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Aims The totality of atherosclerotic plaque derived from coronary computed tomography angiography (CCTA) emerges as a comprehensive measure to assess the intensity of medical treatment that patients need. This study examines the differences in age onset and prognostic significance of atherosclerotic plaque burden between sexes. Methods and results From a large multi-center CCTA registry the Leiden CCTA score was calculated in 24 950 individuals. A total of 11 678 women (58.5 ± 12.4 years) and 13 272 men (55.6 ± 12.5 years) were followed for 3.7 years for major adverse cardiovascular events (MACE) (death or myocardial infarction). The age where the median risk score was above zero was 12 years higher in women vs. men (64–68 years vs. 52–56 years, respectively, P < 0.001). The Leiden CCTA risk score was independently associated with MACE: score 6–20: HR 2.29 (1.69–3.10); score > 20: HR 6.71 (4.36–10.32) in women, and score 6–20: HR 1.64 (1.29–2.08); score > 20: HR 2.38 (1.73–3.29) in men. The risk was significantly higher for women within the highest score group (adjusted P-interaction = 0.003). In pre-menopausal women, the risk score was equally predictive and comparable with men. In post-menopausal women, the prognostic value was higher for women [score 6–20: HR 2.21 (1.57–3.11); score > 20: HR 6.11 (3.84–9.70) in women; score 6–20: HR 1.57 (1.19–2.09); score > 20: HR 2.25 (1.58–3.22) in men], with a significant interaction for the highest risk group (adjusted P-interaction = 0.004). Conclusion Women developed coronary atherosclerosis approximately 12 years later than men. Post-menopausal women within the highest atherosclerotic burden group were at significantly higher risk for MACE than their male counterparts, which may have implications for the medical treatment intensity.

The purpose of this study is to offer a comprehensive restatement and critical assessment of Marx’s theory regarding the subsumption of labor under capital (SLC). The core hypothesis of this accoun...

Online spectroscopic measurements can be used to provide unique insight into complex chemical systems, enabling new understanding and optimization of chemical processes. A key example of this is discussed here with the monitoring of pH of various acid systems in real-time. In this work the acids used in multiple chemical separations processes, such as TALSPEAK (Trivalent Actinide-Lanthanide Separation by Phosphorus reagent Extraction from Aqueous Komplexes) and oxalate precipitation, were characterized. Raman spectroscopy, a robust optical approach that can be integrated in corrosive processes, was used to follow the unique fingerprints of the various protonated and deprotonated acid species. This data was analyzed using a hierarchical modeling approach to build a consolidated model scheme using optical fingerprints from all weak acids to measure pH associated with any of the weak acid systems studied here. Validation of system performance included utilizing Raman spectroscopy under dynamic flow conditions to monitor solution pH under changing process conditions in-line. Overall, the Raman based approach provided accurate analysis of weak acid solution pH.

Optical spectroscopy is a powerful characterization tool with applications ranging from fundamental studies to real-time process monitoring. However, it can be difficult to apply to complex samples that contain interfering analytes which are common in processing streams. Multivariate (chemometric) analysis has been examined for providing selectivity and accuracy to the analysis of optical spectra and expanding its potential applications. Here we will discuss chemometric modeling with an in-depth comparison to more simplistic analysis approaches and outline how chemometric modeling works while exploring the limits on modeling accuracy. Understanding the limitations of the chemometric model can provide better analytical assessment regarding the accuracy and precision of the analytical result. This will be explored in the context of UV–Vis absorbance of neodymium (Nd3+) in the presence of interferents, erbium (Er3+) and copper (Cu2+) under conditions simulating the liquid–liquid extraction approach used to recycle plutonium (Pu) and uranium (U) in used nuclear fuel worldwide. The selected chemometric model, partial least squares regression, accurately quantifies Nd3+ with a low percentage error in the presence of interfering analytes and even under conditions that the training set does not describe.

Teaming permits cognitively complex work to be rapidly executed by multiple entities. As artificial agents (AAs) participate in increasingly complex cognitive work, they hold the promise of moving beyond tools to becoming effective members of human–agent teams. Coordination has been identified as the critical process that enables effective teams and is required to achieve the vision of tightly coupled teams of humans and AAs. This paper characterizes coordination on the axes of types, content, and cost. This characterization is grounded in the human and AA literature and is evaluated to extract design implications for human–agent teams. These design implications are the mechanisms, moderators, and models employed within human–agent teams, which illuminate potential AA design improvements to support coordination.

Background Since the emergence of SARS-CoV-2, evolutionary pressure has driven large increases in the transmissibility of the virus. However, with increasing levels of immunity through vaccination and natural infection the evolutionary pressure will switch towards immune escape. Genomic surveillance in regions of high immunity is crucial in detecting emerging variants that can more successfully navigate the immune landscape. Methods We present phylogenetic relationships and lineage dynamics within England (a country with high levels of immunity), as inferred from a random community sample of individuals who provided a self-administered throat and nose swab for rt-PCR testing as part of the REal-time Assessment of Community Transmission-1 (REACT-1) study. During round 14 (9 September–27 September 2021) and 15 (19 October–5 November 2021) lineages were determined for 1322 positive individuals, with 27.1% of those which reported their symptom status reporting no symptoms in the previous month. Results We identified 44 unique lineages, all of which were Delta or Delta sub-lineages, and found a reduction in their mutation rate over the study period. The proportion of the Delta sub-lineage AY.4.2 was increasing, with a reproduction number 15% (95% CI 8–23%) greater than the most prevalent lineage, AY.4. Further, AY.4.2 was less associated with the most predictive COVID-19 symptoms (p = 0.029) and had a reduced mutation rate (p = 0.050). Both AY.4.2 and AY.4 were found to be geographically clustered in September but this was no longer the case by late October/early November, with only the lineage AY.6 exhibiting clustering towards the South of England. Conclusions As SARS-CoV-2 moves towards endemicity and new variants emerge, genomic data obtained from random community samples can augment routine surveillance data without the potential biases introduced due to higher sampling rates of symptomatic individuals.

OBJECTIVES This study is to determine the management and clinical outcomes of patients investigated with coronary computed tomography angiography (CCTA)-derived fractional flow reserve (FFRCT) according to sex.BACKGROUND Women are underdiagnosed with conventional ischemia testing, have lower rates of obstructive coronary artery disease (CAD) at invasive coronary angiography (ICA), yet higher mortality compared to men. Whether FFRCT improves sex-based patient management decisions compared to CCTA alone is unknown.METHODS Subjects with symptoms and CAD on CCTA were enrolled (2015 to 2017). Demographics, symptom status, CCTA anatomy, coronary volume to myocardial mass ratio (V/M), lowest FFRCT values, and management plans were captured. Endpoints included reclassification rate between CCTA and FFRCT management plans, incidence of ICA demonstrating obstructive CAD ($50% stenosis) and revascularization rates.RESULTS A total of 4,737 patients (n = 1,603 females, 33.8%) underwent CCTA and FFRCT. Women were older (age 68 +/- 10 years vs. 65 +/- 10 years; p < 0.0001) with more atypical symptoms (41.5% vs. 33.9%; p < 0.0001). Women had less obstructive CAD (65.4% vs. 74.7%; p < 0.0001) at CCTA, higher FFRCT (0.76 +/- 0.10 vs. 0.73 +/- 0.10; p < 0.0001), and lower likelihood of positive FFRCT

Changes in the geopolitical landscape and increasing technological complexity have prompted the U.S. Military to coin the terms Multi-Domain Operations (MDO) and Joint All-Domain Command and Control (JADC2) as over-arching strategy to frame the complexity of warfare across both traditional and emerging warfighting domains. Teaching new concepts associated with these terms requires both innovation as well as distinct education and training tools in order to realize the cultural change advocated by senior military leaders. Battlespace NextTM (BSN) is a serious game designed to teach concepts integral to MDO and initiate discussion on military strategy while conserving time, money, and manpower. BSN, a Collectable Card Game (CCG), is engineered to provide an engaging learning tool that educates on capabilities in a multi-domain conflict. This paper proposes an extensible game framework for modeling and reasoning about MDO concepts and presents our empirical feedback from over 120 military play testers evaluating a moderate to difficult version of the game. Results reveal the game teaches MDO concepts and delivers an engaging, hands-on learning experience. Specifically, we provide evidence it improved military readiness in seven areas of MDO in at least 62% of participants and 76% of respondents reported they enjoyed playing the game.

Autonomous unmanned aerial systems (UAS) could supplement and eventually subsume a substantial portion of the mission set currently executed by remote pilots, making UAS more robust, responsive, and numerous than can be achieved by teleoperation alone. Unfortunately, the development of robust autonomous systems is difficult, costly, and time-consuming. Furthermore, the resulting systems often make little reuse of proven software components and offer limited adaptability for new tasks. This work presents a development platform for UAS which promotes behavioral flexibility. The platform incorporates the unified behavior framework (a modular, extensible autonomy framework), the robotic operating system (a robotic software framework), and PX4 (an open-source flight controller). Simulation of UBF agents identify a combination of reactive robotic control strategies effective for small-scale navigation tasks by a UAS in the presence of obstacles. Finally, flight tests provide a partial validation of the simulated results. The development platform presented in this work offers robust and responsive behavioral flexibility for UAS agents in simulation and reality using a methodology originally proven on ground robots.

Women with gestational diabetes mellitus have higher rates of perinatal depressive symptoms, compared to healthy pregnant women. In the general population, maternal depressive symptoms have been associated with infant sleep difficulties during the first year postpartum. However, there is lack of data on infants of mothers with gestational diabetes mellitus. This study assessed the prospective associations between maternal perinatal depressive symptoms and infant sleep outcomes. The study population consisted of 95 Swiss women with gestational diabetes mellitus and their infants, enrolled in the control group of the MySweetheart trial (NCT02890693). Perinatal depressive symptoms were assessed with the Edinburgh Postnatal Depression Scale at the first gestational diabetes mellitus visit during pregnancy, at 6-8 weeks postpartum, and 1 year postpartum. The Brief Infant Sleep Questionnaire was used to assess infant sleep (i.e., nocturnal sleep duration, number of night waking, and maternal perception of infant sleep) at 1 year postpartum. Relevant maternal and infant measurements (e.g., infant sex or maternal age or social support) were collected or extracted from medical records as covariates. Antenatal maternal depressive symptoms at the first gestational diabetes mellitus visit were inversely associated with infant nocturnal sleep duration at 1 year postpartum (β = -5.9, p = 0.046). This association became marginally significant when covariates were added (β = -5.3, p = 0.057). Maternal depressive symptoms at 6-8 weeks postpartum were negatively and prospectively associated with infant nocturnal sleep duration (β = -9.35, p = 0.016), even when controlling for covariates (β = -7.32, p = 0.042). The association between maternal depressive symptoms and maternal perception of infant sleep as not a problem at all was significant at 1 year postpartum (β = -0.05, p = 0.006), although it became non-significant when controlling for appropriate covariates. No other significant associations were found. This study solely included measures derived from self-report validated questionnaires. Our findings suggest it is of utmost importance to support women with gestational diabetes mellitus as a means to reduce the detrimental impact of maternal perinatal depressive symptoms on infant sleep, given its predictive role on infant metabolic health.

La instalación de cables para conexión entre equipos de subestaciones eléctricas, se diseñan considerando cargas debidas a corto circuito, peso propio, viento, entre otras, no obstante, omiten condiciones adicionales según la instalación final o excluyen cargas, como las presentes en zonas de alta actividad sísmica, aspectos que complementarían el cálculo de deformación del cable, por otro lado, se suele desconectar el esfuerzo de diseño en los modelos 3D, ya que estos únicamente emplean los puntos de anclaje y “splines” para definir su trayectoria. Conocer la deformación aproximada del cable es importante para la verificación de distancias de seguridad eléctricas, minimizando posibles inconvenientes en la fase de construcción. Este documento, presenta la integración de diversos modelos de cargas para cables, en una representación de elementos finitos con SAP2000, incluyendo condiciones finales de instalación y cargas sísmicas según IEEE 1527, garantizando estabilidad de conexión, distancias de seguridad eléctricas e integridad de equipos. Adicionalmente, se conectan los resultados de deformación con una aplicación desarrollada en Dynamo-Python para complementar el modelo BIM en Revit. La metodología se valida según casos de conexión documentados por el Pacific Earthquake Engineering Research Center (PEER), el cual registra medidas de deformación para cables empleados en subestaciones eléctricas bajo diferentes escenarios de carga e instalación. Con la integración propuesta, se obtienen deformaciones esperadas ante desplazamientos bajos, presentando un mejor ajuste de trayectoria y cálculo de esfuerzos según los reportados por PEER, no obstante para desplazamientos altos, se obtienen diferencias representativas en los esfuerzos medidos, aspecto por mejorar.

Objectives The 1-year data from the international ADVANCE (Assessing Diagnostic Value of Non-invasive FFRCT in Coronary Care) Registry of patients undergoing coronary computed tomography angiography (CTA) was used to evaluate the relationship of fractional flow reserve derived from coronary CTA (FFRCT) with downstream care and clinical outcomes. Background Guidelines for management of chest pain using noninvasive imaging pathways are based on short- to intermediate-term outcomes. Methods Patients (N = 5,083) evaluated for clinically suspected coronary artery disease and in whom atherosclerosis was identified by coronary CTA were prospectively enrolled at 38 international sites from July 15, 2015, to October 20, 2017. Demographics, symptom status, coronary CTA and FFRCT findings and resultant site-based treatment plans, and clinical outcomes through 1 year were recorded and adjudicated by a blinded core laboratory. Major adverse cardiac events (MACE), death, myocardial infarction (MI), and acute coronary syndrome leading to urgent revascularization were captured. Results At 1 year, 449 patients did not have follow-up data. Revascularization occurred in 1,208 (38.40%) patients with an FFRCT ≤0.80 and in 89 (5.60%) with an FFRCT >0.80 (relative risk [RR]: 6.87; 95% confidence interval [CI]: 5.59 to 8.45; p 0.80 (RR: 1.81; 95% CI: 0.96 to 3.43; p = 0.06). Time to first event (all-cause death or MI) occurred in 38 (1.20%) patients with an FFRCT ≤0.80 compared with 10 (0.60%) patients with an FFRCT >0.80 (RR: 1.92; 95% CI: 0.96 to 3.85; p = 0.06). Time to first event (cardiovascular death or MI) occurred cardiovascular death or MI occurred more in patients with an FFRCT ≤0.80 compared with patients with an FFRCT >0.80 (25 [0.80%] vs. 3 [0.20%]; RR: 4.22; 95% CI: 1.28 to 13.95; p = 0.01). Conclusions The 1-year outcomes from the ADVANCE FFRCT Registry show low rates of events in all patients, with less revascularization and a trend toward lower MACE and significantly lower cardiovascular death or MI in patients with a negative FFRCT compared with patients with abnormal FFRCT values. (Assessing Diagnostic Value of Non-invasive FFRCT in Coronary Wave [ADVANCE]; NCT02499679)

Sequence pattern mining (SPM) seeks to find multiple items that commonly occur together in a specific order. One common assumption is that the relevant differences between items are captured through creating distinct items. In some domains, this leads to an exponential increase in the number of items. This paper presents a new SPM, Sequence Mining of Temporal Clusters (SMTC), that allows item differentiation through attribute variables for domains with large numbers of items. It also provides a new technique for addressing interleaving, a phenomena that occurs when two sequences occur simultaneously resulting in their items alternating. By first clustering items temporally and only focusing on sequences after the temporal clusters are established, it sidesteps the traditional interleaving issues. SMTC is evaluated on a digital forensics dataset, a domain with a large number of items and frequent interleaving. Its results are compared with Discontinuous Varied Order Sequence Mining (DVSM) with variables added (DVSM-V). By adding variables, both algorithms reduce the data by 96 percent, and identify 100 percent of the events while keeping the false positive rate below 0.03 percent. SMTC mines the data in 20 percent of the time it takes DVSM-V and provides a lower false positive rate even at higher similarity thresholds.

Moseley (2018) offers a partial reply to my review of his Money and Totality, addressing one comment at length while mentioning a second in passing and ignoring the third. In this rejoinder, I respond to his replies and develop the three main arguments of my review in greater detail, with particular focus on the logical consistency of Moseley’s “algebraic summary” of his macro-monetary reading of Marx’s transformation analysis.

Geographically isolated wetlands (GIWs) are commonly reported as having hardpan or low hydraulic conductivity units underneath that produce perched groundwater, which can sustain surface water levels independently of regional aquifer fluctuations. Despite the potential of GIW‐perched aquifer systems to provide important hydrological and ecological functions such as groundwater storage and native amphibian habitat, little research has studied the hydrologic controls and dynamics of these systems. We compared several ridge‐top depressional GIW‐perched groundwater systems to investigate the role of watershed morphology on hydroregime and groundwater‐surface water interaction. Ridge‐top depressional wetlands in the Daniel Boone National Forest, Kentucky were chosen because they offer natural controls such as lack of apparent connection to surface water bodies, similar climate, and similar soils. Three wetlands with different topographic slopes and hillslope structures were mapped to distinguish key geomorphic parameters and monitored to characterize groundwater‐surface water interaction. Wetlands with soil hummocks and low upland slopes transitioned from infiltration to groundwater discharge conditions in the spring and during storm events. The magnitude and duration of this transition fell along a continuum, where higher topographic slopes and steeper uplands produced comparably smaller and shorter head reversals. This demonstrates that ridge‐top GIW‐perched groundwater systems are largely sensitive to the runoff‐recharge relationship in the upland area which can produce significant groundwater storage on a small‐scale.

The 2018 American College of Cardiology (ACC)/American Heart Association (AHA) cholesterol management guideline recommends risk enhancers in the borderline-risk and statin recommended/intermediate-risk groups. We determined the risk reclassification by the presence and severity of coronary computed tomography angiography (CCTA)-visualized coronary artery disease (CAD) according to statin eligibility groups. Of 35,281 individuals who underwent CCTA, 1,303 asymptomatic patients (age 59, 65% male) were identified. Patients were categorized as low risk, borderline risk, statin recommended/intermediate risk or statin recommended/high risk according to the guideline. CCTA-visualized CAD was categorized as no CAD, nonobstructive, or obstructive. Major adverse cardiovascular events (MACE) were defined as a composite outcome of all-cause mortality, nonfatal myocardial infarction, and late coronary revascularization (>90 days). We tested a reclassification wherein no CAD reclassifies downward, and the presence of any CAD reclassifies upward. During a median follow-up of 2.9 years, 93 MACE events (7.1%) were observed. Among the borderline-risk and statin-recommended/intermediate-risk groups eligible for risk enhancers, the presence or absence of any CCTA-visualized CAD led to a net increase of 2.3% of cases and 22.4% of controls correctly classified (net reclassification index [NRI] 0.27, 95% CI 0.13 to 0.41, p = 0.0002). The NRI was not significant among low- or statin-recommended/high-risk patients (all p > 0.05). The presence or absence of CCTA-visualized CAD, including both obstructive and nonobstructive CAD, significantly improves reclassification in patients eligible for risk enhancers in 2018 ACC/AHA guidelines. Patients in low- and high-risk groups derive no significant improvement in risk reclassification from CCTA. (C) 2019 Published by Elsevier Inc.

In a posthumously published article, Pierangelo Garegnani (2018. ‘On the Labour Theory of Value in Marx and in the Marxist Tradition.’) depicts Marx’s project in Capital as that of ‘developing syst...

Microfluidics is an appealing analytical tool in the global effort to close the nuclear fuel cycle. Using a microfluidic chip permits the analysis of greatly reduced sample volumes compared to what is necessary for traditional analytical methods. There is a commensurate reduction in disposal volume and cost. The development of novel sensors is necessary to take full advantage of the microchip configuration, where optical-spectroscopy-based approaches offer a powerful route to characterize chemical composition. This study uses simultaneously applied UV-vis and micro-Raman spectroscopies adapted to function on the microscale to analyze in situ both the Nd3+ (UV-vis-active) and HNO3 (Raman-active) concentrations in the same sample. An adjustable translation platform was designed to hold the micro-Raman probe above and perpendicular to the chip face and the UV-vis probe in the plane of the chip. These complimentary spectral techniques when processed through multivariate partial least-squares (PLS) models gave an accurate picture of the widely varying solution concentrations as a function of time for each solution component. Solution matrix effects can drastically alter analyte signatures as measured by both UV-vis absorbance and Raman spectroscopy. PLS methods successfully modeled these spectral changes and accurately measured concentrations of components of interest within the microfluidic chip.

Loss of user engagement with automation in increasingly complex environments, such as driving a car, can have increasingly unexpected and consequential impacts. This paper presents a three-step pro...

A variant of John Roemer’s accumulation economy is studied in which agents have identical payoff functions characterized by decreasing marginal impatience (DMI), such that time discount rates are d...

P Perioperative administration of single-dose dexamethasone helps reduce postoperative nausea and vomiting, inflammation, and pain. However, it is unclear which dose achieves these effects while minimizing the hyperglycemic impact in patients with diabetes. The purpose of this review was to elucidate the most appropriate perioperative dose of dexamethasone for diabetic patients, and whether it is necessary to withhold it in patients with poor glycemic control.A systematic review.A literature search using PubMed and Cochrane Database of Systematic Reviews revealed 17 potential evidence sources. Eight sources met the inclusion criteria. Sources included one systematic review with meta-analysis, one randomized control trial, and six observational studies.Evidence suggests diabetic patients who receive dexamethasone perioperatively are more likely to develop postoperative hyperglycemia, with a maximum blood glucose increase of 30 to 45 mg/dL in the first 24 hours following a single dose. One study described increased blood glucose levels with escalating doses, but no other sources have supported that finding. The available studies were markedly heterogeneous in both design and proportion of diabetic subjects included, and most were of low quality.There is not enough evidence to quantify the hyperglycemic effect of commonly used dexamethasone doses, and rigorous studies are needed to inform practice.

Complex chemical systems that exhibit varied and matrix-dependent speciation are notoriously difficult to monitor and characterize online and in real-time. Optical spectroscopy is an ideal tool for in situ characterization of chemical species that can enable quantification as well as species identification. Chemometric modeling, a multivariate method, has been successfully paired with optical spectroscopy to enable measurement of analyte concentrations even in complex solutions where univariate methods such as Beer's law analysis fail. Here, Raman spectroscopy is used to quantify the concentration of phosphoric acid and its three deprotonated forms during a titration. In this system, univariate approaches would be difficult to apply due to multiple species being present simultaneously within the solution as the pH is varied. Locally weighted regression (LWR) modeling was used to determine phosphate concentration from spectral signature. LWR results, in tandem with multivariate curve resolution modeling, provide a direct measurement of the concentration of each phosphate species using only the Raman signal. Furthermore, results are presented within the context of fundamental solution chemistry, including Pitzer equations, to compensate for activity coefficients and nonidealities associated with high ionic strength systems.

Background Coronary artery fractional flow reserve (FFR) derived from CT angiography (FFTCT) enables functional assessment of coronary stenosis. Prior clinical trials showed 13%-33% of coronary CT angiography studies had insufficient quality for quantitative analysis with FFRCT. Purpose To determine the rejection rate of FFRCT analysis and to determine factors associated with technically unsuccessful calculation of FFRCT. Materials and Methods Prospectively acquired coronary CT angiography scans submitted as part of the Assessing Diagnostic Value of Noninvasive FFRCT in Coronary Care (ADVANCE) registry (https://ClinicalTrials.gov: NCT02499679) and coronary CT angiography series submitted for clinical analysis were included. The primary outcome was the FFRCT rejection rate (defined as an inability to perform quantitative analysis with FFRCT). Factors that were associated with FFRCT rejection rate were assessed with multiple linear regression. Results In the ADVANCE registry, FFRCT rejection rate due to inadequate image quality was 2.9% (80 of 2778 patients; 95% confidence interval [CI]: 2.1%, 3.2%). In the 10 621 consecutive patients who underwent clinical analysis, the FFRCT rejection rate was 8.4% (n = 892; 95% CI: 6.2%, 7.2%; P < .001 vs the ADVANCE cohort). The main reason for the inability to perform FFRCT analysis was the presence of motion artifacts (63 of 80 [78%] and 729 of 892 [64%] in the ADVANCE and clinical cohorts, respectively). At multivariable analysis, section thickness in the ADVANCE (odds ratio [OR], 1.04; 95% CI: 1.001, 1.09; P = .045) and clinical (OR, 1.03; 95% CI: 1.02, 1.04; P < .001) cohorts and heart rate in the ADVANCE (OR, 1.05; 95% CI: 1.02, 1.08; P < .001) and clinical (OR, 1.06; 95% CI: 1.05, 1.07; P < .001) cohorts were independent predictors of rejection. Conclusion The rates for technically unsuccessful CT-derived fractional flow reserve in the ADVANCE registry and in a large clinical cohort were 2.9% and 8.4%, respectively. Thinner CT section thickness and lower patient heart rate may increase rates of completion of CT fractional flow reserve analysis. Published under a CC BY 4.0 license. Online supplemental material is available for this article. See also the editorial by Sakuma in this issue.

Transmission of SARS-CoV-2 is uncontrolled in many parts of the world; control is compounded in some areas by the higher transmission potential of the B.1.1.7 variant1, which has now been reported in 94 countries. It is unclear whether the response of the virus to vaccines against SARS-CoV-2 on the basis of the prototypic strain will be affected by the mutations found in B.1.1.7. Here we assess the immune responses of individuals after vaccination with the mRNA-based vaccine BNT162b22. We measured neutralizing antibody responses after the first and second immunizations using pseudoviruses that expressed the wild-type spike protein or a mutated spike protein that contained the eight amino acid changes found in the B.1.1.7 variant. The sera from individuals who received the vaccine exhibited a broad range of neutralizing titres against the wild-type pseudoviruses that were modestly reduced against the B.1.1.7 variant. This reduction was also evident in sera from some patients who had recovered from COVID-19. Decreased neutralization of the B.1.1.7 variant was also observed for monoclonal antibodies that target the N-terminal domain (9 out of 10) and the receptor-binding motif (5 out of 31), but not for monoclonal antibodies that recognize the receptor-binding domain that bind outside the receptor-binding motif. Introduction of the mutation that encodes the E484K substitution in the B.1.1.7 background to reflect a newly emerged variant of concern (VOC 202102/02) led to a more-substantial loss of neutralizing activity by vaccine-elicited antibodies and monoclonal antibodies (19 out of 31) compared with the loss of neutralizing activity conferred by the mutations in B.1.1.7 alone. The emergence of the E484K substitution in a B.1.1.7 background represents a threat to the efficacy of the BNT162b2 vaccine.

Supplemental material, sj-pdf-1-asp-10.1177_00037028211053852 for Measuring Nd(III) Solution Concentration in the Presence of Interfering Er(III) and Cu(II) Ions: A Partial Least Squares Analysis of Ultraviolet���Visible Spectra by Poki Tse, Jenifer Shafer, Samuel A. Bryan, Gilbert L. Nelson and Amanda M. Lines in Applied Spectroscopy

Background The current study aimed to examine the independent prognostic value of whole-heart atherosclerosis progression by serial coronary computed tomography angiography (CCTA) for major adverse cardiovascular events (MACE). Methods The multi-center PARADIGM study includes patients undergoing serial CCTA for symptomatic reasons, ≥2 years apart. Whole-heart atherosclerosis was characterized on a segmental level, with co-registration of baseline and follow-up CCTA, and summed to per-patient level. The independent prognostic significance of atherosclerosis progression for MACE (non-fatal myocardial infarction [MI], death, unplanned coronary revascularization) was examined. Patients experiencing interval MACE were not omitted. Results The study population comprised 1166 patients (age 60.5 ​± ​9.5 years, 54.7% male) who experienced 139 MACE events during 8.2 (IQR 6.2, 9.5) years of follow up (15 death, 5 non-fatal MI, 119 unplanned revascularizations). Whole-heart percent atheroma volume (PAV) increased from 2.32% at baseline to 4.04% at follow-up. Adjusted for baseline PAV, the annualized increase in PAV was independently associated with MACE: OR 1.23 (95% CI 1.08, 1.39) per 1 standard deviation increase, which was consistent in multiple subpopulations. When categorized by composition, only non-calcified plaque progression associated independently with MACE, while calcified plaque did not. Restricting to patients without events before follow-up CCTA, those with future MACE showed an annualized increase in PAV of 0.93% (IQR 0.34, 1.96) vs 0.32% (IQR 0.02, 0.90), P ​ Conclusions Whole-heart atherosclerosis progression examined by serial CCTA is independently associated with MACE, with a prognostic threshold of 1.0% increase in PAV per year.

Serious games provide a method for teaching students in an engaging, non-threatening way. To be useful educational tools, these games need to be designed with the lesson objectives in mind. This paper uses the Game Design Matrix to design a game from learning objectives. The lesson objectives focus on software development, security and operations (DevSecOps). DevSecOps requires judging the cost and risk trade offs between secure and unsecured software aspects including code, data and usability; devising a strategy to produce a system under threat; comprehending that partial security may equate to no security; and identifying examples of insecure code and methods of mitigating it. These lesson objectives combined with the teaching environment drive design decisions that produce a game that fits well into a graduate level course in secure software design and development. We evaluate the game in a graduate course on secure software design and development. Learner surveys confirm that DevSecOps conveys the learning objectives in an engaging way.

BACKGROUND: The association of age with coronary plaque dynamics is not well characterized by coronary computed tomography angiography (CCTA). METHODS: From a multinational registry of patients who underwent serial CCTA, 1153 subjects (61 ± 5 years old, 61.1% male) were analyzed. Annualized volume changes of total, fibrous, fibrofatty, necrotic core, and dense calcification plaque components of the whole heart were compared by age quartile groups. Clinical events, a composite of all-cause death, acute coronary syndrome, and any revascularization after 30 days of the initial CCTA, were also analyzed. Random forest analysis was used to define the relative importance of age on plaque progression. RESULTS: With a 3.3-years' median interval between the two CCTA, the median annual volume changes of total plaque in each age quartile group was 7.8, 10.5, 10.8, and 12.1 mm3/year and for dense calcification, 2.5, 4.6, 5.4, and 7.1 mm3/year, both of which demonstrated a tendency to increase by age (p-for-trend = 0.001 and

Since October 2001, more than 2.7 million men and women of the armed forces have been deployed to Iraq, Afghanistan, or in support of the “Global War on Terrorism.” Like previous wars, our nation will feel the after-effects of those deployments for a generation to come, as the wounds of war do not just affect the veteran, but impact their family and friends once they return to the home front. But unlike previous wars, less than 1% of our population serves their country in an all-volunteer military. This small percentage of Americans who volunteer to serve us and protect our freedoms (no matter what you might think about the politics surrounding wars) is increasingly removed from the rest of the population who choose other careers and options. Therefore, most of us are uneducated and unconnected to the often isolating experiences and frustrations of our veterans when they return to the home front and try to retake the stage of their former lives. In this discussion, we share the compelling stories of military members and veterans who struggle with infertility. We describe the need for policy and expansion of services for infertility care in the Department of Defense and Veterans Health Administration, and the challenges and opportunities that exist.

CT coronary angiography (CTA) with Fractional Flow Reserve as determined by CT (FFRPatients' in the ADVANCE (Assessing Diagnostic Value of Non-invasive FFRCT in Coronary Care) registry, were stratified into those ≥65 or65 years of age. The impact of FFRFFRThe findings of this study point to a low risk of MACE events or need for revascularisation in those aged ​≥ ​or65 with a FFR

Reverse engineers are in high demand in digital forensics for their ability to investigate malicious cyberspace threats. This group faces unique challenges due to the security-intensive environment, such as working in isolated networks, a limited ability to share files with others, immense time pressure, and a lack of cognitive support tools supporting the iterative exploration of binary executables. This paper presents an exploratory study that interviewed experienced reverse engineers’ work processes, tools, challenges, and visualization needs. The findings demonstrate that engineers have difficulties managing hypotheses, organizing results, and reporting findings during their analysis. By considering the provenance support techniques of existing research in other domains, this study contributes new insights about the needs and opportunities for reverse engineering provenance tools.

Aims In patients without obstructive coronary artery disease (CAD), we examined the prognostic value of risk factors and atherosclerotic extent. Methods and results Patients from the long-term CONFIRM registry without prior CAD and without obstructive (≥50%) stenosis were included. Within the groups of normal coronary computed tomography angiography (CCTA) (N = 1849) and non-obstructive CAD (N = 1698), the prognostic value of traditional clinical risk factors and atherosclerotic extent (segment involvement score, SIS) was assessed with Cox models. Major adverse cardiac events (MACE) were defined as all-cause mortality, non-fatal myocardial infarction, or late revascularization. In total, 3547 patients were included (age 57.9 ± 12.1 years, 57.8% male), experiencing 460 MACE during 5.4 years of follow-up. Age, body mass index, hypertension, and diabetes were the clinical variables associated with increased MACE risk, but the magnitude of risk was higher for CCTA defined atherosclerotic extent; adjusted hazard ratio (HR) for SIS >5 was 3.4 (95% confidence interval [CI] 2.3–4.9) while HR for diabetes and hypertension were 1.7 (95% CI 1.3–2.2) and 1.4 (95% CI 1.1–1.7), respectively. Exclusion of revascularization as endpoint did not modify the results. In normal CCTA, presence of ≥1 traditional risk factors did not worsen prognosis (log-rank P = 0.248), while it did in non-obstructive CAD (log-rank P = 0.025). Adjusted for SIS, hypertension and diabetes predicted MACE risk in non-obstructive CAD, while diabetes did not increase risk in absence of CAD (P-interaction = 0.004). Conclusion Among patients without obstructive CAD, the extent of CAD provides more prognostic information for MACE than traditional cardiovascular risk factors. An interaction was observed between risk factors and CAD burden, suggesting synergistic effects of both.

Contains fulltext : 220894.pdf (Publisher’s version ) (Closed access) AIMS: We aimed to compare semiquantitative coronary computed tomography angiography (CCTA) risk scores - which score presence, extent, composition, stenosis and/or location of coronary artery disease (CAD) - and their prognostic value between patients with and without diabetes mellitus (DM). Risk scores derived from general chest-pain populations are often challenging to apply in DM patients, because of numerous confounders. METHODS: Out of a combined cohort from the Leiden University Medical Center and the CONFIRM registry with 5-year follow-up data, we performed a secondary analysis in diabetic patients with suspected CAD who were clinically referred for CCTA. A total of 732 DM patients was 1:1 propensity-matched with 732 non-DM patients by age, sex and cardiovascular risk factors. A subset of 7 semiquantitative CCTA risk scores was compared between groups: 1) any stenosis ≥50%, 2) any stenosis ≥70%, 3) stenosis-severity component of the coronary artery disease-reporting and data system (CAD-RADS), 4) segment involvement score (SIS), 5) segment stenosis score (SSS), 6) CT-adapted Leaman score (CT-LeSc), and 7) Leiden CCTA risk score. Cox-regression analysis was performed to assess the association between the scores and the primary endpoint of all-cause death and non-fatal myocardial infarction. Also, area under the receiver-operating characteristics curves were compared to evaluate discriminatory ability. RESULTS: A total of 1,464 DM and non-DM patients (mean age 58 ± 12 years, 40% women) underwent CCTA and 155 (11%) events were documented after median follow-up of 5.1 years. In DM patients, the 7 semiquantitative CCTA risk scores were significantly more prevalent or higher as compared to non-DM patients (p ≤ 0.022). All scores were independently associated with the primary endpoint in both patients with and without DM (p ≤ 0.020), with non-significant interaction between the scores and diabetes (interaction p ≥ 0.109). Discriminatory ability of the Leiden CCTA risk score in DM patients was significantly better than any stenosis ≥50% and ≥70% (p = 0.003 and p = 0.007, respectively), but comparable to the CAD-RADS, SIS, SSS and CT-LeSc that also focus on the extent of CAD (p ≥ 0.265). CONCLUSION: Coronary atherosclerosis scoring with semiquantitative CCTA risk scores incorporating the total extent of CAD discriminate major adverse cardiac events well, and might be useful for risk stratification of patients with DM beyond the binary evaluation of obstructive stenosis alone.

Significance A fundamental question in contemporary neuroscience is how the remarkable cellular diversity required for the intricate function of the nervous system is achieved. Here, we bridge the gap between a cellular machinery that is known to diversify the transcriptome and the existence of distinct neuronal populations that compose the Drosophila brain. Adenosine-to-inosine (A-to-I) RNA editing is a ubiquitous mechanism that generates transcriptomic diversity in cells by recoding certain adenosines within the pre-mRNA sequence into inosines. We present a spatial map of RNA editing across different neuronal populations in Drosophila brain. Each neuronal population has a distinct editing signature, with the majority of differential editing occurring in highly conserved regions of transcripts that encode ion channels and other essential neuronal genes., Adenosine-to-inosine (A-to-I) RNA editing, catalyzed by ADAR enzymes, is a ubiquitous mechanism that generates transcriptomic diversity. This process is particularly important for proper neuronal function; however, little is known about how RNA editing is dynamically regulated between the many functionally distinct neuronal populations of the brain. Here, we present a spatial RNA editing map in the Drosophila brain and show that different neuronal populations possess distinct RNA editing signatures. After purifying and sequencing RNA from genetically marked groups of neuronal nuclei, we identified a large number of editing sites and compared editing levels in hundreds of transcripts across nine functionally different neuronal populations. We found distinct editing repertoires for each population, including sites in repeat regions of the transcriptome and differential editing in highly conserved and likely functional regions of transcripts that encode essential neuronal genes. These changes are site-specific and not driven by changes in Adar expression, suggesting a complex, targeted regulation of editing levels in key transcripts. This fine-tuning of the transcriptome between different neurons by RNA editing may account for functional differences between distinct populations in the brain.

Background: Coronary computed tomography angiography (cCTA)-derived fractional flow reserve (FFRCT) is a promising diagnostic method for the evaluation of coronary artery disease (CAD). However, clinical data regarding FFRCT in Japan are scarce, so we assessed the clinical impact of using FFRCT in a Japanese population. Methods and Results: The ADVANCE registry is an international prospective FFRCT registry of patients suspected of CAD. Of 5,083 patients, 1,829 subjects enrolled from Japan were analyzed. Demographics, symptoms, cCTA, FFRCT, treatment strategy, and 90-day major cardiovascular events (MACE) were assessed. Reclassification of treatment strategy between cCTA alone and cCTA+FFRCT occurred in 55.8% of site investigations and in 56.9% in the core laboratory analysis. Patients with positive FFR (FFRCT ≤0.80) were less likely to have non-obstructive disease on invasive coronary angiography than patients with negative FFR (FFRCT >0.80) (20.5% vs. 46.1%, P=0.0001). After FFRCT, 67.0% of patients with positive results underwent revascularization, whereas 96.1% of patients with negative FFRCT were medically treated. MACE occurred in 5 patients with positive FFRCT, but none occurred in patients with negative FFRCT within 90 days. Conclusions: In this Japanese population, FFRCT modified the treatment strategy in more than half of the patients. FFRCT showed potential for stratifying patients suspected of CAD properly into invasive or non-invasive management pathways.

Background Values of fractional flow reserve (FFRCT) by coronary computed tomography angiography (CTA) decline from the ostium to the terminal vessel, irrespective of stenosis severity. The purpose of this study is to determine if the site of measurement of FFRCT impacts assessment of ischemia and its diagnostic performance relative to invasive FFR (FFRINV). Methods 1484 patients underwent FFRCT; 1910 vessels were stratified by stenosis severity (normal; 70% stenosis). The rates of positive FFRCT (≤0.8) were determined by measuring FFRCT from the terminal vessel and from distal-to-the-lesion. Reclassification rates from positive to negative FFRCT were calculated. Diagnostic performance of FFRCT relative to FFRINV was evaluated in 182 vessels using linear regression, Bland Altman analysis, and receiver operating characteristic (ROC) curves. Results Positive FFRCT was identified in 24.9% of vessels using terminal vessel FFRCT and 10.1% using FFRCT distal-to-the-lesion (p ​ Conclusion FFRCT values from the terminal vessel should not be used to assess lesion-specific ischemia due to high rates of false positive results. FFRCT measured distal-to-the-lesion improves the diagnostic performance of FFRCT relative to FFRINV, ensures that FFRCT values are due to lesion-specific ischemia, and could reduce the rate of unnecessary invasive procedures.

Background The association between triglyceride glucose (TyG) index and coronary atherosclerotic change remains unclear. We aimed to evaluate the association between TyG index and coronary plaque progression (PP) using serial coronary computed tomography angiography (CCTA). Methods A total of 1143 subjects (aged 60.7 ± 9.3 years, 54.6% male) who underwent serial CCTA with available data on TyG index and diabetic status were analyzed from The Progression of AtheRosclerotic PlAque DetermIned by Computed TomoGraphic Angiography IMaging (PARADIGM) registry. PP was defined as plaque volume (PV) (mm3) at follow-up minus PV at index > 0. Annual change of PV (mm3/year) was defined as PV change divided by inter-scan period. Rapid PP was defined as the progression of percent atheroma volume (PV divided by vessel volume multiplied by 100) ≥ 1.0%/year. Results The median inter-scan period was 3.2 (range 2.6–4.4) years. All participants were stratified into three groups based on TyG index tertiles. The overall incidence of PP was 77.3%. Baseline total PV (group I [lowest]: 30.8 (0.0–117.7), group II: 47.2 (6.2–160.4), and group III [highest]: 57.5 (8.4–154.3); P Conclusion TyG index is an independent predictive marker for the progression of coronary atherosclerosis. Clinical registration ClinicalTrials.gov NCT02803411

Measurement of pH is an integral component of chemical studies and process control; however, traditional pH probes are difficult to utilize in harsh or complex chemical systems. Optical spectroscopy-based online monitoring offers a powerful and novel route for characterizing system parameters, such as pH, and is well adapted to deployment in harsh environments or chemically complex systems. Specifically, Raman spectroscopy combined with chemometric analysis can provide an improved method of online p[H

OBJECTIVES: The aim of the current study was to explore the impact of plaque calcification in terms of absolute calcified plaque volume (CPV) and in the context of its percentage of the total plaque volume at a lesion and patient level on the progression of coronary artery disease. BACKGROUND: Coronary artery calcification is an established marker of risk of future cardiovascular events. Despite this, plaque calcification is also considered a marker of plaque stability, and it increases in response to medical therapy. METHODS: This analysis included 925 patients with 2,568 lesions from the PARADIGM (Progression of Atherosclerotic Plaque Determined by Computed Tomographic Angiography Imaging) registry, in which patients underwent clinically indicated serial coronary computed tomography angiography. Plaque calcification was examined by using CPV and percent CPV (PCPV), calculated as (CPV/plaque volume) × 100 at a per-plaque and per-patient level (summation of all individual plaques). RESULTS: CPV was strongly correlated with plaque volume (r = 0.780; p < 0.001) at baseline and with plaque progression (r = 0.297; p < 0.001); however, this association was reversed after accounting for plaque volume at baseline (r = -0.146; p < 0.001). In contrast, PCPV was an independent predictor of a reduction in plaque volume (r = -0.11; p < 0.001) in univariable and multivariable linear regression analyses. Patient-level analysis showed that high CPV was associated with incident major adverse cardiac events (hazard ratio: 3.01: 95% confidence interval: 1.58 to 5.72), whereas high PCPV was inversely associated with major adverse cardiac events (hazard ratio: 0.529; 95% confidence interval: 0.229 to 0.968) in multivariable analysis. CONCLUSIONS: Calcified plaque is a marker for risk of adverse events and disease progression due to its strong association with the total plaque burden. When considered as a percentage of the total plaque volume, increasing PCPV is a marker of plaque stability and reduced risk at both a lesion and patient level. (Progression of Atherosclerotic Plaque Determined by Computed Tomographic Angiography Imaging [PARADIGM]; NCT02803411).

OBJECTIVES:This study sought to describe the impact of statins on individual coronary atherosclerotic plaques. BACKGROUND:Although statins reduce the risk of major adverse cardiovascular events, their long-term effects on coronary atherosclerosis remain unclear. METHODS:We performed a prospective, multinational study consisting of a registry of consecutive patients without history of coronary artery disease who underwent serial coronary computed tomography angiography at an interscan interval of ≥2 years. Atherosclerotic plaques were quantitatively analyzed for percent diameter stenosis (%DS), percent atheroma volume (PAV), plaque composition, and presence of high-risk plaque (HRP), defined by the presence of ≥2 features of low-attenuation plaque, positive arterial remodeling, or spotty calcifications. RESULTS:Among 1,255 patients (60 ± 9 years of age; 57% men), 1,079 coronary artery lesions were evaluated in statin-naive patients (n = 474), and 2,496 coronary artery lesions were evaluated in statin-taking patients (n = 781). Compared with lesions in statin-naive patients, those in statin-taking patients displayed a slower rate of overall PAV progression (1.76 ± 2.40% per year vs. 2.04 ± 2.37% per year, respectively; p = 0.002) but more rapid progression of calcified PAV (1.27 ± 1.54% per year vs. 0.98 ± 1.27% per year, respectively; p 50% DS were not different (1.0% vs. 1.4%, respectively; p > 0.05). Statins were associated with a 21% reduction in annualized total PAV progression above the median and 35% reduction in HRP development. CONCLUSIONS:Statins were associated with slower progression of overall coronary atherosclerosis volume, with increased plaque calcification and reduction of high-risk plaque features. Statins did not affect the progression of percentage of stenosis severity of coronary artery lesions but induced phenotypic plaque transformation. (Progression of AtheRosclerotic PlAque DetermIned by Computed TomoGraphic Angiography Imaging [PARADIGM]; NCT02803411).

In response to Roemer's reformulation of the Marxian concept of exploitation in terms of comparative wealth distributions (1982, 1996), Vrousalis (2013) treats economic exploitation as an explicitly relational phenomenon in which one party takes advantage of the other's economic vulnerability in order to extract a net benefit. This paper offers a critical assessment of Vrousalis's account, prompting a revised formulation that is analysed in the context of a matching and bargaining model. This analysis yields precise representations of Vrousalis's conditions of economic vulnerability and economic exploitation and facilitates comparison to the alternative conceptions of Marx and Roemer.