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There has been a debate over many decades concerning the benefits of lifelong learning that have been expressed both in economic and non-economic terms, the latter often expressed in terms of contributions to health and well-being, and to civic solidarity. The extent to which these benefits can be evidenced however remains somewhat elusive and at best mixed. In this paper, I trace the ways in which lifelong learning has emerged in policy discourse in the UK since the 1980s, the arguments and evidence for its benefits and the means by which it has been supported and implemented. In particular, the paper is concerned with the role of the higher education sector in the UK with a particular focus on Scotland. [ABSTRACT FROM AUTHOR]

Background and Aims Chronic stress associates with cardiovascular disease, but mechanisms remain incompletely defined. Advanced imaging was used to identify stress-related neural imaging phenotypes associated with atherosclerosis. Methods Twenty-seven individuals with post-traumatic stress disorder (PTSD), 45 trauma-exposed controls without PTSD, and 22 healthy controls underwent 18F-fluorodeoxyglucose positron emission tomography/magnetic resonance imaging (18F-FDG PET/MRI). Atherosclerotic inflammation and burden were assessed using 18F-FDG PET (as maximal target-to-background ratio, TBR max) and MRI, respectively. Inflammation was assessed using high-sensitivity C-reactive protein (hsCRP) and leucopoietic imaging (18F-FDG PET uptake in spleen and bone marrow). Stress-associated neural network activity (SNA) was assessed on 18F-FDG PET as amygdala relative to ventromedial prefrontal cortex (vmPFC) activity. MRI diffusion tensor imaging assessed the axonal integrity (AI) of the uncinate fasciculus (major white matter tract connecting vmPFC and amygdala). Results Median age was 37 years old and 54% of participants were female. There were no significant differences in atherosclerotic inflammation between participants with PTSD and controls; adjusted mean difference in TBR max (95% confidence interval) of the aorta 0.020 (−0.098, 0.138), and of the carotids 0.014 (−0.091, 0.119). Participants with PTSD had higher hsCRP, spleen activity, and aorta atherosclerotic burden (normalized wall index). Participants with PTSD also had higher SNA and lower AI. Across the cohort, carotid atherosclerotic burden (standard deviation of wall thickness) associated positively with SNA and negatively with AI independent of Framingham risk score. Conclusions In this study of limited size, participants with PTSD did not have higher atherosclerotic inflammation than controls. Notably, impaired cortico-limbic interactions (higher amygdala relative to vmPFC activity or disruption of their intercommunication) associated with carotid atherosclerotic burden. Larger studies are needed to refine these findings. [ABSTRACT FROM AUTHOR]

Citizen science initiatives offer an informal way to encourage the general public to engage in science learning, and contributes to the development of a more stable supply of science professionals by arousing volunteers' enthusiasm for a science career. This study aimed to identify the contribution that science service makes to volunteers' experience and the influence it has on the relationship between their experience and beliefs, and on their eventual career orientation. This study tested the effect of social cognitive variables on volunteers' career interests in science using Social Cognitive Career Theory (SCCT). The sample consisted of 241 volunteers taking part in a science volunteer project which is administered by the Ministry of Science and Technology in Taiwan. We used structural equation modeling (SEM) and PROCESS Macro 4.1 to test the structural relationships and mediating hypotheses proposed in this study. Building on the SCCT, our findings indicated that self-efficacy in science service, satisfaction with science service, and social support are contributing factors to the science volunteers' career interest in a scientific profession. This study adds to the SCCT literature by clarifying how a volunteer-based citizen science initiative as an informal science learning platform may affect the participants' career decisions. [ABSTRACT FROM AUTHOR]

This study examined two mediators of university students' behavioural intention to use digital platforms in the context of science service learning in Taiwanese universities. Based on the technology acceptance model (TAM), we proposed two cognitive variables as antecedents, self-efficacy and science trust, to verify their influences on students' behavioural intention. We further investigated two mediators, perceived usefulness and perceived ease of use, to examine to what extent they had effects on students' intention. Questionnaire data were collected from 282 university students who participated in a science service project. A structural equation model (SEM) procedure was used to test the direct and indirect relationships between the variables. The results showed that both self-efficacy and science trust had direct influences on perceived usefulness and perceived ease of use. The two mediators also had direct effects on students' behavioural intention. Nevertheless, as a mediating variable, only perceived ease of use effectively mediated the relationships between both self-efficacy and science trust and students' behavioural intention. Findings of this research could provide some suggestions to enhance students' behavioural intention for institutions where science service learning is a required project/programme. [ABSTRACT FROM AUTHOR]

Importance: The mechanisms underlying the association between chronic stress and higher mortality among individuals with cancer remain incompletely understood. Objective: To test the hypotheses that among individuals with active head and neck cancer, that higher stress-associated neural activity (ie. metabolic amygdalar activity [AmygA]) at cancer staging associates with survival. Design: Retrospective cohort study. Setting: Academic Medical Center (Massachusetts General Hospital, Boston). Participants: 240 patients with head and neck cancer (HNCA) who underwent 18F-FDG-PET/CT imaging as part of initial cancer staging. Measurements: 18F-FDG uptake in the amygdala was determined by placing circular regions of interest in the right and left amygdalae and measuring the mean tracer accumulation (i.e., standardized uptake value [SUV]) in each region of interest. Amygdalar uptake was corrected for background cerebral activity (mean temporal lobe SUV). Results: Among individuals with HNCA (age 59±13 years; 30% female), 67 died over a median follow-up period of 3 years (IQR: 1.7–5.1). AmygA associated with heightened bone marrow activity, leukocytosis, and C-reactive protein (P<0.05 each). In adjusted and unadjusted analyses, AmygA associated with subsequent mortality (HR [95% CI]: 1.35, [1.07–1.70], P = 0.009); the association persisted in stratified subset analyses restricted to patients with advanced cancer stage (P<0.001). Individuals within the highest tertile of AmygA experienced a 2-fold higher mortality rate compared to others (P = 0.01). The median progression-free survival was 25 months in patients with higher AmygA (upper tertile) as compared with 36.5 months in other individuals (HR for progression or death [95%CI], 1.83 [1.24–2.68], P = 0.001). Conclusions and relevance: AmygA, quantified on routine 18F-FDG-PET/CT images obtained at cancer staging, independently and robustly predicts mortality and cancer progression among patients with HNCA. Future studies should test whether strategies that attenuate AmygA (or its downstream biological consequences) may improve cancer survival. [ABSTRACT FROM AUTHOR]

To maximize the utility of PET MPI with myocardial blood flow measurement in patients with SVC syndrome, alternate routes of radiotracer administration may be considered. Introduction Superior vena cava (SVC) syndrome is the constellation of clinical findings resulting from SVC occlusion, commonly due to malignancy or SVC stenosis consequent to central venous catheters and pacemaker/defibrillator leads.[1] SVC syndrome affects circulatory hemodynamics by diverting blood to the right atrium through venous collaterals. B Fused PET-CT image showing excessive pooling of radiotracer in the quadrate lobe of the liver, a consequence of the caval-portal shunts secondary to collateral circulation Graph: Figure 3Severe superior vena cava stenosis. [Extracted from the article]

UDP-glucuronosyltransferases are the principal enzymes involved in the glucuronidation of metabolites and xenobiotics for physiological clearance in humans. Though glucuronidation is an indispensable process in the phase II metabolic pathway, UGT-mediated glucuronidation of most prescribed drugs (> 55%) and clinical evidence of UGT-associated drug resistance are major concerns for therapeutic development. While UGTs are highly conserved enzymes, they manifest unique substrate and inhibitor specificity which is poorly understood given the dearth of experimentally determined full-length structures. Such information is important not only to conceptualize their specificity but is central to the design of inhibitors specific to a given UGT in order to avoid toxicity associated with pan-UGT inhibitors. Here, we provide the 1H, 13C and 15N backbone (~ 90%) and sidechain (~ 62%) assignments for the C-terminal domain of UGT2B17, which can be used to determine the molecular binding sites of inhibitor and substrate, and to understand the atomic basis for inhibitor selectivity between UGT2B17 and other members of the UGT2B subfamily. Given the physiological relevance of UGT2B17 in the elimination of hormone-based cancer drugs, these assignments will contribute towards dissecting the structural basis for substrate specificity, selective inhibitor recognition and other aspects of enzyme activity with the goal of selectively overcoming glucuronidation-based drug resistance. [ABSTRACT FROM AUTHOR]

Background: Air pollution and noise exposures individually associate with major adverse cardiovascular events (MACE) via a mechanism involving arterial inflammation (ArtI); however, their combined impact on ArtI and MACE remains unknown. We tested whether dual (vs. one or neither) exposure associates with greater ArtI and MACE risk and whether MACE risk is mediated via ArtI. Methods: Individuals (N = 474) without active cancer or known cardiovascular disease with clinical 18F-FDG-PET/CT imaging were followed for 5 years for MACE. ArtI was measured. Average air pollution (particulate matter ≤ 2.5 μm, PM2.5) and transportation noise exposure were determined at individual residences. Higher exposures were defined as noise > 55 dBA (World Health Organization cutoff) and PM2.5 ≥ sample median. Results: At baseline, 46%, 46%, and 8% were exposed to high levels of neither, one, or both pollutants; 39 experienced MACE over a median 4.1 years. Exposure to an increasing number of pollutants associated with higher ArtI (standardized β [95% CI:.195 [.052,.339], P =.008) and MACE (HR [95% CI]: 2.897 [1.818–4.615], P <.001). In path analysis, ArtI partially mediated the relationship between pollutant exposures and MACE (P <.05). Conclusion: Air pollution and transportation noise exposures contribute incrementally to ArtI and MACE. The mechanism linking dual exposure to MACE involves ArtI. [ABSTRACT FROM AUTHOR]

Graph: Figure 1 Monitoring for cardiovascular disease resulting from the convergence of baseline risk factors and the effects of cancer therapies in breast cancer patients The study should be interpreted within the context of its design. Among patients with a history of breast cancer, coronary microvascular dysfunction detected by PET MPI appears to serve as an effective biomarker for cardiovascular risk. [Extracted from the article]

The eukaryotic DNA replication fork is a hub of enzymes that continuously act to synthesize DNA, propagate DNA methylation and other epigenetic marks, perform quality control, repair nascent DNA, and package this DNA into chromatin. Many of the enzymes involved in these spatiotemporally correlated processes perform their functions by binding to proliferating cell nuclear antigen (PCNA). A long-standing question has been how the plethora of PCNA-binding enzymes exert their activities without interfering with each other. As a first step towards deciphering this complex regulation, we studied how Chromatin Assembly Factor 1 (CAF-1) binds to PCNA. We demonstrate that CAF-1 binds to PCNA in a heretofore uncharacterized manner that depends upon a cation-pi (π) interaction. An arginine residue, conserved among CAF-1 homologs but absent from other PCNA-binding proteins, inserts into the hydrophobic pocket normally occupied by proteins that contain canonical PCNA interaction peptides (PIPs). Mutation of this arginine disrupts the ability of CAF-1 to bind PCNA and to assemble chromatin. The PIP of the CAF-1 p150 subunit resides at the extreme C-terminus of an apparent long α-helix (119 amino acids) that has been reported to bind DNA. The length of that helix and the presence of a PIP at the C-terminus are evolutionarily conserved among numerous species, ranging from yeast to humans. This arrangement of a very long DNA-binding coiled-coil that terminates in PIPs may serve to coordinate DNA and PCNA binding by CAF-1. [ABSTRACT FROM AUTHOR]

All individuals underwent assessment of BHB and other metabolic biomarkers at three separate time points: approximately four hours before SP 18 sp F-FDG injection, approximately ten minutes before SP 18 sp F-FDG injection, and approximately 45 min after SP 18 sp F-FDG injection. BHB measured four hours prior to SP 18 sp F-FDG injection performed as well or better than measurements performed closer to imaging, which may be useful during inpatient evaluations. [Extracted from the article]

We analyze the expected behavior of an advanced artificial agent with a learned goal planning in an unknown environment. Given a few assumptions, we argue that it will encounter a fundamental ambiguity in the data about its goal. For example, if we provide a large reward to indicate that something about the world is satisfactory to us, it may hypothesize that what satisfied us was the sending of the reward itself; no observation can refute that. Then we argue that this ambiguity will lead it to intervene in whatever protocol we set up to provide data for the agent about its goal. We discuss an analogous failure mode of approximate solutions to assistance games. Finally, we briefly review some recent approaches that may avoid this problem. [ABSTRACT FROM AUTHOR]

We propose an alternative maximum entropy approach to learning the spectra of massive graphs. In contrast to state-of-the-art Lanczos algorithm for spectral density estimation and applications thereof, our approach does not require kernel smoothing. As the choice of kernel function and associated bandwidth heavily affect the resulting output, our approach mitigates these issues. Furthermore, we prove that kernel smoothing biases the moments of the spectral density. Our approach can be seen as an information-theoretically optimal approach to learning a smooth graph spectral density, which fully respects moment information. The proposed method has a computational cost linear in the number of edges, and hence can be applied even to large networks with millions of nodes. We showcase the approach on problems of graph similarity learning and counting cluster number in the graph, where the proposed method outperforms existing iterative spectral approaches on both synthetic and real-world graphs. [ABSTRACT FROM AUTHOR]

Accordingly, through these combined arterial and atrial measurements, FDG PET/CT imaging may provide insight into the risk for ischemic stroke due to both atherosclerotic and cardioembolic sources in patients without AF. FDG PET/CT imaging may potentially improve our ability to assess stroke risk in non-AF patients. Because strokes occurred prior to FDG PET/CT imaging, the temporal relationship between imaging findings and stroke cannot be established. [Extracted from the article]

Moreover, the REPRIEVE trial (NCT02344290), the largest treatment trial in PWH to date, is currently evaluating the clinical impact of statins among nearly eight thousand PWH who have been randomized to pitavastatin vs placebo to evaluate the impact of statin therapy on ASCVD events and several imaging endpoints. In addition to the important observation that statins significantly reduce atherosclerotic inflammation in PWH, several other findings from the current study deserve further consideration.[16] First, the authors report that arterial inflammation decreased by 11.9% among individuals who received 10 mg of rosuvastatin. The study by Boczar et al beautifully leverages PET/CT to identify a beneficial effect of statins on atherosclerotic inflammation in PLW and, further, raises the possibility that statins may act, in part, via reducing leukopoietic activity. Potentially overcoming this limitation, several substantially larger PET/CT imaging trials in PWH are currently studying the effect of other treatments (e.g., alirocumab, canakinumab, tocilizumab, letermovir, and teduglutide, among others) on arterial inflammation in addition to several other imaging and circulating biomarker endpoints. [Extracted from the article]

The quality of patient preparation was reviewed in detail by imaging staff on the day of the SP 18 sp F-FDG PET prior to SP 18 sp F-FDG injection. See related article, https://doi.org/10.1007/s12350-019-01746-4 Cardiac SP 18 sp F-fluorodeoxyglucose positron emission tomography ( SP 18 sp F-FDG PET) has become an important tool in the diagnosis and management of a number of inflammatory cardiovascular pathologies, including cardiac sarcoidosis.[1],[2] The technique utilizes SP 18 sp F-FDG, a radiolabeled glucose analogue that is avidly taken up by highly metabolic tissues. [Extracted from the article]

The human UDP-glucuronosyltransferase (UGT) family of enzymes catalyze the covalent addition of glucuronic acid to a wide range of compounds, generally rendering them inactive. Although important for clearance of environmental toxins and metabolites, UGT activation can lead to inappropriate glucuronidation of therapeutics underlying drug resistance. Indeed, 50% of medications are glucuronidated. To better understand this mode of resistance, we studied the UGT2B7 enzyme associated with glucuronidation of cancer drugs such as Tamoxifen and Sorafenib. We report 1H, 13C and 15N backbone (> 90%) and side-chain assignments (~ 78% completeness according to CYANA) for the C-terminal domain of UGT2B7 (UGT2B7-C). Given the biomedical importance of this family of enzymes, our assignments will provide a key tool for improving understanding of the biochemical basis for substrate selectivity and other aspects of enzyme activity. This in turn will inform on drug design to overcome UGT-related drug resistance. [ABSTRACT FROM AUTHOR]

Accumulating evidence from human-based research has highlighted that the prevalent one-size-fits-all approach for neural and behavioral interventions is inefficient. This approach can benefit one individual, but be ineffective or even detrimental for another. Studying the efficacy of the large range of different parameters for different individuals is costly, time-consuming and requires a large sample size that makes such research impractical and hinders effective interventions. Here an active machine learning technique is presented across participants—personalized Bayesian optimization (pBO)—that searches available parameter combinations to optimize an intervention as a function of an individual's ability. This novel technique was utilized to identify transcranial alternating current stimulation (tACS) frequency and current strength combinations most likely to improve arithmetic performance, based on a subject's baseline arithmetic abilities. The pBO was performed across all subjects tested, building a model of subject performance, capable of recommending parameters for future subjects based on their baseline arithmetic ability. pBO successfully searches, learns, and recommends parameters for an effective neurointervention as supported by behavioral, stimulation, and neural data. The application of pBO in human-based research opens up new avenues for personalized and more effective interventions, as well as discoveries of protocols for treatment and translation to other clinical and non-clinical domains. Author summary: The common one-size-fits-all approach used in biological and behavioral research has shown to be inefficient. This is especially the case in the field of brain stimulation, where many different combinations of stimulation parameters (i.e., frequency and current strength of the applied current) can be used for restorative or enhancement purposes, in clinical and non-clinical populations, respectively. Even intervention protocols that have reported to be effective for certain individuals can be detrimental for others. Here we present an active machine learning method, personalized Bayesian optimization (pBO) that successfully searches, learns, and recommends neurostimulation parameters across individuals. Based on an individual's baseline cognitive ability, the pBO identifies specific combinations of transcranial alternating current stimulation parameters, which are most likely to improve cognitive performance, in which case arithmetic problem solving. This timely approach provides a possible solution for the pressing need for personalization in different disciplines including medicine, psychology, and education. [ABSTRACT FROM AUTHOR]

On February 17, 2021, Dr. Henry Gewirtz (Figure 1) passed away. Graph: Figure 1 Henry Gewirtz, hiking in the Himalayas Dr. Henry Gewirtz was born in Rockville Center, NY (Long Island) in 1945. Acknowledgments We would like to thank Dr. Gewirtz's colleagues, trainees, and friends for sharing with us the wonderful memories of Henry. [Extracted from the article]

Positron emission tomography (PET) imaging can yield unique mechanistic insights into the pathophysiology of atherosclerosis. 18F-fluorodeoxyglucose (18F-FDG), a radiolabeled glucose analog, is retained by cells in proportion to their glycolytic activity. While 18F-FDG accumulates within several cell types in the arterial wall, its retention correlates with macrophage content, providing an index of arterial inflammation (ArtI) which predicts subsequent cardiovascular disease (CVD) events. Furthermore, 18F-FDG-PET imaging allows the simultaneous assessment of metabolic activity in several tissues (e.g., brain, bone marrow) and is performed in conjunction with cross-sectional imaging that enables multi-organ structural assessments. Accordingly, 18F-FDG-PET/computed tomography (CT) imaging facilitates evaluation of disease pathways that span multiple organ systems. Within this paradigm, 18F-FDG-PET/CT imaging has been implemented to study the mechanism linking chronic stress to CVD. To evaluate this, stress-associated neural activity can be quantified (as metabolic activity of the amygdala (AmygA)), while leukopoietic activity, ArtI, and coronary plaque burden are assessed concurrently. Such simultaneous quantification of tissue structures and activities enables the evaluation of multi-organ pathways with the aid of mediation analysis. Using this approach, multi-system 18F-FDG-PET/CT imaging studies have demonstrated that chronically heightened stress-associated neurobiological activity promotes leukopoietic activity and systemic inflammation. This in turn fuels more ArtI and greater non-calcified coronary plaque burden, which result in more CVD events. Subsequent studies have revealed that common stressors, such as chronic noise exposure and income disparities, drive the front end of this pathway to increase CVD risk. Hence, multi-tissue multimodality imaging serves as a powerful tool to uncover complex disease mechanisms. [ABSTRACT FROM AUTHOR]

Aims Activity in the amygdala, a brain centre involved in the perception of and response to stressors, associates with: (i) heightened sympathetic nervous system and inflammatory output and (ii) risk of cardiovascular disease. We hypothesized that the amygdalar activity (AmygA) ratio is heightened among individuals who develop Takotsubo syndrome (TTS), a heart failure syndrome often triggered by acute stress. We tested the hypotheses that (i) heightened AmygA precedes development of TTS and (ii) those with the highest AmygA develop the syndrome earliest. Methods and results Individuals (N =104, median age 67.5 years, 72% female, 86% with malignancy) who underwent clinical 18 F-FDG-PET/CT imaging were retrospectively identified: 41 who subsequently developed TTS and 63 matched controls (median follow-up 2.5 years after imaging). AmygA was measured using validated methods. Individuals with (vs. without) subsequent TTS had higher baseline AmygA (P =0.038) after adjusting for TTS risk factors. Further, AmygA associated with the risk for subsequent TTS after adjustment for risk factors [standardized hazard ratio (95% confidence interval): 1.643 (1.189, 2.270), P =0.003]. Among the subset of individuals who developed TTS, those with the highest AmygA (>mean + 1 SD) developed TTS ∼2 years earlier after imaging vs. those with lower AmygA (P =0.028). Conclusion Higher AmygA associates with an increased risk for TTS among a retrospective population with a high rate of malignancy. This heightened neurobiological activity is present years before the onset of TTS and may impact the timing of the syndrome. Accordingly, heightened stress-associated neural activity may represent a therapeutic target to reduce stress-related diseases, including TTS. [ABSTRACT FROM AUTHOR]

First and foremost, a large retrospective study of patients with prior aortic SP 18 sp F-NaF PET imaging should be performed to determine the relationship between the various imaging endpoints with downstream clinical events and to assess its additive value above conventional risk scores and easily derived measures of arterial macrocalcification. SP 18 sp F-sodium fluoride ( SP 18 sp F-NaF) is a positron emission tomography (PET) tracer which has increasingly been shown to be effective for the assessment of cardiovascular diseases. [Extracted from the article]

Background: While growing evidence suggests a link between periodontal disease (PD) and cardiovascular disease (CVD), the independence of this association and the pathway remain unclear. Herein, we tested the hypotheses that: (1) inflammation of the periodontium (PDinflammation ) predicts future CVD independently of disease risk factors shared between CVD and PD, and (2) the mechanism linking the two diseases involves heightened arterial inflammation.Methods: 18 F-fluorodeoxyglucose positron emission tomography/computed tomography (18 F-FDG-PET/CT) imaging was performed in 304 individuals (median age 54 years; 42.4% male) largely for cancer screening; individuals without active cancer were included. PDinflammation and arterial inflammation were quantified using validated 18 F-FDG-PET/CT methods. Additionally, we evaluated the relationship between PDinflammation and subsequent major adverse cardiovascular events (MACE) using Cox models and log-rank tests.Results: Thirteen individuals developed MACE during follow-up (median 4.1 years). PDinflammation associated with arterial inflammation, remaining significant after adjusting for PD and CVD risk factors (standardized β [95% CI]: 0.30 [0.20-0.40], P < 0.001). PDinflammation predicted subsequent MACE (standardized HR [95% CI]: 2.25 [1.47 to 3.44], P <0.001, remaining significant in multivariable models), while periodontal bone loss did not. Furthermore, mediation analysis suggested that arterial inflammation accounts for 80% of the relationship between PDinflammation and MACE (standardized log odds ratio [95% CI]: 0.438 [0.019-0.880], P = 0.022).Conclusion: PDinflammation is independently associated with MACE via a mechanism that may involve increased arterial inflammation. These findings provide important support for an independent relationship between PDinflammation and CVD. [ABSTRACT FROM AUTHOR]

Aims  Air pollution [i.e. particulate matter with diameter <2.5 μm (PM2.5)] is a risk factor for major adverse cardiovascular events (MACE). While PM2.5 promotes leucopoiesis and atherosclerotic inflammation in experimental models, it is unknown whether this occurs in humans. We tested in humans (a) whether PM2.5 associates with higher leucopoietic tissue activity and arterial inflammation (ArtI), (ii) whether these associations persist after accounting for the effects of potential confounders including socioeconomics, traffic noise, and risk factors, and (iii) whether these tissue effects mediate the association between air pollution and MACE. Methods and results  Individuals (N = 503) without cardiovascular disease (CVD) or active malignancy underwent 18 F-fluorodeoxyglucose positron emission tomography/computed tomography. Major adverse cardiovascular event was adjudicated over 5 years of follow-up. Leucopoietic tissue activity (in bone marrow and spleen) as well as ArtI were measured. Annual PM2.5 levels were assessed at each individual's home address. At baseline, higher PM2.5 associated with increased leucopoietic activity [standardized (95% CI): 0.129 (0.042, 0.215), P = 0.004] as well as ArtI [0.088 (0.006, 0.171), P = 0.036] after adjusting for CVD risk factors. Over a median 4.1 years, 40 individuals experienced MACE. PM2.5 exposure associated with MACE [Cox HR (95% CI): 1.404 (1.135, 1.737), P = 0.002], remaining significant after adjustment for CVD risk factors and other potential confounders. Mediation analysis demonstrated that increased leucopoietic activity and ArtI serially mediate the link between PM2.5 exposure and MACE. Conclusions  Higher air pollution exposure associates with heightened leucopoietic activity and ArtI and independently predicts MACE through a biological pathway that includes higher leucopoietic activity and ArtI in series. [ABSTRACT FROM AUTHOR]

Using the nationally representative sample from the United States in the 2012 Programme for International Student Assessment (N = 7,429 students from 240 schools), I examined the relationship between teacher instructional practices and student mathematics achievement. To account for the multilevel structure of the data with students nested within schools, I used a two-level hierarchical linear model in the data analysis. Teacher instructional practices showed statistically significant effects on student mathematics achievement, even after controlling for socioeconomic status (SES) and sex at the student level and school mean SES and whether the school is public or private at the school level. Furthermore, I found that the relationship between teacher instructional practices and student mathematics achievement varied statistically significantly across schools. [ABSTRACT FROM AUTHOR]

A positron emission tomography (PET) imaging tracer that provides a meaningful and clinically deployable risk assessment in coronary artery disease (CAD) has been sought enthusiastically for over a decade. As the clinical implications of findings from SP 18 sp F-NaF PET imaging in CAD are increasingly clarified, several key knowledge gaps remain (Table 1). [Extracted from the article]

Objective To identify the extent to which administrative tasks carried out by primary care staff in general practice could be automated. Design A mixed-method design including ethnographic case studies, focus groups, interviews and an online survey of automation experts. Setting Three urban and three rural general practice health centres in England selected for differences in list size and organisational characteristics. Participants Observation and interviews with 65 primary care staff in the following job roles: administrator, manager, general practitioner, healthcare assistant, nurse practitioner, pharmacy technician, phlebotomist, practice nurse, pharmacist, prescription clerk, receptionist, scanning clerk, secretary and medical summariser; together with a survey of 156 experts in automation technologies. Methods 330 hours of ethnographic observation and documentation of administrative tasks carried out by staff in each of the above job roles, followed by coding and classification; semistructured interviews with 10 general practitioners and 6 staff focus groups. The online survey of machine learning, artificial intelligence and robotics experts was analysed using an ordinal Gaussian process prediction model to estimate the automatability of the observed tasks. results The model predicted that roughly 44% of administrative tasks carried out by staff in general practice are ‘mostly’ or ‘completely’ automatable using currently available technology. Discussions with practice staff underlined the need for a cautious approach to implementation. Conclusions There is considerable potential to extend the use of automation in primary care, but this will require careful implementation and ongoing evaluation. [ABSTRACT FROM AUTHOR]

Using the nationally representative sample from the United States in the 2012 Programme for International Student Assessment (N = 7,429 students from 240 schools), the present study examined the effects of student help-seeking behaviors on eight measures of student mathematics achievement. To account for the multilevel structure of the data with students nested within schools (i.e., students attending different schools), a two-level hierarchical linear model was used in the data analysis. Student help-seeking behaviors showed statistically significant positive effects on all eight measures of mathematics achievement, even after controlling for student characteristics and school characteristics. Furthermore, for all eight measures of mathematics achievement, the positive effects of student help-seeking behaviors on student mathematics achievement are independent of which schools students attend. [ABSTRACT FROM AUTHOR]

Aims Chronic noise exposure associates with increased cardiovascular disease (CVD) risk; however, the role of confounders and the underlying mechanism remain incompletely defined. The amygdala, a limbic centre involved in stress perception, participates in the response to noise. Higher amygdalar metabolic activity (AmygA) associates with increased CVD risk through a mechanism involving heightened arterial inflammation (ArtI). Accordingly, in this retrospective study, we tested whether greater noise exposure associates with higher: (i) AmygA, (ii) ArtI, and (iii) risk for major adverse cardiovascular disease events (MACE). Methods and results Adults (N  = 498) without CVD or active cancer underwent clinical 18F-fluorodeoxyglucose positron emission tomography/computed tomography imaging. Amygdalar metabolic activity and ArtI were measured, and MACE within 5 years was adjudicated. Average 24-h transportation noise and potential confounders were estimated at each individual's home address. Over a median 4.06 years, 40 individuals experienced MACE. Higher noise exposure (per 5 dBA increase) predicted MACE [hazard ratio (95% confidence interval, CI) 1.341 (1.147–1.567), P  < 0.001] and remained robust to multivariable adjustments. Higher noise exposure associated with increased AmygA [standardized β (95% CI) 0.112 (0.051–0.174), P  < 0.001] and ArtI [0.045 (0.001–0.090), P  = 0.047]. Mediation analysis suggested that higher noise exposure associates with MACE via a serial mechanism involving heightened AmygA and ArtI that accounts for 12–26% of this relationship. Conclusion Our findings suggest that noise exposure associates with MACE via a mechanism that begins with increased stress-associated limbic (amygdalar) activity and includes heightened arterial inflammation. This potential neurobiological mechanism linking noise to CVD merits further evaluation in a prospective population. Open in new tab Download slide Open in new tab Download slide [ABSTRACT FROM AUTHOR]

Viruses have transformed our understanding of mammalian RNA processing, including facilitating the discovery of the methyl-7- guanosine (m7G) cap on the 5' end of RNAs. The m7G cap is required for RNAs to bind the eukaryotic translation initiation factor eIF4E and associate with the translation machinery across plant and animal kingdoms. The potyvirus-derived viral genome-linked protein (VPg) is covalently bound to the 5' end of viral genomic RNA (gRNA) and associates with host eIF4E for successful infection. Divergent models to explain these observations proposed either an unknown mode of eIF4E engagement or a competition of VPg for the m7G cap-binding site. To dissect these possibilities, we resolved the structure of VPg, revealing a previously unknown 3-dimensional (3D) fold, and characterized the VPg-eIF4E complex using NMR and biophysical techniques. VPg directly bound the cap-binding site of eIF4E and competed form7G cap analog binding. In human cells, VPg inhibited eIF4E-dependent RNA export, translation, and oncogenic transformation. Moreover, VPg formed trimeric complexes with eIF4E-eIF4G, eIF4E bound VPg-luciferase RNA conjugates, and these VPg-RNA conjugates were templates for translation. Informatic analyses revealed structural similarities between VPg and the human kinesin EG5. Consistently, EG5 directly bound eIF4E in a similar manner to VPg, demonstrating that this form of engagement is relevant beyond potyviruses. In all, we revealed an unprecedented modality for control and engagement of eIF4E and show that VPg- RNA conjugates functionally engage eIF4E. As such, potyvirus VPg provides a unique model system to interrogate eIF4E. [ABSTRACT FROM AUTHOR]

Although the number of clinical applications for fluorine-18 fluorodeoxyglucose (18F-FDG) cardiac positron emission tomography (PET) has continued to grow, there remains a lack of consensus regarding the ideal method of suppressing normal myocardial glucose utilization for image optimization. This review describes various patient preparation protocols that have been used as well as the success rates achieved in different studies. Collectively, the available literature supports using a high-fat, no-carbohydrate diet for at least two meals with a fast of 4-12 hours prior to 18F-FDG PET imaging and suggests that isolated fasting for less than 12 hours and supplementation with food or drink just prior to imaging should be avoided. Each institution should adopt a protocol and continuously monitor its effectiveness with a goal to achieve adequate myocardial suppression in greater than 80% of patients. [ABSTRACT FROM AUTHOR]

The article offers information on combined molecular and structural imaging using positron emission tomography (PET). Topics discussed emerging research continues to expand the uses for molecular imaging in rheumatic diseases; increasing frequency in rheumatic conditions and which has been useful in the evaluation of large vessel vasculitis; and data to compare the various 18F-FDG– PET-CT synovial measures with clinical measures of disease activity.

The article focuses on how political dynamics can contribute to the history of science and significant developments in the field historiographical science and empire. It mentions historiographical developments by American anthropologists such as Marshall Sahlins, Hayden White or Clifford Geertz, added the one by Indian historians like Gayatri Chakravorty Spivak and Homi Bhabha. It also mentions circumstance's of imperialism promote the appeal to knowledge producers.

The dysregulation of translation contributes to many pathogenic conditions in humans. Discovering new translational mechanisms is important to understanding the diversity of this process and its potential mechanisms. Such mechanisms can be initially observed in viruses. With this in mind, we studied the viral protein genome-linked VPg factor from the largest genus of plant viruses. Studies in plants show that VPg binds to the eukaryotic translation initiation factor eIF4E for translation of viral RNAs. VPg contains no known eIF4E binding motifs and no sequence homology to any known proteins. Thus, as a first step in understanding the structural basis of this interaction, we carried out NMR assignments of the VPg from the potato virus Y potyvirus protein. [ABSTRACT FROM AUTHOR]

Despite UNESCO's Learning Cities agenda, which argues for the mobilisation of resources to promote education across all sectors and environments, there is little evaluative research on Learning City engagement which is both naturalistic and empirically rigorous. The research on informal adult learning in urban contexts is particularly sparse. This paper provides a case study of informal learning and lifewide literacies amongst Glaswegian adults using three distinct approaches to data collection: a household survey capturing rich data on learning attitudes, behaviours, and literacies; GPS trails that track mobility around the city; and the capture of naturally occurring social media. The work operationalises Learning City indicators, and explores domains beyond education, some of which have not previously been considered in surveys of adult learning, for example, physical mobilities and transportation patterns. We use theoretical concepts of social identity and capital to situate inclusion within explanatory frameworks of marginalisation in less tangible domains of informal learning using multi-stranded data. A triangulated analysis of city-wide participation in lifewide learning reveals a demographic picture of groups marginalised from learning opportunities and practices. We conclude with a call for new approaches to exploring learning participation which offer novel methods to evidence informal learning and lifewide literacies. [ABSTRACT FROM AUTHOR]

Predicting fast tidal currents can be a challenging task. Unlike tidal water levels, currents can vary sharply over short distances. The classical approach of harmonic analysis can analyze data at point locations and there is a need for a method that can handle spatiotemporal data, as well as be robust to the uncertainty and noise inevitable in real‐world measurements. In this work, we present a Bayesian machine learning (ML) approach to tackle the problem. The method is based on Gaussian processes, a nonparametric ML technique that uses a kernel function to capture structures in the data. A case study is performed using data from a validated numerical model simulating the tidal dynamics in the Pentland Firth region, UK. Several sampling strategies are explored and the case where measurement location is changed after every sampling is found to produce the lowest average error in the predictions. We show that the presented methodology using data from just a single moving data source can provide a better spatiotemporal description than traditional techniques using continuous data from a large number of locations. The work can be useful to developers of tidal energy farms, navigation, and other purposes. Key Points: This paper introduces a new Bayesian nonparametric machine learning technique for spatiotemporal tidal current predictionIt provides better spatiotemporal description with data from one source than classical techniques using continuous data from multiple sourcesMethod can be applied to spatiotemporal tidal current data from any region [ABSTRACT FROM AUTHOR]

Accurate on-board capacity estimation is of critical importance in lithium-ion battery applications. Battery charging/discharging often occurs under a constant current load, and hence voltage versus time measurements under this condition may be accessible in practice. This paper presents a data-driven diagnostic technique, Gaussian process regression for in situ capacity estimation (GP-ICE), which estimates battery capacity using voltage measurements over short periods of galvanostatic operation. Unlike previous works, GP-ICE does not rely on interpreting the voltage–time data as incremental capacity (IC) or differential voltage (DV) curves. This overcomes the need to differentiate the voltage–time data (a process that amplifies measurement noise), and the requirement that the range of voltage measurements encompasses the peaks in the IC/DV curves. GP-ICE is applied to two datasets, consisting of 8 and 20 cells, respectively. In each case, within certain voltage ranges, as little as 10 s of galvanostatic operation enables capacity estimates with approximately 2%–3% root-mean-squared error (RMSE). [ABSTRACT FROM AUTHOR]

A major component of phase II drug metabolism is the covalent addition of glucuronic acid to metabolites and xenobiotics. This activity is carried out by UDP-glucuronosyltransferases (UGT) which bind the UDP-glucuronic acid donor and catalyze the covalent addition of glucuronic acid sugar moieties onto a wide variety of substrates. UGTs play important roles in drug detoxification and were recently shown to act in an inducible form of multi-drug resistance in cancer patients. Despite their biological importance, structural understanding of these enzymes is limited. The C-terminal domain is identical for all UGT1A family members and required for binding to UDP-glucuronic acid as well as involved in contacts with substrates. Here, we report the backbone assignments for the C-terminal domain of UGT1A. These assignments are a critical tool for the development of a deeper biochemical understanding of substrate specificity and enzymatic activity. [ABSTRACT FROM AUTHOR]

See related article, 10.1007/s12350-019-01786-w. As SP 18 sp F-fluorodeoxyglucose positron emission tomography ( SP 18 sp F-FDG PET) is increasingly used for the detection of pathologic myocardial inflammation, a growing body of research has focused on improving imaging quality by seeking strategies to more successfully suppress background myocardial uptake of SP 18 sp F-FDG, a radioactive glucose analogue. Two of the greatest challenges that remain in SP 18 sp F-FDG PET myocardial imaging are how to prevent focal on diffuse myocardial SP 18 sp F-FDG uptake and how to interpret this pattern. [Extracted from the article]

There is accumulating evidence for the existence of a phenotype of isolated cardiac sarcoidosis (ICS), or sarcoidosis that only involves the heart. In the absence of biopsy-confirmed cardiac sarcoidosis (CS), existing diagnostic criteria require the presence of extra-cardiac sarcoidosis as an inclusion criterion for the diagnosis of CS. Consequently, in the absence of a positive endomyocardial biopsy, ICS is not diagnosable by current guidelines. Therefore, there is uncertainty regarding the epidemiology, pathobiology, clinical characteristics, prognosis, and optimal treatment of ICS. This review will summarize the available data related to the prevalence and prognosis of ICS and will discuss challenges surrounding the diagnosis and management of this under-recognized entity. [ABSTRACT FROM AUTHOR]

In the Global North and increasingly in the Global South, smart city technologies are enthusiastically seen as a solution to urban problems and as an alternative to austerity. However, to move beyond a narrow technological focus, it is necessary to explore the degree to which smart initiatives are committed to building socially inclusive innovation with learning at its core. Using the particular case of the Future City Demonstrator Initiative in Glasgow, United Kingdom, the most high-profile initiative of its kind funded by government, the authors of this article assess the extent to which this smart city adopts such an inclusive approach. They use the quadruple helix model (government - academia - industry - civil society) as a starting point and develop an analytic framework composed of four strands: (1) supporting participation of citizens in decision-making; (2) implementing technological innovation which positions citizens as active users; (3) implementing technological innovation to benefit the community; and (4) evaluating technological innovation in the light of the experiences and needs of citizens. Unlike most analyses, the principal focus of this article is on the fourth element of the helix, civil society. The authors argue that Glasgow’s rhetoric of smart urbanism, while aspiring to problem-solving, devalues certain principles of human agency. They emphasise that urban change, including the city’s desire to become technologically innovative, would more fully facilitate active citizenship, social inclusion and learning opportunities for all if it were underpinned by the broader conceptions and frameworks of learning cities. [ABSTRACT FROM AUTHOR]

We address the two fundamental problems of spatial field reconstruction and sensor selection in heterogeneous sensor networks. We consider the case where two types of sensors are deployed: the first consists of expensive, high quality sensors; and the second, of cheap low quality sensors, which are activated only if the intensity of the spatial field exceeds a pre-defined activation threshold (e.g., wind sensors). In addition, these sensors are powered by means of energy harvesting and their time varying energy status impacts on the accuracy of the measurement that may be obtained. We then address the following two important problems: (i) how to efficiently perform spatial field reconstruction based on measurements obtained simultaneously from both networks; and (ii) how to perform query based sensor set selection with predictive MSE performance guarantee. To overcome this problem, we solve the first problem by developing a low complexity algorithm based on the spatial best linear unbiased estimator (S-BLUE). Next, building on the S-BLUE, we address the second problem, and develop an efficient algorithm for query based sensor set selection with performance guarantee. Our algorithm is based on the Cross Entropy method which solves the combinatorial optimization problem in an efficient manner. We present a comprehensive study of the performance gain that can be obtained by augmenting the high-quality sensors with low-quality sensors using both synthetic and real insurance storm surge database known as the Extreme Wind Storms Catalogue. [ABSTRACT FROM AUTHOR]