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Objective To assess whether an easy-to-use multifaceted intervention for children presenting to primary care with respiratory tract infections would reduce antibiotic dispensing, without increasing hospital admissions for respiratory tract infection. Design Two arm randomised controlled trial clustered by general practice, using routine outcome data, with qualitative and economic evaluations. Setting English primary care practices using the EMIS electronic medical record system. Participants Children aged 0-9 years presenting with respiratory tract infection at 294 general practices, before and during the covid-19 pandemic. Intervention Elicitation of parental concerns during consultation; a clinician focused prognostic algorithm to identify children at very low, normal, or elevated 30 day risk of hospital admission accompanied by antibiotic prescribing guidance; and a leaflet for carers including safety netting advice. Main outcome measures Rate of dispensed amoxicillin and macrolide antibiotics (superiority comparison) and hospital admissions for respiratory tract infection (non-inferiority comparison) for children aged 0-9 years over 12 months (same age practice list size as denominator). Results Of 310 practices needed, 294 (95%) were randomised (144 intervention and 150 controls) representing 5% of all registered 0-9 year olds in England. Of these, 12 (4%) subsequently withdrew (six owing to the pandemic). Median intervention use per practice was 70 (by a median of 9 clinicians). No evidence was found that antibiotic dispensing differed between intervention practices (155 (95% confidence interval 138 to 174) items/year/1000 children) and control practices (157 (140 to 176) items/year/1000 children) (rate ratio 1.011, 95% confidence interval 0.992 to 1.029; P=0.25). Pre-specified subgroup analyses suggested reduced dispensing in intervention practices with fewer prescribing nurses, in single site (compared with multisite) practices, and in practices located in areas of lower socioeconomic deprivation, which may warrant future investigation. Pre-specified sensitivity analysis suggested reduced dispensing among older children in the intervention arm (P=0.03). A post hoc sensitivity analysis suggested less dispensing in intervention practices before the pandemic (rate ratio 0.967, 0.946 to 0.989; P=0.003). The rate of hospital admission for respiratory tract infections in the intervention practices (13 (95% confidence interval 10 to 18) admissions/1000 children) was non-inferior compared with control practices (15 (12 to 20) admissions/1000 children) (rate ratio 0.952, 0.905 to 1.003). Conclusions This multifaceted antibiotic stewardship intervention for children with respiratory tract infections did not reduce overall antibiotic dispensing or increase respiratory tract infection related hospital admissions. Evidence suggested that in some subgroups and situations (for example, under non-pandemic conditions) the intervention slightly reduced prescribing rates but not in a clinically relevant way. Trial registration ISRCTN11405239ISRCTN registry ISRCTN11405239

The success of open source software (OSS) projects depends on sustained contributions by developers who often display a wide variety of contribution patterns. Project leaders and stakeholders would strongly prefer that developers not only maintain but preferably increase their contributions over time as they gain experience. Corporations increasingly complement OSS developer motivations (such as fit in terms of shared values with the project community) by paying them to sustain contributions. However, practitioners argue whether payment helps or hurts projects because monetary compensation may dampen developer motivation in the long run, making it difficult for project leaders to understand what to expect from developers over time. Using Herzberg motivation-hygiene framework, we explore how developer perceptions of value fit with the project and being paid interact to determine the level of code contribution and its rate of change over time (i.e., growth). Using a survey of 564 developers across 431 projects on GitHub, we build a three-level growth model explaining the code contribution and its growth over a six-month period. We find that value fit with the project positively influences both the level and growth of code contribution. However, there are notable differences among paid and unpaid developers in the impact of value fit on their level and growth in code contributions over time. The implications of our work will be of interest to researchers, practitioners, and organizations investing in open source projects.

ObjectivesConducting randomised controlled trials (RCTs) in primary care is challenging; recruiting patients during time-limited or remote consultations can increase selection bias and physical access to patients’ notes is costly and time-consuming. We investigated barriers and facilitators to running a more efficient design.DesignAn RCT aiming to reduce antibiotic prescribing among children presenting with acute cough and a respiratory tract infection (RTI) with a clinician-focused intervention, embedded at the practice level. By using aggregate level, routinely collected data for the coprimary outcomes, we removed the need to recruit individual participants.SettingPrimary care.ParticipantsBaseline data from general practitioner practices and interviews with individuals from Clinical Research Networks (CRNs) in England who helped recruit practices and Clinical Commission Groups (CCGs) who collected outcome data.InterventionThe intervention included: (1) explicit elicitation of parental concerns, (2) a prognostic algorithm to identify children at low risk of hospitalisation and (3) provision of a printout for carers including safety-netting advice.Coprimary outcomesFor 0–9 years old—(1) Dispensing data for amoxicillin and macrolide antibiotics and (2) hospital admission rate for RTI.ResultsWe recruited 294 of the intended 310 practices (95%) representing 336 496 registered 0–9 years old (5% of all 0–9 years old children). Included practices were slightly larger, had slightly lower baseline prescribing rates and were located in more deprived areas reflecting the national distribution. Engagement with CCGs and their understanding of their role in this research was variable. Engagement with CRNs and installation of the intervention was straight-forward although the impact of updates to practice IT systems and lack of familiarity required extended support in some practices. Data on the coprimary outcomes were almost 100%.ConclusionsThe infrastructure for trials at the practice level using routinely collected data for primary outcomes is viable in England and should be promoted for primary care research where appropriate.Trial registration numberISRCTN11405239.

Commitment to a neutral point of view is a pillar of Wikipedia culture. Despite a strong culture, the open nature of the community presents challenges for cultural assimilation. Central contributor...

In multipartite viruses, the genome is split into multiple segments, each of which is transmitted via a separate capsid. The existence of multipartite viruses poses a problem, because replication is only possible when all segments are present within the same host. Given this clear cost, why is multipartitism so common in viruses? Most previous hypotheses try to explain how multipartitism could provide an advantage. In so doing, they require scenarios that are unrealistic and that cannot explain viruses with more than 2 multipartite segments. We show theoretically that selection for cheats, which avoid producing a shared gene product, but still benefit from gene products produced by other genomes, can drive the evolution of both multipartite and segmented viruses. We find that multipartitism can evolve via cheating under realistic conditions and does not require unreasonably high coinfection rates or any group-level benefit. Furthermore, the cheating hypothesis is consistent with empirical patterns of cheating and multipartitism across viruses. More broadly, our results show how evolutionary conflict can drive new patterns of genome organisation in viruses and elsewhere.

In this paper, we report on a panel discussion at the 2019 International Conference on Information Systems (ICIS) held in Munich, Germany. This panel discussed the ethics and politics of engagement with Indigenous peoples in information systems (IS) research. As members of a research team that have studied how Indigenous peoples use social media to collaborate and further their cause, we have recently learnt about some unintended consequences that IS research has. Since others could easily appropriate our findings for political purposes, we believe that we as IS researchers need to become more sensitive to the ways in which we study and engage with “the Other”. Hence, the panelists discussed and debated the nature and extent of a researcher’s engagement when studying Indigenous peoples and how they use information systems/information technology. The panel, which Michael Myers chaired, included three panelists who have studied how Indigenous people use media (Liz Davidson, Amber Young, and Hameed Chughtai) and one panelist who has studied Indigenous theories in IS (Pitso Tsibolane).

International audience; The concentration of chloride in sweat remains the most robust biomarker for confirmatory diagnosis of cystic fibrosis (CF), a common life-shortening genetic disorder. Early diagnosis via quantitative assessment of sweat chloride allows prompt initiation of care and is critically important to extend life expectancy and improve quality of life. The collection and analysis of sweat using conventional wrist-strapped devices and iontophoresis can be cumbersome, particularly for infants with fragile skin, who often have insufficient sweat production. Here, we introduce a soft, epidermal microfluidic device ("sweat sticker") designed for the simple and rapid collection and analysis of sweat. Intimate, conformal coupling with the skin supports nearly perfect efficiency in sweat collection without leakage. Real-time image analysis of chloride reagents allows for quantitative assessment of chloride concentrations using a smartphone camera, without requiring extraction of sweat or external analysis. Clinical validation studies involving patients with CF and healthy subjects, across a spectrum of age groups, support clinical equivalence compared to existing device platforms in terms of accuracy and demonstrate meaningful reductions in rates of leakage. The wearable microfluidic technologies and smartphone-based analytics reported here establish the foundation for diagnosis of CF outside of clinical settings.

This paper reports on a workshop hosted at the University of Massachusetts Amherst in September, 2018. The workshop, called “Giving Voice to the Voiceless: The Use of Digital Technologies by Marginalized Groups”, focused on discussing how marginalized groups use digital technologies to raise their voices. At the workshop, a diverse group of scholars and doctoral students presented research projects and perspectives on the role that digital technologies have in activist projects that represent marginalized groups that have gained momentum in the last few years. The studies and viewpoints presented shed light on four areas in which IS research can expand our understanding about how marginalized groups use digital technologies to address societal challenges: 1) the rise of cyberactivism, 2) resource mobilization for cyberactivism, 3) cyberactivism by and with marginalized groups, and 4) research methods for examining how marginalized groups use digital technologies.

This paper reports on the second Workshop of a World University Network (WUN) Research Development Funded project on “The trans-nationalization of Indigenous movements: The role of digital technologies” at the University of Southampton, UK. The workshop explored interdisciplinarity and how interdisciplinary collaboration can help scholars study complex social phenomenon, such as the ways in which marginalized Indigenous communities use and shape digital technologies (such as social media) to enhance their cause. The workshop brought together scholars from diverse disciplines to engage in a critical debate. In addition to scholars from information systems, scholars from history, political science, geography, literature, arts, and anthropology came together to discuss how marginalized Indigenous communities can use digital media. The workshop highlighted the need for more interdisciplinary research and called for more critical approaches to bring such marginalized topics to the forefront of research in information systems. We consider three broad areas of inquiry in this paper: demarginalizing methodology for interdisciplinary research, interdisciplinary perspectives for demarginalization, and interdisciplinary contexts for demarginalization.

This research examines how an oppressed group, the Klamath Tribes of Oregon, used an information communication technology (ICT) for the human development objective of cultural identity restoration, one component of emancipation. Within this manuscript is depicted a process model of how ICT tools can be used for human development through emancipatory pedagogy, ie, the communication of knowledge in a way that promotes critical reflection and collective action. Combining interpretive and critical methods, I describe how the Klamath's ICT reflected the emancipatory journey of those creating it and empowered the Klamath to lead ICT users toward emancipation. An interpretive approach revealed that ICT framing tools promoted awareness of the Klamath, awareness of the problem the Klamath sought to address, and awareness of societal systems of power that enforced the Klamath's problem, while ICT tactic tools enabled “the aware” to engage in solutions. Notably, the Klamath shirked prevailing practices in ICT for development. Consistent with my critical approach, I use the Klamath case to suggest normative recommendations for the use of ICT for social good.

Machine learning tools are increasingly infiltrating everyday work life with implications for workers. By looking at machine learning tools as part of a sociotechnical system, we explore how machine learning tools enforce oppression of workers. We theorize, normatively, that with reorganizing processes in place, oppressive characteristics could be converted to emancipatory characteristics. Drawing on Paulo Freire’s critical theory of emancipatory pedagogy, we outline similarities between the characteristics Freire saw in oppressive societies and the characteristics of currently designed partnerships between humans and machine learning tools. Freire’s theory offers a way forward in reorganizing humans and machine learning tools in the workplace. Rather than advocating human control or the decoupling of workers and machines, we follow Freire’s theory in proposing four processes for emancipatory organizing of human and machine learning partnership: 1) awakening of a critical consciousness, 2) enabling role freedom, 3) instituting incentives and sanctions for accountability, and 4) identifying alternative emancipatory futures. Theoretical and practical implications of this emancipatory organizing theory are drawn.

Coral reefs are among the most biodiverse ecosystems on Earth in large part owing to their unique three-dimensional (3D) structure, which provides niches for a variety of species. Metrics of structural complexity have been shown to correlate with the abundance and diversity of fish and other marine organisms, but they are imperfect representations of a surface that can oversimplify key structural elements and bias discoveries. Moreover, they require researchers to make relatively uninformed guesses about the features and spatial scales relevant to species of interest. This paper introduces a machine-learning method for automating inferences about fish abundance from reef 3D models. It demonstrates the capacity of a convolutional neural network (ConvNet) to learn ecological patterns that are extremely subtle, if not invisible, to the human eye. It is the first time in the literature that no a priori assumptions are made about the bathymetry–fish relationship.

Hydrocephalus is a common and costly neurological condition caused by the overproduction and/or impaired resorption of cerebrospinal fluid (CSF). The current standard of care, ventricular catheters (shunts), is prone to failure, which can result in nonspecific symptoms such as headaches, dizziness, and nausea. Current diagnostic tools for shunt failure such as computed tomography (CT), magnetic resonance imaging (MRI), radionuclide shunt patency studies (RSPSs), and ice pack–mediated thermodilution have disadvantages including high cost, poor accuracy, inconvenience, and safety concerns. Here, we developed and tested a noninvasive, skin-mounted, wearable measurement platform that incorporates arrays of thermal sensors and actuators for precise, continuous, or intermittent measurements of flow through subdermal shunts, without the drawbacks of other methods. Systematic theoretical and experimental benchtop studies demonstrate high performance across a range of practical operating conditions. Advanced electronics designs serve as the basis of a wireless embodiment for continuous monitoring based on rechargeable batteries and data transmission using Bluetooth protocols. Clinical studies involving five patients validate the sensor’s ability to detect the presence of CSF flow ( P = 0.012) and further distinguish between baseline flow, diminished flow, and distal shunt failure. Last, we demonstrate processing algorithms to translate measured data into quantitative flow rate. The sensor designs, fabrication schemes, wireless architectures, and patient trials reported here represent an advance in hydrocephalus diagnostics with ability to visualize flow in a simple, user-friendly mode, accessible to the physician and patient alike.

Mass media digitization is an unfolding phenomenon, posing novel societal opportunities and challenges that researchers are beginning to note. We build on and extend MIS research on process digitization and digital versus traditional communication media to study how and to what extent social media—one form of digital mass media—are emancipatory (i.e., permitting wide-spread participation in public discourse and surfacing of diverse perspectives) versus hegemonic (i.e., contributing to ideological control by a few). While a pressing concern to activists and scholars, systematic study of this issue has been elusive, owing partially to the complexity of the emancipation and hegemony concepts. Using a case study approach, we iteratively engaged with data on the discourse surrounding the Stop Online Piracy Act (SOPA) and source literature to identify six facets of interpretive media packages (i.e., competing social constructions of an issue) as measurable constructs pertinent to emancipation and hegemony. These facets included three structural constraints (on authorship, citation, and influence) and three content restrictions (on frames, signatures, and emotion). We investigated propositions regarding effects of social versus traditional media and lean versus rich social media on these interpretive media package facets by comparing the SOPA discourse across two lean traditional and social media (newspapers and Twitter) and two rich traditional and social media (television and YouTube). Our findings paradoxically revealed social media to be emancipatory with regard to structural constraints, but hegemonic with regard to an important content restriction (i.e., frames). Lean social media mitigated structural advantages and exacerbated content problems. These findings suggest that, as with traditional media, some inevitable evils accompany the societal benefits of social media and that mass media is having a detrimental effect on public discourse. We offer practical steps by which private and public institutions may counter this effect, theoretical implications for wider consideration of the six interpretive media package facets proposed here, and encouragement to MIS researchers to increase their efforts to compare different digitized processes so that a more comprehensive theory of the effects of different forms of digitized processes can be developed.

Background The ischemic consequences of coronary artery stenosis can be assessed by invasive fractional flow reserve (FFR) or by noninvasive imaging. We sought to determine (1) the concordance between wall thickening assessment during clinically indicated stress echocardiography (SE) and FFR measurements and (2) the factors associated with hard events in these patients. Methods Two hundred twenty-three consecutive patients who underwent SE and invasive FFR measurements in close succession were analyzed retrospectively for diagnostic concordance and clinical outcomes. Results At the vessel level, the sensitivity, specificity, positive predictive value, and negative predictive value of SE for identifying significant disease as assessed by FFR was 68%, 75%, 43%, and 89%, respectively. The greatest discordance was seen in patients with wall thickening abnormalities (WTAs) and negative FFR. During a follow-up of 3.6 ± 2.2 years, there were 23 cardiovascular (CV) events (death and nonfatal myocardial infarction). The number of wall segments with inducible WTAs emerged as the strongest factor associated with CV events (hazard ratio, 1.18 [1.05-1.34]; P = .008). FFR was not associated with outcome. There was a significant increase in event rate in patients with WTA/negative FFR versus no WTA/negative FFR ( P = .01), but no significant difference versus WTA/positive FFR ( P = .85). Conclusions In a patient population with significant CV risk factors, a normal SE had a high negative predictive value for excluding abnormal FFR. WTAs were associated with outcomes regardless of FFR value, suggesting that this is a superior marker of ischemia to FFR.

Background Single-photon emission computed tomography (SPECT) is a well-established method to evaluate patients with coronary artery disease. Myocardial contrast echocardiography (MCE) is an imaging technique that allows the assessment of myocardial perfusion in real time. Previous research has shown that vasodilator MCE is superior to SPECT for the prediction of hard events. The aim of this study was to investigate the long-term association of SPECT and MCE with clinical outcomes in patients with known or suspected coronary artery disease. Methods Accordingly, 258 patients who underwent MCE and SPECT as part of multicenter studies performed prospectively were followed up for hard events (all-cause mortality and nonfatal myocardial infarction). The mean age was 63.4 ± 5.5 years, 186 (72.1%) were men, and 32 (12.4%) had left ventricular systolic dysfunction. We calculated the ratio of the number of abnormal segments (at rest and/or stress) to the total number of segments expressed as MCE and SPECT indices. Results Over a mean follow-up period of 80.4 ± 6.1 months, 46 patients had hard events. MCE and SPECT indices were associated with all-cause mortality on univariate analysis ( P = .008 and P = .035, respectively) but only MCE index was independently associated with hard events (hazard ratio, 4.24; 95% CI, 1.27–14.15; P = .019), beyond clinical data and left ventricular function, and independently associated with hard cardiac events (hazard ratio, 4.78; 95% CI, 1.06–21.59; P = .042). Conclusions MCE but not SPECT showed a long-term association with outcome. These results thus favor the routine use of MCE in the long-term assessment of patients with known or suspected coronary artery disease.

Digital technologies such as social media have drastically transformed the contexts and processes associated with collective action. New actors have gotten involved in efforts at changing the societal status quo, existing actors have adjusted to new ways of organizing digitally, and original forms of social movements have emerged and grown. All these developments do not, however, hold the potential for unequivocally positive societal impact. New forms of abuse and many unintended consequences have also multiplied. It is high time to take stock of the insights from current scholarship on these important issues. Here we bring together major findings from existing scholarship and introduce the papers of this special issue. We also propose an agenda for future research by highlighting ongoing debates and issues that require further consideration. Questions associated with the increasingly intricated participation of human and technological agents deserve attention, for instance. Careful considerations of the actual impact of digital organizing at different levels (e.g., individual, group, organization, society) also require further scholarship. We finally caution researchers to be ethical and to remain careful of the potential for use and misuse of their scholarship on these important and often polemical topics.

We report on a series of experiments showing how immersive experience (i.e. placing people in virtual and alternative states of the world in time and location) ties to the making and keeping of sus...

Introduction Although stress echocardiography (SE) is invaluable in younger populations, its prognostic value may be attenuated in the elderly due to shorter life expectancy and the frequent presence of severe comorbidities. This study sought to evaluate the clinical effectiveness of SE in octogenarians, particularly its prognostic value over clinical variables, in predicting hard events. Methods A total of 374 consecutive octogenarians who underwent SE for evaluation of coronary artery disease (CAD) were assessed for feasibility, diagnostic accuracy and safety of the test, and followed up for hard outcomes (all-cause mortality, cardiovascular (CV) deaths and non-fatal myocardial infarction (NFMI)). Cox regression analysis was performed to identify predictors of outcome. Results Of the 374 tests, 360 (96.3%) were diagnostic. Of the 50 patients with inducible ischaemia, 33 patients (66%) proceeded to angiography of which 27 (82%) patients had significant CAD. During long-term follow-up of 4.0±2.0 years, there were 127 deaths and 36 NFMIs. The annualised mortality, NFMI and combined mortality /NFMI rates were 8.1%, 1.8% and 9.4% for patients with a normal SE and 12.1%, 5.5% and 14.1% for those with an abnormal SE, respectively. Predictors of NFMI on multivariate analysis were prior CAD (HR 2.89, CI 1.03 to 8.15, p=0.045), peripheral vascular disease (HR 3.33, CI 1.18 to 9.45, p=0.02), and inducible ischaemia (HR 3.97, CI 1.49 to 10.55, p=0.006). In patients without prior history of CAD, inducible ischaemia was the only independent predictor of NFMI (HR 8.72, CI 1.46 to 52.2, p=0.018). The larger the extent of ischaemia, the greater the incidence of NFMI. The independent predictors of CV events (NFMI or CV mortality) were PAD (HR 2.81, CI 1.21 to 6.52, p=0.016) and peak wall motion score index (HR 5.71, CI 1.67 to 19.6, p=0.006). Although inducible ischaemia predicted all-cause mortality on unadjusted analysis, it did not on multivariate analysis. Conclusions In octogenarians, SE demonstrated excellent feasibility, safety and diagnostic accuracy. SE parameters were independent predictors of NFMI and CV events, and the presence of inducible ischaemia was associated with a 50% increase in all-cause mortality.

Background Single photon emission computed tomography (SPECT) is a well-established method to evaluate patients with coronary artery disease (CAD). Myocardial contrast echocardiography (MCE) is an imaging technique that allows assessment of myocardial perfusion in a real-time setting. Very short term prognostic study has shown that vasodilator MCE is superior to SPECT for the prediction of hard events. We sought to investigate the long term prognostic value of SPECT and MCE in the assessment of patients with known or suspected CAD. Methods We retrospectively followed-up patients with suspected or known CAD who were scheduled for coronary angiography and who also underwent MCE and SPECT at our institute, as part of multicentre studies performed between January 2002 and December 2009. Rest and vasodilator SPECT was performed after injection of 99mTc-sestamibi using the standard technique on separate days. Coronary Angiography (CA) was performed within thirty days of stress imaging. We calculated the ratio of the number of abnormal segments (at rest and/or stress) to the total number of segments expressed as% for both MCE and SPECT in order to obtain a uniform assessment of the total ischaemic and scar burden (MCE and SPECT indexes). This population was followed up in 2016 to obtain a long term prognostic value of MCE and SPECT for hard events, all-cause mortality and non-fatal myocardial infarction (NFMI). Results Of the 277 patients who were analysed, 262 followed up and 15 were lost to follow up (5.4%). The mean age was 63.4 years and 186 (71.8%) patients were male, 82 (31.7%) had diabetes, 180 (69.5%) hypertension, 189 (73%) dyslipidaemia, 26 (10%) family history of CAD (FHCAD) and 64 (24.7%) were smokers. Prior CAD (angina, known acute myocardial infarction (AMI) or coronary revascularisation) was present in 178 (68.7%) patients, left ventricular systolic dysfunction in 32 (12.4%) and chronic kidney disease in 16 (6.2%). Over a mean follow-up period of 80 months(6.6 years)±6 months, 18 patients suffered NFMI and 29 died (18% hard events, annualised hard events 2.7%). Both MCE and SPECT indexes were significant predictors on univariate analysis for all-cause mortality (p=0.008 and p=0.035 respectively), but MCE index was the only independent predictor for hard events (HR 3.711, 95% CI(1.13–12.14), p=0.03). Figure 1 demonstrates the Kaplan-Meier curve for the long-term prognostic value in all-cause mortality and NFMI of abnormal versus normal MCE. The annualised event rate for the abnormal MCE is 3.8% versus 1.0% for the normal MCE. Conclusion This is the first study to our knowledge that investigated the long-term prognostic value of SPECT and MCE in patients with suspected or known CAD. MCE was the only independent predictor of hard events. These results further support the routine use of MCE and not SPECT for the long-term prognostication of patients with known or suspected CAD.

Nicotine and other nicotinic agents are thought to regulate mood in human subjects and have antidepressant-like properties in animal models. Recent studies have demonstrated that blockade of nicotinic acetylcholine receptors (nAChRs) including those containing the beta2 subunit (beta2(*)), results in antidepressant-like effects. Previous studies have shown that cytisine, a partial agonist at alpha4/beta2(*) nAChRs, and a full agonist at alpha3/beta4(*) and alpha7 nAChRs, has antidepressant-like properties in several rodent models of antidepressant efficacy; however, it is not clear whether more selective partial agonists will also be effective in these models. We tested cytisine and two derivatives, 5-bromo-cytisine (5-Br-Cyt) and 3-(pyridin-3'-yl)-cytisine (3-pyr-Cyt) for their ability to act as a partial agonist of different nAChR subtypes and to show antidepressant-like activity in C57/BL6 mice in the tail suspension, the forced-swim, and the novelty-suppressed feeding tests. 3-pyr-Cyt was a partial agonist with very low efficacy at alpha4/beta2(*) nAChRS but had no agonist effects at other nAChRs normally targeted by cytisine, and it was effective in mouse models of antidepressant efficacy. Animals showed dose-dependent antidepressant-like effects in all three behavioral paradigms. 5-Br-Cyt was not effective in behavioral tests when administered peripherally, probably because of its inability to penetrate the blood-brain barrier, because it efficiently reduced immobility in the tail suspension test when administered intraventricularly. These results suggest that novel nicotinic partial agonists may provide new possibilities for development of drugs to treat mood disorders.

Aims Exercise electrocardiography (ExECG) is widely used in suspected stable angina (SA) as the initial test for the evaluation of coronary artery disease (CAD). We hypothesized that exercise stress echo (ESE) would be efficacious with cost advantage over ExECG when utilized as the initial test. Methods and results Consecutive patients with suspected SA, without known CAD were randomized into ExECG or ESE. Patients with positive tests were offered coronary angiography (CA) and with inconclusive tests were referred for further investigations. All patients were followed-up for cardiac events (death, myocardial infarction, and unplanned revascularization). Cost to diagnosis of CAD was calculated by adding the cost of all investigations, up to and including CA. In the 194 and 191 patients in the ExECG vs. ESE groups, respectively, pre-test probability of CAD was similar (34 ± 23 vs. 35 ± 25%, P = 0.6). Results of ExECG were: 108 (55.7%) negative, 14 (7.2%) positive, 72 (37.1%) inconclusive and of ESE were 181 (94.8%) negative, 9 (4.7%) positive, 1 (0.5%) inconclusive, respectively. Patients with obstructive CAD following positive ESE vs. Ex ECG were 9/9 vs. 9/14, respectively ( P = 0.04). Cost to diagnosis of CAD was £266 for ESE vs. £327 for ExECG ( P = 0.005). Over a mean follow-up period of 21 ± 5 months, event rates were similar between the two groups. Conclusion In this first randomized study, ESE was more efficacious and demonstrated superior cost-saving, compared with ExECG when used as the initial investigation for the evaluation of CAD in patients with new-onset suspected SA without known CAD.

Entrepreneurs signal the worth of their ventures using the technological capabilities of their crowdfunding platforms. Additionally, social media allows others to create "buzz" about the venture, which can also influence funding outcomes. Moreover, these two antecedents can interact with each other, whereby venture signals are either amplified or diluted by buzz about the project. Our study examined how the effects of technological cues and social media "buzz" about a crowdfunded venture affect its success. Our results indicate a differential effect of "buzz" -- depending on the social media platform and the type of signal conveyed -- on crowdfunding success.

Background: A host of technologies exists for the separation of living, nonadherent cells, with separation decisions typically based on fluorescence or immunolabeling of cells. Methods to separate adherent cells as well as to broaden the range of possible sorting criteria would be of high value and complementary to existing strategies. Methods: Cells were cultured on arrays of releasable pallets. The arrays were screened and individual cell(s)/pallets were released and collected. Results: Conventional fluorescence and immunolabeling of cells were compatible with the pallet arrays, as were separations based on gene expression. By varying the size of the pallet and the number of cells cultured on the array, single cells or clonal colonies of cells were isolated from a heterogeneous population. Since cells remained adherent throughout the isolation process, separations based on morphologic characteristics, for example cell shape, were feasible. Repeated measurements of each cell in an array were performed permitting the selection of cells based on their temporal behavior, e.g. growth rate. Conclusions: The pallet array system provides the flexibility to select and collect adherent cells based on phenotypic and temporal criteria and other characteristics not accessible by alternative methods. © 2007 International Society for Analytical Cytology

Multiple factors ranging from globalization to ecosystem disruption are presenting the global community with evolving biological threats to local, national, and global security that reach beyond the realm of traditional bioweapon threats. As a result, mitigation strategies have adapted necessarily to the increased diversity of biological threats. In general, response and preparedness strategies have largely shifted from being primarily reactive to traditional biological weapons to more proactive in nature. In this review, we briefly explore biological threats through a wider aperture, to embrace a greater appreciation of viral pathogens, antimicrobial resistance, and agricultural pathogens, and their potential to cause civil, economic, and political devastation. In addition, we discuss current mitigation strategies codified by the Global Health Security Agenda and the One Health paradigm as well as some of the available tools to assist with their sustainable implementation.

The selection and collection of single cells from within a heterogeneous population is required to produce genetically engineered cell lines, to develop new stem cell lines, and for single-cell studies. We describe a new platform for the positive selection of single live mammalian cells while the cells remain adherent to their growth surface. Cells were grown on arrays of microfabricated, releasable elements composed of SU-8 polymer termed "cell pallets". The presence of air between the elements restricted the cells to the top surfaces of the pallets. Single pallets situated within large arrays of pallets were released on demand using a single, focused, laser pulse. The laser pulses were low in energy (2-5 muJ) and did not detach nearby, nontargeted pallets. Since the SU-8 pallets and the underlying glass substrate were optically transparent, the cells on the pallets could be visualized by microscopy before and after release. Over 90% of cells remained attached to the pallet during laser-based release. The feasibility of growing the cells from the released pallets into clonal colonies was demonstrated. The pallet array system permits adherent cells to be inspected using conventional microscopy and selected cells released for further analysis. The ability to assess cells while they remain adherent to a surface will broaden the number of attributes that can be utilized for cell separation, for example, cell shape, cytoskeletal properties, and other attributes.

Introduction Haemodynamically significant coronary artery disease (CAD) is an important indication for revascularisation. Wall motion analysis during stress echocardiography (SE) is a noninvasive alternative to invasive fractional flow reserve (FFR) for evaluating hemodynamically significant CAD. We sought to determine the diagnostic accuracy of SE compared with invasive coronary angiography with FFR for the diagnosis of hemodynamically significant CAD. Methods and Results Between January 2008 and April 2015, all patients that underwent clinically indicated FFR measurements during invasive angiography and SE in close succession were analysed. Patients were excluded if tests were not done within 6 months of each other, or an intervening percutaneous coronary procedure or acute coronary syndrome occurred. 184 patients (mean age 66.5yrs, 59 (32%) female) were identified. The majority of patients underwent coronary angiography following SE. The prevalence of known CAD, diabetes and chronic kidney disease were 46%, 43% and 13% respectively, and 14 (8%) patients had previous coronary artery bypass surgery. Exercise SE was performed in 84 (46%) patients and Dobutamine SE in 100 (54%) patients. Contrast was used in 158 patients (86%). In 108 patients (59%), the SE was positive for inducible ischaemia. From 217 vessels analysed, the Left Anterior Descending Artery, Right Coronary Artery, Left Circumflex Artery and Left Main Coronary artery were involved in 120 (55%), 47 (22%), 30 (14%), 18 (8%) respectively, with 2 vessels being grafts. 46 FFR measurements were positive (21%) and 171 were negative (79%), using a cut off of≤ 0.80. At the vessel level, the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of SE for identifying significant disease as assessed by FFR was 70%, 77%, 45% and 90% respectively. In 73 patients, there was single vessel disease on angiography. At the vessel level, the sensitivity, specificity, PPV and NPV were 85%, 68%, 37% and 95%. Conclusion To date this is the largest study comparing SE and FFR for the assessment of the physiological significance of a coronary lesion, and reflects real world experience. SE demonstrates good diagnostic accuracy and excellent NPV for excluding flow-limiting disease. The low PPV is likely to represent the commencement of medical therapy following a positive SE, as well as referral bias (since only patients with positive SE underwent angiography) as well as the low prevalence of positive FFR measurements in this population. The presence of a haemodynamically significant stenosis can be accurately ruled out with SE.

Background Presence of carotid artery disease has been shown to predict cardiovascular risk beyond traditional risk factors. However, the potential impact of carotid disease (CD) in patients undergoing stress echocardiography (SE) for new-onset chest pain without known coronary artery disease (CAD) is unknown. We hypothesised that information of ischemia and atherosclerosis which can be achieved simultaneously by ultrasound (SE and carotid ultrasound) can provide incremental prognostic information in these patients. Methods Consecutive patients with no previous history of CAD investigated with SE for suspected angina underwent a simultaneous carotid ultrasound. Carotid plaque burden was assessed. Patients were followed up for combined major adverse cardiac events (MACE) of all-cause mortality, non-fatal myocardial infarction and unplanned coronary revascularization. Results Of the 591 patients, (269 male (46%), mean age 59 ± 11 years), 67 (11%) demonstrated myocardial ischemia by SE. Prevalence of carotid plaque disease was higher (59%) but similar in normal and abnormal SE patients (58% vs. 66%, p = 0.22). At a mean of 37 months, 580 (98%) could be followed up during which 40 MACE occurred. In the multivariable model pre-test probability of CAD (p = 0.001), abnormal SE (p , respectively. Figure demonstrates the prognostic value of simultaneous carotid plaque assessment and SE. When prognosis was assessed in a hierarchical manner as done clinically (pre-test probability of CAD followed by SE and carotid ultrasound), it showed significant increment in global chi square from 22.1 to 48.9 to 78.5 (p Conclusion In patients with suspected stable angina but without known CAD simultaneous SE (for ischemia) and carotid ultrasound (for atherosclerosis) provided synergistic prognostic value. This study supports simultaneous carotid ultrasound in such patients investigated by SE and has implications in primary prevention treatment.

In this paper, we employ a hermeneutic approach to examine the question: How do cultural productions of websites enable enactments of power, change, and society in Native American groups? We collected longitudinal data from 15 redesigns of the Chickasaw Nation and Klamath Tribes websites. Text from each website redesign, as well as each redesign of the tribes' "History" pages, was analyzed using linguistic inquiry and word count software. These texts and other design elements were examined from an interpretive perspective. Our analyses depicts the role of website design in the production of culture. Furthermore, we find support for the notion that although technology adoption has traditionally occurred parallel to globalization and aided in assimilation, tribal organizations are now finding ways to use technology for constructive purposes such as cultural preservation, identity restoration and healing.

Aims Patients with symptomatic left bundle branch block (LBBB) may have myocardial ischaemia due to both coronary artery disease and/or cardiomyopathy (microcirculatory abnormalities) and may have concomitant left ventricular (LV) dysfunction. We aimed to assess the feasibility and prognostic value of contemporary stress echocardiography (SE), which can uncover both pathophysiologies in LBBB patients in routine clinical practice, and also aimed to assess the additive value of contrast SE. Methods and results Accordingly, 190 consecutive patients (age 70.5 ± 11.3 years, LV ejection fraction = 50.1 ± 10%) with symptomatic LBBB who underwent SE over 6 years were assessed, of which 142 (75%) underwent contrast SE and 176 (92.6%) had diagnostic SE. Inducible ischaemia was present in 25 (14.2%) patients. During follow-up (35.4 ± 20.2 months) there were 32 deaths (18%) and 18 (10.2%) first cardiovascular (CV) events (acute myocardial infarction/mortality) in the 176 patients with diagnostic studies. Wall thickening score index at peak stress (WTSIpeak), which measures combined LV function and inducible ischaemia, was an independent predictor of mortality (HR = 3.78, 95% CI = 1.39–10.31, P = 0.01) and CV events (HR = 3.96, 95% CI = 1.1–14.3, P = 0.036). An abnormal SE (myocardial ischaemia and/or abnormal LV function) predicted an almost three-fold increase in all-cause mortality and CV events compared with normal SE. Amongst the confounders affecting assessment of wall thickening in LBBB and conventional prognostic variables, use of contrast was an independent predictor ( P = 0.034) of WTSI1.16 (optimal predictor of mortality/CV outcome). Conclusion SE in patients with LBBB demonstrated high feasibility and the combination of LV systolic function and myocardial ischaemia provided important prognostic information. Contrast-enhanced SE improved the prediction of outcome.