bluuebunny/crossref_metadata_2025 huggingface dataset:
Gathering Validity Evidence for Surgical Simulation
Authors: Borgersen Nanna Jo , Naur Therese M. H. , Sørensen Stine M. D. , Bjerrum Flemming , Konge Lars , Subhi Yousif , Thomsen Ann Sofia S.
Published: January 2018

Objective:

To identify current trends in the use of validity frameworks in surgical simulation, to provide an overview of the evidence behind the assessment of technical skills in all surgical specialties, and to present recommendations and guidelines for future validity studies.

Summary of Background Data:

Validity evidence for assessment tools used in the evaluation of surgical performance is of paramount importance to ensure valid and reliable assessment of skills.

Methods:

We systematically reviewed the literature by searching 5 databases (PubMed, EMBASE, Web of Science, PsycINFO, and the Cochrane Library) for studies published from January 1, 2008, to July 10, 2017. We included original studies evaluating simulation-based assessments of health professionals in surgical specialties and extracted data on surgical specialty, simulator modality, participant characteristics, and the validity framework used. Data were synthesized qualitatively.

Results:

We identified 498 studies with a total of 18,312 participants. Publications involving validity assessments in surgical simulation more than doubled from 2008 to 2010 (∼30 studies/year) to 2014 to 2016 (∼70 to 90 studies/year). Only 6.6% of the studies used the recommended contemporary validity framework (Messick). The majority of studies used outdated frameworks such as face validity. Significant differences were identified across surgical specialties. The evaluated assessment tools were mostly inanimate or virtual reality simulation models.

Conclusion:

An increasing number of studies have gathered validity evidence for simulation-based assessments in surgical specialties, but the use of outdated frameworks remains common. To address the current practice, this paper presents guidelines on how to use the contemporary validity framework when designing validity studies.
Immunosuppression Adherence in Stable Kidney Transplant Patients Converted From Immediate- to Prolonged-Release Tacrolimus in Clinical Practice: A Norwegian Study
Authors: Abedini Sadollah , Gøransson Lasse , Cockburn Elinor , Kilany Suzanne , Holdaas Hallvard
Published: January 2018

Background

This study investigated medication adherence in kidney transplant patients (KTPs) converted from immediate-release tacrolimus (IR-T) to prolonged-release tacrolimus (PR-T)-based immunosuppression in routine practice.

Methods

Noninterventional, observational, multicenter study in Norway. Included adult KTPs with stable graft function, converted from IR-T (baseline) to PR-T (1 mg:1 mg) in routine practice. Data were collected at baseline, and months 1, 3, 6, and 12 postconversion. Primary endpoint: adherence using the Basel Assessment of Adherence to Immunosuppressive Medication Scale. Secondary assessments: tacrolimus dose and trough levels (target, 3-7 ng/mL), clinical laboratory parameters (eg, estimated glomerular filtration rate [Modified Diet in Renal Disease]), and adverse events.

Results

Ninety-one KTPs (mean ± SD age 47.7 ± 14.3 years) were analyzed. Mean ± SD change in PR-T dose from baseline (4.4 ± 2.4 mg/d) to month 12 was −0.1 ± 0.9 mg/d; mean tacrolimus trough levels remained within target. Overall medication adherence increased from 45.6% at baseline to 58.1% at month 1, but was similar to baseline thereafter; taking and timing adherence followed a similar pattern. Odds ratio (OR) for adherence at month 1 (but not at other time points) was greater versus baseline for overall (OR, 1.71; P = 0.0205), taking (OR, 3.38; P = 0.0004), and timing (OR, 1.77, P = 0.0252) dimensions. Mean ± SD Basel Assessment of Adherence to Immunosuppressive Medication Scale visual analogue scale score at baseline was 96.4 ± 5.5%, and increased postconversion. Estimated glomerular filtration rate remained stable (month 12, 61.6 ± 17.7 mL/min per 1.73 m2), as did other laboratory parameters. Two (2.2%) patients had adverse events considered probably/possibly treatment-related.

Conclusions

There was disparity between high, patient-perceived and low, actual adherence. Converting stable KTPs from IR-T to PR-T in routine practice did not impact long-term adherence to immunosuppression; renal function remained stable.
Open-Access Electronic Diary for Motor Fluctuation and Dyskinesia Evaluation in Parkinson Disease: Comparison With Paper Diary
Authors: Terroba-Chambi Cinthia , Bruno Veronica , Medina-Escobar Alex , Nanni Federico , Cerquetti Daniel , Rossi Malco , Merello Marcelo
Published: January 2018

Objective

To determine the utility of an electronic diary for registering motor fluctuations and dyskinesia in Parkinson disease (PD).

Methods

Free, open-access touch screen software suitable for Android 4.4 or higher, with medication alarms, adjustable intervals, and medication dose settings was developed to evaluate ON-OFF periods and dyskinesia. Prospective evaluation included a first phase conducted to make adjustments concerning motor limitations when using the tablet, as well as for proper motor complication identification, and a second phase of 3 days of use at home with a prior diary training session comparing a modified paper version of Core Assessment Program for Surgical Interventional Therapies in PD and the electronic diary.

Results

All patients correctly identified ON-OFF periods and dyskinesia. Rater/patient matching ON-OFF fluctuations ranged between 94% and 100% for evaluations of different motor states. Dyskinesia matching percentage was 100% for patients with dyskinesia interfering with activities of daily living and 88% for those who reported no-interference. No significant differences between paper and electronic diaries were identified when reporting ON-OFF motor states or in the number of errors when filling the diaries.

Conclusions

This electronic motor diary proved to be reliable for ON-OFF state and dyskinesia identification and classification. However, no advantage to paper diary has been observed in terms of number of erroneous entries. Based on these results, to improve home motor fluctuations, detection efforts should be directed toward the development of automatic wearable devices rather than digital versions of current available ON-OFF diaries.
Synchronous diversification of Sulawesi’s iconic artiodactyls driven by recent geological events
Authors: Frantz Laurent A. F. , Rudzinski Anna , Nugraha Abang Mansyursyah Surya , Evin Allowen , Burton James , Hulme-Beaman Ardern , Linderholm Anna , Barnett Ross , Vega Rodrigo , Irving-Pease Evan K. , Haile James , Allen Richard , Leus Kristin , Shephard Jill , Hillyer Mia , Gillemot Sarah , van den Hurk Jeroen , Ogle Sharron , Atofanei Cristina , Thomas Mark G. , Johansson Friederike , Haris Mustari Abdul , Williams John , Mohamad Kusdiantoro , Damayanti Chandramaya Siska , Wiryadi Ita Djuwita , Obbles Dagmar , Mona Stephano , Day Hally , Yasin Muhammad , Meker Stefan , McGuire Jimmy A. , Evans Ben J. , von Rintelen Thomas , Ho Simon Y. W. , Searle Jeremy B. , Kitchener Andrew C. , Macdonald Alastair A. , Shaw Darren J. , Hall Robert , Galbusera Peter , Larson Greger
Published: January 2018

The high degree of endemism on Sulawesi has previously been suggested to have vicariant origins, dating back 40 Myr ago. Recent studies, however, suggest that much of Sulawesi’s fauna assembled over the last 15 Myr. Here, we test the hypothesis that recent uplift of previously submerged portions of land on Sulawesi promoted diversification, and that much of the its faunal assemblage is much younger than the island itself. To do so, we combined palaeogeographical reconstructions with genetic and morphometric data sets derived from Sulawesi’s three largest mammals: the Babirusa, Anoa, and Sulawesi warty pig. Our results indicate that although these species most likely colonized the area that is now Sulawesi at different times (14 Myr ago to 2-3 Myr ago), they experienced an almost synchronous expansion from the central part of the island. Geological reconstructions indicate that this area was above sea level for most of the last 4 Myr, unlike most parts of the island. We conclude that recent emergence of land on Sulawesi (~1–2 Myr) may have allowed species to expand synchronously. Altogether, our results indicates that the establishment of the highly endemic faunal assemblage on Sulawesi was driven by geological events over the last few million years.
Targeting the DNM3OS / miR-199a~214 cluster for the treatment of fibroproliferative diseases
Authors: Savary G. , Buscot M. , Dewaeles E. , Diazzi S. , Nottet N. , Courcot E. , Fassy J. , Lebrigand K. , Henaoui I. S. , Martis N. , Van der Hauwaert C. , Leroy S. , Plantier L. , Paquet A. , Lino Cardenas C. L. , Vassaux G. , Crestani B. , Wallaert B. , Rezzonico R. , Brousseau T. , Glowacki F. , Bellusci S. , Perrais M. , Broly F. , Barbry P. , Marquette C. H. , Cauffiez C. , Mari B. , Pottier N.
Published: January 2018

Given the paucity of effective treatments for fibrotic disorders, new insights into the deleterious mechanisms controlling fibroblast activation, the key cell type driving the fibrogenic process, are essential to develop new therapeutic strategies. Here, we identified the long non-coding RNA DNM3OS as a critical downstream effector of TGF-β-induced myofibroblast activation. Mechanistically, DNM3OS regulates this process in trans by giving rise to 3 distinct profibrotic mature miRNAs (i.e. miR-199a-5p/3p and miR-214-3p), which influence both SMAD and non-SMAD components of TGF-β signaling in a multifaceted way, through two modes of action consisting of either signal amplification or mediation. Finally, we provide preclinical evidence that interfering with DNM3OS function using distinct strategies not only prevents lung and kidney fibrosis but also improves established lung fibrosis, providing thus a novel paradigm for the treatment of refractory fibrotic diseases such as idiopathic pulmonary fibrosis.

One Sentence Summary

The DNM3OS lncRNA is a reservoir of fibromiRs with major functions in fibroblast response to TGF-β and represents a valuable therapeutic target for refractory fibrotic diseases such as idiopathic pulmonary fibrosis (IPF).
High-magnitude innovators as keystone individuals in the evolution of culture
Authors: Arbilly Michal
Published: January 2018

Borrowing from the concept of keystone species in ecological food webs, a recent focus in the field of animal behaviour has been keystone individuals: individuals whose impact on population dynamics is disproportionally larger than their frequency in the population. In populations evolving culture, such may be the role of high-magnitude innovators: individuals whose innovations are a major departure from the population’s existing behavioural repertoire. Their effect on cultural evolution is twofold: they produce innovations that constitute a ‘cultural leap’, and, once copied, their innovations may induce further innovations by conspecifics (socially induced innovations), as they explore the new behaviour themselves. I use computer simulations to study the co-evolution of independent innovations, socially induced innovations, and innovation magnitude, and show that while socially induced innovation is assumed here to be less costly than independent innovation, it does not readily evolve. When it evolves, it may in some conditions select against independent innovation and lower its frequency, despite it requiring independent innovation in order to operate; at the same time, however, it leads to much faster cultural evolution. These results confirm the role of high-magnitude innovators as keystones, and suggest a novel explanation for low frequency of independent innovation.
NvERTx: A gene expression database to compare Embryogenesis and Regeneration in the sea anemoneNematostella vectensis
Authors: Warner Jacob F. , Guerlais Vincent , Amiel Aldine R. , Johnston Hereroa , Nedoncelle Karine , Röttinger Eric
Published: January 2018

For more than a century researchers have been comparing embryogenesis and regeneration hoping that lessons learned from embryonic development will unlock hidden regenerative potential. This problem has historically been a difficult one to investigate since the best regenerative model systems are poor embryonic models and vice versa. Recently however, the comparison of embryogenesis and regeneration has seen renewed interest as emerging models including the sea anemoneNematostella vectensishave allowed researchers to investigate these processes in the same organism. This interest has been further fueled by the advent of high-throughput transcriptomic analyses that provide virtual mountains of data. Unfortunately much of this data remains in raw unanalyzed formats that are difficult to access or browse. Here we presentNematostellavectensisEmbryogenesis andRegenerationTranscriptomics- NvERTx, the first platform for comparing gene expression during embryogenesis and regeneration. NvERTx is comprised of close to 50 RNAseq datasets spanning embryogenesis and regeneration inNematostella. These data were used to perform a robustde novotranscriptome assembly which users can search, BLAST and plot expression of multiple genes during these two developmental processes. The site is also home to the results of gene clustering analyses, to further mine the data and identify groups of co-expressed genes. The site can be accessed athttp://nvertx.kahikai.org.
Generalizing Genetic Risk Scores from Europeans to Hispanics/Latinos
Authors: Grinde Kelsey E. , Qi Qibin , Thornton Timothy A. , Liu Simin , Shadyab Aladdin H. , Chan Kei Hang K. , Reiner Alexander P. , Sofer Tamar
Published: January 2018

Genetic risk scores (GRSs) are weighted sums of risk allele counts of single nucleotide polymorphisms (SNPs) associated with a disease or trait. Construction of GRSs is typically based on published results from Genome-Wide Association Studies (GWASs), the majority of which have been performed in large populations of European ancestry (EA) individuals. While many genotype-trait associations have been shown to generalize from EA populations to other populations, such as Hispanics/Latinos, the optimal choice of SNPs and weights for GRSs may differ between populations due to different linkage disequilibrium (LD) and allele frequency patterns. This is further complicated by the fact that different Hispanic/Latino populations may have different admixture patterns, so that LD and allele frequency patterns may not be the same among non-EA populations. Here, we compare various approaches for GRS construction, using GWAS results from both large EA studies and a smaller study in Hispanics/Latinos, the Hispanic Community Health Study/Study of Latinos (HCHS/SOL, n = 12, 803). We consider multiple ways to select SNPs from association regions and to calculate the SNP weights. We study the performance of the resulting GRSs in an independent study of Hispanics/Latinos from the Woman Health Initiative (WHI, n = 3, 582). We support our investigation with simulation studies of potential genetic architectures in a single locus. We observed that selecting variants based on EA GWASs generally performs well, as long as SNP weights are calculated using Hispanics/Latinos GWASs, or using the meta-analysis of EA and Hispanics/Latinos GWASs. The optimal approach depends on the genetic architecture of the trait.
Cryo-EM structure of an early precursor of large ribosomal subunit reveals a half assembled intermediate
Authors: Zhou Dejian , Zhu Xing , Zheng Sanduo , Tan Dan , Dong Meng-Qiu , Ye Keqiong
Published: January 2018

Assembly of eukaryotic ribosome is a complicated and dynamic process that involves a series of intermediates. How the highly intertwined structure of 60S large ribosomal subunits is established is unknown. Here, we report the structure of an early nucleolar pre-60S ribosome determined by cryo-electron microscopy at 3.7 Å resolution, revealing a half assembled subunit. Domains I, II and VI of 25S/5.8S rRNA tightly pack into a native-like substructure, but domains III, IV and V are not assembled. The structure contains 12 assembly factors and 19 ribosomal proteins, many of which are required for early processing of large subunit rRNA. The Brx1-Ebp2 complex would interfere with the assembly of domains IV and V. Rpf1, Mak16, Nsa1 and Rrp1 form a cluster that consolidates the joining of domains I and II. Our structure reveals a key intermediate on the path to the establishment of the global architecture of 60S subunits.
Gemin4is an essential gene in mice, and its overexpression in human cells causes relocalization of the SMN complex to the nucleoplasm
Authors: Meier Ingo D. , Walker Michael P. , Matera A. Gregory
Published: January 2018

Gemin4 is a member of the Survival Motor Neuron (SMN) protein complex, which is responsible for the assembly and maturation of Sm-class small nuclear ribonucleoproteins (snRNPs). In metazoa, Sm snRNPs are assembled in the cytoplasm and subsequently imported into the nucleus. We previously showed that the SMN complex is required for snRNP importin vitro, although it remains unclear which specific components direct this process. Here, we report that Gemin4 overexpression drives SMN and the other Gemin proteins from the cytoplasm into the nucleus. Moreover, it disrupts the subnuclear localization of the Cajal body marker protein, coilin, in a dose-dependent manner. We identified three putative nuclear localization signal (NLS) motifs within Gemin4, one of which is necessary and sufficient to direct nuclear import. Overexpression of Gemin4 constructs lacking this NLS sequestered Gemin3 and, to a lesser extent Gemin2, in the cytoplasm but had little effect on the nuclear accumulation of SMN. We also investigated the effects of Gemin4 depletion in the laboratory mouse,mus musculus. Gemin4null mice die early in embryonic development, demonstrating that Gemin4 is an essential mammalian protein. When crossed onto a severe SMA mutant background, heterozygous loss ofGemin4failed to modify the early postnatal mortality phenotype of SMA type I (Smn-/-;SMN2+/+) mice. We conclude that Gemin4 plays an essential role in mammalian snRNP biogenesis, and may facilitate import of the SMN complex (or subunits thereof) into the nucleus.
Acute Hyperalgesia and Delayed Dry Eye After Corneal Abrasion Injury
Authors: Hegarty Deborah M. , Hermes Sam M. , Morgan Michael M. , Aicher Sue A.
Published: January 2018

Corneal nerves mediate pain from the ocular surface, lacrimation, and blinking, all of which protect corneal surface homeostasis and help preserve vision. Corneal nerve density correlates with neuropathic pain states and is used as an assessment of small fiber neuropathies. Because pain, lacrimation and blinking are rarely assessed at the same time, it is not known if their regulatory mechanisms have similar temporal dynamics after acute corneal injury. We examined changes in corneal nerve density, evoked and spontaneous pain, and ocular homeostasis in Sprague-Dawley male rats after a superficial epithelial injury with heptanol that acutely abolished nerve endings within the central cornea. Despite a profound loss of epithelial nerve endings, pain was transiently enhanced after abrasion injury, while basal tear production was normal. We found no relationship between epithelial nerve density and pain or homeostatic responses. Axotomy following corneal abrasion increased expression of both ATF3 (a nerve injury marker) and CGRP (a nociceptive peptide) in trigeminal ganglia 24 hours after injury. These molecular changes were absent on the contralateral side, despite reductions in corneal epithelial nerve density in the uninjured eye. ATF3 and CGRP levels in trigeminal ganglion were normal at one week post-injury when pain responses were normal. In contrast, CGRP was upregulated in peripheral corneal endings one week after injury, when dry eye symptoms emerged. Our results demonstrate dynamic trafficking of CGRP within trigeminal sensory nerves, with elevations in the ganglion correlated with pain behaviors and elevations in peripheral endings correlated with dry eye symptoms.
Phylogenetic distribution of roseobacticides in the Roseobacter group and their effect on microalgae
Authors: Sonnenschein Eva C. , Phippen Christopher Broughton William , Bentzon-Tilia Mikkel , Rasmussen Silas Anselm , Nielsen Kristian Fog , Gram Lone
Published: January 2018

The Roseobacter-group species Phaeobacter inhibens produces the antibacterial tropodithietic acid (TDA) and the algaecidal roseobacticides with both compound classes sharing part of the same biosynthetic pathway. The purpose of this study was to investigate the production of roseobacticides more broadly in TDA-producing roseobacters and to compare the effect of producers and non-producers on microalgae. Of 33 roseobacters analyzed, roseobacticide production was a unique feature of TDA-producing P. inhibens, P. gallaeciensis and P. piscinae strains. One TDA-producing Phaeobacter strain, 27-4, was unable to produce roseobacticides, possibly due to a transposable element. TDA-producing Ruegeria mobilis and Pseudovibrio did not produce roseobacticides. Addition of roseobacticide-containing bacterial extracts affected the growth of the microalgae Rhodomonas salina, Thalassiosira pseudonana and Emiliania huxleyi, while growth of Tetraselmis suecica was unaffected. During co-cultivation, growth of E. huxleyi was initially stimulated by the roseobacticide producer DSM 17395, while the subsequent decline in algal cell numbers during senescence was enhanced. Strain 27-4 that does not produce roseobacticides had no effect on algal growth. Both bacterial strains, DSM 17395 and 27-4, grew during co-cultivation presumably utilizing algal exudates. Furthermore, TDA-producing roseobacters have potential as probiotics in marine larviculture and it is promising that the live feed Tetraselmis was unaffected by roseobacticides-containing extracts.

Originality-significance statement

Some Roseobacter-group bacteria produce the antibacterial compound tropodithetic acid (TDA) and have potential as probiotics in marine aquaculture. However, a few of these strains additionally produce algaecidal compounds, the roseobacticides, which would restrict their use in marine larviculture where algae are used as live feed for fish larvae. We herein found that roseobacticides are limited to TDA-producing Phaeobacter strains and were not biosynthesized by TDA-producers outside this genus. Roseobacticides affected several strains of microalgae, but not the chlorophyte that is used as live feed in the aquaculture industry. Thus, the application of Roseobacter strains as probiotics is not hampered. Furthermore, these results demonstrate how Roseobacter-group strains act as gardeners of microalgae and thereby would be involved in environmental processes on a larger scale.
Anterior thalamic excitation and feed-forward inhibition of presubicular neurons projecting to medial entorhinal cortex
Authors: Nassar Mérie , Simonnet Jean , Huang Li-Wen , Mathon Bertrand , Cohen Ivan , Bendels Michael H.K. , Beraneck Mathieu , Miles Richard , Fricker Desdemona
Published: January 2018

The presubiculum contains head direction cells that are crucial for spatial navigation. Here, we examined the connectivity and strengths of thalamic inputs to presubicular layer 3 neurons projecting to the medial entorhinal cortex in the mouse. We recorded pairs of projection neurons and interneurons while optogenetically stimulating afferent fibers from the anterior thalamic nuclei (ATN). Thalamic input differentially affects presubicular neurons: layer 3 pyramidal neurons and fast-spiking parvalbumin expressing (PV) interneurons are directly and monosynaptically activated, with depressing dynamics, while somatostatin (SST) expressing interneurons are indirectly excited, during repetitive ATN activity. This arrangement ensures that the thalamic excitation of layer 3 cells is often followed by disynaptic inhibition. Feed-forward inhibition is largely mediated by PV interneurons which have a high probability of connection to presubicular pyramidal cells. Our data point to a specific role of presubicular microcircuits in shaping thalamic head-direction signals transmitted to medial entorhinal cortex: Short-latency PV cell activation may enforce temporally precise head direction tuning during fast turns. However, depression at ATN-PV synapses during repeated activation tends to facilitate pyramidal cell firing when head direction is maintained. Operations performed in presubicular layer 3 circuits seem well-adapted for spatial fine-tuning of head direction signals sent to the medial entorhinal cortex.

SIGNIFICANCE STATEMENT

How microcircuits participate in shaping neural inputs is crucial to understanding information processing in the brain. Here, we show how the presubiculum may process thalamic head directional information before transmitting it to the medial entorhinal cortex. Synaptic inputs from the anterior thalamic nuclei (ATN) excite layer 3 pyramidal cells (PC) and parvalbumin (PV) interneurons, which mediate disynaptic feed-forward inhibition. Somatostatin (SST) interneurons are excited indirectly. Presubicular circuits may switch between two regimes according to the angular velocity of head movements. During immobility, SST-PC interactions support maintained head directional firing with attractor-like dynamics. During rapid head turns, in contrast, PV mediated feed-forward inhibition acts to tune the head direction signal transmitted to medial entorhinal cortex.
Inferring identical by descent sharing of sample ancestors promotes high resolution relative detection
Authors: Ramstetter Monica D. , Shenoy Sushila A. , Dyer Thomas D. , Lehman Donna M. , Curran Joanne E. , Duggirala Ravindranath , Blangero John , Mezey Jason G. , Williams Amy L.
Published: January 2018

As genetic datasets increase in size, the fraction of samples with one or more close relatives grows rapidly, resulting in sets of mutually related individuals. We present DRUID—Deep Relatedness Utilizing Identity by Descent—a method that works by inferring the identical by descent (IBD) sharing profile of an ungenotyped ancestor of a set of close relatives. Using this IBD profile, DRUID infers relatedness between unobserved ancestors and more distant relatives, thereby combining information from multiple samples to remove one or more generations between the deep relationships to be identified. DRUID constructs sets of close relatives by detecting full siblings and also uses a novel approach to identify the aunts/uncles of two or more siblings, recovering 92.2% of real aunts/uncles with zero false positives. In real and simulated data, DRUID correctly infers up to 10.5% more relatives than PADRE when using data from two sets of distantly related siblings, and 10.7–31.3% more relatives given two sets of siblings and their aunts/uncles. DRUID frequently infers relationships either correctly or within one degree of the truth, with PADRE classifying 43.3–58.3% of tenth degree relatives in this way compared to 79.6–96.7% using DRUID.
The Amyloid Clearance Defect in ApoE4 Astrocytes is Corrected by Epigenetic Restoration of NHE6
Authors: Prasad Hari , Rao Rajini
Published: January 2018

The accumulation of amyloid protein Aβ in senile plaques is a key driver and hallmark of Alzheimer disease (AD), a major cause of death and dementia in the elderly. The strongest genetic risk factor in sporadic AD is the ε4 allele of Apolipoprotein E (ApoE4), which potentiates pre-symptomatic endosomal dysfunction and defective clearance of Aβ, although how these two pathways are linked has been unclear. Here, we show that aberrant accumulation of endosomal protons in ApoE4 astrocytes traps the LRP1 receptor in non-productive intracellular compartments, leading to loss of surface expression and Aβ clearance. Hyperacidification of endosomal pH is caused by selective down regulation of the Na+/H+ exchanger NHE6, which functions as a critical proton leak pathway, in ApoE4 brain and astrocytes. In vivo, the NHE6KO mouse model shows elevated Aβ in the brain. Epigenetic restoration of NHE6 expression with histone deacetylase inhibitors normalized ApoE4-specific defects in endosomal pH, LRP1 trafficking and amyloid clearance. Thus, NHE6 is a prominent effector of ApoE4 and emerges as a promising therapeutic target in Alzheimer disease.
Investigating the viral ecology of global bee communities with high-throughput metagenomics
Authors: Galbraith David A. , Fuller Zachary L. , Brockmann Axel , Frazier Maryann , Gikungu Mary W. , Kapheim Karen M. , Kerby Jeffrey T. , Kocher Sarah D. , Losyev Oleksiy , Muli Elliud , Patch Harland M. , Sakamoto Joyce M. , Stanley Scott , Vaudo Anthony D. , Grozinger Christina M.
Published: January 2018

Bee viral ecology is a fascinating emerging area of research: viruses exert a range of effects on their hosts, exacerbate the impacts of other environmental stressors, and, importantly, are readily shared across multiple bee species in a community. However, our understanding of bee viral communities is limited, as it is primarily derived from studies of North American and European Apis mellifera populations. Here, we examined viruses in populations of A. mellifera and 11 other bee species from 9 countries, across 5 continents and Oceania. We developed a novel pipeline to rapidly, inexpensively, and robustly screen for bee viruses. This pipeline includes purification of encapsulated RNA/DNA viruses, sequence-independent amplification, high throughput sequencing, integrated assembly of contigs, and filtering to identify contigs specifically corresponding to viral sequences. We identified sequences corresponding to (+)ssRNA, (-)ssRNA, dsRNA, and ssDNA viruses. Overall, we found 127 contigs corresponding to novel viruses (i.e. previously not observed in bees), with 29 represented by >0.1 % of the reads in a given sample. These viruses and viral families were distributed across multiple regions and species. This study provides a robust pipeline for metagenomics analysis of viruses, and greatly expands our understanding of the diversity of viruses found in bee communities.
Impact of stimulus size and orientation on individual face decoding in monkey face-selective cortex
Authors: Taubert Jessica , Van Belle Goedele , Vogels Rufin , Rossion Bruno
Published: January 2018

Face-selective neurons in the monkey temporal cortex discharge at different rates in response to pictures of different faces. Here we tested whether the population response of neurons in the face-selective area ML (located in the middle Superior Temporal Sulcus) tolerates two affine transformations; one, picture-plane inversion, known to have a deleterious impact on the average response of face-selective neurons and the other, stimulus size, thought to have little or no impact on face-selective neurons. We recorded the response of 57 ML neurons in two monkeys. Face stimuli were presented at two sizes (10 and 5 degrees of visual angle) and two orientations (upright and inverted). The results indicate that different faces elicited distinct patterns of activity across ML neurons that were tolerant of changes in size. However, the results of the orientation manipulation were mixed; despite observing a reduced response to inverted faces, classifier performance was above chance for both upright and inverted faces and the classification score did not differ significantly for inverted and upright faces. We conclude that population responses in area ML to different faces are dependent on stimulus orientation but are more tolerant to changes in stimulus size.
Managing e-books in a business school library: case study of Ebrary Academic Complete
Authors: Anilkumar Hanumappa , Dora Mallikarjun , Desai Asha
Published: January 2018

Purpose

The purpose of the study is to review the e-books collection, namely, Ebrary Academic Complete, by understanding its features, cost and usage at Vikram Sarabhai Library, Indian Institute of Management Ahmedabad (IIMA). The study attempts to understand the usefulness of Ebrary in terms of its currency of titles, publishers, subjects and cost.

Design/methodology/approach

The paper is based on five-year usage data of Ebrary Academic Complete at Vikram Sarabhai Library, IIMA. The data on usage of Ebrary was downloaded and analyzed on different parameters to find out the overall value or use of Ebrary Academic Complete package from the perspective of a management library.

Findings

The research concluded that there was an increase in usage of Ebrary Academic Complete over time. The subject analysis revealed that titles from “Business and Economics”, “Computers” and “Social Science” were the highest used. The publisher analysis indicated that John Wiley & Sons topped in both the highest number of titles in the package and highest used titles. The annual subscription fee model of Ebrary Academic Complete adopted by Vikram Sarabhai Library was working well with a gradual increase in usage bringing down the per title access costs.

Originality/value

The study helps in understanding the approach to evaluating e-book collections in terms of currency of content, subjects covered, publishers included and costs involved. The detailed analysis would assist libraries in decision-making with regard to e-book collection development.
Transitioning from unemployment to self-employment for over 50s
Authors: Kenny Breda , Rossiter Isabel
Published: January 2018

Purpose

The purpose of this paper is to identify the entrepreneurial learning and support needs of older unemployed, highlighting the barriers that need to be addressed, and to explore the impact of a tailored entrepreneurship training programme.

Design/methodology/approach

An interpretivist philosophical standpoint is adopted with an action research approach to engage key informants to design, implement and evaluate the programme. Focus groups and interviews with 132 older unemployed individuals and 50 stakeholders across six countries were conducted as well as pre- and post-programme evaluations and surveys with 55 programme participants across three countries.

Findings

This research provides a deeper understanding of the entrepreneurial learning and support needs of older unemployed.

Research limitations/implications

The small sample size of participants measured using a hybrid measure of ESE is a limitation.

Practical implications

For entrepreneurship educators, the components of designing and delivering an entrepreneurship programme for older unemployed are identified. For enterprise and unemployment support agencies, it provides evidence of the initial and ongoing support needs for starting and running a business in later life.

Originality/value

A framework specific to older unemployed individuals turning towards self-employment or entrepreneurship is proposed and tested in this paper. The framework proposes that individual and contextual antecedents influence the decision to become self-employed in later life and that the training, support and entrepreneurial experience helps to overcome barriers and shapes individual and societal outcomes.
Beyond effectuation
Authors: Murdock Karen A. , Varnes Claus J.
Published: January 2018

Purpose

The purpose of this paper is to show that the entrepreneurial project ongoingly is transformed. Empirically, three defining junctions demonstrate the malleability of the entrepreneurial project in perpetual action, expanding beyond effectuation theory on what constitutes given means, affordable loss, and other key concepts from this theoretical perspective. Drawing upon actor-network theory (ANT), this study demonstrates how different framing and support devices implicate different human and non-human actors in changing interpositions within the entrepreneurial process.

Design/methodology/approach

This study uses a longitudinal case study design. The case provides an overview of a new business’s emergence based on three identified translations, each representing critical junctures in the business’s development. An ethnographic approach is selected, which combines observations with qualitative interviews. This design allows the authors to focus on how the project emerges and is continuously supported by allies but is sometimes not supported by various human and non-human actors.

Findings

This study demonstrates that the entrepreneurial project undertaken by the entrepreneurial network changes as new humans or non-humans become part of it. Including a resource in the network means simultaneously changing the network. This interactionism shows that what sparks interest or attracts resources to a business idea is not simply an influx of additional resources but is simultaneously a dynamic definition of the entrepreneurial endeavour.

Originality/value

This paper examines how ideas are transformed into business ventures by using the ANT to expand understanding from effectuation theory. This shows that means, for instance, are not given but are co-created by the process of translation. In addition, which losses are affordable can be determined by the process within which the entrepreneur frames the project and manages to associate allies within and into the network.
Growth expectations through innovative entrepreneurship
Authors: Poblete Carlos
Published: January 2018

Purpose

The purpose of this paper is to propose a model suggesting that innovation may act as a motivating force that increases entrepreneurs’ growth expectations, in which entrepreneurs’ growth expectations are shaped by their subjective values and entrepreneurial experience moderates this relationship.

Design/methodology/approach

This paper conducts statistical analysis on a sample of 11,579 entrepreneurs from 24 countries who participated in the IIIP survey of innovation in 2011 under the Global Entrepreneurship Monitor project.

Findings

The results suggest that entrepreneurs involved in innovative entrepreneurship are more likely to have higher growth expectations, with subjective values playing a direct and indirect role in entrepreneurs’ expectations of firm growth. Additionally, the results indicate that the duration of entrepreneurial experience moderates the relationship between strategic orientation and confidence in innovation. This finding suggests there is feedback between having beliefs about the benefits of innovation and being an innovative entrepreneur, resulting in an over-estimation – at least in comparative terms – regarding firm growth rates. This relationship is stronger for novice entrepreneurs since experienced entrepreneurs tend to be more cautious about their expectations of growing.

Originality/value

This study deepens our understanding of the complex processes through which organizational-level decisions ultimately influence individual-level factors. The present findings contribute to progress in this task by suggesting that strategies aimed at cultivating innovation feed entrepreneurs’ subjective values of innovation as well as expectations of growth. Although the duration of entrepreneurial experience moderates the relationship between acting as an innovative entrepreneur and subjective values of innovation, the results suggest that entrepreneurs’ expectations are primarily driven by their internal perceptions of reality.
The perceptions of Australian senior entrepreneurs on the drivers of their entrepreneurial activity
Authors: Perenyi Aron , Zolin Roxanne , Maritz Alex
Published: January 2018

Purpose

Why is self-employment an attractive option for certain seniors and what drives seniors into business start-ups? In this study, the motivations and preferences of senior entrepreneurs in Australia, to become self-employed, by means of business start-ups, are explored. The purpose of this paper is to provide empirical basis for policy implications.

Design/methodology/approach

A mixed methods study is conducted. Members of the National Senior’s Association in Australia were interviewed and surveyed. The semi-structured interviews identified the key factors influencing senior entrepreneurs in relation to self-employment and entrepreneurial choices at a later career stage. The survey collected information on intentionality, motivation, skills, opportunities, success, satisfaction, participation, barriers, benefits, education and training, and perceptions of policy support for senior entrepreneurs.

Findings

Respondents gave an account of the prevalence of pull factors motivating their choice of an entrepreneurial career. Multivariate statistical analysis of survey responses showed that senior entrepreneurs are more driven by opportunity than necessity and are primarily internally motivated.

Research limitations/implications

Results of this study suggest a weak link between motivation by others and the act of start-up, but this may also imply that those seniors who are more likely to become entrepreneurs are more likely to ignore the impulses from their social context. This requires further investigation to ensure a robust identification of drivers and an elimination of contextual effects. Further research is suggested to compose a relevant model structure in different contexts and a representative sample to confirm the model outcomes.

Originality/value

This is the first mixed methods study of the antecedents of senior entrepreneurs’ start-up intentions in Australia. The study also uses entrepreneurial activity as opposed to intention as its dependent variable, which allows for a more accurate evaluation of antecedents to the senior entrepreneurship phenomenon.
Intellectual and physical shared workspace
Authors: Carpenter Daniel
Published: January 2018

Purpose

The purpose of this paper is to explore shared workspace and professional learning community (PLC) interactions in schools. The collaborative culture and PLCs were parts of the school culture. The collaborative culture of each school was designed to ensure teachers share intellectual and physical contributions in learning to investigate the impact of teaching and learning on students. The workspace overlap for teachers was part of the culture of each school and a function of the PLC interactions. PLCs provided opportunities for collaboration and therefore opportunities to share intellectual and physical workspace.

Design/methodology/approach

A grounded theory research approach was taken to this investigation, primarily because of the common experiences of educators in schools (Creswell, 2013). Collaborative process between educators in schools was qualitatively investigated as a function of PLC interactions. In all, three communities, five schools, and 70 educators were purposefully selected to participate. Data were collected, including semi-structured interviews, observations, artifacts, and researcher field notes.

Findings

The workspace interactions include shared leadership, decision making, teaching and learning practice, and accountability measures. Attributes and characteristics of effective collaboration and PLCs greatly affect the outcomes of PLCs. An emergent framework is provided that includes attributes of effective collaboration and the characteristics of effective PLCs that merge into intellectual and physical shared workspace.

Originality/value

This paper focuses on the connections between PLCs, school culture, and professional educator collaboration. This paper proposes to provide a unique model called the shared workspace. The model combines the intellectual and physical aspects of group members to ensure the effectiveness of collaborative systems that promote quality practice in schools through functional PLCs as part of a positive school culture. This paper further offers extensions to the shared leadership concept (Carpenter, 2015) in how schools, administrators, and teachers should work together, thus more collaboratively through a continuous improvement process of the school as a workplace and a learning organization.
Management style and school violence: South African perspectives
Authors: Netshitangani Tshilidzi
Published: January 2018

Purpose

The purpose of this paper is to examine the reduction of school violence from the management point of view. It reflects on the utterances by teachers, principals, learners and members of school governing bodies (SGBs) to establish the influence that school management practices can have on the prevalence of school violence.

Design/methodology/approach

This was a qualitative case study. Thus, semi-structured interviews with teachers, principals, learners and members of SGBs were conducted. In addition, focus group interviews with pupils and observations were used to collect data.

Findings

Findings suggest that most schools were still run in an authoritarian manner. Resultantly, it was also found that an authoritarian school management style practiced seemed to encourage the persistence of violence in schools.

Practical implications

Policies should incorporate and emphasise the use of pragmatic, critical democratic style of management to address school violence. This is important because a well-run, inclusive and more democratic school can help to reduce external and internal forms of violence. The results from this study further indicate that a poorly run and badly organised school is more prone to various forms of violence.

Originality/value

The paper adds to the growing body of knowledge in the field of educational management and offers a reference point for further research in the pursuit to eliminate violence in schools. The findings may also be a useful resource for school principals, teachers, policy-makers and other stakeholders who are seeking to eliminate violence in schools.
National strategy for promotion of Russian universities in the world market of education services
Authors: Mushketova Natalia , Bydanova Elizaveta , Rouet Gilles
Published: January 2018

Purpose

The export of Russian educational services worldwide was not considered by the Russian Government as a full-fledged economic sector until recently. However, the situation has changed since the early 2000s, when in 2002, the Russian Government approved the national strategy for higher education promotion abroad and since then has been actively working on development of incentives and measures to support Russian universities to better market themselves in a global competitive market place of higher education. The paper aims to discuss these issues.

Design/methodology/approach

In this paper, the authors use a systematic approach to analyze different instruments for promoting higher education services abroad, consider the current state of this issue in Russia and look at what difficulties may arise at various levels when the state attempts to implement its strategy.

Findings

They are formulated as a set of marketing activities at different levels (national, regional and institutional), allowing a more advantage positioning of Russian universities in the global environment.

Practical implications

This paper focuses on the development of a marketing strategy for universities in a dynamic setting. The urgency of the problem is determined by the fact that today universities have to deal with a number of challenges: the reduced funding; increased competition at the regional, national and global markets; the growth of the importance of international and national rankings; and demographic and social challenges. Effective positioning in the global market place can be viewed as a source of new opportunities, as well as a challenge, not easy to master in some cases.

Originality/value

The paper scrutinizes strategies for the promotion of Russian universities to increase effectiveness of their positioning and create for them comfortable conditions for development in the world markets of educational services. The topic of marketing of educational services worldwide for a post-Soviet country is not an issue commonly addressed in the literature today.