bluuebunny/crossref_metadata_2025 huggingface dataset:
Fall downs should not fall out: Blunt cerebrovascular injury in geriatric patients after low-energy trauma is common
Authors: Flashburg Erika , Ong Adrian W. , Muller Alison , Sherwood Alicia , Wilhelm Sara , Zavilla Jared , Martin Anthony P. , Castor Laura , Barbera Spencer C. , Reinhart Reid , Layser Shane , McBride William C. , Romeo Michael , Fernandez Forrest B.
Published: March 2019

BACKGROUND

There are limited data examining the impact of screening for blunt cerebrovascular injury (BCVI) in the geriatric population sustaining falls. We hypothesize that BCVI screening in this cohort would rarely identify injuries that would change management.

METHODS

A retrospective study (2012–2016) identified patients 65 years or older with Abbreviated Injury Scores for the head and neck region or face region of 1 or greater after falls of 5 ft or less. Patients who met the expanded Denver criteria for BCVI screening were included for analysis. Outcomes were change in management (defined as the initiation of medical, surgical or endovascular therapy for BCVI), stroke attributable to BCVI, in-hospital mortality and acute kidney injury. Univariate analysis was performed where appropriate. A p value less than 0.05 was considered significant.

RESULTS

Of 997 patients, 257 (26%) met criteria for BCVI screening after exclusions. The BCVI screening occurred in 100 (39%), using computed tomographic angiography for screening in 85% of patients. Patients who were not screened (n = 157) were more likely to be on preinjury antithrombotic drugs and to have worse renal function compared with the screened group. There were 23 (23%) BCVIs diagnosed in the screened group while one (0.7%) in the nonscreened group had a delayed diagnosis of BCVI. Of the 24 patients with BCVI, 15 (63%) had a change in management, consisting of the initiation of antiplatelet therapy. Comparing the screened to the nonscreened groups, 14% versus 0.7% (p < 0.0001) had a change in management. The screened group had a higher 30-day stroke rate (7% vs. 1%, p = 0.03) but there were no differences in the stroke rate attributable to BCVI (1% vs. 0.7%, p = 0.99), mortality (6% vs. 8%, p = 0.31) or acute kidney injury (5% vs. 6%, p = 0.40).

CONCLUSION

In geriatric patients with low-energy falls meeting criteria for BCVI screening, BCVIs were commonly diagnosed when screened, and the majority of those with BCVI had a change in management. These findings support BCVI screening in this geriatric cohort.

LEVEL OF EVIDENCE

Therapeutic/care management, level IV.
The Dopamine Receptor Antagonism of Opipramol: Relevance to Parkinsonism?
Authors: Rozanski Verena , Laux Gerd , Schwarz Johannes
Published: March 2019

Drug-induced Parkinsonism (DIP) represents the second most-frequent etiology of Parkinson syndromes after neurodegenerative disorders. It has been described mainly for antipsychotics, Ca++-channel blockers, antiemetics, and gastrointestinal prokinetics. In this article, we present a clinical case series of 10 patients, retrieved within our movement disorders hospital, with DIP under intake of opipramol. Symptoms completely resolved after drug withdrawal, and associated risk factors were old age, high doses, and presence of cortical atrophy. This frequently prescribed anxiolytic drug has so far not been associated with DIP. Our objective is to raise awareness of DIP as an adverse effect of opipramol.
Levetiracetam-Related Mania-Like Symptoms: An Adolescent Case
Authors: Ekinci Nuran , Güneş Serkan , Ekinci Özalp , Kalinli Merve , Okuyaz Çetin , Direk Meltem Çobanoğullari
Published: March 2019

Levetiracetam is an antiepileptic agent that is used for partial and generalized epilepsy. Although it is well tolerated in most cases, behavioral and nonbehavioral adverse effects may be observed. Among behavioral symptoms, depression, hostility, and agitation have been frequently reported. However, mania or mania-like symptoms are relatively rare, especially in children and adolescents. Hereby, we report mania-like symptoms with levetiracetam use in a 15-year-old boy. Mania-like symptoms emerged 3 weeks after starting levetiracetam and disappeared after adding risperidone to ongoing levetiracetam treatment.
Effects of Varying Intranasal Treatment Regimens in ST266-Mediated Retinal Ganglion Cell Neuroprotection
Authors: Khan Reas S. , Dine Kimberly , Wessel Howard , Brown Larry , Shindler Kenneth S.
Published: March 2019

Introduction:

Previous studies have shown that intranasally administered ST266, a novel biological secretome of amnion‐derived multipotent progenitor cells containing multiple growth factors and anti-inflammatory cytokines, attenuated visual dysfunction and prevented retinal ganglion cell (RGC) loss in experimental optic neuritis. Long-term effects and dose escalation studies examined here have not been reported previously.

Methods:

Optic neuritis was induced in the multiple sclerosis model experimental autoimmune encephalomyelitis (EAE). EAE and control mice were treated once or twice daily with intranasal placebo/vehicle or ST266 beginning after onset of optic neuritis for either 15 days or continuously until sacrifice. Visual function was assessed by optokinetic responses (OKRs). RGC survival and optic nerve inflammation and demyelination were measured.

Results:

Both once and twice daily continuous intranasal ST266 treatment from disease onset to 56 days after EAE induction significantly increased OKR scores, decreased RGC loss, and reduced optic nerve inflammation and demyelination compared with placebo (saline, nonspecific protein solution, or cell culture media)-treated EAE mice. ST266 treatment given for just 15 days after disease onset, then discontinued, only delayed OKR decreases, and had limited effects on RGC survival and optic nerve inflammation 56 days after disease induction.

Conclusions:

ST266 is a potential neuroprotective therapy to prevent RGC damage, and intranasal delivery warrants further study as a novel mechanism to deliver protein therapies for optic neuropathies. Results suggest that once daily ST266 treatment is sufficient to sustain maximal benefits and demonstrate that neuroprotective effects promoted by ST266 are specific to the combination of factors present in this complex biologic therapy.
Risk and Economic Burden of Peristomal Skin Complications Following Ostomy Surgery
Authors: Taneja Charu , Netsch Debra , Rolstad Bonnie Sue , Inglese Gary , Eaves Deanna , Oster Gerry
Published: March 2019

PURPOSE:

The purpose of this study was to examine the incidence and economic burden of peristomal skin complications (PSCs) following ostomy surgery.

DESIGN:

Retrospective cohort study based on electronic health records and administrative data stores at a large US integrated healthcare system.

SUBJECTS AND SETTINGS:

The sample comprised 168 patients who underwent colostomy (ICD-9-CM 46.1X) (n = 108), ileostomy (46.2X) (n = 40), cutaneous ureteroileostomy (56.5X), or other external urinary diversion (56.6X) (n = 20) between January 1, 2012, and December 31, 2014. The study setting was an integrated health services organization that serves more than 2 million persons in the northeastern United States.

METHODS:

We scanned electronic health records of all study subjects to identify those with evidence of PSCs within 90 days of ostomy surgery and then examined healthcare utilization and costs over 120 days, beginning with date of surgery, among patients with and without evidence of PSCs. Testing for differences in continuous measures between the 3 ostomy groups was based on one-way analysis of variance; testing for differences in such measures between the PSC and non-PSC groups was based on a t statistic, and the χ2 statistic was used to test for differences in categorical measures.

RESULTS:

Sixty-one subjects (36.3%) had evidence of PSCs within 90 days of ostomy surgery (ileostomy, 47.5%; colostomy, 36.1%; urinary diversion, 15.0%; P < .05 for differences between groups). Among patients with evidence of PSCs, the mean (SD) time from surgery to first notation of this complication was 26.4 (19.0) days; it was 24.1 (13.2) days for ileostomy, 27.2 (21.1) days for colostomy, and 31.7 (25.7) days for urinary diversion (P = .752). Patients with PSCs were more likely to be readmitted to hospital by day 120 (55.7% vs 35.5% for those without PSCs; P = .011). The mean length of stay for patients readmitted to hospital was 11.0 days for those with PSCs and 6.8 days for those without PSCs (P = .111). The mean total healthcare cost over 120 days was $58,329 for patients with evidence of PSCs and $50,298 for those without evidence of PSCs (P = .251).

CONCLUSIONS:

Approximately one-third of ostomy patients developed PSCs within 90 days of their surgery. Peristomal skin complications are associated with a greater likelihood of hospital readmission. Our findings corroborate results of earlier studies.
Nursing Education Program for Hospital-Acquired Pressure Injury Prevention in Adult Acute Care Setting
Authors: Henry Michelle
Published: March 2019

The purpose of this Quality Improvement project was to develop a multimedia hospital-acquired pressure injury (HAPI) prevention education program. The project setting was 3 adult critical care units plus a step-down unit located in the Mid-Atlantic region of the United States. A multimedia educational intervention was developed, which comprised 4 modules designed to improve nursing knowledge and competency in HAPI prevention. A posteducation program staff survey was also administered to evaluate nurse satisfaction with the program. Nurse knowledge of HAPI prevention was measured before and following implementation of the educational intervention. One hundred twenty-nine participants completed the education program, and 117 completed the satisfaction survey. Analysis revealed a statistically significant increase in knowledge after the education course (P < .05). Findings also indicated participants were satisfied that the program met stated aims.
Hospitalists' Needs Assessment and Perceived Barriers in Wound Care Management
Authors: Walker Cynthia A. , Rahman Alphonsa , Gipson-Jones Trina L. , Harris Ché Matthew
Published: March 2019

The purpose of this quality improvement project was to determine hospitalists' knowledge, practices, and perspectives related to management of pressure injuries and neuropathic/diabetic foot complications (having a foot ulcer or subsequent development of a foot infection because of a foot ulcer). We also sought to identify resources for and knowledge-based barriers to management of these wounds. This quality improvement effort targeted an interdisciplinary group of 55 hospitalists in internal medicine that consisted of 8 nurse practitioners, 10 physician assistants, and 38 physicians. The site of this initiative was the Johns Hopkins Bayview Medical Center, a 342-bed academic hospital located in the mid-Atlantic United States (Baltimore Maryland). The first phase of our quality improvement project comprised an online survey to identify hospitalists' knowledge, practices, and opinions on inpatient management of pressure injuries and diabetic foot complications. The second phase involved semistructured focus groups attended by hospitalists to identify resource gaps and barriers inferred by survey results. Twenty-nine of 55 (52%) hospitalists responded to the survey; 72% indicated no formal training in wound care. Over 90% had little to no confidence in management of pressure injuries and diabetic foot complications. In a separate ranking section of the survey, respondents selected lack of knowledge/confidence 12 of 29 (41.3%) and resources 9 of 29 (31.0%) as number 1 barriers to wound care. Managing patients with obesity was identified as a second major barrier from 10 of 29 selected options (34.5%). Eighteen of 55 (33%) hospitalists attended focus group sessions acknowledging barriers to wound care that included provider education, information technology, system factors, and interprofessional engagement. Attendees welcomed additional educational and ancillary resource support.
Nurses' Knowledge and Practices Related to Pressure Injury
Authors: Aydın Arzu Karabağ , Karadağ Ayişe , Gül Şenay , Avşar Pınar , Baykara Zehra Göçmen
Published: March 2019

PURPOSE:

The purpose of this study was to determine nurses' knowledge and practices regarding pressure injury and identify relationships between these factors and professional nurse characteristics.

DESIGN:

Cross-sectional, descriptive study.

SETTING AND SUBJECTS:

The sample comprised 347 nurses attending the 2013 and 2015 Wound Management Congresses. The meetings were organized by the Wound Management Association located in Antalya, Turkey.

METHODS:

A 35-item data collection form was designed for purposes of this study. It divided into 2 parts: 8 items queried demographic and professional characteristics of nurse respondents. The second part comprised 9 cases describing patients with pressure injury; these cases were associated with 27 items querying pressure injury-related knowledge and practices. Demographic and professional characteristics of nurse respondents were summarized via descriptive statistics. The Kruskal-Wallis H and Mann-Whitney U tests were used to identify relationships between nurse characteristics and pressure injury knowledge and practices.

RESULTS:

The mean score for the 27 items related to pressure injury knowledge and practices was 57.37 ± 14.26 out of 100 points. Pressure injury knowledge and practices were positively associated with nurses having a bachelor's and/or postgraduate degree (P = .012), nurses caring for a higher number of patients with pressure injuries per week (P = .042), nurses practicing in intensive care units and wound care clinics (P = .011), nurses with specific education in pressure injury (P = .000), and those indicating adequate skills and knowledge in pressure injury (P = .005).

CONCLUSIONS:

Nurses' knowledge and practices regarding pressure injuries were lower than anticipated in this sample. We recommend additional education and training activities to increase nurses' knowledge and practices related to pressure injury.
BDNF Genotype and Baseline Serum Levels in Relation to Electroconvulsive Therapy Effectiveness in Treatment-Resistant Depressed Patients
Authors: Maffioletti Elisabetta , Gennarelli Massimo , Gainelli Giulio , Bocchio-Chiavetto Luisella , Bortolomasi Marco , Minelli Alessandra
Published: March 2019

Objectives

Electroconvulsive therapy (ECT) represents one of the most effective therapies for treatment-resistant depression (TRD). The brain-derived neurotrophic factor (BDNF) is a neurotrophin implicated in major depressive disorder and in the effects of different therapeutic approaches, including ECT. Both BDNF peripheral levels and Val66Met polymorphism have been suggested as biomarkers of treatment effectiveness. The objective of this study was to test the potential of serum BDNF levels and Val66Met polymorphism in predicting ECT outcome in TRD patients.

Methods

Seventy-four TRD patients scheduled to undergo ECT were included in the study. Illness severity was assessed through the Montgomery and Asberg Depression Rating Scale before beginning ECT (T0), the day after the end of ECT (T1), and 1 month after the end of ECT (T2). At T1, patients were classified as responders/nonresponders and remitters/nonremitters, whereas at T2, they were classified as sustained responders/nonresponders and sustained remitters/nonremitters. Serum concentrations of BDNF were measured at T0, and the BDNF Val66Met polymorphism was genotyped.

Results

No difference in BDNF concentrations was observed in responders versus nonresponders, in remitters versus nonremitters, in sustained responders versus sustained nonresponders, and in sustained remitters versus sustained nonremitters. No association of Val66Met polymorphism was detected with both the response and the remission status.

Conclusions

Baseline serum BDNF levels and the BDNF Val66Met polymorphism showed no clinical utility in predicting ECT outcome in TRD patients.
Afucosylated maternal anti-dengue IgGs are a biomarker for susceptibility to dengue disease in their infants
Authors: Thulin Natalie K. , Brewer R. Camille , Sherwood Robert , Bournazos Stylianos , Edwards Karlie G. , Ramadoss Nitya S. , Taubenberger Jeffery K. , Memoli Matthew , Jagannathan Prasanna , Zhang Sheng , Libraty Daniel H. , Wang Taia T.
Published: March 2019

Infant mortality from dengue disease is a devastating global health burden that could be minimized with the ability to identify susceptibility for severe disease prior to infection. While most primary infant dengue infections are asymptomatic, maternally derived anti-dengue IgGs present during infection can trigger progression to severe disease through antibody-dependent enhancement mechanisms. Importantly, specific characteristics of maternal IgGs that herald progression to severe infant dengue are unknown. Here, we define ≥10% afucosylation of maternal anti-dengue IgGs as a biomarker for susceptibility of infants to symptomatic dengue infections. Mechanistic experiments show that anti-dengue afucosylation, a modification that enhances Fc affinity for the activating receptor FcγRIIIa, promotes infection of FcγRIIIa+ monocytes. FcγRIIIa signaling, in turn, enhances a post-entry step of dengue virus replication. These studies identify a biomarker that can be applied to reduce mortality associated with dengue viruses and define a mechanism by which afucosylated antibodies and FcγRIIIa enhance dengue infections.
GSTM1 copy number is not associated with risk of kidney failure in a large cohort
Authors: Zhang Yanfei , Zafar Waleed , Hartzel Dustin N. , Williams Marc S. , Tin Adrienne , Chang Alexander R. ,   Regeneron Genetics Center, Lee Ming Ta M. ,   on behalf of the DiscovEHR collaboration
Published: March 2019

Deletion of glutathione S-transferase µ1 (GSTM1) is common in populations and has been asserted to associate with chronic kidney disease progression in some research studies. The association needs to be validated. We estimated GSTM1 copy number using whole exome sequencing data in the DiscovEHR cohort. Kidney failure was defined as requiring dialysis or receiving kidney transplant using data from the electronic health record and linkage to the United States Renal Data System, or the most recent eGFR < 15 ml/min/1.73m2. In a cohort of 46,983 unrelated participants, 28.8% of blacks and 52.1% of whites had 0 copies of GSTM1. Over a mean of 9.2 years follow-up, 645 kidney failure events were observed in 46,187 white participants, and 28 in 796 black participants. No significant association was observed between GSTM1 copy number and kidney failure in Cox regression adjusting for age, sex, BMI, smoking status, genetic principal components, or co-morbid conditions (hypertension, diabetes, heart failure, coronary artery disease, and stroke), whether using a genotypic, dominant, or recessive model. In sensitivity analyses, GSTM1 copy number was not associated with kidney failure in participants that were 45 years or older at baseline, had baseline eGFR < 60 ml/min per 1.73 m2, or with baseline year between 1996-2002. In conclusion, we found no association between GSTM1 copy number and kidney failure in a large cohort study.

Translational Statement

Deletion of GSTM1 has been shown to be associated with higher risk of kidney failure. However, inconsistent results have been reported. We used electronic health record and whole exome sequencing data of a large cohort from a single healthcare system to evaluate the association between GSTM1 copy number and risk of kidney failure. We found no significant association between GSTM1 copy number and risk of kidney failure overall, or in multiple sensitivity and subgroup analyses.
Mechanistic characterization of RASGRP1 variants identifies an hnRNP K-regulated transcriptional enhancer contributing to SLE susceptibility
Authors: Molineros Julio E. , Singh Bhupinder , Terao Chikashi , Okada Yukinori , Kaplan Jakub , McDaniel Barbara , Akizuki Shuji , Sun Celi , Webb Carol , Looger Loren L. , Nath Swapan K.
Published: March 2019

Systemic lupus erythematosus (SLE) is an autoimmune disease with a strong genetic component. We recently identified a novel SLE susceptibility locus near RASGRP1, which governs the ERK/MAPK kinase cascade and B-/T-cell differentiation and development. However, precise causal RASGRP1 functional variant(s) and their mechanisms of action in SLE pathogenesis remain undefined. Our goal was to fine-map this locus, prioritize genetic variants according to likely functionality, experimentally validate the contribution of three SNPs to SLE risk, and experimentally determine their biochemical mechanisms of action. We performed a meta-analysis across six Asian and European cohorts (9,529 cases; 22,462 controls), followed by in silico bioinformatic and epigenetic analyses to prioritize potentially functional SNPs. We experimentally validated the functional significance and mechanism of action of three SNPs in cultured T-cells. Meta-analysis identified 18 genome-wide significant (p<5×10−8) SNPs, mostly concentrated in two haplotype blocks, one intronic and the other intergenic. Epigenetic fine-mapping, allelic, eQTL and imbalance analyses predicted three transcriptional regulatory regions with four SNPs (rs7170151, rs11631591-rs7173565, and rs9920715) prioritized for functional validation. Luciferase reporter assays indicated significant allele-specific enhancer activity for intronic rs7170151 and rs11631591-rs7173565 in T-lymphoid (Jurkat) cells, but not in HEK293 cells. Following up with EMSA, mass spectrometry and ChIP-qPCR, we detected allele-dependent interactions between heterogeneous nuclear ribonucleoprotein K (hnRNP-K) and rs11631591. Furthermore, inhibition of hnRNP-K in Jurkat and primary T-cells downregulated RASGRP1 and ERK/MAPK signaling. Comprehensive association, bioinformatics, and epigenetic analyses yielded putative functional variants of RASGRP1, which were experimentally validated. Notably, intronic variant (rs11631591) is located in a cell type-specific enhancer sequence, where its risk allele binds to the hnRNP-K protein and modulates RASGRP1 expression in Jurkat and primary T-cells. As risk allele dosage of rs11631591 correlates with increased RASGRP1 expression and ERK activity, we suggest that this SNP may underlie SLE risk at this locus.
Implicit semantic prediction error can account for N400 effects on articles that do not differ in meaning: A neural network model
Authors: Rabovsky Milena
Published: March 2019

N400 effects on indefinite articles (a/an) compatible or incompatible with expected nouns have been initially taken as strong evidence for probabilistic pre-activation of phonological word forms, and recently been intensely debated because they have been difficult to replicate. Here, we simulate these effects using a neural network model of sentence comprehension that we previously used to simulate a broad range of empirical N400 effects. The model produces the effects when the cue validity of the articles concerning upcoming noun meaning is high, but fails to produce the effects when the cue validity of the articles is low due to adjectives presented between articles and nouns during training, providing a possible explanation for the small size of the effects in empirical studies. The model accounts for article induced N400 effects without assuming pre-activation of word forms, and instead simulates these effects as the stimulus-induced change in a probabilistic representation of meaning corresponding to an implicit semantic prediction error.
High ribulose-1,5-bisphosphate carboxylase/oxygenase content in northern diatom species
Authors: Gerecht A. C. , Eriksen G. K. , Uradnikova M. , Eilertsen H. C.
Published: March 2019

Ribulose-1,5-bisphosphate carboxylase/oxygenase (RuBisCO) is a fundamental enzyme in CO2-fixation in photoautotrophic organisms. Nonetheless, it has been recently suggested that the contribution of this enzyme to total cellular protein is low in phytoplankton, including diatoms (< 6%). Here we show that RuBisCO content is high in some diatom species isolated from northern waters (> 69°N). Two species contained the highest RuBisCO levels ever reported for phytoplankton (36% of total protein). These high RuBisCO requirements do not increase these species’ requirements for nitrogen and do not impart a fitness disadvantage in terms of growth rate. On the contrary, high RuBisCO levels in psychrophilic diatoms may be a necessary mechanism to maintain high growth rates at low temperature at which enzymatic rates are low.
The midbody interactome reveals new unexpected roles for PP1 phosphatases in cytokinesis
Authors: Capalbo Luisa , Bassi Zuni I. , Geymonat Marco , Todesca Sofia , Copoiu Liviu , Enright Anton , Callaini Giuliano , Riparbelli Maria Giovanna , Yu Lu , Choudhary Jyoti , Ferrero Enrico , Wheatley Sally , Douglas Max E. , Mishima Masanori , D’Avino Pier Paolo
Published: March 2019

The midbody is an organelle assembled at the intercellular bridge that connects the two daughter cells at the end of mitosis. It is composed of a multitude of proteins, organized in a precise and stereotyped pattern, that control the final separation of the daughter cells and prevent incorrect genome segregation. Furthermore, recent evidence indicates that the midbody is involved in many other important processes, including cell fate, pluripotency, apical-basal polarity, tissue organization, and cilium and lumen formation. Understanding the regulation and interactions of midbody proteins is therefore essential to unravel how this organelle executes its multiple functions. Here, we report the first experimentally-based characterization of the intricate midbody protein-protein interaction network (interactome), which identifies a plethora of novel interactions and provides an extremely valuable resource for dissecting the multiple roles of the midbody. Initial analysis of this interactome already revealed that PP1β-MYPT1 phosphatase regulates microtubule dynamics in late cytokinesis and de-phosphorylates the kinesin component MKLP1/KIF23 of the centralspindlin complex, a key cytokinesis regulator. This de-phosphorylation antagonizes Aurora B kinase in order to modify the functions of centralspindlin and its interactions in late cytokinesis. Our findings expand the repertoire of PP1 functions during mitosis and indicate that spatiotemporal changes in the distribution of kinases and counteracting phosphatases finely tune the activity of cytokinesis proteins.
Decoding P300 Variability using Convolutional Neural Networks
Authors: Solon Amelia J. , Lawhern Vernon J. , Touryan Jonathan , McDaniel Jonathan R. , Ries Anthony J. , Gordon Stephen M.
Published: March 2019

Deep convolutional neural networks (CNN) have previously been shown to be useful tools for signal decoding and analysis in a variety of complex domains, such as image processing and speech recognition. By learning from large amounts of data, the representations encoded by these deep networks are often invariant to moderate changes in the underlying feature spaces. Recently, we proposed a CNN architecture that could be applied to electroencephalogram (EEG) decoding and analysis. In this article, we train our CNN model using data from prior experiments in order to later decode the P300 evoked response from an unseen, hold-out experiment. We analyze the CNN output as a function of the underlying variability in the P300 response and demonstrate that the CNN output is sensitive to the experiment-induced changes in the neural response. We then assess the utility of our approach as a means of improving the overall signal-to-noise ratio in the EEG record. Finally, we show an example of how CNN-based decoding can be applied to the analysis of complex data.
The flickering connectivity system of the north Andean páramos
Authors: Flantua Suzette G.A. , O’Dea Aaron , Onstein Renske E. , Hooghiemstra Henry
Published: March 2019

ABSTRACT AND KEYWORDS

Aim

To quantify the effect of Pleistocene climate fluctuations on habitat connectivity across páramos in the Neotropics.

Location

The Northern Andes

Methods

The unique páramos habitat underwent dynamic shifts in elevation in response to changing climate conditions during the Pleistocene. The lower boundary of the páramos is defined by the upper forest line, which is known to be highly responsive to temperature. Here we reconstruct the extent and connectivity of páramos over the last 1 million years (Myr) by reconstructing the UFL from the long fossil pollen record of Funza09, Colombia, and applying it to spatial mapping on modern topographies across the Northern Andes for 752 time slices. Data provide an estimate of how often and for how long different elevations were occupied by páramos and estimates their connectivity to provide insights into the role of topography in biogeographic patterns of páramos.

Results

Our findings show that connectivity amongst páramos of the Northern Andes was highly dynamic, both within and across mountain ranges. Connectivity amongst páramos peaked during extreme glacial periods but intermediate cool stadials and mild interstadials dominated the climate system. These variable degrees of connectivity through time result in what we term the ‘flickering connectivity system’. We provide a visualization (video) to showcase this phenomenon. Patterns of connectivity in the Northern Andes contradict patterns observed in other mountain ranges of differing topographies.

Main conclusions

Pleistocene climate change was the driver of significant elevational and spatial shifts in páramos causing dynamic changes in habitat connectivity across and within all mountain ranges. Some generalities emerge, including the fact that connectivity was greatest during the most ephemeral of times. However, the timing, duration and degree of connectivity varied substantially among mountain ranges depending on their topographic configuration. The flickering connectivity system of the páramos uncovers the dynamic settings in which evolutionary radiations shaped the most diverse alpine biome on Earth.
Development of high throughput method for the analysis of anthelmintic resistance allele frequencies in field populations of gastrointestinal nematodes
Authors: Sargison Neil D. , MacLeay Madison , Morrison Alison A. , Bartley David J. , Evans Mike , Chaudhry Umer
Published: March 2019

Drug resistant helminths have become a major cause of poor health and production in sheep and goats, and there is a need for diagnostic markers and tools to determine the frequency of resistance alleles in field parasite populations. Gastrointestinal nematode resistance to benzimidazole drugs is caused by a mutation in one of three positions on the isotype 1 β-tubulin locus, and in the absence of markers for resistance to other broad spectrum anthelmintic classes, these provide a relevant study example. Determination of the prevalence of these single nucleotide polymorphisms in field gastrointestinal nematode populations can be impractical using conventional molecular methods, which may be error prone or lack sensitivity at low levels of resistance. Here, we report the development of a novel method based on an Illumina Mi-seq deep amplicon sequencing platform; to sequence the isotype 1 β-tubulin locus of the small ruminant gastrointestinal nematode,Teladorsagia circumcincta, and determine the frequency of the benzimidazole resistance mutations. We validated the method by assessing sequence representation bias in the isotype 1 β-tubulin locus, comparing the results of Illumina Mi-seq and pyrosequencing, and applying the method to populations containing known proportions of resistant and susceptible L3. Finally, we applied the method to field samples collected from ewes and lambs on over a period of one year on three farms, each highlighting different aspects of sheep management and approaches to parasite control. The results show opportunities to build hypotheses with reference to selection pressures leading to differences in resistance allele frequencies between sampling dates, farms and ewes or lambs, and to consider the impact of their genetic fixation or otherwise. This study provides proof of concept of a practical, accurate, sensitive and scalable method to determine frequency of anthelmintic drug resistance mutations in gastrointestinal nematodes in field studies and as a management tool for livestock farmers.
Machine learning Classification of Dyslexic Children based on EEG Local Network Features
Authors: Rezvani Z. , Zare M. , Žarić G. , Bonte M. , Tijms J. , Van der Molen M.W. , Fraga González G.
Published: March 2019

Machine learning can be used to find meaningful patterns characterizing individual differences. Deploying a machine learning classifier fed by local features derived from graph analysis of electroencephalographic (EEG) data, we aimed at designing a neurobiologically-based classifier to differentiate two groups of children, one group with and the other group without dyslexia, in a robust way. We used EEG resting-state data of 29 dyslexics and 15 typical readers in grade 3, and calculated weighted connectivity matrices for multiple frequency bands using the phase lag index (PLI). From the connectivity matrices, we derived weighted connectivity graphs. A number of local network measures were computed from those graphs, and 37 False Discovery Rate (FDR) corrected features were selected as input to a Support Vector Machine (SVM) and a commonKNearest Neighbors (KNN) classifier. Cross validation was employed to assess the machine-learning performance and random shuffling to assure the performance appropriateness of the classifier and avoid features overfitting. The best performance was for the SVM using a polynomial kernel. Children were classified with 95% accuracy based on local network features from different frequency bands. The automatic classification techniques applied to EEG graph measures showed to be both robust and reliable in distinguishing between typical and dyslexic readers.
Genetic Basis of Alternative Polyadenylation is an Emerging Molecular Phenotype for Human Traits and Diseases
Authors: Li Lei , Gao Yipeng , Peng Fanglue , Wagner Eric J. , Li Wei
Published: March 2019

Genome-wide association studies have identified thousands of non-coding variants that are statistically associated with human traits and diseases. However, functional interpretation of these variants remains a major challenge. Here, we describe the first atlas of human 3’-UTR alternative polyadenylation (APA) Quantitative Trait Loci (3’QTLs), i.e. ∼0.4 million genetic variants associated with APA of target genes across 46 Genotype-Tissue Expression (GTEx) tissues from 467 individuals. APA occurs in approximately 70% of human genes and substantively impacts cellular proliferation, differentiation and tumorigenesis. Mechanistically, 3’QTLs could alter polyA motifs and RNA-binding protein binding sites, leading to thousands of APA changes. Importantly, 3’QTLs can be used to interpret ∼16.1% of trait-associated variants and are largely distinct from other QTLs such as eQTLs. The genetic basis of APA (3’QTLs) thus represent a novel molecular phenotype to explain a large fraction of non-coding variants and to provide new insights into complex traits and disease etiologies.

Highlights

The first atlas of human 3’QTLs: ∼0.4 million genetic variants associated with alternative polyadenylation of target genes across 46 tissues from 467 individuals

3’QTLs could alter polyA motifs and RNA-binding protein binding sites

3’QTLs can be used to interpret ∼16.1% of trait-associated variants

Many disease-associated 3’QTLs contribute to phenotype independent of gene expression
A cancer-associated missense mutation in PP2A-Aα increases centrosome clustering during mitosis
Authors: Antao Noelle V. , Marcet-Ortega Marina , Cifani Paolo , Kentsis Alex , Foley Emily A.
Published: March 2019

A single incidence of whole-genome doubling (WGD) is common early in tumorigenesis. In addition to increasing ploidy, WGD doubles centrosome number. In the ensuing mitoses, excess centrosomes form a multipolar spindle, resulting in a lethal multipolar cell division. To survive, cells must cluster centrosomes into two poles to allow a bipolar cell division. Cancer cells are typically more proficient at centrosome clustering than untransformed cells, but the mechanism behind increased clustering ability is not well understood. Heterozygous missense mutations in PPP2R1A, which encodes the alpha isoform of the A-subunit of protein phosphatase 2A (PP2A-Aα), positively correlate with WGD. To understand this correlation, we introduced a heterozygous hotspot mutation, P179R, in endogenous PP2A-Aα in human tissue culture cells. We find that PP2A-AαP179R decreases PP2A assembly and targeting. Strikingly, when centrosome number is increased, either through cytokinesis failure or centrosome amplification, PP2A-Aα mutant cells are more proficient than WT cells at centrosome clustering, likely due to PP2A-Aα loss-of-function. PP2A-AαP179R appears to enhance centrosome clustering by altering the interactions between centrosomes and the cell cortex. Thus, cancer-associated mutations in PP2A-Aα may increase cellular fitness after WGD by enhancing centrosome clustering.
Student persistence in open and distance learning: success factors and challenges
Authors: Au Oliver Tat-Sheung , Li K. , Wong T.M.
Published: March 2019

Purpose

The purpose of this paper is to identify the success factors and challenges for students studying in an open and distance learning (ODL) mode and recommend strategies for student persistence based on the findings.

Design/methodology/approach

Three groups of ODL students with various levels of study performance – nine high-level, nine mid-level and eight low-level students – were invited to participate in three focus group interviews. They were asked about their motivation, success factors and challenges in their studies.

Findings

The different groups of participants showed observable variations in their response. The mid-level students believed that word-by-word rote memorisation was their best strategy in preparing for examinations. The low-level students believed that they needed to master multitasking to learn well in tight schedules. All these weak student participants considered quitting at some points, but no high-level student did so. To improve student persistence, the authors focus on meeting the needs of weak students and recommend the following actions for student persistence: add a time management and study skills component to existing courses for students to practise; appoint advisors to distance learning students to help them create an appropriate study plan and acquire a sense of belonging; make learning videos short and engaging; consider adopting student leaders or peer tutors that have been used successfully in full-time study; and conduct focus periodically with students to hear their views.

Originality/value

This study revealed the factors contributing to student persistence in ODL for the students of various levels of study performance. The results help in formulating measures to meet the diverse needs of ODL students for persistence in their studies.
Overtourism and the night-time economy: a case study of Budapest
Authors: Pinke-Sziva Ivett , Smith Melanie , Olt Gergely , Berezvai Zombor
Published: March 2019

Purpose

The purpose of this paper is to analyse the phenomenon of overtourism with specific reference to the night-time economy (NTE) in Budapest, Hungary.

Design/methodology/approach

The research took place between September and December 2017 in the so-called “party quarter” of Budapest – District VII. The chosen methods included mapping, observation, interviews and questionnaires with local residents, visitors and tourists.

Findings

Partying opportunities are valued highly by tourists and the majority of customers in the bars are tourists. Many people feel that there are too many tourists in the area, although few had a bad experience with tourists. The most common complaints were the dirt and litter, public urination, street crime and noise. Most respondents would welcome a better cleaning service, more bins, more police, more public toilets and better street lighting.

Research limitations/implications

The research was not undertaken in the high season, older residents were slightly under-represented and wider research across the whole city would give a more balanced perspective.

Practical implications

Recommendations are made for managing the NTE better in order to improve the experience of tourists and visitors and to improve the local resident quality of life.

Social implications

It is hoped that this research may prompt local authorities to take local resident perceptions and experiences into account by creating better management measures and regulations.

Originality/value

This is the first paper to provide data from the perspective of three main stakeholder groups in the context of the NTE in Budapest.
Mind your metaphors: early warning signals when rolling out strategy
Authors: Jonczyk Sédès Claudia
Published: March 2019

Purpose

While metaphors are widely used in strategy teaching and development, this study aims to present an approach how to benefit from metaphor analysis in strategy implementation. The authors find that metaphors used by organizational actors in strategy implementation processes carry a great range of implicit meanings and tacit knowledge that – when made explicit and critically examined – may serve as early warning signals to anticipate difficult or problematic developments in the strategy rollout phase.

Design/methodology/approach

The authors conducted narrative interviews with the main protagonists involved in the implementation of a strategic knowledge management project for the sales force of a multinational telecommunication solution provider. The data collected resulted in the surfacing of distinct groups of metaphors used by different organizational groups at different phases of the project implementation.

Findings

The metaphor analysis showed that metaphors not only reflect but also foreshadow project developments, and thereby reveal organizational conflicts that may erupt at later stages of the strategy implementation. Learning through metaphors can be realized through a sensitization to the detrimental effects of particular metaphors, as well as through the revelation of inconsistencies between the metaphors used and the exposed behaviors.

Research limitations/implications

The study is an in-depth case study of a strategy implementation project in one organization. While the findings are related to the particular case context, the methodological approach to use metaphor analysis as an early warning signal in strategy implementation can be replicated for strategy implementation processes in general.

Practical implications

Organizations may use metaphor analysis as a tool to calibrate to what extent their strategy implementation is aligned with initial strategic objectives. Metaphor analysis will be particularly helpful to check if there is an alignment in the implementation approach between different organizational groups. Such analysis can serve as an early warning signal for the strategy implementation phase.

Originality/value

The approach provides an inexpensive but very effective way of anticipating problematic project developments and unforeseen difficult collaborations during strategy implementation processes. With its focus on metaphors, it captures implicit meanings and connotations that business languages tend to filter out, yet that play a powerful role for enabling or obstructing strategy implementation.
How social media can fuel innovation in businesses: a strategic roadmap
Authors: Barlatier Pierre-Jean , Mention Anne-Laure
Published: March 2019

Purpose

This paper aims to present a framework to guide managerial action for social media (SM) strategies for innovation by exploring its constituent elements – the “what” (SM types), the “who” (stakeholders to be reached), the “for” (innovation types) and the “how” (innovation process stages), as well as the value, benefits and barriers.

Design/methodology/approach

A comprehensive and critical review of literature at the intersection of SM and innovation guides the development of a typology of SM types and their use across innovation types and stages.

Findings

SM type and use tend to differ across innovation processes. The authors identify four types of SM in use across four stages of innovation, supporting six types of innovation, influenced by five categories of barriers, benefits and stakeholders each.

Research limitations/implications

The research provides an integrative set of building blocks to consider for developing further studies of SM and innovation.

Practical implications

By highlighting the intertwined aspects of SM and innovation in an open and collaborative environment, the paper calls for development of an SM readiness organisational diagnosis. It empowers managers with a coherent framework of different elements they should take into consideration when defining their SM strategies for innovation.

Originality/value

Research on SM adoption and the extent of its usage for innovation purposes is still at its infancy. Given the increasingly open and collaborative innovation settings, the authors draw managerial attention to the need of SM strategies for innovation activities and provide a coherent analytical framework to guide action for organisational diagnosis.
How patents became documents, or dreaming of technoscientific order, 1895-1937
Authors: Hemmungs Wirtén Eva
Published: March 2019

Purpose

The purpose of this paper is to show how the documentation movement associated with the utopian thinkers Paul Otlet and Henri La Fontaine relied on patent offices as well as the documents most closely associated with this institutional setting – the patents themselves – as central to the formation of the document category. The main argument is that patents not only were subjected to and helped construct, but also in fact engineered the development of technoscientific order during 1895–1937.

Design/methodology/approach

The paper draws on an interdisciplinary approach to intellectual property, document theory and insights from media archeology. Focused on the historical period 1895–1937, this study allows for an analysis that encapsulates and accounts for change in a number of comparative areas, moving from bibliography to documentation and from scientific to technoscientific order. Primary sources include Paul Otlet’s own writings, relevant contemporary sources from the French documentation movement and theCongrès Mondial de la documentation universellein 1937.

Findings

By understanding patent offices and patents as main drivers behind those processes of sorting and classification that constitute technoscientific order, this explorative paper provides a new analytical framework for the study of intellectual property in relation to the history of information and documentation. It argues that the idea of the document may serve to rethink the role of the patent in technoscience, offering suggestions for new and underexplored venues of research in the nexus of several overlapping research fields, from law to information studies.

Originality/value

Debates over the legitimacy and rationale of intellectual property have raged for many years without signs of abating. Universities, research centers, policy makers, editors and scholars, research funders, governments, libraries and archives all have things to say on the legitimacy of the patent system, its relation to innovation and the appropriate role of intellectual property in research and science, milieus that are of central importance in the knowledge-based economy. The value of this paper lies in proposing a new way to approach patents that could show a way out of the current analytical gridlock of either/or that for many years has earmarked the “openness-enclosure” dichotomy. The combination of intellectual property scholarship and documentation theory provides important new insight into the historical networks and processes by which patents and documents have consolidated and converged during the twentieth century.