bluuebunny/crossref_metadata_2025 huggingface dataset:
Endoscopic Carpal Tunnel Release with and without Sedation
Authors: Tulipan Jacob E. , Kim Nayoung , Ilyas Asif M. , Matzon Jonas L.
Published: November 2017

Background:

This study evaluated outcomes and complications with endoscopic carpal tunnel release performed with local anesthesia only versus local anesthesia with sedation. The authors hypothesized that patient outcomes and satisfaction would be equivalent in both groups irrespective of anesthesia type.

Methods:

One hundred fifty-four consecutive patients undergoing endoscopic carpal tunnel release with local anesthesia either with or without sedation were prospectively enrolled in a study of satisfaction and outcomes. Patients were surveyed preoperatively and at 2 weeks and 3 months postoperatively to evaluate satisfaction, symptoms, complications, and disability using the 11-question Disabilities of the Arm, Shoulder, and Hand questionnaire survey; the Levine-Katz carpal tunnel survey; and a customized Likert scale.

Results:

The hypothesis was upheld. Patients reported high levels of satisfaction (96 percent in the local anesthesia group and 93 percent in the local anesthesia with sedation group at 3 weeks). Disability, pain, and symptom scores did not differ significantly between groups at either postoperative time point. After surgery, patients in the sedation group recalled more mean preoperative anxiety (four of 10 versus 2.03 of 10 at 3 months). If they were to undergo surgery again, patients in the sedation group were likely to desire either sedation (68 percent) or general anesthesia (29 percent), whereas patients in the local anesthesia–only group were likely to wish for similar local-only anesthesia (78 percent). There were no reoperations or epinephrine-related complications in either group.

Conclusions:

Patients undergoing endoscopic carpal tunnel release with the local anesthesia or local anesthesia plus sedation experience similar levels of satisfaction and outcomes. Both methods of anesthesia provide excellent results and allow surgeons and patients to choose freely between the two anesthetic techniques.
Reconstruction of Microtias with Constricted Ear Features: A 22-Year Experience
Authors: Park Chul , Park Jung Youl
Published: November 2017

Background:

The surgical correction of microtias with constricted ear features has remained a challenge because of the variable shape and large volume of the remnant cartilage and skin involved. To clarify how this remnant cartilage and skin should be treated, the authors have reviewed and analyzed cases operated on at their center.

Methods:

A total of 167 cases of microtia with constricted ear features, operated on from 1992 to 2014, were included in the study. They were reviewed through medical records and photographs, analysis of surgical methods, and postoperative outcomes.

Results:

A total of 141 cases (84 percent) were followed for 2 months to 13 years (average, 28 months). The average score given for the aesthetic outcomes, rated on a four-point Likert scale (i.e., 1 = poor, 2 = fair, 3 = good, and 4 = excellent), was 3.1. For framework construction, the authors used remnant cartilage-saving methods (n = 37) or remnant cartilage-replacement methods (n = 104). The average scores for the aesthetic outcome for these methods were 2.56 (median, 3) and 3.36 (median, 4), respectively. The difference in these scores was statistically significant (p < 0.001). For the coverage of new frameworks, various flap techniques were used.

Conclusion:

To correct microtias with constricted ear features with consistent postoperative results, the deformed cartilage remnant should be completely replaced with a costal cartilage framework, and the remnant skin should be maximally saved.
Epidemiology of community-acquired bacterial meningitis
Authors: Brouwer Matthijs C. , van de Beek Diederik
Published: November 2017

Purpose of review

The epidemiology of bacterial meningitis has been dynamic in the past 30 years following introduction of conjugated vaccines against Haemophilus influenzae type B, Streptococcus pneumoniae and Neisseria meningitidis. The purpose of this review is to describe recent developments in bacterial meningitis epidemiology.

Recent findings

The incidence of bacterial meningitis in Western countries (Finland, Netherlands, and the United States) gradually declined by 3–4% per year to 0.7–0.9 per 100 000 per year in the past 10–20 years. In African countries (Burkina Faso and Malawi), incidence rates are still substantially higher at 10–40 per 100 000 persons per year. Introduction of pneumococcal conjugate vaccines have not consistently decreased overall pneumococcal meningitis incidence because of serotype replacement. Following the introduction of serogroup A and C meningococcal vaccines, the incidence of meningococcal meningitis because of these serogroups strongly decreased. Novel outbreaks in the African meningitis belt by serogroup C and increased incidence of serogroup W in the United Kingdom and the Netherlands were observed recently.

Bacterial meningitis remains an important infectious disease, despite a gradual decline in incidence after large-scale vaccination campaigns. Further development of vaccines with broader coverage is important, as is continuous surveillance of bacterial meningitis cases.
Contemporary management of rectal injuries at Level I trauma centers: The results of an American Association for the Surgery of Trauma multi-institutional study
Authors: Brown Carlos V.R. , Teixeira Pedro G. , Furay Elisa , Sharpe John P. , Musonza Tashinga , Holcomb John , Bui Eric , Bruns Brandon , Hopper H. Andrew , Truitt Michael S. , Burlew Clay C. , Schellenberg Morgan , Sava Jack , VanHorn John , Eastridge PA-C, Brian , Cross Alicia M. , Vasak Richard , Vercruysse Gary , Curtis Eleanor E. , Haan James , Coimbra Raul , Bohan Phillip , Gale Stephen , Bendix Peter G.
Published: November 2017

INTRODUCTION

Rectal injuries have been historically treated with a combination of modalities including direct repair, resection, proximal diversion, presacral drainage, and distal rectal washout. We hypothesized that intraperitoneal rectal injuries may be selectively managed without diversion and the addition of distal rectal washout and presacral drainage in the management of extraperitoneal injuries are not beneficial.

METHODS

This is an American Association for the Surgery of Trauma multi-institutional retrospective study from 2004 to 2015 of all patients who sustained a traumatic rectal injury and were admitted to one of the 22 participating centers. Demographics, mechanism, location and grade of injury, and management of rectal injury were collected. The primary outcome was abdominal complications (abdominal abscess, pelvic abscess, and fascial dehiscence).

RESULTS

After exclusions, there were 785 patients in the cohort. Rectal injuries were intraperitoneal in 32%, extraperitoneal in 58%, both in 9%, and not documented in 1%. Rectal injury severity included the following grades I, 28%; II, 41%; III, 13%; IV, 12%; and V, 5%. Patients with intraperitoneal injury managed with a proximal diversion developed more abdominal complications (22% vs 10%, p = 0.003). Among patients with extraperitoneal injuries, there were more abdominal complications in patients who received proximal diversion (p = 0.0002), presacral drain (p = 0.004), or distal rectal washout (p = 0.002). After multivariate analysis, distal rectal washout [3.4 (1.4–8.5), p = 0.008] and presacral drain [2.6 (1.1–6.1), p = 0.02] were independent risk factors to develop abdominal complications.

CONCLUSION

Most patients with intraperitoneal injuries undergo direct repair or resection as well as diversion, although diversion is not associated with improved outcomes. While 20% of patients with extraperitoneal injuries still receive a presacral drain and/or distal rectal washout, these additional maneuvers are independently associated with a three-fold increase in abdominal complications and should not be included in the treatment of extraperitoneal rectal injuries.

LEVEL OF EVIDENCE

Therapeutic study, level III.
The changing role of endovascular stenting for blunt cerebrovascular injuries
Authors: Shahan Charles P. , Sharpe John P. , Stickley Shaun M. , Manley Nate R. , Filiberto Dina M. , Fabian Timothy C. , Croce Martin A. , Magnotti Louis J.
Published: November 2017

BACKGROUND

Few injuries have produced as much debate with respect to management as have blunt cerebrovascular injuries (BCVIs). Without question, early anticoagulation is the mainstay of therapy for these injuries. However, the role of endovascular stenting for BCVI remains controversial. Our purpose was to examine the use of endovascular stents for BCVI and outcomes and describe which injuries are being treated with stents.

METHODS

Patients with BCVI from 2011 to 2016 were identified and stratified by age, sex, and injury severity. Patients were then divided into two groups (previous study [PS] = 2011–2012 and current study [CS] = 2013–2016) based on a paradigm shift in BCVI diagnosis and treatment at our institution. Beginning in 2013, a multidisciplinary team assumed care of patients with BCVI from interventional radiology. Digital subtraction angiography was used to confirmatory injuries in both groups and heparin used for initial therapy.

RESULTS

In the CS, 237 patients were diagnosed with BCVI compared with 128 patients in the PS. Both groups were clinically similar with no difference in distribution of vessels injured. Beginning in 2013, there was a significant decrease in the use of stents for these injuries. In fact, in the CS, only 21 (8.9%) patients were treated with endovascular stenting compared to 44 (34%) patients in the PS. Of patients in the CS, 14 had grade III pseudoaneurysms and seven had grade II dissections. Despite this reduction in stenting, there was no significant change in the BCVI-related stroke rate between the CS and the PS (4.2% vs. 3.9%).

CONCLUSION

Anticoagulation alone is adequate therapy for the majority of BCVI. Nevertheless, there is still a role for endovascular stents in the treatment of BCVI. Their use should be reserved for enlarging carotid pseudoaneurysms and dissections with significant narrowing. The prospect of determining which injuries benefit from stent placement warrants prospective investigation.

LEVEL OF EVIDENCE

Therapuetic/care management, level IV.
Thermoregulatory role of insensible evaporative water loss constancy in a heterothermic marsupial
Authors: Cooper Christine Elizabeth , Withers Philip Carew
Published: November 2017

‘Insensible’ evaporative water loss of mammals has been traditionally viewed as a passive process, but recent studies suggest that insensible water loss is under regulatory control, although the physiological role of this control is unclear. We test the hypothesis that regulation of insensible water loss has a thermoregulatory function by quantifying for the first time evaporative water loss control, along with metabolic rate and body temperature, of a heterothermic mammal during normothermia and torpor. Evaporative water loss was independent of ambient relative humidity at ambient temperatures of 20 and 30°C, but not at 25°C or during torpor at 20°C. Evaporative water loss per water vapour pressure deficit had a positive linear relationship with relative humidity at ambient temperatures of 20 and 30°C, but not at 25°C or during torpor at 20 or 25°C. These findings suggest that insensible water loss deviates from a physical model only during thermoregulation, providing support for the hypothesis that regulation of insensible evaporative water loss has a thermoregulatory role.
Urbanism and the division of labour in the Roman Empire
Authors: Hanson J. W. , Ortman S. G. , Lobo J.
Published: November 2017

One of the hallmarks of human agglomeration is an increase in the division of labour, but the exact nature of this relationship has been debated among anthropologists, sociologists, economists, and historians and archaeologists. Over the last decade, researchers investigating contemporary urban systems have suggested a novel explanation for the links between the numbers of inhabitants in settlements and many of their most important characteristics, which is grounded in a view of settlements as social networks embedded in built environments. One of the remarkable aspects of this approach is that it is not based on the specific conditions of the modern world (such as capitalism or industrialization), which raises the issue of whether the relationships observed in contemporary urban systems can also be detected in pre-modern urban or even non-urban systems. Here, we present a general model for the relationship between the population and functional diversity of settlements, where the latter is viewed as an indicator of the division of labour. We then explore the applicability of this model to pre-modern contexts, focusing on cities in the Roman Empire, using estimates of their numbers of inhabitants, numbers of documented professional associations, and numbers of recorded inscriptions to develop an index of functional diversity. Our results are consistent with theoretical expectations, adding further support to the view that urban systems in both contemporary and pre-modern contexts reflect a common set of generative processes.
Modelling the effects of phylogeny and body size on within-host pathogen replication and immune response
Authors: Banerjee Soumya , Perelson Alan S. , Moses Melanie
Published: November 2017

Understanding how quickly pathogens replicate and how quickly the immune system responds is important for predicting the epidemic spread of emerging pathogens. Host body size, through its correlation with metabolic rates, is theoretically predicted to impact pathogen replication rates and immune system response rates. Here, we use mathematical models of viral time courses from multiple species of birds infected by a generalist pathogen (West Nile Virus; WNV) to test more thoroughly how disease progression and immune response depend on mass and host phylogeny. We use hierarchical Bayesian models coupled with nonlinear dynamical models of disease dynamics to incorporate the hierarchical nature of host phylogeny. Our analysis suggests an important role for both host phylogeny and species mass in determining factors important for viral spread such as the basic reproductive number, WNV production rate, peak viraemia in blood and competency of a host to infect mosquitoes. Our model is based on a principled analysis and gives a quantitative prediction for key epidemiological determinants and how they vary with species mass and phylogeny. This leads to new hypotheses about the mechanisms that cause certain taxonomic groups to have higher viraemia. For example, our models suggest that higher viral burst sizes cause corvids to have higher levels of viraemia and that the cellular rate of virus production is lower in larger species. We derive a metric of competency of a host to infect disease vectors and thereby sustain the disease between hosts. This suggests that smaller passerine species are highly competent at spreading the disease compared with larger non-passerine species. Our models lend mechanistic insight into why some species (smaller passerine species) are pathogen reservoirs and some (larger non-passerine species) are potentially dead-end hosts for WNV. Our techniques give insights into the role of body mass and host phylogeny in the spread of WNV and potentially other zoonotic diseases. The major contribution of this work is a computational framework for infectious disease modelling at the within-host level that leverages data from multiple species. This is likely to be of interest to modellers of infectious diseases that jump species barriers and infect multiple species. Our method can be used to computationally determine the competency of a host to infect mosquitoes that will sustain WNV and other zoonotic diseases. We find that smaller passerine species are more competent in spreading the disease than larger non-passerine species. This suggests the role of host phylogeny as an important determinant of within-host pathogen replication. Ultimately, we view our work as an important step in linking within-host viral dynamics models to between-host models that determine spread of infectious disease between different hosts.
Multi-scale tarsal adhesion kinematics of freely-walking dock beetles
Authors: Gernay Sophie Marie , Labousse Simon , Lambert Pierre , Compère Philippe , Gilet Tristan
Published: November 2017

In this experimental study, living dock beetles are observed during their free upside-down walk on a smooth horizontal substrate. Their weight is balanced by the adhesion of hairy structures present on their tarsomeres. The motions involved in the attachment and detachment of these structures were characterized by simultaneously imaging the beetle from the side at the body scale, and from the top at the scale of a single tarsal chain. The observed multi-scale three-dimensional kinematics of the tarsi is qualitatively described, then quantified by image processing and physically modelled. A strong asymmetry is systematically observed between attachment and detachment kinematics, in terms of both timing and directionality.
The unrealized potential of herbaria for global change biology
Authors: Meineke Emily K. , Davis Charles C. , Davies T. Jonathan
Published: November 2017

Plant and fungal specimens in herbaria are becoming primary resources for investigating how plant phenology and geographic distributions shift with climate change, greatly expanding inferences across spatial, temporal, and phylogenetic dimensions. However, these specimens contain a wealth of additional data—including nutrients, defensive compounds, herbivore damage, disease lesions, and signatures of physiological processes—that capture ecological and evolutionary responses to the Anthropocene but which are less frequently utilized. Here, we outline the diversity of herbarium data, global change topics to which they have been applied, and new hypotheses they could inform. We find that herbarium data have been used extensively to study impacts of climate change and invasive species, but that such data are less commonly used to address other drivers of biodiversity loss, including habitat conversion, pollution, and overexploitation. In addition, we note that fungal specimens are under-explored relative to vascular plants. To facilitate broader application of plant and fungal specimens in global change research, we outline the limitations of these data and modern sampling and statistical tools that may be applied to surmount challenges they present. Using a case study of insect herbivory, we illustrate how novel herbarium data may be employed to test hypotheses for which few data exist, despite potentially large biases. With the goal of positioning herbaria as hubs for global change research, we suggest future research directions and curation priorities.
Reduced cellular diversity and an altered basal progenitor cell state inform epithelial barrier dysfunction in human type 2 immunity
Authors: Ordovas-Montanes Jose , Dwyer Daniel F. , Nyquist Sarah K. , Buchheit Kathleen M. , Deb Chaarushena , Wadsworth Marc H. , Hughes Travis K. , Kazer Samuel W. , Yoshimoto Eri , Bhattacharyya Neil , Katz Howard R. , Laidlaw Tanya M. , Boyce Joshua A. , Barrett Nora A. , Shalek Alex K.
Published: November 2017

Tissue barrier dysfunction is a poorly defined feature hypothesized to drive chronic human inflammatory disease1,2. The epithelium of the upper respiratory tract represents one such barrier, responsible for separating inhaled agents, such as pathogens and allergens, from the underlying submucosa. Specialized epithelial subsets—including secretory, glandular, and ciliated cells—differentiate from basal progenitors to collectively realize this role3-5. Allergic inflammation in the upper airway barrier can develop from persistent activation of Type 2 immunity (T2I), resulting in the disease spectrum known as chronic rhinosinusitis (CRS), ranging from rhinitis to severe nasal polyps6-8. Whether recently identified epithelial progenitor subsets, and their differentiation trajectory, contribute to the clinical presentation and barrier dysfunction in T2I-mediated disease in humans remains unexplored3,9,10. Profiling twelve primary human samples spanning the range of clinical severity with the Seq-Well platform11 for massively-parallel single-cell RNA-sequencing (scRNA-seq), we report the first single-cell transcriptomes for human respiratory epithelial cell subsets, immune cells, and parenchymal cells (18,036 total cells) from a T2I inflammatory disease, and map key mediators. We find striking differences between non-polyp and polyp tissues within the epithelial compartments of human T2I cellular ecosystems. More specifically, across 10,383 epithelial cells, we identify a global reduction in epithelial diversity in polyps characterized by basal cell hyperplasia, a concomitant decrease in glandular and ciliated cells, and phenotypic shifts in secretory cell function. We validate these findings through flow cytometry, histology, and bulk tissue RNA-seq of an independent cohort. Furthermore, we detect an aberrant basal progenitor differentiation trajectory in polyps, and uncover cell-intrinsic and extrinsic factors that may lock polyp basal cells into an uncommitted state. Overall, our data define severe T2I barrier dysfunction as a reduction in epithelial diversity, characterized by profound functional shifts stemming from basal cell defects, and nominate a cellular mechanism for the persistence and chronicity of severe human respiratory disease.
What drives results in Bayesian morphological clock analyses?
Authors: Parins-Fukuchi Caroline , Brown Joseph W.
Published: November 2017

Recently, approaches that estimate species divergence times using fossil taxa and models of morphological evolution have exploded in popularity. These methods incorporate diverse biological and geological information to inform posterior reconstructions, and have been applied to several high-profile clades to positive effect. However, there are important examples where morphological data are misleading, resulting in unrealistic age estimates. While several studies have demonstrated that these approaches can be robust and internally consistent, the causes and limitations of these patterns remain unclear. In this study, we dissect signal in Bayesian dating analyses of three mammalian clades. For two of the three examples, we find that morphological characters provide little information regarding divergence times as compared to geological range information, with posterior estimates largely recapitulating those recovered under the prior. However, in the cetacean dataset, we find that morphological data do appreciably inform posterior divergence time estimates. We supplement these empirical analyses with a set of simulations designed to explore the efficiency and limitations of binary and 3-state character data in reconstructing node ages. Our results demonstrate areas of both strength and weakness for morphological clock analyses, and help to outline conditions under which they perform best and, conversely, when they should be eschewed in favour of purely geological approaches.
Beyond pseudotime: Following T-cell maturation in single-cell RNAseq time series
Authors: Fischer David S. , Fiedler Anna K. , Kernfeld Eric , Genga Ryan M. J. , Hasenauer Jan , Maehr Rene , Theis Fabian J.
Published: November 2017

Cellular development has traditionally been described as a series of transitions between discrete cell states, such as the sequence of double negative, double positive and single positive stages in T-cell development. Recent advances in single cell transcriptomics suggest an alternative description of development, in which cells follow continuous transcriptomic trajectories. A cell’s state along such a trajectory can be captured with pseudotemporal ordering, which however is not able to predict development of the system in real time. We present pseudodynamics, a mathematical framework that integrates time-series and genetic knock-out information with such transcriptome-based descriptions in order to describe and analyze the real-time evolution of the system. Pseudodynamics models the distribution of a cell population across a continuous cell state coordinate over time based on a stochastic differential equation along developmental trajectories and random switching between trajectories in branching regions. To illustrate feasibility, we use pseudodynamics to estimate cell-state-dependent growth and differentiation of thymic T-cell development. The model approximates a developmental potential function (Waddington’s landscape) and suggests that thymic T-cell development is biphasic and not strictly deterministic before beta-selection. Pseudodynamics generalizes classical discrete population models to continuous states and thus opens possibilities such as probabilistic model selection to single cell genomics.
Peak gamma frequency and cortical laminar processing are modified across the healthy menstrual cycle
Authors: Sumner R.L. , McMilllan R.L. , Shaw A. D. , Singh K.D. , Sundram F. , Muthukumaraswamy S.D.
Published: November 2017

Fluctuations in gonadal hormones over the course of the menstrual cycle are known to cause functional brain changes and are thought to modulate changes in the balance of cortical excitation and inhibition. Animal research has shown this occurs primarily via the major metabolite of progesterone, allopregnanolone, and its action as a positive allosteric modulator of the GABAA receptor. Our study used EEG to record gamma oscillations induced in the visual cortex using stationary and moving gratings. Recordings took place during twenty females’ mid-luteal phase when progesterone and oestradiol are highest, and early follicular phase when progesterone and oestradiol are lowest. Significantly higher (~5 Hz) gamma frequency was recorded during the luteal compared to the follicular phase for both stimuli types. Using dynamic causal modelling these changes were linked to stronger self-inhibition of superficial pyramidal cells in the luteal compared to the follicular phase. In addition the connection from inhibitory interneurons to deep pyramidal cells was found to be stronger in the follicular compared to the luteal phase. These findings show that complex functional changes in synaptic microcircuitry occur across the menstrual cycle and that menstrual cycle phase should be taken into consideration when including female participants in research into gamma-band oscillations.
Ultra-rare variants drive substantialcis-heritability of human gene expression
Authors: Hernandez Ryan D. , Uricchio Lawrence H. , Hartman Kevin , Ye Chun , Dahl Andrew , Zaitlen Noah
Published: November 2017

The vast majority of human mutations have minor allele frequencies (MAF) under 1%, with the plurality observed only once (i.e., “singletons”). While Mendelian diseases are predominantly caused by rare alleles, their cumulative contribution to complex phenotypes remains largely unknown. We develop and rigorously validate an approach to jointly estimate the contribution of all alleles, including singletons, to phenotypic variation. We apply our approach to transcriptional regulation, an intermediate between genetic variation and complex disease. Using whole genome DNA and lymphoblastoid cell line RNA sequencing data from 360 European individuals, we conservatively estimate that singletons contribute ~25% ofcis-heritability across genes (dwarfing the contributions of other frequencies). Strikingly, the majority (~76%) of singleton heritability derives from ultra-rare variants absent from thousands of additional samples. We develop a novel inference procedure to demonstrate that our results are consistent with rampant purifying selection shaping the regulatory architecture of most human genes.
Large protein complex production using the SmartBac System - Strategies and Applications
Authors: Zhai Yujia , Zhang Danyang , Yu Leiye , Sun Fang , Sun Fei
Published: November 2017

Recent revolution of cryo-electron microscopy has opened a new door to solve high-resolution structures of macromolecule complexes without crystallization while how to efficiently obtain homogenous macromolecule complex sample is therefore becoming a bottleneck. Here we report SmartBac, an easy and versatile system for constructing large-sized transfer plasmids used to generate recombinant baculoviruses that express large multiprotein complexes in insect cells. The SmartBac system integrates the univector plasmid-fusion system, Gibson assembly method and polyprotein strategy to construct the final transfer plasmids. The fluorescent proteins are designed to be co-expressed with recombinant proteins to monitor transfection and expression efficiencies. A scheme of screening an optimal tagged subunit for effective purification is provided. Six large multiprotein complexes including the human exocyst complex and dynactin complex were successfully expressed, suggesting a great potential of SmartBac for its wide application in the future structural biology study.
Species abundance plays a dominant role in local and regional extinctions in freshwater communities and allows the identification of selective extinctions
Authors: Almeida Ryan J. , Biro Elizabeth G. , Woods Lauren M. , Smith Kevin G.
Published: November 2017

Recent declines in global biodiversity emphasize that understanding the factors that determine extinction risk should be a priority for ecologists and conservation biologists. A key question is whether extinctions are nonrandom and selective, in which case knowledge of selectivity may help predict and prevent future extinction. We suggest, however, that a premature focus on the identification of selective, trait-based determinants of extinctions risk is problematic if the potential importance of stochastic extinction processes are not first considered. Within this context we aimed to determine the roles that stochastic extinction and species abundance play in extinction risk by applying a rarefaction-based null model approach to analyzing biodiversity declines and extinctions in an experimental system. We focused on aquatic macroinvertebrate declines and extinction caused by predation by fish (Lepomis cyanellus) in semi-natural freshwater mesocosms. We found that null-predicted local extirpations based on the random loss of individuals were a significant predictor of observed local extirpations, and that the majority of observed extinctions were consistent with stochastic mechanisms of extinction, as predicted by a rarefaction model. We were able to identify a number of selective extinctions that were not predicted by the rarefaction model, and while these were relatively rare, they contributed to greater-than-expected loss of diversity at both local (mesocosm) and regional (whole experiment) spatial scales. Our results confirm that species abundance and occupancy are among the most important factors in identifying extinction risk in response to a disturbance. Moreover, owing to our use of a stochastic null model, we also conclude that measures of abundance are important indicators of extinction probability because they are operated on by the random loss of individuals, suggesting that stochastic extinction is an important process in this system and in biodiversity loss in general.
Transcriptional integration of mitogenic and mechanical signals by Myc and YAP
Authors: Croci Ottavio , De Fazio Serena , Biagioni Francesca , Donato Elisa , Caganova Marieta , Curti Laura , Doni Mirko , Sberna Silvia , Aldeghi Deborah , Biancotto Chiara , Verrecchia Alessandro , Olivero Daniela , Amati Bruno , Campaner Stefano
Published: November 2017

Mammalian cells must integrate environmental cues to determine coherent physiological responses. The transcription factors Myc and YAP–TEAD act downstream from mitogenic signals, with the latter responding also to mechanical cues. Here, we show that these factors coordinately regulate genes required for cell proliferation. Activation of Myc led to extensive association with its genomic targets, most of which were prebound by TEAD. At these loci, recruitment of YAP was Myc-dependent and led to full transcriptional activation. This cooperation was critical for cell cycle entry, organ growth, and tumorigenesis. Thus, Myc and YAP–TEAD integrate mitogenic and mechanical cues at the transcriptional level to provide multifactorial control of cell proliferation.
Rapid molecular assays to study human centromere genomics
Authors: Contreras-Galindo Rafael , Fischer Sabrina , Saha Anjan K. , Lundy John D. , Cervantes Patrick W. , Mourad Mohamad , Wang Claire , Qian Brian , Dai Manhong , Meng Fan , Chinnaiyan Arul , Omenn Gilbert S. , Kaplan Mark H. , Markovitz David M.
Published: November 2017

The centromere is the structural unit responsible for the faithful segregation of chromosomes. Although regulation of centromeric function by epigenetic factors has been well-studied, the contributions of the underlying DNA sequences have been much less well defined, and existing methodologies for studying centromere genomics in biology are laborious. We have identified specific markers in the centromere of 23 of the 24 human chromosomes that allow for rapid PCR assays capable of capturing the genomic landscape of human centromeres at a given time. Use of this genetic strategy can also delineate which specific centromere arrays in each chromosome drive the recruitment of epigenetic modulators. We further show that, surprisingly, loss and rearrangement of DNA in centromere 21 is associated with trisomy 21. This new approach can thus be used to rapidly take a snapshot of the genetics and epigenetics of each specific human centromere in nondisjunction disorders and other biological settings.
Chromatin accessibility dynamics reveal novel functional enhancers in C. elegans
Authors: Daugherty Aaron C. , Yeo Robin W. , Buenrostro Jason D. , Greenleaf William J. , Kundaje Anshul , Brunet Anne
Published: November 2017

Chromatin accessibility, a crucial component of genome regulation, has primarily been studied in homogeneous and simple systems, such as isolated cell populations or early-development models. Whether chromatin accessibility can be assessed in complex, dynamic systems in vivo with high sensitivity remains largely unexplored. In this study, we use ATAC-seq to identify chromatin accessibility changes in a whole animal, the model organism Caenorhabditis elegans, from embryogenesis to adulthood. Chromatin accessibility changes between developmental stages are highly reproducible, recapitulate histone modification changes, and reveal key regulatory aspects of the epigenomic landscape throughout organismal development. We find that over 5000 distal noncoding regions exhibit dynamic changes in chromatin accessibility between developmental stages and could thereby represent putative enhancers. When tested in vivo, several of these putative enhancers indeed drive novel cell-type- and temporal-specific patterns of expression. Finally, by integrating transcription factor binding motifs in a machine learning framework, we identify EOR-1 as a unique transcription factor that may regulate chromatin dynamics during development. Our study provides a unique resource for C. elegans, a system in which the prevalence and importance of enhancers remains poorly characterized, and demonstrates the power of using whole organism chromatin accessibility to identify novel regulatory regions in complex systems.
Sleep increases explicit solutions and reduces intuitive judgments of semantic coherence
Authors: Zander Thea , Volz Kirsten G. , Born Jan , Diekelmann Susanne
Published: November 2017

Sleep fosters the generation of explicit knowledge. Whether sleep also benefits implicit intuitive decisions about underlying patterns is unclear. We examined sleep's role in explicit and intuitive semantic coherence judgments. Participants encoded sets of three words and after a sleep or wake period were required to judge the potential convergence of these words on a common fourth associate. Compared with wakefulness, sleep increased the number of explicitly named common associates and decreased the number of intuitive judgments. This suggests that sleep enhances the extraction of explicit knowledge at the expense of the ability to make intuitive decisions about semantic coherence.
Effects of regulatory BC1 RNA deletion on synaptic plasticity, learning, and memory
Authors: Chung Ain , Dahan Nessy , Alarcon Juan Marcos , Fenton André A.
Published: November 2017

Nonprotein coding dendritic BC1 RNA regulates translation of mRNAs in neurons. We examined two lines of BC1 knockout mice and report that loss of BC1 RNA exaggerates group I mGluR-stimulated LTD of the Schaffer collateral synapse, with one of the lines showing a much more enhanced DHPG-induced LTD than the other. When the animals were given the hippocampus-synaptic plasticity-dependent active place avoidance task, learning and memory were impaired in the BC1-KO line with the more severely altered DHPG-induced LTD. These findings indicate a role for BC1 RNA control of mGluR-dependent synaptic function in hippocampus and associated cognitive ability.
The serine protease inhibitor neuroserpin is required for normal synaptic plasticity and regulates learning and social behavior
Authors: Reumann Rebecca , Vierk Ricardo , Zhou Lepu , Gries Frederice , Kraus Vanessa , Mienert Julia , Romswinkel Eva , Morellini Fabio , Ferrer Isidre , Nicolini Chiara , Fahnestock Margaret , Rune Gabriele , Glatzel Markus , Galliciotti Giovanna
Published: November 2017

The serine protease inhibitor neuroserpin regulates the activity of tissue-type plasminogen activator (tPA) in the nervous system. Neuroserpin expression is particularly prominent at late stages of neuronal development in most regions of the central nervous system (CNS), whereas it is restricted to regions related to learning and memory in the adult brain. The physiological expression pattern of neuroserpin, its high degree of colocalization with tPA within the CNS, together with its dysregulation in neuropsychiatric disorders, suggest a role in formation and refinement of synapses. In fact, studies in cell culture and mice point to a role for neuroserpin in dendritic branching, spine morphology, and modulation of behavior. In this study, we investigated the physiological role of neuroserpin in the regulation of synaptic density, synaptic plasticity, and behavior in neuroserpin-deficient mice. In the absence of neuroserpin, mice show a significant decrease in spine-synapse density in the CA1 region of the hippocampus, while expression of the key postsynaptic scaffold protein PSD-95 is increased in this region. Neuroserpin-deficient mice show decreased synaptic potentiation, as indicated by reduced long-term potentiation (LTP), whereas presynaptic paired-pulse facilitation (PPF) is unaffected. Consistent with altered synaptic plasticity, neuroserpin-deficient mice exhibit cognitive and sociability deficits in behavioral assays. However, although synaptic dysfunction is implicated in neuropsychiatric disorders, we do not detect alterations in expression of neuroserpin in fusiform gyrus of autism patients or in dorsolateral prefrontal cortex of schizophrenia patients. Our results identify neuroserpin as a modulator of synaptic plasticity, and point to a role for neuroserpin in learning and memory.
Exports-performance relationship in Russian manufacturing companies
Authors: Bykova Anna , Lopez-Iturriaga Felix
Published: November 2017

Purpose

The purpose of this paper is to examine the relationship between export activity and firm performance for a positive impact of foreign direct investments (FDIs). The authors also analyze two possible causes of the effect: technology transfer and financial support. The theoretical background is rooted in the resource-based approach taking into account multinational companies’ perspective and the specifics of emerging markets.

Design/methodology/approach

The authors propose testable hypotheses based on a review of the theory. To test the hypotheses, the authors build a sample of over 500 Russian public manufacturing firms covering the period from 2004 to 2014 and estimate regression models. Given concerns about endogeneity, the instrumental variable approach for panel data, using the GMM-estimator, is implemented.

Findings

Consistent with the view that FDIs generate spillover effects, the results support the positive impact of foreign ownership on the link between exports and firms’ performance. The results underline the importance of foreign ownership: shareholders from developed countries can provide benefits to exporting companies through transferring advanced technologies and loosening financial constraints by lowering interest and raising availability of bank loans.

Originality/value

The authors provide new insights on the relationship between exports and firm performance. Given our focus on Russia, a market with high potential to draw foreign investments, the research sheds some light on how emerging country firms can benefit from having foreign shareholders with paying attention to geographical distribution of such investments. Specifically, through the overcoming of technological barriers and loosening of financial constraints, the authors show empirically that foreign capital can make up for weak local institutional infrastructure and enhance the company’s returns from internationalization.
Prediction and improvement of labor productivity using hybrid system dynamics and agent-based modeling approach
Authors: Khanzadi Mostafa , Nasirzadeh Farnad , Mir Mostafa , Nojedehi Pouya
Published: November 2017

Purpose

The purpose of this paper is to present a hybrid simulation approach for predicting the value of labor productivity taking account of various continuous influencing factors and the interactions between different agents involved in the project.

Design/methodology/approach

The various continuous factors affecting labor productivity are simulated using system dynamics (SD). The heterogeneity of different agents involved in the project and their interactions is accounted using agent-based modelling (ABM). The developed ABM and SD models are finally integrated to simulate the value of labor productivity taking account of all the influencing factors.

Findings

The proposed hybrid simulation tool is implemented in a real project to evaluate its perfomance. The value of labor productivity is simulated by taking account of all the influencing factors. The most appropriate execution strategy is then selected using the developed hybrid SD-ABM approach to improve productivity. It is shown that the number of working groups and their movement patterns affect the severity of the groups’ interferences which will in turn affect the value of labor productivity.

Practical implications

This research helps project managers to predict and improve the value of labor productivity taking account of all the influencing factors.

Originality/value

It is believed that the proposed hybrid SD-ABM simulation approach offers a novel and robust tool for modeling labor productivity because the effects of various continuous influencing factors and the interactions between different agents are taken into account through the combination of SD and ABM. Many complex problems faced in construction projects involve interacting elements of a different nature, and the integration of SD with ideas from ABM offers potential to combine the strengths of the two methodologies to solve the problem.
Design thinking: breaking fixation for new relationships between organizations
Authors: Lewis Mark , Hayward Scott , Hornyak Rob
Published: November 2017

Purpose

The purpose of this paper is to show how design thinking can be a useful approach for helping interorganizational partnerships create higher levels of value creation for both parties. By integrating concepts related to human cognition, contracts and performance, the authors show how interorganizational relationships often hit a brick wall. The authors show how they can break through such obstacles in a systematic way using design thinking.

Design/methodology/approach

The authors anchor their conceptual and prescriptive advice in a real-life case study between a large logistics company and a global technology firm. The case study was conducted over a multiyear period with many sources of data collected: interview data, observational, participant observation, archival presentations, etc.

Findings

The authors show the factors that lead to rigidity in interorganizational relationships over time, and the cycle of confirmation and exploitation that truly squeezes the life out of relationships if firms are not careful. They offer a prescriptive approach for addressing this issue that should be valuable for many firms across the globe.

Research limitations/implications

The study is based on a single-case study, so generalizability is always an issue. However, we think that most practicing managers who have been involved (in any way) with managing an interorganizational relationship will attest to the fact that they often experience the patterns that the authors illuminate in their study.

Practical implications

By applying the design thinking methodology within the context of interorganizational relationships, managers will help their firms break fixation and enter entirely new plateaus of value creation for both firms.

Social implications

The world of work occurs through partnerships and relationships, companies rarely “go it alone”. Thus, developing the capacities in managers to continuously assess relationship efficacy, break from inertia and discover new ways of creating value will lead to positive social implications. Additionally, the design thinking methodology is based on developing empathy for others, and the authors would argue that such capabilities are sorely needed in this world.

Originality/value

There is a lot of work on interorganizational partnerships, but an absence of help for practicing managers on how to make such relationships great. Grounded in a real-life case study, this paper provides practical contributions to those currently managing such relationships.
Correcting the Count: Improving Vital Statistics Data Regarding Deaths Related to Obesity
Authors: McCleskey Brandi C. , Davis Gregory G. , Dye Daniel W.
Published: November 2017

Obesity can involve any organ system and compromise the overall health of an individual, including premature death. Despite the increased risk of death associated with being obese, obesity itself is infrequently indicated on the death certificate. We performed an audit of our records to identify how often “obesity” was listed on the death certificate to determine how our practices affected national mortality data collection regarding obesity‐related mortality. During the span of nearly 25 years, 0.2% of deaths were attributed to or contributed by obesity. Over the course of 5 years, 96% of selected natural deaths were likely underreported as being associated with obesity. We present an algorithm for certifiers to use to determine whether obesity should be listed on the death certificate and guidelines for certifying cases in which this is appropriate. Use of this algorithm will improve vital statistics concerning the role of obesity in causing or contributing to death.