bluuebunny/crossref_metadata_2025 huggingface dataset:
Predictors of 30-day All-cause Mortality in Veterans with First Recurrence of Clostridium difficile Infection (CDI)
Authors: Morrill Haley , Beganovic Maya , Caffrey Aisling , LaPlante Kerry
Published: October 2017

Background

Recurrent CDI is an important cause of mortality, however few studies have evaluated independent predictors of mortality in patients with recurrent CDI.

Methods

We conducted a case–control study nested in a national cohort of adult Veterans with a CDI episode (defined as a positive stool sample for C. difficile toxin(s) & receipt of >2 days of CDI treatment [IV or PO metronidazole, PO or PR vancomycin, or fidaxomicin]) during an inpatient admission or outpatient encounter at a Veterans Affairs facility from 2010–2014. Only patients with a first recurrence were included, defined as a subsequent CDI episode within 30 days from the end of treatment of the first CDI occurrence. Cases were those that experienced 30-day all-cause mortality and controls included survivors matched to cases on year of episode, facility, and severity. Multivariable conditional logistic regression was used to identify predictors of mortality.

Results

110 cases were matched to 440 controls (1:4). Five predictors of mortality were identified including concurrent use of any antibiotic (OR 4.61, 95% CI 2.45–8.69), pulmonary heart disease (OR 4.707, 95% CI 1.30–17.06), the use of proton pump inhibitors within 7 days prior to CDI treatment (OR 3.59, 95% CI 2.01–6.42), nutrition deficiency (OR 2.62, 95% CI 1.28–5.38) and age (OR 1.04, 95% CI 1.02–1.07).

Conclusion

Increasing age, proton pump inhibitors, previous antibiotic exposure, and underlying comorbidities were important predictors of death among those with first recurrence of CDI. Our data is among the first to investigate predictors of morality in patients with first recurrence, and these data may assist healthcare providers in optimizing patient care.

Disclosures

H. Morrill, The University of Rhode Island: Investigator, Research grant; A. Caffrey, Merck: Grant Investigator, Research grant; The Medicines Company: Grant Investigator, Research grant; Pfizer: Grant Investigator, Research grant; K. LaPlante, Merck: Grant Investigator, Grant recipient; Pfizer: Grant Investigator, Grant recipient; Cempra: Scientific Advisor, Consulting fee; The Medicines Company: Grant Investigator, Grant recipient; Allergan: Scientific Advisor, Consulting fee; Bard/ Davol: Scientific Advisor, Consulting fee; Ocean Spray: Grant Investigator and Scientific Advisor, Consulting fee and Grant recipient; Zavante: Scientific Advisor, Consulting fee; Achaogen: Scientific Advisor, Consulting fee
Genotypic Correlation between Cases of Clostridium difficile (CDI) with Community-Onset Diagnosis after Recent Hospital Discharge and Their Prior Unit-Based Contacts
Authors: Aslam Anoshé , Brite Jennifer , McMillen Tracy , Chow Hoi Yan , Babady N Esther , Kamboj Mini
Published: October 2017

Background

The incubation period of C. difficile infection (CDI) is highly variable. Infections may be diagnosed weeks after initial acquisition of bacterial spores. Such cases of CDI have onset in the community after a recent hospitalization, or upon readmission, and are characterized as community-onset healthcare-facility associated (CO-HCFA) by current surveillance methods.

Aim: With the application of multi-locus sequence typing (MLST), our study seeks to characterize genetic concordance between CO-HCFA cases and prior unit-based contacts (donors) sharing the same strain type (ST).

Methods

For all laboratory-identified cases of CDI from January 1, 2015, through December 31, 2016, patients with CDI onset within 8 weeks of hospital discharge were included in the study. Infection control database was queried to identify putative donors using the following criteria: previous unit occupants with CDI who had been discharged from the same unit less than 4 weeks, 4–8 weeks, and 8–12 weeks before admission of CO-HCFA cases. Intensity of exposure was further characterized by same room or same unit occupancy. Analysis was restricted to endemic strains at our institution (ST 1, 2, 3, 8, 11 and 42).

Results

During the two year period, 1330 cases were diagnosed with a new CDI episode, 425 community-onset (32%), 440 hospital-onset (33%) and 465 CO-HCFA (35%) cases. Among the 314 unique CO-HCFA patients due to endemic strains, there were a total of 92 same unit contacts with a concordant strain type, and 1035 same unit contacts with a discordant strain type. The proportion of concordant same unit occupants did not differ by time between cases (P = 0.8120).

Conclusion

CO-HCFA cases account for a third of all new cases of CDI. Genotypic concordance as potential donors was observed among 8% of all indirect unit based CDI contacts of CO-HCFA cases. This association did not vary significantly as the interval between potential exposure and CDI onset in CO-HCFA cases increased.

Disclosures

All authors: No reported disclosures.
Sorting the Wheat from the Chaff: Vaccine-Associated Rash Illness Occurring amidst a Large Measles Outbreak—Minnesota, 2017
Authors: Martin Karen , Mody Rajal , Desilva Malini , Banerjee Emily , Strain Anna , Holzbauer Stacy , Kenyon Cynthia , McMahon Melissa , Rota Paul , Gastanaduy Paul , Muscoplat Miriam , Hall Victoria , Ehresmann Kristen
Published: October 2017

Background

During April–June 2017, Minnesota experienced the state’s largest measles outbreak in 27 years. A vaccination campaign was implemented. Numerous vaccine-associated rash illnesses (VARI) were detected. VARI is non-contagious, but difficult to distinguish from measles clinically. Often, public health control measures need to be implemented before wild-type measles can be differentiated from VARI by viral genotyping. We compared clinical characteristics of VARI and confirmed measles cases to inform testing practices.

Methods

We defined measles cases per the Council of State and Territorial Epidemiologists. VARI was defined as a rash occurring in a person within 21 days after receipt of measles, mumps, and rubella (MMR) vaccine, and in whom a measles vaccine strain (genotype A) was detected in naso/oro- pharyngeal swab or urine samples. Minnesota’s immunization information system monitored MMR doses administered. We collected clinical information through routine case investigation.

Results

Over 42,000 MMR doses above expected were administered during the outbreak. We identified 71 measles cases and 30 VARI. The median age of VARI patients was 1.2 years (range 10 months–48 years) and for measles cases 2.8 years (range 3 months–57 years). VARI diagnosis increased with rising MMR administration (figure); rash onset occurred a median of 11 (range 7–18) days after MMR receipt. Most VARI (97%) occurred following first MMR dose. The presence of fever was similar among VARI and measles cases (97% of VARI vs. 100% of measles cases; P = 0.12), but differences were seen in the proportion with cough (30% vs. 96%; P < 0.001), coryza (47% vs. 85%; P < 0.001), conjunctivitis (23% vs. 68%; P < 0.001), and exposure to infectious measles cases (0% vs. 96%).

Conclusions

Surges in MMR administration and heightened community awareness during a measles outbreak can result in a large number of VARI, consuming considerable public health resources. When evaluating the need to suspect measles among patients with febrile rash, clinicians should consider time since MMR administration, clinical presentation, and history of measles exposure. Collecting appropriate specimens for timely virus genotyping could inform appropriate public health action.

Disclosures

All authors: No reported disclosures.
Exserohilum turcicum Race Population Distribution in the North Central United States
Authors: Weems Japheth D. , Bradley Carl A.
Published: October 2017

Northern leaf blight (NLB) of corn, caused by Exserohilum turcicum, is a foliar disease common across corn production regions of the world, including those in the north central United States. Previous race population distribution studies identified five physiological races present in the United States, prior to 1995. For this study, 156 E. turcicum isolates were screened on corn differential lines containing Ht1, Ht2, Ht3, Htm1, and Htn1 resistance genes. Isolates were collected from fields in Iowa, Illinois, Indiana, Minnesota, North Carolina, Ohio, and Wisconsin, which included 143 isolates collected between 2007 and 2014 and 13 isolates collected between 1979 and 1985. Twenty different physiological races were observed based on the symptom response of the differential corn lines. E. turcicum race 0, 1, and 1mn were the most prevalent races, comprising 21, 27, and 13% of the 156 isolates, respectively. Race populations were diverse within states and years. Virulence to multiple Ht resistance genes within individual isolates was observed in 47% of those tested, with 3% of the isolates conferring virulence to all Ht resistance genes. Virulence to the Ht1, Ht2, Ht3, Htm1, and Htn1 resistance genes was present in 64, 20, 18, 32, and 27% of the E. turcicum isolates, respectively. Virulence to Ht resistance genes was fairly evenly distributed across states, in isolates collected after 2008. Virulence to Ht2, Ht3, Htm1, and Htn1 decreased after 2010. Variations in race population diversity are difficult to explain without knowing the level of selection pressure present in fields, and information regarding Ht resistance gene deployment in commercial varieties is not publicly available. Although virulence was observed against all Ht resistance genes, qualitative Ht resistance genes could be used in conjunction with quantitative resistance to increase NLB control.
High Resolution DNA Melting Assays for Detection of Rx1 and Rx2 for High-Throughput Marker-Assisted Selection for Extreme Resistance to Potato virus X in Tetraploid Potato
Authors: Nie Xianzhou , Dickison Virginia L. , Brooks Sydney , Nie Bihua , Singh Mathuresh , De Koeyer David L. , Murphy Agnes M.
Published: October 2017

Assessment of the existing PCR-gel electrophoresis-based methods for detection of Rx1 and Rx2, the genes that independently control extreme resistance (ER) to Potato virus X (PVX), indicated that the 5Rx1F/5Rx1R primer pair led to reliable detection of Rx1, whereas the 106Rx2F/106Rx2R primer pair detected Rx2 despite some nonspecific reactions in potato clones/cultivars without Rx2. However, the methodology is time consuming and does not differentiate the absence of Rx1/Rx2 from a failed PCR reaction. A newly designed primer pair that targets Rx1 and Rx2 as well as rx1 and rx2 produced an amplicon for all alleles. When the primer pair was combined with 5Rx1F/5Rx1R, respective amplicons were produced, although they were not distinguishable by regular agarose gel electrophoresis. When subjected to a high-resolution DNA melting (HRM) assay, two distinct melting profiles for Rx1 and rx1, respectively, were detected. Triplex PCR-gel electrophoresis and -HRM assay for detection of Rx1, Rx2, and rx1/rx2 were also performed. The efficacy of the HRM assays were validated in potato cultivars/clones with known phenotypes, indicating its potential for high-throughput selection of potato clones/cultivars carrying Rx1 or Rx2. Duplex PCR-HRM assays of over 600 progeny from 12 crosses involving various parents correctly detected the presence or absence of Rx1 in each progeny, allowing accurate prediction of the phenotype. Progeny that tested positive for Rx1 by HRM exhibited ER to PVX whereas progeny that tested negative for Rx1 were susceptible to PVX infection. The genotype of each parent and the possible presence of Nx in two Rx1-possessing parents are also discussed.
Brazilian Payment for Performance (PMAQ) Seen From a Global Health and Public Policy Perspective
Authors: Saddi Fabiana C. , Peckham Stephen
Published: October 2017

This supplement of the Journal of Ambulatory Care Management on the Brazilian National Program for Improving Access and Quality of Primary Care (PMAQ) reveals a relevant gap in the Brazilian literature on pay for performance/PMAQ, and is therefore an opportunity to bring contributions from global health and public policy to the debate. We discuss the relevant gap in the light of developments in evaluation and policy analysis. We afterward present the state of knowledge regarding global health and public policy in pay for performance, giving attention to diverse themes, methods, types of analyses, theoretical contributions, and limitations. Finally, we suggest some possible implications for research and policy in Brazil.
A New Lease on Life: Preliminary Needs Assessment for the Development of a Survivorship Program for Young Adult Survivors of Cancer in South Texas
Authors: Schmidt Susanne , Shay L. Aubree , King Harriet V. , Buckley Jordan , Embry Leanne , Parsons Helen M.
Published: October 2017

Priorities for young adult survivorship care from the survivors’ perspective are not well documented. To address this within our patient population, we conducted a multimethod needs assessment of young adult survivors of pediatric, adolescent, and young adult cancer in South Texas to get a better understanding of the ongoing challenges and priorities for their survivorship needs and related services. Participants were 18 to 39 years at the time of the needs assessment and predominately Hispanic. In an online survey, survivors most commonly cited being concerned about their physical and mental health, long-term treatment effects, recurrence, and health insurance issues. Participants stated that they received critical support from family, friends, and medical staff, but they would like to receive additional support from other cancer survivors through peer mentorship opportunities and survivor retreats/social events.
Role of the microbiota in cancer growth and necrosis: the challenges and opportunities of bacteriotherapy for cancer and its complications
Authors: Pan Wei , Kang Yongbo
Published: October 2017

Possessing a selective growth advantage by influencing proliferation barrier, immune system, metabolism, and cell proliferation and death in tissues, is a critical event in cancer formation, progression, and suppression, indicating that specific microbes and microbiotas may enhance or dwindle cancer susceptibility. A host's microbiota may affect not only immune responses in developing tumor environment by inducing proinflammatory or immunosuppressive events but also response to cancer diagnosis, treatment, and relevant complications. As gifts to both cancer biology and microbiology, increased interrogating technologies have shed light on host–microbiota interactions and their roles in human health and disease. The interacting network of cancer, host, and microbial genotypes is identified in this review to assess how microorganism may play an important role in carcinogenesis, developing novel therapeutic and diagnostic strategies for cancer and its complications.
Spatial organization and interactions of harvester ants during foraging activity
Authors: Davidson Jacob D. , Gordon Deborah M.
Published: October 2017

Local interactions, when individuals meet, can regulate collective behaviour. In a system without any central control, the rate of interaction may depend simply on how the individuals move around. But interactions could in turn influence movement; individuals might seek out interactions, or their movement in response to interaction could influence further interaction rates. We develop a general framework to address these questions, using collision theory to establish a baseline expected rate of interaction based on proximity. We test the models using data from harvester ant colonies. A colony uses feedback from interactions inside the nest to regulate foraging activity. Potential foragers leave the nest in response to interactions with returning foragers with food. The time series of interactions and local density of ants show how density hotspots lead to interactions that are clustered in time. A correlated random walk null model describes the mixing of potential and returning foragers. A model from collision theory relates walking speed and spatial proximity with the probability of interaction. The results demonstrate that although ants do not mix homogeneously, trends in interaction patterns can be explained simply by the walking speed and local density of surrounding ants.
Effects of motion in structured populations
Authors: Krieger Madison S. , McAvoy Alex , Nowak Martin A.
Published: October 2017

In evolutionary processes, population structure has a substantial effect on natural selection. Here, we analyse how motion of individuals affects constant selection in structured populations. Motion is relevant because it leads to changes in the distribution of types as mutations march towards fixation or extinction. We describe motion as the swapping of individuals on graphs, and more generally as the shuffling of individuals between reproductive updates. Beginning with a one-dimensional graph, the cycle, we prove that motion suppresses natural selection for death–birth (DB) updating or for any process that combines birth–death (BD) and DB updating. If the rule is purely BD updating, no change in fixation probability appears in the presence of motion. We further investigate how motion affects evolution on the square lattice and weighted graphs. In the case of weighted graphs, we find that motion can be either an amplifier or a suppressor of natural selection. In some cases, whether it is one or the other can be a function of the relative reproductive rate, indicating that motion is a subtle and complex attribute of evolving populations. As a first step towards understanding less restricted types of motion in evolutionary graph theory, we consider a similar rule on dynamic graphs induced by a spatial flow and find qualitatively similar results, indicating that continuous motion also suppresses natural selection.
Sex-dependent expression of behavioural genetic architectures and the evolution of sexual dimorphism
Authors: Han Chang S. , Dingemanse Niels J.
Published: October 2017

Empirical studies imply that sex-specific genetic architectures can resolve evolutionary conflicts between males and females, and thereby facilitate the evolution of sexual dimorphism. Sex-specificity of behavioural genetic architectures has, however, rarely been considered. Moreover, as the expression of genetic (co)variances is often environment-dependent, general inferences on sex-specific genetic architectures require estimates of quantitative genetics parameters under multiple conditions. We measured exploration and aggression in pedigreed populations of southern field crickets (Gryllus bimaculatus) raised on either naturally balanced (free-choice) or imbalanced (protein-deprived) diets. For each dietary condition, we measured for each behavioural trait (i) level of sexual dimorphism, (ii) level of sex-specificity of survival selection gradients, (iii) level of sex-specificity of additive genetic variance, and (iv) strength of the cross-sex genetic correlation. We report here evidence for sexual dimorphism in behaviour as well as sex-specificity in the expression of genetic (co)variances as predicted by theory. The additive genetic variances of exploration and aggression were significantly greater in males compared with females. Cross-sex genetic correlations were highly positive for exploration but deviating (significantly) from one for aggression; findings were consistent across dietary treatments. This suggests that genetic architectures characterize the sexually dimorphic focal behaviours across various key environmental conditions in the wild. Our finding also highlights that sexual conflict can be resolved by evolving sexually independent genetic architectures.
Predictive Coding of Novel versus Familiar Stimuli in the Primary Visual Cortex
Authors: Homann Jan , Koay Sue Ann , Glidden Alistair M. , Tank David W. , Berry Michael J.
Published: October 2017

To explore theories of predictive coding, we presented mice with repeated sequences of images with novel images sparsely substituted. Under these conditions, mice could be rapidly trained to lick in response to a novel image, demonstrating a high level of performance on the first day of testing. Using 2-photon calcium imaging to record from layer 2/3 neurons in the primary visual cortex, we found that novel images evoked excess activity in the majority of neurons. When a new stimulus sequence was repeatedly presented, a majority of neurons had similarly elevated activity for the first few presentations, which then decayed to almost zero activity. The decay time of these transient responses was not fixed, but instead scaled with the length of the stimulus sequence. However, at the same time, we also found a small fraction of the neurons within the population (∼2%) that continued to respond strongly and periodically to the repeated stimulus. Decoding analysis demonstrated that both the transient and sustained responses encoded information about stimulus identity. We conclude that the layer 2/3 population uses a two-channel predictive code: a dense transient code for novel stimuli and a sparse sustained code for familiar stimuli. These results extend and unify existing theories about the nature of predictive neural codes.
Native and engineered clifednamide biosynthesis in multipleStreptomycesspp
Authors: Qi YuncI , Ding Edward , Blodgett Joshua A.V.
Published: October 2017

Polycyclic tetramate macrolactam (PTM) natural products are produced by actinomycetes and other bacteria. PTMs are often bioactive, and the simplicity of their biosynthetic clusters make them attractive for bioengineering. Clifednamide-type PTMs fromStreptomycessp. JV178 contain a distinctive ketone group, suggesting the existence of a novel PTM oxidizing enzyme. Here, we report the new cytochrome P450 enzyme (CftA) is required for clifednamide production. Genome mining was used to identify several new clifednamide producers, some having improved clifednamide yields. Using a parallel synthetic biology approach, CftA isozymes were used to engineer the ikarugamycin pathway ofStreptomycessp. NRRL F-2890 to yield clifednamides. Further, we observed that strong CftA expression leads to the production of a new PTM, clifednamide C. We demonstrate the utility of both genome mining and synthetic biology to rapidly increase clifednamide production and identify a PTM tailoring enzyme for rational molecule design.
The experience of vivid autobiographical reminiscence is supported by personal semantic representations in the precuneus
Authors: Sreekumar Vishnu , Nielson Dylan M. , Smith Troy A. , Dennis Simon J. , Sederberg Per B.
Published: October 2017

Recent studies have suggested that the human posteromedial cortex (PMC), which includes core regions of the default mode network (DMN), plays an important role in episodic memory. Whereas various roles relating to self-relevant processing and memory retrieval have been attributed to different subsystems within this broad network, the nature of representations and the functional roles they support in these brain regions remain unspecified. Here, we describe the whole-brain networks that representsubjective, self-relevant aspects of real-world events during autobiographical recollection. Nine participants wore a device to record images from their lives for a period of two to four weeks (lifelogging phase) and indicated the personally-salient attributes (i.e., personal semantics) of each episode by choosing multiple content tags. Two to four weeks after the lifelogging phase, participants relived their experiences in an fMRI scanner cued by images chosen from their own lives. Representational Similarity Analysis revealed a broad network, including parts of the DMN, that represented personal semantics during autobiographical reminiscence. Furthermore, within this network, the right precuneus represented personally relevant content during vivid recollection but not during non-vivid recollection. The precuneus is a hub within the DMN and has been implicated in metacognitive ability for memory retrieval. Our results suggest a more specific mechanism underlying the phenomenology of vivid reminiscence, supported by personal semantic representations in the precuneus.
Finding cell-specific expression patterns in the early Ciona embryo with single-cell RNA-seq
Authors: Ilsley Garth R. , Suyama Ritsuko , Noda Takeshi , Satoh Nori , Luscombe Nicholas M.
Published: October 2017

Single-cell RNA-seq has been established as a reliable and accessible technique enabling new types of analyses, such as identifying cell types and studying spatial and temporal gene expression variation and change at single-cell resolution. Recently, single-cell RNA-seq has been applied to developing embryos, which offers great potential for finding and characterising genes controlling the course of development along with their expression patterns. In this study, we applied single-cell RNA-seq to the 16-cell stage of the Ciona embryo, a marine chordate and performed a computational search for cell-specific gene expression patterns. We recovered many known expression patterns from our single-cell RNA-seq data and despite extensive previous screens, we succeeded in finding new cell-specific patterns, which we validated by in situ and single-cell qPCR.
NGSphy: phylogenomic simulation of next-generation sequencing data
Authors: Escalona Merly , Rocha Sara , Posada David
Published: October 2017

Motivation

Advances in sequencing technologies have made it feasible to obtain massive datasets for phylogenomic inference, often consisting of large numbers of loci from multiple species and individuals. The phylogenomic analysis of next-generation sequencing (NGS) data implies a complex computational pipeline where multiple technical and methodological decisions are necessary that can influence the final tree obtained, like those related to coverage, assembly, mapping, variant calling and/or phasing.

Results

To assess the influence of these variables we introduce NGSphy, an open-source tool for the simulation of Illumina reads/read counts obtained from haploid/diploid individual genomes with thousands of independent gene families evolving under a common species tree. In order to resemble real NGS experiments, NGSphy includes multiple options to model sequencing coverage (depth) heterogeneity across species, individuals and loci, including off-target or uncaptured loci. For comprehensive simulations covering multiple evolutionary scenarios, parameter values for the different replicates can be sampled from user-defined statistical distributions.

Availability

Source code, full documentation and tutorials including a quick start guide are available athttp://github.com/merlyescalona/ngsphy.

Contact

merlyescalona@uvigo.es.dposada@uvigo.es
Interactions of pathogenic and commensal strains of Mannheimia haemolytica with differentiated bovine airway epithelial cells grown at an air-liquid interface
Authors: Cozens Daniel , Sutherland Erin , Lauder Miquel , Taylor Geraldine , Berry Catherine C. , Davies Robert L.
Published: October 2017

Mannheimia haemolyticaserotype A2 is a common commensal species present in the nasopharynx of healthy cattle. However, prior to the onset of bovine pneumonic pasteurellosis, there is sudden increase inM. haemolyticaserotype A1 within the upper respiratory tract. The events during this selective proliferation of serotype A1 strains are poorly characterised. In this investigation, a differentiated bovine airway epithelial cell culture was used to study the interactions of A1 and A2 bovine isolates with the respiratory epithelium. This model reproduced the key defences of the airway epithelium, including tight junctions and mucociliary clearance. Although initial adherence of the serotype A1 strains was low, by 12 hours post-infection the bacteria was able to traverse the tight junctions to form foci of infection below the apical surface. The size, density and number of these foci increased with time, as did the cytopathic effects observed in the bovine bronchial epithelial cells. Penetration ofM. haemolyticaA1 into the sub-apical epithelium was shown to be through transcytosis but not paracytosis. Commensal A2 bovine isolates however were not capable of colonising the model to a high degree, and did not penetrate the epithelium following initial adherence at the apical surface. This difference in their ability to colonise the respiratory epithelium may account for the sudden proliferation of serotype A1 in the onset of pneumonia pasteurellosis. The pathogenesis observed was replicated by virulent A2 ovine isolates; however colonisation was 10-fold lower in comparison to bovine A1 strains. This investigation provides new insight into the interactions ofM. haemolyticawith bovine airway epithelial cells which are occurringin vivoduring pneumonia pasteurellosis.
Allele-specific CRISPR/Cas9 genome editing of the single-base P23H mutation for rhodopsin associated dominant retinitis pigmentosa
Authors: Li Pingjuan , Kleinstiver Benjamin P. , Leon Mihoko Y. , Prew Michelle S. , Navarro-Gomez Daniel , Greenwald Scott H. , Pierce Eric A. , Joung J. Keith , Liu Qin
Published: October 2017

Treatment strategies for dominantly inherited disorders typically involve silencing or ablating the pathogenic allele. CRISPR/Cas nucleases have shown promise in allele-specific knockout approaches when the dominant allele creates unique protospacer adjacent motifs (PAMs) that can lead to allele restricted targeting. Here, we present a spacer-mediated allele-specific knockout approach that utilizes both SpCas9 variants and truncated single guide RNAs (trusgRNAs) to achieve efficient discrimination of a single-nucleotide mutation in rhodopsin (Rho)-P23H mice, a model of dominant retinitis pigmentosa (RP). We found that approximately 45% of the mutant P23H allele was edited at DNA level, and that the relative RNA expression of wild-type Rho was about 2.8 times more than that of mutant Rho in treated retinas. Furthermore, the progression of photoreceptor cell degeneration in outer nuclear layer was significantly delayed in treated regions of the Rho-P23H retinas at five weeks of age. Our proof-of-concept study therefore outlines a general strategy that could potentially be expanded to examine the therapeutic benefit of allele-specific gene editing approach to treat human P23H patient. Our study also extends allele-specific editing strategies beyond discrimination within the PAM sites, with potentially broad applicability to other dominant diseases.
Predicting cancer outcomes from histology and genomics using convolutional networks
Authors: Mobadersany Pooya , Yousefi Safoora , Amgad Mohamed , Gutman David A , Barnholtz-Sloan Jill S , Velazquez Vega Jose Enrique , Brat Daniel J , Cooper Lee AD
Published: October 2017

Cancer histology reflects underlying molecular processes and disease progression, and contains rich phenotypic information that is predictive of patient outcomes. In this study, we demonstrate a computational approach for learning patient outcomes from digital pathology images using deep learning to combine the power of adaptive machine learning algorithms with traditional survival models. We illustrate how this approach can integrate information from both histology images and genomic biomarkers to predict time-to-event patient outcomes, and demonstrate performance surpassing the current clinical paradigm for predicting the survival of patients diagnosed with glioma. We also provide techniques to visualize the tissue patterns learned by these deep learning survival models, and establish a framework for addressing intratumoral heterogeneity and training data deficits.
A blueprint for human whole-cell modeling
Authors: Szigeti Balázs , Roth Yosef D. , Sekar John A. P. , Goldberg Arthur P. , Pochiraju Saahith C. , Karr Jonathan R.
Published: October 2017

Whole-cell models of human cells are a central goal of systems biology. Such models could help researchers understand cell biology and help physicians treat disease. Despite significant challenges, we believe that human whole-cell models are rapidly becoming feasible. To develop a plan for achieving human whole-cell models, we analyzed the existing models of individual cellular pathways, surveyed the biomodeling community, and reflected on our experience developing whole-cell models of bacteria. Based on these analyses, we propose a plan for a project, termed theHuman Whole-Cell Modeling Project, to achieve human whole-cell models. The foundations of the plan include technology development, standards development, and interdisciplinary collaboration.
Harvesting straw in Poland and Finland
Authors: Joensuu Katri , Sinkko Taija
Published: October 2017

Purpose

There is growing interest in using crop residues, particularly cereal straw, to replace fossil fuels in heat and electricity production. The purpose of the present study was to assess and compare the environmental impacts of straw production in two European Union countries, Poland and Finland.

Design/methodology/approach

The selected environmental impacts were greenhouse gas (GHG) emissions, biodiversity and soil physical quality. The latter was represented by the indicators of soil erosion and compaction. For biodiversity and erosion assessment, the authors used two methods that could be used with existing easily accessible data and thus did not require excessive fieldwork.

Findings

Compared to the fossil reference fuel, coal, straw production caused minimal GHG emissions in both of the subject countries. Biodiversity and erosion impacts were greater in Poland, while the potential risk of soil compaction caused by field traffic is greater in Finland.

Originality/value

The study provides insight into the impacts of bioenergy production on biodiversity and soil quality, of which there is currently limited knowledge.
Professional value and ethical self-regulation in the development of modern librarianship
Authors: Hansson Joacim
Published: October 2017

Purpose

The purpose of this paper is twofold: first, to make a contribution to the theoretical understanding of documents and documentary agency in society through examples from a defined institutional and professional setting; and second, to create an understanding for the role of ethical codes in the process of defining and developing modern librarianship.

Design/methodology/approach

This study analyses the role of documentation carrying content of professional ethics in the formulation of modern librarianship. This is done through a series of example documents of various kinds, such as founding charters, peer handbooks and ethical codes systematically analysed through the use of document theory and theory on institutional change.

Findings

The findings of this study suggest that documents pronouncing ethical self-regulation within librarianship play a primarily legitimising role in situations where new types of libraries emerge or when libraries adapt to social change. The study proposes legitimacy as a key aspect of documentality, thus supplementing the established understanding of the concept.

Originality/value

This study is the first to analyse the role of ethical codes in libraries using document theory. It brings new knowledge to the role of ethical self-regulation in librarianship over time and in different institutional contexts. In suggesting a developed definition of documentality, it contributes to the theoretical understanding of the role of documents and documentation in institutions and in society at large.
“Google is not fun”: an investigation of how Swedish teenagers frame online searching
Authors: Andersson Cecilia
Published: October 2017

Purpose

The purpose of this paper is to investigate the role of Google in everyday online searching activities of Swedish teenagers in different contexts.

Design/methodology/approach

The study is qualitative and material has been produced through interviews and observations in two different schools with participants aged 15-16. Goffman’s frame analysis provides the analytical lens for studying how activities are assigned meaning.

Findings

Three different framings in relation to using Google and googling are identified in the material: Google and fact-finding, Google as a neutral infrastructure, and Google as an authority. There is an interplay between activity, context, and interaction in defining the role of Google. In relation to school, the fact-finding framing is more pronounced whereas the infrastructure framing comes forth more in their free time activities. The authority framing cuts across both framings and underpins their trust in the search engine.

Originality/value

The study addresses the way that Google is embedded in online activities and how the search engine is viewed in various contexts, as well as how it is made invisible in some contexts. Previous research has not addressed Google’s role in specific in relation to various everyday uses.
Social relevance assessments for virtual worlds
Authors: Costello Kaitlin Light
Published: October 2017

Purpose

The purpose of this paper is to introduce the concept of social relevance assessments, which are judgments made by individuals when they seek out information within virtual social worlds such as online support groups (OSGs).

Design/methodology/approach

Constructivist grounded theory was employed to examine the phenomenon of information exchange in OSGs for chronic kidney disease. In-depth interviews were conducted with 12 participants, and their posts in three OSGs were also harvested. Data were analyzed using inductive content analysis and the constant comparative method. Theoretical sampling was conducted until saturation was reached. Member checking, peer debriefing, and triangulation were used to verify results.

Findings

There are two levels of relevance assessment that occur when people seek out information in OSGs. First, participants evaluate the OSG to determine whether or not the group is an appropriate place for information exchange about kidney disease. Second, participants evaluate individual users on the OSG to see if they are appropriate people with whom to exchange information. This often takes the form of similarity assessment, whereby people try to determine whether or not they are similar to specific individuals on the forums. They use a variety of heuristics to assess similarity as part of this process.

Originality/value

This paper extends the author’s understanding of relevance in information science in two fundamental ways. Within the context of social information exchange, relevance is socially constructed and is based on social characteristics, such as age, shared beliefs, and experience. Moreover, relevance is assessed both when participants seek out information and when they disclose information, suggesting that the conception of relevance as a process that occurs primarily during information seeking is limited.
Three key affordances for serendipity
Authors: Björneborn Lennart
Published: October 2017

Purpose

Serendipity is an interesting phenomenon to study in information science as it plays a fundamental – but perhaps underestimated – role in how we discover, explore, and learn in all fields of life. The purpose of this paper is to operationalize the concept of serendipity by providing terminological “building blocks” for understanding connections between environmental and personal factors in serendipitous encounters. Understanding these connections is essential when designing affordances in physical and digital environments that can facilitate serendipity.

Design/methodology/approach

In this paper, serendipity is defined as what happens when we, in unplanned ways, encounter resources (information, things, people, etc.) that we find interesting. In the outlined framework, serendipity is understood as an affordance, i.e., a usage potential when environmental and personal factors correspond with each other. The framework introduces three key affordances for facilitating serendipity: diversifiability, traversability, and sensoriability, covering capacities of physical and digital environments to be diversified, traversed, and sensed. The framework is structured around couplings between the three key affordances and three key personal serendipity factors: curiosity, mobility, and sensitivity. Ten sub-affordances for serendipity and ten coupled personal sub-factors are also briefly outlined. Related research is compared with and mapped into the framework aiming at a theoretical validation. The affordance approach to serendipity is discussed, including different degrees and types of serendipity.

Findings

All the terminological “building blocks” in the framework are seen to resonate with the included related research. Serendipity is found to be a commonplace phenomenon in everyday life. It is argued that we cannot “engineer” nor “design” serendipityper se, but can design affordances for serendipity. Serendipity may thus be intended by designers, but must always be unplanned by users. The outlined affordance approach to serendipity points to the importance of our sensory-motor abilities to discover and explore serendipitous affordances.

Research limitations/implications

Implications of the framework for designing physical and digital environments with affordances for serendipity are briefly considered. It is suggested that physical environments may have a primacy regarding affordances of sensoriability for facilitating serendipity, and digital environments a primacy regarding traversability, whereas physical and digital environments may afford similar degrees of diversifiability. In future research, the framework needs further empirical validation in physical and digital environments.

Originality/value

No other research has been found addressing affordances for serendipity and connections between environmental and personal factors in similarly detailed ways. The outlined framework and typology may function as a baseline for further serendipity studies.
Cultural heritage as digital noise: nineteenth century newspapers in the digital archive
Authors: Jarlbrink Johan , Snickars Pelle
Published: October 2017

Purpose

The purpose of this paper is to explore and analyze the digitized newspaper collection at the National Library of Sweden, focusing on cultural heritage as digital noise. In what specific ways are newspapers transformed in the digitization process? If the digitized document is not the same as the source document – is it still a historical record, or is it transformed into something else?

Design/methodology/approach

The authors have analyzed the XML files fromAftonbladet1830 to 1862. The most frequent newspaper words not matching a high-quality references corpus were selected to zoom in on the noisiest part of the paper. The variety of the interpretations generated by optical character recognition (OCR) was examined, as well as texts generated by auto-segmentation. The authors have made a limited ethnographic study of the digitization process.

Findings

The research shows that the digital collection ofAftonbladetcontains extreme amounts of noise: millions of misinterpreted words generated by OCR, and millions of texts re-edited by the auto-segmentation tool. How the tools work is mostly unknown to the staff involved in the digitization process? Sticking to any idea of a provenance chain is hence impossible, since many steps have been outsourced to unknown factors affecting the source document.

Originality/value

The detail examination of digitally transformed newspapers is valuable to scholars depending on newspaper databases in their research. The paper also highlights the fact that libraries outsourcing digitization processes run the risk of losing control over the quality of their collections.
Getting-to-know
Authors: Sköld Olle
Published: October 2017

Purpose

The purpose of this paper is to investigate the sociocultural underpinnings of wiki-based knowledge production in the videogame domain, and to elucidate how these underpinnings relate to the formation of wikis as resources of videogame documentation.

Design/methodology/approach

The paper is based on a three-month ethnographic investigation of knowledge practices on the Dark Souls Wiki (DSW). In focus of the analysis were the boundaries and knowledge aims of the DSW, together with how its contributors organized inquiries and used various sources, methods of investigation, and ways of warranting knowledge claims.

Findings

The principal result of the paper is an empirical account of how the DSW functions as a culture of knowledge production, and how the content and structure of the wiki connects to the knowledge practices of its contributors. Four major factors that influenced knowledge practices on the wiki were identified: the structures and practices established by the community’s earlier wiki efforts; principles and priorities that informed wiki knowledge practices; the characteristics of the videogame in focus of the site’s knowledge-building work; the extent and types of relevant documentation provided by videogame industry, the videogaming press included.

Originality/value

Previous research has shown interest in investigating the mechanisms by which community-created knowledge and online resources of documentation emerge, and how these are utilized in play. There is, however, little research seeking to elucidate the sociocultural structures and practices that determine and sustain collaborative online videogame knowledge production.
Service quality and global competitiveness: evidence from global service firms
Authors: Sun Wenbin , Pang Jing
Published: October 2017

Purpose

The purpose of this paper is to explore the relationship between service quality and firms’ global competitiveness in the service industry. A set of moderating effects is formulated to further reveal how the relationship varies under different situations.

Design/methodology/approach

This paper tests the model with data collected from multiple sources such as World’s Most Admired Companies and COMPUSTAT. Two types of robust regressions for panel data are employed in the empirical model estimation.

Findings

Service quality is found to significantly drive global competitiveness. Specifically, its impact is stronger for large service firms and when the global environment is characterized as low munificence, high dynamism, or high complexity.

Practical implications

The paper provides a set of implications for managers of service firms regarding global expansion and quality management. It generates useful guidelines of maximizing the power of service quality when a firm’s global competitive advantage is considered.

Originality/value

This paper takes the first attempt to formulate service quality’s influence on firm’s global competitiveness with a consideration of specific situational factors.