bluuebunny/crossref_metadata_2025 huggingface dataset:
Images
Authors: Holt Robin
Published: January 2018

This chapter considers strategy as an aesthetic as much as a social and economic design of organizational form. It brings into question the nature and use of images to convey and embody strategic vision, notably in questioning the aspiration of those for whom strategy is to institute conforming patterns of thinking and behavior within an organization. Illustrations to the argument come from the planned redevelopment of the city of Paris, first from Haussmann and then Le Corbusier.
Authority
Authors: Holt Robin
Published: January 2018

In light of the discussion of leadership and the idea of a public, this chapter considers what it is to be in a position of strategic authority constituted by unhomely spectating and hence judgment. Illustrations come from Sophocles’ Antigone and Creon.
The Judge
Authors: Holt Robin
Published: January 2018

The judge is the singular source of authority, the figure in whose action judgment is embodied. Using Georges Rouault’s painting, The Judges, this chapter discusses the relationship between law, spectating, and feeling. Taking up a refrain from Walt Whitman, a poetic form of judging is argued for. Poetic judgment brings about a world framed by the creation of forms by which we can educate ourselves in the collective business of living. Strategy, understood as the presentation of an organization to itself and others, becomes a judgmental condition of bringing together general sensibility and particular experience to re-frame the places in which we live and work. This chapter introduces a reversal of visionary forms of strategy. With poetic judgment, strategy becomes an aesthetic process of creating organizational forms and we become increasingly and collectively aware of the vulnerable ordinary and its panoply of elusive and sometimes strange occurrences.
Introduction
Authors: Ruban Anatoly I.
Published: January 2018

This book investigates high-Reynolds number flows, and analyses flows that can be described in the framework of Prandtl’s 1904 classical boundary-layer theory, including Blasius’s boundary layer on a flat plate, Falkner–Skan solutions for the boundary layer on a wedge surface, and other applications of Prandtl’s theory. It then discusses separated flows, and considers the so-called ‘self-induced separation’ in supersonic flow, and which led to the ‘triple-deck model’. It also presents Sychev’s 1972 theory of the boundary-layer separation in an incompressible fluid flow past a circular cylinder. It discusses the triple-deck flow near the trailing edge of a flat plate, and then considers the incipience of the separation at corner points of the body surface in subsonic and supersonic flows. It covers the Marginal Separation theory—a special version of the triple-deck theory—and describes the formation and bursting of short separation bubbles at the leading edge of a thin aerofoil.
Boundary-Layer Separation
Authors: Ruban Anatoly I.
Published: January 2018

Chapter 2 discusses the experimental observations of the boundary-layer separation in subsonic and supersonic flows that lead to a formulation of the concept of viscous-inviscid interaction. It then turns to the so-called ‘self-induced separation’ of the boundary layer in supersonic flows. This theory is formulated based on the asymptotic analysis of the Navier–Stokes equations at large values of the Reynolds number. As a part of the flow analysis, this chapter also introduces the ‘triple-deck model’. It then shows how this model may be used to describe the classical problem of the boundary-layer separation in an incompressible fluid flow past a circular cylinder.
Neuroscience, Psychology, Reduction, and Functional Analysis
Authors: Roth Martin , Cummins Robert
Published: January 2018

The pressure for reduction in science is an artifact of what we call the nomic conception of science (NCS): the idea that the content of science is a collection of laws, together with the deductive-nomological model of explanation. NCS in effect identifies explanation with reduction, thus making no room for the explanatory autonomy of function-analytical explanations. When we replace NCS with something more descriptively accurate, however, we find that the kind of explanatory autonomy of functional-analytic explanations is ubiquitous in the sciences. Key to showing this is a distinction between horizontal and vertical explanation. Horizontal explanations explain the capacities of a complex system by appeal to the design of the system. Vertical explanations, by contrast, explain how a design is implemented in a system. We argue that the distinction between horizontal and vertical explanations provides us with a better picture of the relationship between functional analysis and mechanistic explanation.
Brains and Beliefs
Authors: Murphy Dominic
Published: January 2018

I suggest there are three ways to see the role of folk psychology in a mature cognitive neuroscience. First, integration says that folk psychology plays a decisive role in defining the objects of scientific inquiry and guiding that inquiry. Second, autonomy is the view that folk psychology deals in personal rather than subpersonal explanations and as such has aims that are incompatible with science. Third is eliminativism, which argues that folk psychology will be replaced by a scientific theory of the mind. I argue that the integrationist perspective is an unstable position because folk psychology cannot play the role that integrationists have in mind for it. Any psychology that plays this role must be heavily revised enough to count as a successor theory, and that is a vindication of eliminativism from the point of view of scientific theory-construction.
Hand Edema in Patients at Risk of Breast Cancer–Related Lymphedema: Health Professionals Should Take Notice
Authors: Brunelle Cheryl L , Swaroop Meyha N , Skolny Melissa N , Asdourian Maria S , Sayegh Hoda E , Taghian Alphonse G
Published: January 2018

Background

There is little research on hand edema in the population at risk for breast cancer–related lymphedema (BCRL).

Objectives

Study aims included reporting potential importance of hand edema (HE) as a risk factor for progression of edema in patients treated for breast cancer at risk for BCRL, reporting risk factors for BCRL, and reporting treatment of HE.

Design/Methods

This was a retrospective analysis of 9 patients treated for breast cancer in Massachusetts General Hospital's lymphedema screening program who presented with isolated HE. Limb volumes via perometry, BCRL risk factors, and HE treatment are reported.

Results

Edema was mostly isolated to the hand. Three patients had arm edema >5% on perometry; and 2 of these had edema outside the hand on clinical examination. Patients were at high risk of BCRL with an average of 2.9/5 known risk factors. Arm edema progressed to >10% in 2 high-risk patients. Treatment resulted in an average hand volume reduction of 10.2% via perometry and improvement upon clinical examination.

Limitations

The small sample size and lack of validated measures of subjective data were limitations.

Conclusions

In this cohort, patients with HE carried significant risk factors for BCRL. Two out of 9 (22%), both carrying ≥4/5 risk factors, progressed to edema >10%. Isolated HE may be a prognostic factor for edema progression in patients treated for breast cancer at risk for BCRL. Further research is warranted.
What distinguishes tenascin from fibronectin?
Authors: Chiquet‐Ehrismann Ruth
Published: January 2018

Tenascin and fibronectin are two major extracellular matrix glycoproteins. They both consist of large disulfide‐linked subunits composed of multiple structural domains. More than half of each molecule consists of so‐called fibronectin type III repeats, but the other domains differ. Fibronectin is a dimer, whereas tenascin is a hexamer. Often fibronectin and tenascin are colocalized in tissues, but the occurrence of tenascin is much more restricted when compared with fibronectin. Tenascin is transiently expressed in many developing organs such as connective tissues, the mesenchyme of epithelial organs, and also the central and peripheral nervous systems, and it reappears in the stroma of many tumors. The distinctive and highly regulated expression of tenascin has provoked interest in trying to identify possible functions of tenascin in cell‐cell and cell‐substratum adhesion, cell migration, growth, and cell differentiation during morphogenesis.—Chiquet‐Ehrismann, R. What distinguishes tenascin from fibronectin? FASEB J. 4: 2598‐2604; 1990.
Recombinant gene expression in pulmonary vascular endothelial cells: polarized secretion in vivo
Authors: Bernstein Shelly C. , Skoskiewicz Marek J. , Jones Rosemary , Zapol Warren M. , Russell Paul S.
Published: January 2018

A unique, spontaneously immortalized rat pulmonary endothelial cell line was transfected with a human growth hormone (hGH) fusion gene generating a line of stably transfected cells that expresses high levels of hGH (Ec/XGH‐1). These cells produced significant serum levels of hGH when implanted intraperitoneally, subcutaneously, or intravenously into nude mice. Implantation of Ec/XGH‐1 cells under the renal capsule resulted in the formation of large cysts that contained concentrations of hGH that were several thousand times greater than those in serum assayed simultaneously from the same animals. This study presents a new technique for in vivo gene expression using a convenient line of pulmonary vascular endothelial cells as gene carriers. In addition, this system demonstrates the special physiological features of transfected endothelial cells in forming large cysts.— Bernstein, S. C.; Skoskiewicz, M. J.; Jones, R.; Zapol, W. M.; Russell, P. S. Recombinant gene expression in pulmonary vascular endothelial cells: polarized secretion in vivo. FASEB J. 4: 2665‐2670; 1990.
Binding of a mouse monoclonal IgE (anti‐DNP) antibody to radio‐derivatized polystyrene‐DNP complexes
Authors: Varga Janos M. , Klein Georg F. , Fritsch Peter
Published: January 2018

Polystyrene (PS) labware products (microtiter plates, test tubes, etc.) show radiation (gamma) dose‐dependent carbodiimide (EDC)‐mediated uptake of carboxyl‐containing molecules such as DNP‐[3H]Gly. The presence of water during irradiation increases, and oxygen decreases the coupling capacity of irradiated PS. The EDC‐mediated attachment of DNP‐Gly to PS is stable because it resists prolonged exposure to acids at low or high salt concentrations; the bond is sensitive to bases and oxidizing agents. Commercially available radiation‐sterilized PS labware products also show elevated EDC‐mediated uptake of DNP‐[3H]Gly. Nonirradiated PS products or non‐PS materials in these studies were inactive. Commercially irradiated PS microtiter plates were coated with DNP‐amino acids in an EDC‐mediated reaction, and the binding of a radiolabeled mouse monoclonal IgE (aDNP) to DNP‐coated plates was studied. 1) The minimal ligand (DNP‐Gly) and reagent (EDC) concentrations for plate coating to reach saturating antibody binding were found to be 0.2 mM and 0.2 mg/ml, respectively. High coating densities were suboptimal for antibody binding; 2) five to 60 min of coupling times yielded optimal coating densities; 3) The binding of antibody to DNP‐Gly‐coated plates reached half‐maximal levels in approximately 40 min; 4) Dissociation of antibody from DNP‐Gly and DNP‐Ser‐coated plates was very slow. Intra‐ and interassay coefficients of variation of antibody binding to plates coated with DNP‐Gly under optimal conditions were generally below 3%. We conclude that the PS‐bound DNP produced by this method is recognizable by anti‐DNP antibodies. The optical quality of PS is not affected by radio‐derivatization, and the ligand‐coated plates obtained by these methods are suitable for colorimetric assays. All brands of heavily irradiated PS examined were suitable carriers for EDC‐mediated coupling of DNP‐aminoacids.—Varga, J. M.; Klein, G. F.; Fritsch, P. Binding of a mouse monoclonal IgE (anti DNP) antibody to radio‐derivatized polystyrene‐DNP complexes. FASEB J. 4: 2678‐2683, 1990.
A Mixed-Methods Approach to Humanistic Interprofessional Faculty Development
Authors: Fornari Alice , Tortez Leanne M. , Lay Monika , Hirsch Bruce , Tanzi Donna , Friedman Isabel , Ricardo Alison P. , Pekmezaris Renee , Branch William
Published: January 2018

Introduction:

This study evaluated the effectiveness of the Mentoring and Professionalism in Training (MAP-IT) program, a longitudinal, interprofessional faculty development curriculum designed to enhance clinicians' humanistic mentoring skills, specifically nurses and physicians.

Methods:

During 2014 to 2016, two consecutive cohorts of nurses and physicians completed the MAP-IT program. Participants included 169 high potential mentors (HPMs) and 61 facilitator leaders. Each 10-month program consisted of small group work, experiential learning, and critical reflection aimed at enhancing humanistic mentoring skills. Throughout the program, facilitator leaders served as mentors for the HPMs. Both quantitative and qualitative data were collected to measure changes in skill levels specific to humanistic teaching practices, as well as overall evaluation of the program's curriculum and logistics. Quantitative data were analyzed using the Wilcoxon signed-rank test, descriptive statistics, and Fisher exact test, as appropriate. Qualitative data assessing the overall impact and applicability of the program to the clinical setting were analyzed using content analysis methodology.

Results:

Across cohorts, HPMs demonstrated significant increases in perceptions of humanistic teaching skills. During objective structured teaching simulations, significant increases were also found in HPMs' self-reported mentoring skills and their skills as rated by a standardized RN/MD. Qualitative analyses revealed themes of the program to be skill development and application, mentorship, humanism, mindfulness, self-care, and acknowledgment of overlapping interprofessional roles.

Discussion:

Utilizing an interprofessional education approach, the MAP-IT program was determined to be a feasible strategy to positively impact the personal and professional development of nurses and physicians.
Reducing Disparities in Severe Maternal Morbidity and Mortality
Authors: HOWELL ELIZABETH A.
Published: January 2018

Significant racial and ethnic disparities in maternal morbidity and mortality exist in the United States. Black women are 3 to 4 times more likely to die a pregnancy-related death as compared with white women. Growing research indicates that quality of health care, from preconception through postpartum care, may be a critical lever for improving outcomes for racial and ethnic minority women. This article reviews racial and ethnic disparities in severe maternal morbidities and mortality, underlying drivers of these disparities, and potential levers to reduce their occurrence.
Treatment of Postpartum Depression: Recommendations for the Clinician
Authors: O’HARA MICHAEL W. , ENGELDINGER JANE
Published: January 2018

Postpartum depression is a significant public health problem affecting almost 600,000 US women every year. It may arise de novo in the postpartum period or continue from pregnancy. A number of evidence-based psychotherapies and medical treatments exist for major depression and postpartum depression. The obstetrical team has many opportunities to identify high risk and depressed women and refer them to mental health professionals or begin treatment with antidepressant medication. Careful assessment of risk factors for postpartum depression during pregnancy and monitoring depressive symptoms during pregnancy and the postpartum period will lead to better outcomes for women and their families.
Sphenoid Dysplasia: A Rare Presentation of Infantile Myofibroma
Authors: Kini Ashwini , Syed Reema , Compton Christopher , Hata Jessica L. , Ramasubramanian Aparna
Published: January 2018

The authors report a case of isolated congenital orbital myofibroma causing sphenoid dysplasia and presenting as global restriction of extraocular motility and ptosis in a neonate. Sphenoid wing dysplasia is most commonly associated neurofibromatosis 1 but this patient had no evidence of neurofibromatosis on clinical examination and genetic testing. Congenital orbital myofibroma can have secondary effects on bone and likely the lesion was present early in development leading to aplasia of the sphenoid bone. To the best of the authors’ knowledge, this is the first reported case of sphenoid wing aplasia secondary to congenital orbital myofibroma independent of neurofibromatosis 1.
Predictors of Health-related Quality of Life in Irritable Bowel Syndrome Patients Compared With Healthy Individuals
Authors: Addante Raymond , Naliboff Bruce , Shih Wendy , Presson Angela P. , Tillisch Kirsten , Mayer Emeran A. , Chang Lin
Published: January 2018

Background:

Irritable bowel syndrome (IBS) reduces health-related quality of life (HRQOL). It is unclear how having IBS modifies the impact of gastrointestinal (GI), psychosocial, and somatic symptom variables on HRQOL compared with healthy controls (HCs).

Aims:

(1) Determine psychosocial, somatic, and physical status variables most predictive of HRQOL in IBS and HCs and (2) determine if IBS status modifies relationships between predictive factors and HRQOL.

Methods:

IBS patients and HCs completed validated questionnaires measuring GI symptoms, psychosocial/somatic variables, and physical [physical component score (PCS)] and mental [mental component score (MCS)] HRQOL via the Short-Form-36. Associations between these variables and HRQOL were evaluated with multiple linear regressions. Variables were standardized to determine the strongest predictors of HRQOL. Statistical significance level was 0.01.

Results:

Mean HRQOL was higher in 417 HCs versus 290 IBS subjects (PCS: 55.6 vs. 48.6, P<0.001; MCS: 53.7 vs. 44.8, P<0.001). The GI symptom measures were negatively associated with PCS in IBS, but only usual severity was associated with MCS (P<0.01). In all subjects, psychosocial and somatic measures were associated with MCS and not PCS excluding GI symptom anxiety, which correlated with both (P<0.01). The strongest predictor of MCS was perceived stress in IBS and depression symptoms in HCs. GI symptom anxiety was the strongest predictor of PCS in both. Greater perceived stress and somatic symptom severity and less mindfulness was linked to larger reductions in HRQOL for IBS compared with HCs (P<0.01).

Conclusions:

GI symptom severity and anxiety correlate with PCS, whereas psychosocial/somatic measures parallel MCS. However, HRQOL is comparable in IBS and HCs when perceived stress, somatic symptom severity, and mindfulness are at optimal levels. These findings may have important implications in the management of IBS.
Defining the Urethritis Syndrome in Men Using Patient Reported Symptoms
Authors: Jordan Stephen J. , Aaron Kristal J. , Schwebke Jane R. , Van Der Pol Barbara J. , Hook Edward W.
Published: January 2018

To evaluate self-reported symptoms to guide urethritis diagnosis, symptomatic men being evaluated for urethritis were asked about 7 symptoms captured during history taking. Discharge and dysuria were significantly associated with urethritis and, when combined with genital irritation and itching, identified 95% of urethritis cases; odor and urinary frequency performed poorly.
The Complex Association of Race/Ethnicity With Pain Treatment Quality in an Urban Medical Center With 2 Pediatric Emergency Departments
Authors: Kipping Erika M. , Chamberlain James M.
Published: January 2018

Objective

This study aimed to explore racial differences in analgesia quality.

Methods

A retrospective cross-sectional study of 24,733 visits by individuals 21 years or younger with pain scores of 4 to 10 was performed using electronic medical records. We compared 2 process metrics, treatment with any analgesics within 60 minutes and treatment with opioids within 60 minutes, and one outcome metric, a reduction in pain score by 2 or more points within 90 minutes. Multivariable logistic regression adjusted for the effects of patient characteristics and health status. We also determined variations in analgesia quality among those with severe pain.

Results

When compared with white children, black children were more likely to receive any analgesia (adjusted odds ratio [aOR], 1.94; 95% confidence interval, 1.71–2.21), but both blacks (aOR, 0.66; 0.51–0.85) and Hispanics (aOR, 0.56; 0.39–0.80) were less likely to receive opioids. Blacks were more likely to reduce their pain score (aOR, 1.50; 1.28–1.76).

Among children with severe pain, both blacks and Hispanics were more likely to receive any analgesia (black: aOR, 2.05 [1.71–2.46]; Hispanic: aOR, 1.29 [1.05–1.59]), and Hispanic children were less likely to receive opioids (aOR, 0.58; 0.37–0.91). Again, black children were more likely to reduce their pain score (aOR, 1.42; 1.13–1.79).

Conclusions

The relationship between race/ethnicity and analgesia is complex. Although minority children were less likely to receive opioids, black children had better treatment outcomes. Future studies should explore clinical response to analgesia in addition to process measures to better understand if differential treatment may be justified to achieve equitable care outcomes.
Clinical Application of Real-Time Shear Wave Elastography in Identifying the Histological Components of Parotid Adenolymphoma
Authors: Huang Kun , Gao Ningning , Wang Xuemei , Bian Donglin , Liu Yanjun , Zhai Qixi
Published: January 2018

Objective

This study aimed to investigate the relationship between the elastic modulus and the histological components of parotid adenolymphoma by using real-time shear wave elastography.

Methods

A total of 157 patients, histologically confirmed as having parotid adenolymphoma, were enrolled in the study. The maximum and the mean elastic modulus of the parotid mass were measured by using preoperative shear wave elastography. Parotid adenolymphoma was histopathologically subdivided into different types based on the relative proportion of stromal to cellular components.

Results

The maximal elasticity of parotid adenolymphoma ranged from 20.67 to 160.90 kPa, and the mean elasticity was 83.18 ± 39.15 kPa. The maximal elasticity of the 3 types of parotid adenolymphoma was 34.21 to 155.20, 20.67 to 104.20, and 45.89 to 160.90 kPa, respectively. The mean elasticity of the 3 types of parotid adenolymphoma was 89.16 ± 40.62, 63.24 ± 28.07, and 111.10 ± 37.85 kPa, respectively. The difference in the maximal elasticity among 3 groups was significant (P < 0.01). There was no significant difference in maximal elasticity of type II and type III as compared with type I adenolymphoma (P > 0.05). The maximal elasticity of type III adenolymphoma was significantly higher than that of type II (P < 0.05, t = 3.12).

Conclusion

Shear wave elastography depicts parotid adenolymphoma with a variable appearance because of the relative proportions of stromal to cellular contents in the mass.
“To Err Is Human” but Disclosure Must be Taught
Authors: Crimmins Ashley C. , Wong Ambrose H. , Bonz James W. , Tsyrulnik Alina , Jubanyik Karen , Dziura James D. , Dodge Kelly L. , Evans Leigh V.
Published: January 2018

Introduction

Although error disclosure is critical in promoting safety and patient-centered care, physicians are inconsistently trained in its practice, and few objective methods to assess competence exist. We used an immersive simulation scenario to determine whether providers with varying levels of clinical experience adhere to the disclosure safe practice guidelines when exposed to a serious adverse event simulation scenario.

Methods

This was a prospective cohort study with medical students, junior emergency medicine (EM) residents (PGY 1–2), senior EM residents (PGY 3–4), and attending EM physicians participating in a simulated case in which a scripted medication overdose resulted in an adverse event. Each scenario was videotaped and scored by two expert raters based on a 6-component, 21-point disclosure assessment instrument.

Results

There were 12 participants in each study group (N = 48). There was good interrater reliability (κ = 0.70). Total scores improved significantly as the level of training increased: medical student = 10.3 (2.7), PGY 1–2 = 12.3 (6.2), PGY 3–4 = 13.7 (3.2), and attending physicians = 12.8 (3.7) (P = 0.03). Seventy-five percent of participants did not address preventing recurrence of the error. Fifty-six percent offered no apology or only offered it with prompting from the patient; only 23% offered an apology with the initial disclosure.

Conclusions

We demonstrated suboptimal adherence to best practices guidelines for error disclosure when providers are assessed in an immersive simulation setting. Despite a correlation in performance of medical error disclosure with increased physician experience, this study suggests that healthcare providers may need additional training to comply with safe practice guidelines for disclosure of unanticipated adverse events.
Learner-Adaptive Educational Technology for Simulation in Healthcare
Authors: Lineberry Matthew , Dev Parvati , Lane H. Chad , Talbot Thomas B.
Published: January 2018

Summary Statement

Despite evidence that learners vary greatly in their learning needs, practical constraints tend to favor ''one-size-fits-all'' educational approaches, in simulation-based education as elsewhere. Adaptive educational technologies - devices and/or software applications that capture and analyze relevant data about learners to select and present individually tailored learning stimuli - are a promising aid in learners' and educators' efforts to provide learning experiences that meet individual needs. In this article, we summarize and build upon the 2017 Society for Simulation in Healthcare Research Summit panel discussion on adaptive learning. First, we consider the role of adaptivity in learning broadly. We then outline the basic functions that adaptive learning technologies must implement and the unique affordances and challenges of technology-based approaches for those functions, sharing an illustrative example from healthcare simulation. Finally, we consider future directions for accelerating research, development, and deployment of effective adaptive educational technology and techniques in healthcare simulation.
Transcriptional changes when Myxococcus xanthus preys on Escherichia coli suggest myxobacterial predators are constitutively toxic but regulate their feeding
Authors: Livingstone Paul G. , Millard Andrew D. , Swain Martin T. , Whitworth David E.
Published: January 2018

Predation is a fundamental ecological process, but within most microbial ecosystems the molecular mechanisms of predation remain poorly understood. We investigated transcriptome changes associated with the predation of Escherichia coli by the myxobacterium Myxococcus xanthus using mRNA sequencing. Exposure to pre-killed prey significantly altered expression of 1319 predator genes. However, the transcriptional response to living prey was minimal, with only 12 genes being significantly up-regulated. The genes most induced by prey presence (kdpA and kdpB, members of the kdp regulon) were confirmed by reverse transcriptase quantitative PCR to be regulated by osmotic shock in M. xanthus, suggesting indirect sensing of prey. However, the prey showed extensive transcriptome changes when co-cultured with predator, with 40 % of its genes (1534) showing significant changes in expression. Bacteriolytic M. xanthus culture supernatant and secreted outer membrane vesicles (OMVs) also induced changes in expression of large numbers of prey genes (598 and 461, respectively). Five metabolic pathways were significantly enriched in prey genes up-regulated on exposure to OMVs, supernatant and/or predatory cells, including those for ribosome and lipopolysaccharide production, suggesting that the prey cell wall and protein production are primary targets of the predator’s attack. Our data suggest a model of the myxobacterial predatome (genes and proteins associated with predation) in which the predator constitutively produces secretions which disable its prey whilst simultaneously generating a signal that prey is present. That signal then triggers a regulated feeding response in the predator.
Do long-tailed macaques engage in intuitive statistics?
Authors: Placì Sarah , Eckert Johanna , Rakoczy Hannes , Fischer Julia
Published: January 2018

Human infants, apes and capuchins have been found to engage in intuitive statistics, generating predictions from populations to samples based on proportional information. This suggests that statistical reasoning might depend on some core knowledge that is shared with other species. Here, we investigated whether such intuitive statistical reasoning is also present in a species of Old World monkeys, to aid in the reconstruction of the evolution of this capacity. In a series of 7 test conditions, 11 long-tailed macaques were offered different pairs of populations containing varying proportions of preferred vs. neutral food items. One population always contained a higher proportion of preferred items than the other. An experimenter simultaneously drew one item out of each population, hid them in her fists and presented them to the monkey to choose. Results revealed that at least one individual seemed to make systematic population-to-sample inferences and consistently chose the sample from the population with the more favorable distribution of preferred vs. neutral food items. While it is not clear whether she used relative or absolute quantities of food, she seemed to understand the difference between a correct choice and a favorable draw and thus some basic principles of intuitive statistics.
Simulation based benchmarking of isoform quantification in single-cell RNA-seq
Authors: Westoby Jennifer , Sjoberg Marcela , Ferguson-Smith Anne , Hemberg Martin
Published: January 2018

Single-cell RNA-seq has the potential to facilitate isoform quantification as the confounding factor of a mixed population of cells is eliminated. We carried out a benchmark for five popular isoform quantification tools. Performance was generally good when run on simulated data based on SMARTer and SMART-seq2 data, but was poor for simulated Drop-seq data. Importantly, the reduction in performance for single-cell RNA-seq compared with bulk RNA-seq was small. An important biological insight comes from our analysis of real data which showed that genes that express two isoforms in bulk RNA-seq predominantly express one or neither isoform in individual cells.
Mathematical modeling of navigational decisions based on intensity versus directionality in Drosophila larval phototaxis
Authors: de Andres-Bragado Lucia , Mazza Christian , Senn Walter , Sprecher Simon G.
Published: January 2018

Organisms use environmental cues for directed navigation. Depending on the sensory modality and complexity of the involved sensory organs, different types of information may be processed. Understanding the basic logic behind navigational decisions critically depends on the complexity of the nervous system. Due to the comparably simple organization of the nervous system of the fruit fly larva, it stands as a powerful model to study decision-making processes that underlie directed navigation. Here, we formulate a stochastic method based on biased Markov chains to model the behavioral basis of negative phototaxis. We have quantitatively measured phototaxis in response to defined sensory inputs. We find that larvae make navigational decisions by taking into account both light intensities and its spatial gradients, and our model allows us to quantify how larvae minimize their exposure to light intensity and at the same time maximize their distance to the source of light. The response to the light field is a non-linear response and saturates above an intensity threshold. Our mathematical model simulates and predicts larval behavioral dynamics only using light intensity and directionality as input parameters. Moreover, it allows us to evaluate the relative importance of these two factors governing visual navigation. The model has been validated with experimental biological data yielding insight into the strategy that larvae use to achieve their goal with respect to the navigational cue of light, paving the way for future work to study the role of the different neuronal components in this mechanism.

Author Summary

Navigational decision-making is a complex process during which the nervous system is able to decipher external input through molecular and cellular mechanisms to produce a spatially-coordinated behavioral output. Drosophila larvae provide an excellent model to understand these decision-making mechanisms as we can measure the behavioral output (larval navigation) in response to quantifiable external input (different light conditions). We have performed experiments to quantify larval light avoidance in order to subsequently design a mathematical model that quantitatively reproduces larval behavior. Our results allow us to characterize the relative importance of light intensity and directionality and yield insight into the neural algorithms used in the decision-making mechanism of larval phototaxis.
Navigating in vitro bioactivity data: investigating available resources using model compounds
Authors: Ilmjärv Sten , Augsburger Fiona , Bolleman Jerven Tjalling , Liechti Robin , Bridge Alan James , Sandström Jenny , Jaquet Vincent , Xenarios Ioannis , Krause Karl-Heinz
Published: January 2018

Modern medicine and an increasingly complex environment contribute to exposure of humans to a large number of chemical compounds, that can potentially be toxic. Although widely used, compound testing in animals has important limitations. In vitro testing provides a promising alternative. However, because of the relative inaccessibility and fragmentation of available data, the in vitro approach largely underperforms its potential. The aim of this study is to investigate how available public online resources (tools and databases) support accessing and distribution of in vitro compound data. We examined 19 public online resources, mapped their features, and evaluated their usability with a set of four model compounds (aspirin, rosiglitazone, valproic acid, and tamoxifen). By investigating compound names and identifiers, we observed extensive variation and inconsistencies in available resources: the synonyms were different, compounds’ structural identifiers (InChI, InChIKey, SMILES and IUPAC systematic name) underperformed in omics databases, identification of compound related metadata (e.g. concentrations used in the experiments) from omics experiments was complex and none of the available resources clearly distinguished between in vivo and in vitro data. In addition, we estimated accessibility of selected public resources using computational queries. Only a few public resources provided access to compound-related data using semantic web technology. The general quality of experiment annotations created further difficulties in identifying data of interest. Therefore, we identified several standardized ontologies with potential to provide an increased accuracy for extensive data retrieval of in vitro compound data. Furthermore, using the examples of our model compounds, we provide recommendations on the use of ontologies by suggesting specific ontology terms to annotate in vitro experimental data when being published.
A host-pathogen interaction screen identifiesada2as a mediator ofCandida glabratadefences against reactive oxygen species
Authors: Kounatidis Ilias , Ames Lauren , Mistry Rupal , Ho Hsueh-lui , Haynes Ken , Ligoxygakis Petros
Published: January 2018

Candida glabrata (C. glabrata) forms part of the normal human gut microbiota but can cause life-threatening invasive infections in immune-compromised individuals.C. glabratadisplays high resistance to common azole antifungals, which necessitates new treatments. In this investigation, we identified fiveC. glabratadeletion mutants (Δada2, Δbas1, Δhir3,Δino2andΔmet31) from a library of 196 transcription factor mutants that were unable to grow and activate an immune response inDrosophilalarvae. This highlighted the importance of these transcription factors inC. glabratainfectivity. Furtherex vivoinvestigation into these mutants revealed the requirement ofC. glabrata ADA2for oxidative stress tolerance. We confirmed this observationin vivowhereby growth of theC. glabrata Δada2strain was permitted only in flies with suppressed production of reactive oxygen species (ROS). Conversely, overexpression ofADA2promotedC. glabratareplication in infected wild type larvae resulting in larval killing. We propose thatADA2orchestrates the response ofC. glabrataagainst ROS-mediated immune defences during infection. With the need to find alternative antifungal treatment forC. glabratainfections, genes required for survival in the host environment, such asADA2, provide promising potential targets.
Adaptation decorrelates shape representations
Authors: Mattar Marcelo G. , Olkkonen Maria , Epstein Russell A. , Aguirre Geoffrey K.
Published: January 2018

Perception and neural responses are modulated by sensory history. Visual adaptation, an example of such an effect, has been hypothesized to improve stimulus discrimination by decorrelating responses across a set of neural units. While a central theoretical model, behavioral and neural evidence for this theory is limited and inconclusive. Here, we use a parametric 3D shape-space to test whether adaptation decorrelates shape representations in humans. In a behavioral experiment with 20 subjects, we find that adaptation to a shape class improves discrimination of subsequently presented stimuli with similar features. In a BOLD fMRI experiment with 10 subjects we observe that adaptation to a shape class decorrelates the multivariate representations of subsequently presented stimuli with similar features in object-selective cortex. These results support the long-standing proposal that adaptation improves perceptual discrimination and decorrelates neural representations, offering insights into potential underlying mechanisms.
Ostreococcus tauri is a high-lipid content green algae that extrudes clustered lipid droplets
Authors: Smallwood Chuck R. , Chrisler William , Chen Jian-Hua , Patello Emma , Thomas Mathew , Boudreau Rosanne , Ekman Axel , Wang Hongfei , McDermott Gerry , Evans James E.
Published: January 2018

Lipid droplet biogenesis, accumulation and secretion is an important field of research spanning biofuel feedstock production in algae and yeast to plant-microbe symbiosis or human metabolic disorders and other diseases. Here we evaluate the critical elements that influence lipid accumulation in the highly simplified and smallest known eukaryote Ostreococcus tauri and identify several conditions that satisfy its classification as an oleaginous green alga. In addition, these experiments revealed the release of excess lipids in pea-pod like structures where many dense lipid droplets are clustered in a linear fashion surrounded by an enveloping membrane which contrasts with known mechanisms from other eukaryotes. These results highlight the potential for Ostreococcus tauri to probe the evolution of lipid droplet dynamics as an emerging model organism with a compacted eukaryotic genome and also to impact lipid feedstock bioproduction applications either directly or using synthetic biology.

One Sentence Summary

The smallest known eukaryote Ostreococcus tauri is oleaginous and sheds lipid droplets as pea-pod like membrane enclosed clusters.
Mutations in efflux pump Rv1258c (Tap) cause resistance to pyrazinamide and other drugs inM. tuberculosis
Authors: Liu Jiayun , Shi Wanliang , Zhang Shuo , Cassell Gail , Maslov Dmitry A. , Shur Kirill V. , Bekker Olga B. , Danilenko Valery N. , Hao Xiaoke , Zhang Ying
Published: January 2018

Although drug resistance inM. tuberculosisis mainly caused by mutations in drug activating enzymes or drug targets, there is increasing interest in possible role of efflux in causing drug resistance. Previously, efflux genes are shown upregulated upon drug exposure or implicated in drug resistance in overexpression studies, but the role of mutations in efflux pumps identified in clinical isolates in causing drug resistance is unknown. Here we investigated the role of mutations in efflux pump Rv1258c (Tap) from clinical isolates in causing drug resistance inM. tuberculosisby constructing point mutations V219A, S292L in Rv1258c in the chromosome ofM. tuberculosisand assessed drug susceptibility of the constructed mutants. Interestingly, V219A, S292L point mutations caused clinically relevant drug resistance to pyrazinamide (PZA), isoniazid (INH), and streptomycin (SM), but not to other drugs inM. tuberculosis. While V219A point mutation conferred a low level resistance, the S292L mutation caused a higher level of resistance. Efflux inhibitor piperine inhibited INH and PZA resistance in the S292L mutant but not in the V219A mutant. S292L mutant had higher efflux activity for pyrazinoic acid (the active form of PZA) than the parent strain. We conclude that point mutations in the efflux pump Rv1258c in clinical isolates can confer clinically relevant drug resistance including PZA and could explain some previously unaccounted drug resistance in clinical strains. Future studies need to take efflux mutations into consideration for improved detection of drug resistance inM. tuberculosisand address their role in affecting treatment outcome in vivo.
Interpretive Summary. Heat detection alerts and LH surge. Adriaens
Authors: Adriaens Ines , Saeys Wouter , Lamberigts Chris , Berth Mario , Geerinckx Katleen , Leroy Jo , Ketelaere Bart De , Aernouts Ben
Published: January 2018

Both estrus detection and timely insemination are important factors in optimizing fertility management. The latter is dependent on ovulation time, which is preceded by the LH surge. The performance of an estrus detection system based on activity and based on milk progesterone was evaluated and the timing of the alerts was contrasted against the moment of the LH surge. Activity alerts had a sensitivity of 83% and a positive predictive value of 66%; the LH surge followed average 9.4 ± 16.1 hours later. Using milk progesterone, one can reliably detect luteolysis, which is followed by the LH surge after 62 ± 12 hours.
CWL-Airflow: a lightweight pipeline manager supporting Common Workflow Language
Authors: Kotliar Michael , Kartashov Andrey V. , Barski Artem
Published: January 2018

Background

Massive growth in the amount of research data and computational analysis has led to increased utilization of pipeline managers in biomedical computational research. However, each of more than 100 such managers uses its own way to describe pipelines, leading to difficulty porting workflows to different environments and therefore poor reproducibility of computational studies. For this reason, the Common Workflow Language (CWL) was recently introduced as a specification for platform-independent workflow description, and work began to transition existing pipelines and workflow managers to CWL.

Findings

Here, we present CWL-Airflow, an extension for the Apache Airflow pipeline manager supporting CWL. CWL-Airflow utilizes CWL v1.0 specification and can be used to run workflows on standalone MacOS/Linux servers, on clusters, or on a variety of cloud platforms. A sample CWL pipeline for processing of ChIP-Seq data is provided.

Conclusions

CWL-Airflow will provide users with the features of a fully-fledged pipeline manager and an ability to execute CWL workflows anywhere Airflow can run—from a laptop to cluster or cloud environment.

Availability

CWL-Airflow is available under Apache license v.2 and can be downloaded from https://barski-lab.github.io/cwl-airflow, http://doi.org/10.5281/zenodo.2669582, RRID: SCR_017196.
Accurate analysis of genuine CRISPR editing events with ampliCan
Authors: Labun Kornel , Guo Xiaoge , Chavez Alejandro , Church George , Gagnon James , Valen Eivind
Published: January 2018

We present ampliCan, an analysis tool for genome editing that unites highly precise quantification and visualization of genuine genome editing events. ampliCan features nuclease-optimized alignments, filtering of experimental artifacts, event-specific normalization, off-target read detection and quantifies insertions, deletions, HDR repair as well as targeted base editing. It is scalable to thousands of amplicon sequencing-based experiments from any genome editing experiment, including CRISPR. It enables automated integration of controls and accounts for biases at every step of the analysis. We benchmarked ampliCan on both real and simulated datasets against other leading tools, demonstrating that it outperformed all in the face of common confounding factors.
Modifying assurance practices to meet the needs of integrated reporting
Authors: Maroun Warren
Published: January 2018

Purpose

Traditional methods of assurance outlined by current professional standards are risk-based models where the emphasis is on the veracity of published data rather than on the rigour of the interpretation or analysis of information provided to users. As such, they are not well suited for expressing an opinion on qualitative, subjective or forward-looking assessments typically included in integrated reports. In this context, the purpose of this paper is to describe an alternate approach to assurance and identifies the initial elements of an “interpretive assurance model”.

Design/methodology/approach

The research is exploratory/interpretive. It relies on detailed interviews with experienced auditors and preparers to develop an initial approach for providing some level of assurance over an integrated report.

Findings

The research identifies elements of an interpretive assurance model which focusses on providing assurance on the interpretation and analysis of information included in an integrated report rather than on underlying data. These include an examination of the completeness of the explanation of the value creation process provided in an integrated report; the methods used to support management discussion and analysis; and the reasonability of the review process used to ensure the reliability of qualitative, subjective and forward-looking representations contained in an integrated report.

Research limitations/implications

The study is conducted in a South African setting. While limiting the study to a single jurisdiction may be seen as a limitation, local preparers and auditors have had at least five years of experience with the application of an integrated reporting framework and are in a strong position to provide detailed insights.

Practical implications

An interpretive assurance model shifts the focus from objective verification of data using defined test procedures to evaluation of the interpretation and analysis process used to prepare an integrated report. Application of the proposed model will require practitioners and auditing students to be trained extensively in qualitative analytical techniques. The inherent complexity of contemporary business models and the multi-dimensional focus of integrated reports will also result in changes in the composition of audit teams which are currently dominated by experts in financial reporting rather than integrated or strategic business management.

Originality/value

The paper is the first to offer a practical approach for providing assurance over an integrated report. It responds to calls form the International Integrated Reporting Council and International Auditing and Assurance Standards Board for more innovative assurance models for addressing the reporting needs of contemporary organisations.