Showing papers by "University of Turku published in 2017"

Expert consensus document: The International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of prebiotics

Abstract: With the continued interest in the role of the gut microbiota in health, attention has now turned to how to harness the microbiota for the benefit of the host. This Consensus Statement outlines the definition and scope of the term 'prebiotic' as determined by an expert panel convened by the International Scientific Association for Probiotics and Prebiotics in December 2016. In December 2016, a panel of experts in microbiology, nutrition and clinical research was convened by the International Scientific Association for Probiotics and Prebiotics to review the definition and scope of prebiotics. Consistent with the original embodiment of prebiotics, but aware of the latest scientific and clinical developments, the panel updated the definition of a prebiotic: a substrate that is selectively utilized by host microorganisms conferring a health benefit. This definition expands the concept of prebiotics to possibly include non-carbohydrate substances, applications to body sites other than the gastrointestinal tract, and diverse categories other than food. The requirement for selective microbiota-mediated mechanisms was retained. Beneficial health effects must be documented for a substance to be considered a prebiotic. The consensus definition applies also to prebiotics for use by animals, in which microbiota-focused strategies to maintain health and prevent disease is as relevant as for humans. Ultimately, the goal of this Consensus Statement is to engender appropriate use of the term 'prebiotic' by relevant stakeholders so that consistency and clarity can be achieved in research reports, product marketing and regulatory oversight of the category. To this end, we have reviewed several aspects of prebiotic science including its development, health benefits and legislation.

Traumatic brain injury: integrated approaches to improve prevention, clinical care, and research

Abstract: Additional co-authors: Endre Czeiter, Marek Czosnyka, Ramon Diaz-Arrastia, Jens P Dreier, Ann-Christine Duhaime, Ari Ercole, Thomas A van Essen, Valery L Feigin, Guoyi Gao, Joseph Giacino, Laura E Gonzalez-Lara, Russell L Gruen, Deepak Gupta, Jed A Hartings, Sean Hill, Ji-yao Jiang, Naomi Ketharanathan, Erwin J O Kompanje, Linda Lanyon, Steven Laureys, Fiona Lecky, Harvey Levin, Hester F Lingsma, Marc Maegele, Marek Majdan, Geoffrey Manley, Jill Marsteller, Luciana Mascia, Charles McFadyen, Stefania Mondello, Virginia Newcombe, Aarno Palotie, Paul M Parizel, Wilco Peul, James Piercy, Suzanne Polinder, Louis Puybasset, Todd E Rasmussen, Rolf Rossaint, Peter Smielewski, Jeannette Soderberg, Simon J Stanworth, Murray B Stein, Nicole von Steinbuchel, William Stewart, Ewout W Steyerberg, Nino Stocchetti, Anneliese Synnot, Braden Te Ao, Olli Tenovuo, Alice Theadom, Dick Tibboel, Walter Videtta, Kevin K W Wang, W Huw Williams, Kristine Yaffe for the InTBIR Participants and Investigators

Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines—2016 revision

Abstract: Background Allergic rhinitis (AR) affects 10% to 40% of the population. It reduces quality of life and school and work performance and is a frequent reason for office visits in general practice. Medical costs are large, but avoidable costs associated with lost work productivity are even larger than those incurred by asthma. New evidence has accumulated since the last revision of the Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines in 2010, prompting its update. Objective We sought to provide a targeted update of the ARIA guidelines. Methods The ARIA guideline panel identified new clinical questions and selected questions requiring an update. We performed systematic reviews of health effects and the evidence about patients' values and preferences and resource requirements (up to June 2016). We followed the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) evidence-to-decision frameworks to develop recommendations. Results The 2016 revision of the ARIA guidelines provides both updated and new recommendations about the pharmacologic treatment of AR. Specifically, it addresses the relative merits of using oral H1-antihistamines, intranasal H1-antihistamines, intranasal corticosteroids, and leukotriene receptor antagonists either alone or in combination. The ARIA guideline panel provides specific recommendations for the choice of treatment and the rationale for the choice and discusses specific considerations that clinicians and patients might want to review to choose the management most appropriate for an individual patient. Conclusions Appropriate treatment of AR might improve patients' quality of life and school and work productivity. ARIA recommendations support patients, their caregivers, and health care providers in choosing the optimal treatment.

A kilonova as the electromagnetic counterpart to a gravitational-wave source

Abstract: Gravitational waves were discovered with the detection of binary black-hole mergers and they should also be detectable from lower-mass neutron-star mergers. These are predicted to eject material rich in heavy radioactive isotopes that can power an electromagnetic signal. This signal is luminous at optical and infrared wavelengths and is called a kilonova. The gravitational-wave source GW170817 arose from a binary neutron-star merger in the nearby Universe with a relatively well confined sky position and distance estimate. Here we report observations and physical modelling of a rapidly fading electromagnetic transient in the galaxy NGC 4993, which is spatially coincident with GW170817 and with a weak, short γ-ray burst. The transient has physical parameters that broadly match the theoretical predictions of blue kilonovae from neutron-star mergers. The emitted electromagnetic radiation can be explained with an ejected mass of 0.04 ± 0.01 solar masses, with an opacity of less than 0.5 square centimetres per gram, at a velocity of 0.2 ± 0.1 times light speed. The power source is constrained to have a power-law slope of -1.2 ± 0.3, consistent with radioactive powering from r-process nuclides. (The r-process is a series of neutron capture reactions that synthesise many of the elements heavier than iron.) We identify line features in the spectra that are consistent with light r-process elements (atomic masses of 90-140). As it fades, the transient rapidly becomes red, and a higher-opacity, lanthanide-rich ejecta component may contribute to the emission. This indicates that neutron-star mergers produce gravitational waves and radioactively powered kilonovae, and are a nucleosynthetic source of the r-process elements.

Digital Supply Chain Transformation toward Blockchain Integration

Abstract: Digital supply chain integration is becoming increasingly dynamic. Access to customer demand needs to be shared effectively, and product and service deliveries must be tracked to provide visibility in the supply chain. Business process integration is based on standards and reference architectures, which should offer end-to-end integration of product data. Companies operating in supply chains establish process and data integration through the specialized intermediate companies, whose role is to establish interoperability by mapping and integrating companyspecific data for various organizations and systems. This has typically caused high integration costs, and diffusion is slow. This paper investigates the requirements and functionalities of supply chain integration. Cloud integration can be expected to offer a cost-effective business model for interoperable digital supply chains. We explain how supply chain integration through the blockchain technology can achieve disruptive transformation in digital supply chains and networks.

SynergyFinder: a web application for analyzing drug combination dose-response matrix data.

Abstract: Summary Rational design of drug combinations has become a promising strategy to tackle the drug sensitivity and resistance problem in cancer treatment. To systematically evaluate the pre-clinical significance of pairwise drug combinations, functional screening assays that probe combination effects in a dose-response matrix assay are commonly used. To facilitate the analysis of such drug combination experiments, we implemented a web application that uses key functions of R-package SynergyFinder, and provides not only the flexibility of using multiple synergy scoring models, but also a user-friendly interface for visualizing the drug combination landscapes in an interactive manner. Availability and implementation The SynergyFinder web application is freely accessible at https://synergyfinder.fimm.fi ; The R-package and its source-code are freely available at http://bioconductor.org/packages/release/bioc/html/synergyfinder.html . Contact jing.tang@helsinki.fi.

YAP regulates cell mechanics by controlling focal adhesion assembly

Abstract: Hippo effectors YAP/TAZ act as on-off mechanosensing switches by sensing modifications in extracellular matrix (ECM) composition and mechanics. The regulation of their activity has been described by a hierarchical model in which elements of Hippo pathway are under the control of focal adhesions (FAs). Here we unveil the molecular mechanism by which cell spreading and RhoA GTPase activity control FA formation through YAP to stabilize the anchorage of the actin cytoskeleton to the cell membrane. This mechanism requires YAP co-transcriptional function and involves the activation of genes encoding for integrins and FA docking proteins. Tuning YAP transcriptional activity leads to the modification of cell mechanics, force development and adhesion strength, and determines cell shape, migration and differentiation. These results provide new insights into the mechanism of YAP mechanosensing activity and qualify this Hippo effector as the key determinant of cell mechanics in response to ECM cues.

Bullying in schools: the state of knowledge and effective interventions.

Abstract: During the school years, bullying is one of the most common expressions of violence in the peer context. Research on bullying started more than forty years ago, when the phenomenon was defined as 'aggressive, intentional acts carried out by a group or an individual repeatedly and over time against a victim who cannot easily defend him- or herself'. Three criteria are relevant in order to define aggressive behaviour as bullying: (1) repetition, (2) intentionality and (3) an imbalance of power. Given these characteristics, bullying is often defined as systematic abuse of power by peers. It is recognised globally as a complex and serious problem. In the present paper, we discuss the prevalence, age and gender differences, and various types of bullying, as well as why it happens and how long it lasts, starting from the large surveys carried out in western countries and to a lower extent in low- and middle-income countries. The prevalence rates vary widely across studies; therefore, specific attention will be devoted to the definition, time reference period and frequency criterion. We will also focus on risk factors as well as short- and long-term outcomes of bullying and victimisation. Finally, a section will be dedicated to review what is known about effective prevention of bullying.

Electronic health records to facilitate clinical research.

Abstract: Electronic health records (EHRs) provide opportunities to enhance patient care, embed performance measures in clinical practice, and facilitate clinical research. Concerns have been raised about the increasing recruitment challenges in trials, burdensome and obtrusive data collection, and uncertain generalizability of the results. Leveraging electronic health records to counterbalance these trends is an area of intense interest. The initial applications of electronic health records, as the primary data source is envisioned for observational studies, embedded pragmatic or post-marketing registry-based randomized studies, or comparative effectiveness studies. Advancing this approach to randomized clinical trials, electronic health records may potentially be used to assess study feasibility, to facilitate patient recruitment, and streamline data collection at baseline and follow-up. Ensuring data security and privacy, overcoming the challenges associated with linking diverse systems and maintaining infrastructure for repeat use of high quality data, are some of the challenges associated with using electronic health records in clinical research. Collaboration between academia, industry, regulatory bodies, policy makers, patients, and electronic health record vendors is critical for the greater use of electronic health records in clinical research. This manuscript identifies the key steps required to advance the role of electronic health records in cardiovascular clinical research.

Overweight, obesity, and risk of cardiometabolic multimorbidity: pooled analysis of individual-level data for 120 813 adults from 16 cohort studies from the USA and Europe

Abstract: Summary Background Although overweight and obesity have been studied in relation to individual cardiometabolic diseases, their association with risk of cardiometabolic multimorbidity is poorly understood Here we aimed to establish the risk of incident cardiometabolic multimorbidity (ie, at least two from: type 2 diabetes, coronary heart disease, and stroke) in adults who are overweight and obese compared with those who are a healthy weight Methods We pooled individual-participant data for BMI and incident cardiometabolic multimorbidity from 16 prospective cohort studies from the USA and Europe Participants included in the analyses were 35 years or older and had data available for BMI at baseline and for type 2 diabetes, coronary heart disease, and stroke at baseline and follow-up We excluded participants with a diagnosis of diabetes, coronary heart disease, or stroke at or before study baseline According to WHO recommendations, we classified BMI into categories of healthy (20·0–24·9 kg/m 2 ), overweight (25·0–29·9 kg/m 2 ), class I (mild) obesity (30·0–34·9 kg/m 2 ), and class II and III (severe) obesity (≥35·0 kg/m 2 ) We used an inclusive definition of underweight ( 2 ) to achieve sufficient case numbers for analysis The main outcome was cardiometabolic multimorbidity (ie, developing at least two from: type 2 diabetes, coronary heart disease, and stroke) Incident cardiometabolic multimorbidity was ascertained via resurvey or linkage to electronic medical records (including hospital admissions and death) We analysed data from each cohort separately using logistic regression and then pooled cohort-specific estimates using random-effects meta-analysis Findings Participants were 120 813 adults (mean age 51·4 years, range 35–103; 71 445 women) who did not have diabetes, coronary heart disease, or stroke at study baseline (1973–2012) During a mean follow-up of 10·7 years (1995–2014), we identified 1627 cases of multimorbidity After adjustment for sociodemographic and lifestyle factors, compared with individuals with a healthy weight, the risk of developing cardiometabolic multimorbidity in overweight individuals was twice as high (odds ratio [OR] 2·0, 95% CI 1·7–2·4; p Interpretation The risk of cardiometabolic multimorbidity increases as BMI increases; from double in overweight people to more than ten times in severely obese people compared with individuals with a healthy BMI Our findings highlight the need for clinicians to actively screen for diabetes in overweight and obese patients with vascular disease, and pay increased attention to prevention of vascular disease in obese individuals with diabetes Funding NordForsk, Medical Research Council, Cancer Research UK, Finnish Work Environment Fund, and Academy of Finland

Higher predation risk for insect prey at low latitudes and elevations

Abstract: Biotic interactions underlie ecosystem structure and function, but predicting interaction outcomes is difficult We tested the hypothesis that biotic interaction strength increases toward the equator, using a global experiment with model caterpillars to measure predation risk Across an 11,660-kilometer latitudinal gradient spanning six continents, we found increasing predation toward the equator, with a parallel pattern of increasing predation toward lower elevations Patterns across both latitude and elevation were driven by arthropod predators, with no systematic trend in attack rates by birds or mammals These matching gradients at global and regional scales suggest consistent drivers of biotic interaction strength, a finding that needs to be integrated into general theories of herbivory, community organization, and life-history evolution

Self-monitoring of blood pressure in hypertension: A systematic review and individual patient data meta-analysis

Abstract: © 2017 Tucker et al. Background: Self-monitoring of blood pressure (BP) appears to reduce BP in hypertension but important questions remain regarding effective implementation and which groups may benefit most. This individual patient data (IPD) meta-analysis was performed to better understand the effectiveness of BP self-monitoring to lower BP and control hypertension. Methods and findings: Medline, Embase, and the Cochrane Library were searched for randomised trials comparing self-monitoring to no self-monitoring in hypertensive patients (June 2016). Two reviewers independently assessed articles for eligibility and the authors of eligible trials were approached requesting IPD. Of 2,846 articles in the initial search, 36 were eligible. IPD were provided from 25 trials, including 1 unpublished study. Data for the primary outcomes—change in mean clinic or ambulatory BP and proportion controlled below target at 12 months—were available from 15/19 possible studies (7,138/8,292 [86%] of randomised participants). Overall, self-monitoring was associated with reduced clinic systolic blood pressure (sBP) compared to usual care at 12 months (−3.2 mmHg, [95% CI −4.9, −1.6 mmHg]). However, this effect was strongly influenced by the intensity of co-intervention ranging from no effect with self-monitoring alone (−1.0 mmHg [−3.3, 1.2]), to a 6.1 mmHg (−9.0, −3.2) reduction when monitoring was combined with intensive support. Self-monitoring was most effective in those with fewer antihypertensive medications and higher baseline sBP up to 170 mmHg. No differences in efficacy were seen by sex or by most comorbidities. Ambulatory BP data at 12 months were available from 4 trials (1,478 patients), which assessed self-monitoring with little or no co-intervention. There was no association between self-monitoring and either lower clinic or ambulatory sBP in this group (clinic −0.2 mmHg [−2.2, 1.8]; ambulatory 1.1 mmHg [−0.3, 2.5]). Results for diastolic blood pressure (dBP) were similar. The main limitation of this work was that significant heterogeneity remained. This was at least in part due to different inclusion criteria, self-monitoring regimes, and target BPs in included studies. Conclusions: Self-monitoring alone is not associated with lower BP or better control, but in conjunction with co-interventions (including systematic medication titration by doctors, pharmacists, or patients; education; or lifestyle counselling) leads to clinically significant BP reduction which persists for at least 12 months. The implementation of self-monitoring in hypertension should be accompanied by such co-interventions.

Tailored approaches in drug development and diagnostics: from molecular design to biological model systems

Abstract: Approaches to increase the efficiency in developing drugs and diagnostics tools, including new drug delivery and diagnostic technologies, are needed for improved diagnosis and treatment of major diseases and health problems such as cancer, inflammatory diseases, chronic wounds, and antibiotic resistance. Development within several areas of research ranging from computational sciences, material sciences, bioengineering to biomedical sciences and bioimaging is needed to realize innovative drug development and diagnostic (DDD) approaches. Here, an overview of recent progresses within key areas that can provide customizable solutions to improve processes and the approaches taken within DDD is provided. Due to the broadness of the area, unfortunately all relevant aspects such as pharmacokinetics of bioactive molecules and delivery systems cannot be covered. Tailored approaches within (i) bioinformatics and computer-aided drug design, (ii) nanotechnology, (iii) novel materials and technologies for drug delivery and diagnostic systems, and (iv) disease models to predict safety and efficacy of medicines under development are focused on. Current developments and challenges ahead are discussed. The broad scope reflects the multidisciplinary nature of the field of DDD and aims to highlight the convergence of biological, pharmaceutical, and medical disciplines needed to meet the societal challenges of the 21st century.

Job strain as a risk factor for clinical depression: systematic review and meta-analysis with additional individual participant data

Abstract: BACKGROUND: Adverse psychosocial working environments characterized by job strain (the combination of high demands and low control at work) are associated with an increased risk of depressive symptoms among employees, but evidence on clinically diagnosed depression is scarce. We examined job strain as a risk factor for clinical depression. METHOD: We identified published cohort studies from a systematic literature search in PubMed and PsycNET and obtained 14 cohort studies with unpublished individual-level data from the Individual-Participant-Data Meta-analysis in Working Populations (IPD-Work) Consortium. Summary estimates of the association were obtained using random-effects models. Individual-level data analyses were based on a pre-published study protocol. RESULTS: We included six published studies with a total of 27 461 individuals and 914 incident cases of clinical depression. From unpublished datasets we included 120 221 individuals and 982 first episodes of hospital-treated clinical depression. Job strain was associated with an increased risk of clinical depression in both published [relative risk (RR) = 1.77, 95% confidence interval (CI) 1.47-2.13] and unpublished datasets (RR = 1.27, 95% CI 1.04-1.55). Further individual participant analyses showed a similar association across sociodemographic subgroups and after excluding individuals with baseline somatic disease. The association was unchanged when excluding individuals with baseline depressive symptoms (RR = 1.25, 95% CI 0.94-1.65), but attenuated on adjustment for a continuous depressive symptoms score (RR = 1.03, 95% CI 0.81-1.32). CONCLUSIONS: Job strain may precipitate clinical depression among employees. Future intervention studies should test whether job strain is a modifiable risk factor for depression.

CoNLL 2017 Shared Task: Multilingual Parsing from Raw Text to Universal Dependencies

Abstract: The Conference on Computational Natural Language Learning (CoNLL) features a shared task, in which participants train and test their learning systems on the same data sets. In 2017, the task was devoted to learning dependency parsers for a large number of languages, in a real-world setting without any gold-standard annotation on input. All test sets followed a unified annotation scheme, namely that of Universal Dependencies. In this paper, we define the task and evaluation methodology, describe how the data sets were prepared, report and analyze the main results, and provide a brief categorization of the different approaches of the participating systems.

Music-based interventions in neurological rehabilitation

Abstract: Summary During the past ten years, an increasing number of controlled studies have assessed the potential rehabilitative effects of music-based interventions, such as music listening, singing, or playing an instrument, in several neurological diseases. Although the number of studies and extent of available evidence is greatest in stroke and dementia, there is also evidence for the effects of music-based interventions on supporting cognition, motor function, or emotional wellbeing in people with Parkinson's disease, epilepsy, or multiple sclerosis. Music-based interventions can affect divergent functions such as motor performance, speech, or cognition in these patient groups. However, the psychological effects and neurobiological mechanisms underlying the effects of music interventions are likely to share common neural systems for reward, arousal, affect regulation, learning, and activity-driven plasticity. Although further controlled studies are needed to establish the efficacy of music in neurological recovery, music-based interventions are emerging as promising rehabilitation strategies.

Genome-wide physical activity interactions in adiposity. A meta-analysis of 200,452 adults

Abstract: Physical activity (PA) may modify the genetic effects that give rise to increased risk of obesity. To identify adiposity loci whose effects are modified by PA, we performed genome-wide interaction meta-analyses of BMI and BMI-adjusted waist circumference and waist-hip ratio from up to 200,452 adults of European (n = 180,423) or other ancestry (n = 20,029). We standardized PA by categorizing it into a dichotomous variable where, on average, 23% of participants were categorized as inactive and 77% as physically active. While we replicate the interaction with PA for the strongest known obesity-risk locus in the FTO gene, of which the effect is attenuated by ~30% in physically active individuals compared to inactive individuals, we do not identify additional loci that are sensitive to PA. In additional genome-wide meta-analyses adjusting for PA and interaction with PA, we identify 11 novel adiposity loci, suggesting that accounting for PA or other environmental factors that contribute to variation in adiposity may facilitate gene discovery.

Observation of the Identical Rigidity Dependence of He, C, and O Cosmic Rays at High Rigidities by the Alpha Magnetic Spectrometer on the International Space Station

Abstract: We report the observation of new properties of primary cosmic rays He, C, and O measured in the rigidity (momentum/charge) range 2 GV to 3 TV with 90×106 helium, 8.4×106 carbon, and 7.0×106 oxygen nuclei collected by the Alpha Magnetic Spectrometer (AMS) during the first five years of operation. Above 60 GV, these three spectra have identical rigidity dependence. They all deviate from a single power law above 200 GV and harden in an identical way.

Role of microbial biofilms in the maintenance of oral health and in the development of dental caries and periodontal diseases. Consensus report of group 1 of the joint efp/orca workshop on the boundaries between caries and periodontal disease

Abstract: BACKGROUND AND AIMS: The scope of this working group was to review (1) ecological interactions at the dental biofilm in health and disease, (2) the role of microbial communities in the pathogenesis of periodontitis and caries, and (3) the innate host response in caries and periodontal diseases. RESULTS AND CONCLUSIONS: A health-associated biofilm includes genera such as Neisseria, Streptococcus, Actinomyces, Veillonella and Granulicatella. Microorganisms associated with both caries and periodontal diseases are metabolically highly specialized and organized as multispecies microbial biofilms. Progression of these diseases involves multiple microbial interactions driven by different stressors. In caries, the exposure of dental biofilms to dietary sugars and their fermentation to organic acids results in increasing proportions of acidogenic and aciduric species. In gingivitis, plaque accumulation at the gingival margin leads to inflammation and increasing proportions of proteolytic and often obligately anaerobic species. The natural mucosal barriers and saliva are the main innate defence mechanisms against soft tissue bacterial invasion. Similarly, enamel and dentin are important hard tissue barriers to the caries process. Given that the present state of knowledge suggests that the aetiologies of caries and periodontal diseases are mutually independent, the elements of innate immunity that appear to contribute to resistance to both are somewhat coincidental.

Genome-wide association analyses for lung function and chronic obstructive pulmonary disease identify new loci and potential druggable targets

Abstract: Chronic obstructive pulmonary disease (COPD) is characterized by reduced lung function and is the third leading cause of death globally. Through genome-wide association discovery in 48,943 individuals, selected from extremes of the lung function distribution in UK Biobank, and follow-up in 95,375 individuals, we increased the yield of independent signals for lung function from 54 to 97. A genetic risk score was associated with COPD susceptibility (odds ratio per 1 s.d. of the risk score (∼6 alleles) (95% confidence interval) = 1.24 (1.20-1.27), P = 5.05 × 10(-49)), and we observed a 3.7-fold difference in COPD risk between individuals in the highest and lowest genetic risk score deciles in UK Biobank. The 97 signals show enrichment in genes for development, elastic fibers and epigenetic regulation pathways. We highlight targets for drugs and compounds in development for COPD and asthma (genes in the inositol phosphate metabolism pathway and CHRM3) and describe targets for potential drug repositioning from other clinical indications.

Genome-wide Association Study Identifies 27 Loci Influencing Concentrations of Circulating Cytokines and Growth Factors

Abstract: Circulating cytokines and growth factors are regulators of inflammation and have been implicated in autoimmune and metabolic diseases. In this genome-wide association study (GWAS) of up to 8,293 Finns we identified 27 genome-widely significant loci (p −9 ) for one or more cytokines. Fifteen of the associated variants had expression quantitative trait loci in whole blood. We provide genetic instruments to clarify the causal roles of cytokine signaling and upstream inflammation in immune-related and other chronic diseases. We further link inflammatory markers with variants previously associated with autoimmune diseases such as Crohn disease, multiple sclerosis, and ulcerative colitis and hereby elucidate the molecular mechanisms underpinning these diseases and suggest potential drug targets.

The superluminous transient ASASSN-15lh as a tidal disruption event from a Kerr black hole

Abstract: When a star passes within the tidal radius of a supermassive black hole, it will be torn apart1. For a star with the mass of the Sun (M ⊙) and a non-spinning black hole with a mass 108 M ⊙ 12,13, a star with the same mass as the Sun could be disrupted outside the event horizon if the black hole were spinning rapidly14. The rapid spin and high black hole mass can explain the high luminosity of this event.

Gamified crowdsourcing: Conceptualization, literature review, and future agenda

Abstract: Two parallel phenomena are gaining attention in human–computer interaction research: gamification and crowdsourcing Because crowdsourcing's success depends on a mass of motivated crowdsourcees, crowdsourcing platforms have increasingly been imbued with motivational design features borrowed from games; a practice often called gamification While the body of literature and knowledge of the phenomenon have begun to accumulate, we still lack a comprehensive and systematic understanding of conceptual foundations, knowledge of how gamification is used in crowdsourcing, and whether it is effective We first provide a conceptual framework for gamified crowdsourcing systems in order to understand and conceptualize the key aspects of the phenomenon The paper's main contributions are derived through a systematic literature review that investigates how gamification has been examined in different types of crowdsourcing in a variety of domains This meticulous mapping, which focuses on all aspects in our framework, enables us to infer what kinds of gamification efforts are effective in different crowdsourcing approaches as well as to point to a number of research gaps and lay out future research directions for gamified crowdsourcing systems Overall, the results indicate that gamification has been an effective approach for increasing crowdsourcing participation and the quality of the crowdsourced work; however, differences exist between different types of crowdsourcing: the research conducted in the context of crowdsourcing of homogenous tasks has most commonly used simple gamification implementations, such as points and leaderboards, whereas crowdsourcing implementations that seek diverse and creative contributions employ gamification with a richer set of mechanics

How to design gamification? A method for engineering gamified software

Abstract: Context Since its inception around 2010, gamification has become one of the top technology and software trends. However, gamification has also been regarded as one of the most challenging areas of software engineering. Beyond traditional software design requirements, designing gamification requires the command of disciplines such as (motivational/behavioral) psychology, game design, and narratology, making the development of gamified software a challenge for traditional software developers. Gamification software inhabits a finely tuned niche of software engineering that seeks for both high functionality and engagement; beyond technical flawlessness, gamification has to motivate and affect users. Consequently, it has also been projected that most gamified software is doomed to fail. Objective This paper seeks to advance the understanding of designing gamification and to provide a comprehensive method for developing gamified software. Method We approach the research problem via a design science research approach; firstly, by synthesizing the current body of literature on gamification design methods and by interviewing 25 gamification experts, producing a comprehensive list of design principles for developing gamified software. Secondly, and more importantly, we develop a detailed method for engineering of gamified software based on the gathered knowledge and design principles. Finally, we conduct an evaluation of the artifacts via interviews of ten gamification experts and implementation of the engineering method in a gamification project. Results As results of the study, we present the method and key design principles for engineering gamified software. Based on the empirical and expert evaluation, the developed method was deemed as comprehensive, implementable, complete, and useful. We deliver a comprehensive overview of gamification guidelines and shed novel insights into the nature of gamification development and design discourse. Conclusion This paper takes first steps towards a comprehensive method for gamified software engineering.

PSEN1 Mutant iPSC-Derived Model Reveals Severe Astrocyte Pathology in Alzheimer's Disease.

Abstract: Summary Alzheimer's disease (AD) is a common neurodegenerative disorder and the leading cause of cognitive impairment. Due to insufficient understanding of the disease mechanisms, there are no efficient therapies for AD. Most studies have focused on neuronal cells, but astrocytes have also been suggested to contribute to AD pathology. We describe here the generation of functional astrocytes from induced pluripotent stem cells (iPSCs) derived from AD patients with PSEN1 ΔE9 mutation, as well as healthy and gene-corrected isogenic controls. AD astrocytes manifest hallmarks of disease pathology, including increased β-amyloid production, altered cytokine release, and dysregulated Ca 2+ homeostasis. Furthermore, due to altered metabolism, AD astrocytes show increased oxidative stress and reduced lactate secretion, as well as compromised neuronal supportive function, as evidenced by altering Ca 2+ transients in healthy neurons. Our results reveal an important role for astrocytes in AD pathology and highlight the strength of iPSC-derived models for brain diseases.

Effort-Reward Imbalance at Work and Incident Coronary Heart Disease: A Multicohort Study of 90,164 Individuals.

Abstract: Background: Epidemiologic evidence for work stress as a risk factor for coronary heart disease is mostly based on a single measure of stressful work known as job strain, a combination of high deman ...