especially computer ethics and privacy by design. We conclude that policy should not accede to the idea that some systems are of necessity inscrutable. Effective governance of algorithms comes from demanding rigorous science and engineering in system design, operation and evaluation to make systems verifiably trustworthy. Rather than seeking explanations for each behaviour of a computer system, policies should formalize and make known the assumptions, choices, and adequacy determinations associated with a system.

This article is part of the theme issue ‘Governing artificial intelligence: ethical, legal, and technical opportunities and challenges’.
Harnessing the Anti-Cancer Natural Product Nimbolide for Targeted Protein Degradation
Authors: Spradlin Jessica N. , Hu Xirui , Ward Carl C. , Brittain Scott M. , Jones Michael D. , Ou Lisha , To Milton , Proudfoot Andrew , Ornelas Elizabeth , Woldegiorgis Mikias , Olzmann James A. , Bussiere Dirksen E. , Thomas Jason R. , Tallarico John A. , McKenna Jeffrey M. , Schirle Markus , Maimone Thomas J. , Nomura Daniel K.
Published: October 2018

Nimbolide, a terpenoid natural product derived from the Neem tree, impairs cancer pathogenicity across many types of human cancers; however, the direct targets and mechanisms by which nimbolide exerts its effects are poorly understood. Here, we used activity-based protein profiling (ABPP) chemoproteomic platforms to discover that nimbolide reacts with a novel functional cysteine crucial for substrate recognition in the E3 ubiquitin ligase RNF114. Nimbolide impairs breast cancer cell proliferation in-part by disrupting RNF114 substrate recognition, leading to inhibition of ubiquitination and degradation of the tumor-suppressors such as p21, resulting in their rapid stabilization. We further demonstrate that nimbolide can be harnessed to recruit RNF114 as an E3 ligase in targeted protein degradation applications and show that synthetically simpler scaffolds are also capable of accessing this unique reactive site. Our study highlights the utility of ABPP platforms in uncovering unique druggable modalities accessed by natural products for cancer therapy and targeted protein degradation applications.
Still poor HAART adherence has great impact on HIV/AIDS treatment failure in Ethiopia
Authors: Endalamaw Aklilu , Mekonen Mengistu , Debebe Demeke , Ambaw Fekadu , Tesera Hiwot , Habtewold Tesfa Dejenie
Published: October 2018

Background

The pooled burden of HIV treatment failure and its associated factors in Ethiopian context is required to provide evidence towards renewed ambitious future goal.

Methods

Ethiopian Universities’ (University of Gondar and Addis Ababa University) online repository library, Google scholar, PubMed, Web of Science, and Scopus were used to get the research articles. I-squared statistics was used to see heterogeneity. Publication bias was checked by Egger’s regression test. The DerSimonian-Laird random effects model was employed to estimate the overall prevalence. Subgroup analysis based on geographical location of the study, study population by age, treatment failure type, and study design was conducted to see variation in outcomes. The sensitivity analysis was also employed to see whether the outlier result found in the included studies.

Results

Overall HIV treatment failure found to be 15.9% (95% CI: 11.6%-20.1%). Using immunological definition, HIV treatment failure was 10.2% (6.9%-13.6%); using virological definition of treatment failure (5.6% (95% CI: 2.9%-8.3%) and clinical definition of treatment failure (6.3% (4.6%-8.0%)) were also determined. The pooled effects of WHO clinical stage III/IV (AOR=1.9; 95% CI: 1.3-2.6), presence of opportunistic infections (AOR=1.8; 95% CI: 1.2-2.4), and poor HAART adherence (AOR= 8.1; 95% CI: 4.3-11.8) on HIV treatment failure are estimated.

Conclusions

HIV treatment failure in Ethiopia found to be high. HIV intervention programs need to address the specified contributing factors of HIV treatment failure. Behavioral intervention to prevent treatment interruption is required to sustain HIV treatment adherence.

Protocol Registration

It has been registered in the PROSPERO database (CRD42018100254).
NAP (davunetide) preferential interaction with dynamic 3-repeat Tau explains differential protection in selected tauopathies
Authors: Ivashko-Pachima Yanina , Maor Maya , Gozes Illana
Published: October 2018

The microtubule (MT) associated protein Tau is instrumental for the regulation of MT assembly and dynamic instability, orchestrating MT-dependent cellular processes. Aberration in Tau post-translational modifications ratio deviation of spliced Tau isoforms 3 or 4 MT binding repeats (3R/4R) have been implicated in neurodegenerative tauopathies. Activity-dependent neuroprotective protein (ADNP) is vital for brain formation and cognitive function. ADNP deficiency in mice causes pathological Tau hyperphosphorylation and aggregation, correlated with impaired cognitive functions. It has been previously shown that the ADNP-derived peptide NAP protects against ADNP deficiency, exhibiting neuroprotection, MT interaction and memory protection. NAP prevents MT degradation by recruitment of Tau and end-binding proteins to MTs and expression of these proteins is required for NAP activity. Clinically, NAP (davunetide, CP201) exhibited efficacy in prodromal Alzheimer’s disease patients (Tau3R/4R tauopathy) but not in progressive supranuclear palsy (increased Tau4R tauopathy). Here, we examined the potential preferential interaction of NAP with 3R vs. 4R Tau, toward personalized treatment of tauopathies. Affinity-chromatography showed that NAP preferentially interacted with Tau3R protein from rat brain extracts and fluorescence recovery after photobleaching assay indicated that NAP induced increased recruitment of human Tau3R to MTs under zinc intoxication, in comparison to Tau4R. Furthermore, we showed that NAP interaction with tubulin (MTs) was inhibited by obstruction of Tau-binding sites on MTs, confirming the requirement of Tau-MT interaction for NAP activity. The preferential interaction of NAP with Tau3R may explain clinical efficacy in mixed vs. Tau4R pathologies, and suggest effectiveness in Tau3R neurodevelopmental disorders.
Dissociation rate compensation mechanism for budding yeast pioneer transcription factors
Authors: Donovan Benjamin T. , Chen Hengye , Jipa Caroline , Bai Lu , Poirier Michael G.
Published: October 2018

Nucleosomes restrict the occupancy of most transcription factors (TF) by reducing binding and accelerating dissociation, while a small group of TFs have high affinities to nucleosome-embedded sites and facilitate nucleosome displacement. To mechanistically understand this process, we investigated two S. cerevisiae TFs, Reb1 and Cbf1. We show these factors bind their sites within nucleosomes with similar affinities to naked DNA, trapping a partially unwrapped nucleosome without histone eviction. Both the binding and dissociation rates of Reb1 and Cbf1 are significantly slower at the nucleosomal sites relative to DNA, demonstrating that the high affinities are achieved by increasing the dwell time on nucleosomes to compensate for reduced binding. Reb1 also shows slow migration rate in the yeast nuclei. These properties are similar to human pioneer factors (PFs), suggesting the mechanism of nucleosome targeting is conserved from yeast to human.
Redundancy in the central tachykinin systems safeguards puberty onset and fertility
Authors: León Silvia , Fergani Chrysanthi , Talbi Rajae , Simavli Serap , Maguire Caroline A. , Gerutshang Achi , Seminara Stephanie B. , Navarro Víctor M.
Published: October 2018

The tachykinin neurokinin B (NKB, Tac2) is critical for GnRH release. NKB signaling deficiency leads to infertility in humans. However, some patients reverse this hypogonadism resembling the fertile phenotype of Tac2KO and Tacr3KO (encoding NKB receptor, NK3R) mice despite the absence of NKB signaling. Here, we demonstrate that in the absence of NKB signaling, other tachykinins (substance P and neurokinin A [NKA], encoded by Tac1) may take over to preserve fertility. The complete absence of tachykinins in Tac1/Tac2KO mice leads to delayed puberty onset in both sexes and infertility in 80% of females (but not males), in contrast to the 100% fertile phenotype of Tac1KO and Tac2KO mice separately. Furthermore, we demonstrate that NKA controls puberty onset and LH release through NKB-independent mechanisms in the presence of sex steroids and NKB-dependent mechanisms in their absence. In summary, tachykinins interact in a coordinated manner to ensure reproductive success in female mice.
On statistical tests of functional connectome fingerprinting
Authors: Wang Zeyi , Sair Haris , Crainiceanu Ciprian , Lindquist Martin , Landman Bennett A. , Resnick Susan , Vogelstein Joshua T. , Caffo Brian
Published: October 2018

Fingerprinting of functional connectomes is an increasingly standard measure of reproducibility in functional magnetic resonance imaging connectomics. In such studies, one attempts to match a subject’s first session image with their second, in a blinded fashion, in a group of subjects measured twice. The number or percentage of correct matches is usually reported as a statistic. In this manuscript, we investigate the statistical tests of matching based on exchangeability assumption in the fingerprinting analysis. We show that a nearly universal Poisson(1) approximation applies for different matching schemes. We theoretically investigate the permutation tests and explore the issue that the test is overly sensitive to uninteresting directions in the alternative hypothesis, such as clustering due to familial status or demographics. We perform a numerical study on two functional magnetic resonance imaging (fMRI) resting state datasets, the Human Connectome Project (HCP) and the Baltimore Longitudinal Study of Aging (BLSA). These datasets are instructive, as the HCP includes techinical replications of long scans and includes monozygotic and dyzogotic twins as well as non-twin siblings. In contrast, the BLSA study incorporates more typical length resting state scans in a longitudinal study. Finally, a study of single regional connections is performed on the HCP data.
An application of higher order multivariate cumulants in modelling of myoelectrical activity of porcine uterus during early pregnancy
Authors: Domino Malgorzata , Domino Krzysztof , Gajewski Zdzislaw
Published: October 2018

The analysis of the uterine contraction have become a general practice in an effort to improve the clinical management of uterine contractions during pregnancy and labour in human beings. The fluctuations in uterine activity may occur without affecting progress of gestation, however the painful and fashion contractions may be the first threat of miscarriage. While pigs were considered as an referential preclinical model, the computational modelling of spontaneous myoelectrical activity of complex systems of porcine myometrium in peri-fertilization period has been proposed. The higher order statistic, multivariate cumulants and Joint Skewness Band Selection method, have been applied to study the dependence structure of electromyographic (EMG) signal with an effective EMG feature. Than the model of recognition of multivariate, myoelectricaly changes according to crucial stages for successful fertilization and early pregnancy maintenance has been estimated. We found that considering together time and frequency features of EMG signal was extremely non-Gaussian distributed and the higher order multivariate statistics such as cumulants, have to be used to determine the pattern of myoelectrical activity in reproductive tract. We confirmed the expectance that the probabilistic model changes on a daily base. We demonstrated the changes in proposed model at the crucial time points of in peri-fertilization period. We speculate the activity of the middle of uterine horn and the power (minimum and maximum) and pauses between myoelectrical burst features are essential for the functional role of uterine contractility in peri-fertilization period.
4D imaging and analysis of multicellular tumour spheroid cell migration and invasion
Authors: Richards Rosalie , Mason David , Kelly Rebecca , Lévy Raphaël , Bearon Rachel , Sée Violaine
Published: October 2018

Studying and characterising tumour cell migration is critical for understanding disease progression and for assessing drug efficacy. Whilst tumour cell migration occurs fundamentally in 3 spatial dimensions (3D), for practical reasons, most migration studies to date have performed analysis in 2D. Here we imaged live multicellular tumour spheroids with lightsheet fluorescence microscopy to determine cellular migration and invasion in 3D over time (4D). We focused on glioblastoma, which are aggressive brain tumours, where cell invasion into the surrounding normal brain remains a major clinical challenge. We developed a workflow for analysing complex 3D cell movement, taking into account migration within the spheroid as well as invasion into the surrounding matrix. This provided metrics characterising cell motion, which we used to evaluate the efficacy of chemother-apeutics on invasion. These rich datasets open avenues for further studies on drug efficacy, microenvironment composition, as well as collective cell migration and metastatic potential.
Conserved allosteric pathways for activation of TRPV3 revealed through engineering vanilloid-sensitivity
Authors: Zhang Feng , Swartz Kenton , Jara-Oseguera Andres
Published: October 2018

The Transient Receptor Potential Vanilloid 1 (TRPV) channel is activated by an array of stimuli, including heat and vanilloid compounds. The TRPV1 homologues TRPV2 and TRPV3 are also activated by heat, but sensitivity to vanilloids and many other agonists is not conserved among TRPV subfamily members. It was recently discovered that four mutations in TRPV2 are sufficient to render the channel sensitive to the TRPV1-specific vanilloid agonist resiniferatoxin (RTx). Here we show that mutation of six residues in TRPV3 corresponding to the vanilloid site in TRPV1 is sufficient to engineer RTx binding. However, robust activation of TRPV3 by RTx requires facilitation of channel opening by introducing individual mutations in the pore, temperatures > 30°C, or co-stimulation with another agonist. Our results demonstrate that the energetics of channel activation can determine the apparent sensitivity to a stimulus and suggest that allosteric pathways for activation are conserved in the TRPV family.
Breakdown of gametophytic self-incompatibility in subdivided populations
Authors: Brom Thomas , Castric Vincent , Billiard Sylvain
Published: October 2018

Many hermaphroditic flowering plants species possess a genetic self-incompatibility (SI) system that prevents self-fertilization and is typically controlled by a single multiallelic locus, the S-locus. The conditions under which SI can be stably maintained in single isolated populations are well known and depend chiefly on the level of inbreeding depression and the number of SI alleles segregating at the S-locus. However, while both the number of SI alleles and the level of inbreeding depression are potentially affected by population subdivision, the conditions for the maintenance of SI in subdivided populations remain to be studied. In this paper, we combine analytical predictions and two different individual-based simulation models to show that population subdivision can severely compromise the maintenance of SI. Under the conditions we explored, this effect is mainly driven by the decrease of the local diversity of SI alleles rather than by a change in the dynamics of inbreeding depression. We discuss the implications of our results for the interpretation of empirical data on the loss of SI in natural populations.

Data accessibility statement

No data to be archived
Diagnosing the translation gap
Authors: Kamla Rania , Komori Naoko
Published: October 2018

Purpose

The purpose of this paper is to break the silence surrounding the politics of translation that influence cross-language/cultural accounting research. It gives due consideration to the ways in which translation gaps are produced and re-produced in qualitative interdisciplinary accounting research (IAR).

Design/methodology/approach

First, the authors discuss backstage insights and the authors’ own life experiences vis-à-vis translating cross-cultural/language research. The authors provide a critical self-reflection on the process as non-Western female researchers publishing in English-language accounting journals. Second, the authors carry out a content analysis to examine reported translation practices in three long-established interdisciplinary accounting journals from 2015 to 2017. The conclusion integrates these analyses to discuss the reproduction process of the translation gap in accounting research and its outcomes.

Findings

The study identifies inherent contradictions in IAR and its emancipatory agenda, where translation gaps are structural outcomes of overlaps between the politics of translation and the politics of publishing IAR. The study highlights the IAR community’s lack of awareness regarding political and methodological sensitivities in dealing with particularities in cultural contexts. The authors argue that this reflects the institutional norms for publishing in IAR, which contributes to neutralising cultural diversity and complex translation processes in the name of objectivity. This could ultimately lead to further marginalisation of non-Western cultural knowledge and values, while producing academic “elites” within the IAR community, meanwhile missing opportunities for innovation.

Originality/value

By opening the “black box” pertaining to translation gaps in the context of cross-language/cultural accounting research, the study calls for IAR scholars to help raise awareness of their role and identity as “cultural brokers”.
Simless GSM positioning for navigation in GPS-denied environments
Authors: Soldado Serrano Inmaculada , García Doblado José , Finazzi Ignazio Federico , Martín Prats María Ángeles
Published: October 2018

Purpose

Until now, air navigation systems have mainly relied on global navigation satellite systems (GNSS) on the worldwide spread global positioning system. However, the so-called GNSS-denied environments open a new research line which pursues the development of alternative technologies which will cover this gap in positioning systems’ services.

Design/methodology/approach

This paper presents the possibility of using positioning systems based on global system for mobile communications (GSM) signal. This approach developed in a standalone device will provide real-time information. The presented algorithm pursues a new methodology for providing useful information.

Findings

Among all the different technologies aimed at giving a navigation solution in the absence of any kind of GNSS in which this paper is based, it advocates for the use of the signals of opportunity, particularly the usage of GSM.

Practical implications

Technology is currently immersed in an era of continuous progress and expansion of navigation systems. These are evolving toward high performance systems, offering precise, efficient and safe air navigation. In addition, the growing demand for unmanned aerial vehicles increases the level of exigency on this activity even more. Therefore, in the context of the development of unmanned navigation technologies, the aim is to implement positioning systems that will allow high precision even in though environments.

Originality/value

Referencing the SIMless concept, a SIM-free system is described in this paper. The SIM-free system is supported by open data bases and permits the positioning based on the information sniffed from the signals broadcast by a set of several nearby base station of the GSM network. Hence, it provides same and in some cases even better accuracies than the already developed techniques, not being necessary to synchronize the link between the mobile terminal and the base station transceiver (BTS).
Efficient structural analysis of gas turbine blades
Authors: Rogge Timo , Berger Ricarda , Pohle Linus , Rolfes Raimund , Wallaschek Jörg
Published: October 2018

Purpose

The purpose of this study a fast procedure for the structural analysis of gas turbine blades in aircraft engines. In this connection, investigations on the behavior of gas turbine blades concentrate on the analysis and evaluation of starting dynamics and fatigue strength. Besides, the influence of structural mistuning on the vibration characteristics of the single blade is analyzed and discussed.

Design/methodology/approach

A basic computation cycle is generated from a flight profile to describe the operating history of the gas turbine blade properly. Within an approximation approach for high-frequency vibrations, maximum vibration amplitudes are computed by superposition of stationary frequency responses by means of weighting functions. In addition, a two-way coupling approach determines the influence of structural mistuning on the vibration of a single blade. Fatigue strength of gas turbine blades is analyzed with a semi-analytical approach. The progressive damage analysis is based on MINER’s damage accumulation assuming a quasi-stable behavior of the structure.

Findings

The application to a gas turbine blade shows the computational capabilities of the approach presented. Structural characteristics are obtained by robust and stable computations using a detailed finite element model considering different load conditions. A high quality of results is realized while reducing the numerical costs significantly.

Research limitations/implications

The method used for analyzing the starting dynamics is based on the assumption of a quasi-static state. For structures with a sufficiently high stiffness, such as the gas turbine blades in the present work, this procedure is justified. The fatigue damage approach relies on the existence of a quasi-stable cyclic stress condition, which in general occurs for isotropic materials, as is the case for gas turbine blades.

Practical implications

Owing to the use of efficient analysis methods, a fast evaluation of the gas turbine blade within a stochastic analysis is feasible.

Originality/value

The fast numerical methods and the use of the full finite element model enable performing a structural analysis of any blade structure with a high quality of results.
A distributed and integrated method for cooperative mission planning of multiple heterogeneous UAVs
Authors: WU Weinan , Cui Naigang
Published: October 2018

Purpose

The purpose of this paper is to develop a distributed and integrated method to get a fast and feasible solution for cooperative mission planning of multiple heterogeneous unmanned aerial vehicles (UAVs).

Design/methodology/approach

In this study, the planning process is conducted in a distributed framework; the cooperative mission planning problem is reformulated with some specific constraints in the real mission; a distributed genetic algorithm is the algorithm proposed for searching for the optimal solution; genes of the chromosome are modified to adapt to the heterogeneous characteristic of UAVs; a fixed-wing UAV’s six degrees-of-freedom (DOF) model with a path following method is used to test the proposed mission planning method.

Findings

This method not only has the ability to obtain good feasible solutions but also improves the operating rate vastly.

Research limitations/implications

This study is only applied to the case where the communication among UAVs is linked during the mission.

Practical implications

This study is expected to be practical for a real mission because of its fast operating rate and good feasible solution.

Originality/value

This solution is tested on a fixed-wing UAV’s 6-DOF model by a path following method, so it is believable from the perspective of an autonomous UAV guidance and control system.
What drives consumers’ mobile shopping? 4Ps or shopping preferences?
Authors: Chen Hsiu-Ju
Published: October 2018

Purpose

Mobile shopping emerges, but the marketing factors driving consumers’ mobile shopping lack clarification. Literature gaps also exist to view mobile shopping from a consumer behavior’s perspective. The purpose of this paper therefore is to empirically explore the issue based on the lifestyle perspective, 4Ps marketing theory and the information system (IS) success model.

Design/methodology/approach

A survey method was adopted. Data were gathered from consumers who had experience in mobile shopping. The collected data were analyzed with PLS to explore the issues.

Findings

The results showed that platform use habit, price comparison preference, shopping independence preference and promotion marketing quality were significantly associated with consumers’ use of mobile shopping apps/websites. They also showed that promotion marketing quality, price marketing quality and product marketing quality were the important marketing factors driving consumers’ user satisfaction of mobile shopping apps/websites. Finally, the results also indicated the importance of both consumers’ use and user satisfaction of mobile shopping apps/websites in arousing their continuous use intention.

Research limitations/implications

The results of the study bridge the gap between the 4Ps marketing theory and the IS success model. They provide a direction for further studies to bridge the marketing theories and the IS theories in exploring the development of mobile commerce.

Practical implications

The results facilitate the management of mobile shopping apps/websites in building and keeping a long-term relationship with consumers through providing good marketing qualities in the core marketing mix. The results also indicate the importance of user satisfaction in branding management and relationship management of mobile shopping apps/websites.

Originality/value

The results showed that price comparison preference and shopping independence preference were significantly associated with consumers’ use of mobile shopping apps/websites due to the convenient access empowered by mobility in shopping services. The results also suggest that with good design in 4Ps marketing qualities of mobile shopping apps/websites, including product, price and promotion, mobile shopping could be a suitable lifestyle satisfying consumers. However, the results also showed that factors driving consumers’ system use and user satisfaction of mobile shopping apps/websites were not the same. Finally, the results validated the significant impact of both system use and user satisfaction in activating consumers’ continuance intention of mobile shopping. They provided a positive link between consumers’ mobile shopping apps/websites use to their keeping the lifestyle of mobile shopping.