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BACKGROUND: Chronic total occlusions (CTO) are frequent among patients with coronary artery disease. Revascularization with percutaneous coronary intervention (PCI) is safe and feasible in experienced hands. However, randomized data are needed to demonstrate symptomatic as well as prognostic effect of CTO-PCI compared to optimal medical therapy alone.METHODS AND DESIGN: This trial aims to evaluate the effect of CTO PCI in patients with a CTO lesion and target vessel diameter ≥ 2.5 mm, and myocardial ischemia in the relevant territory. First, all patients are subjected to optimal medical therapy (OMT) for at least for 3 months and non-CTO lesions are managed according to guidelines. Subsequently, prior to randomization myocardial ischemia and quality of life (Seattle Questionnaire (SAQ)) is assessed. Patients are divided into two cohorts based on their SAQ score and randomized to either OMT alone or OMT and CTO-PCI. Cohort A is defined as Low- or asymptomatic patients with a quality-of-life score > 60 and/or CCS class < 2, and more than 10 % ischemia in the left ventricle (LV). Cohort B is symptomatic patients with a quality-of-life score < 60 or CCS class angina > 1 and at least ischemia in 5% of the LV. The primary end-point in cohort A is a composite of major adverse cardiac and cerebral events, hospitalization for heart failure and malignant ventricular arrhythmias. The primary endpoint in cohort B is difference in quality of life 6 months after randomization.IMPLICATIONS: This trial is designed to investigate if CTO-PCI improves QoL and MACCE. Both positive and negative outcome of the trial will affect future guidelines and recommendations on how to treat patients with CTO.

Objectives The purpose of the study was to investigate whether postpartum depression is associated with a risk of depression during perimenopause. Study design This is a Danish nationwide register-based cohort study of 270,613 individuals who were born in 1960–1968, who gave birth to a liveborn child recorded in the Medical Birth Register before the age of 40, and who lived in Denmark when turning 47 years old. The association between postpartum depression and depression during perimenopause was analyzed using a Cox proportional hazards model adjusted for education level, marital status, and age at first delivery. Main outcome measures Depression during perimenopause was identified by a diagnosis of depression during nine years of follow-up registered in the Danish National Patient Registry. Results A total of 7694 (2.9 %) study participants were diagnosed with depression during perimenopause. Postpartum depression was associated with 12.82 [95 % confidence interval (CI): 8.93;18.41] times higher hazard of depression during perimenopause, while depression prior to study baseline was associated with 11.91 [95 % CI: 11.14;12.73] times higher hazard compared with individuals with no history of depression. There was no difference in the association between postpartum depression and depression prior to study baseline for depression during perimenopause. Conclusion Prior depression, no matter the timing, is associated with markedly higher risk of depression during perimenopause. Thus, individuals who have experienced postpartum depression do not experience a greater risk of depression during perimenopause compared with individuals who have experienced depression unrelated to periods of hormonal changes during their fertile life.

A key clinical problem in psychiatry is predicting the diagnostic future of patients presenting with psychopathology for the first time. The objective of this study was to establish a comprehensive map of subsequent diagnoses after a first psychiatric hospital diagnosis.Through the Danish National Patient Registry, we identified patients aged 18 years or older with an inpatient or outpatient psychiatric hospital contact and who had received one of the 20 most common first-time psychiatric diagnoses (defined at the ICD-10 two-cipher level, F00-F99) between Jan 1, 1995, and Dec 31, 2008. For each first-time diagnosis, the 20 most frequent subsequent psychiatric diagnoses (F00-F99), and death, occurring during 10 years of follow-up were identified as outcomes. To assess diagnostic stability, we used social sequence analyses, assigning a subsequent diagnosis to each state with a length of 6 months following each first-time diagnosis. The subsequent diagnosis was defined as the last diagnosis given within each 6-month period. We calculated the normalised entropy of each sequence to show the uncertainty of predicting the states in a given sequence. Cox proportional hazards models were used to assess the risk of receiving a subsequent diagnosis (at the one-cipher level, F0-F9) after each first-time diagnosis.The cohort consisted of 184 949 adult patients (77 129 [41·7%] men and 107 820 [58·3%] women, mean age 42·5 years [SD 18·5; range 18 to100). Ethnicity data were not recorded. Over 10 years of follow-up, 86 804 (46·9%) patients had at least one subsequent diagnosis that differed from their first-time diagnosis. Measured by mean normalised entropy values, persistent delusional disorders (ICD-10 code F22), mental and behavioural disorders due to multiple drug use and use of other psychoactive substances (F19), and acute and transient psychotic disorders (F23) had the highest diagnostic variability, whereas eating disorders (F50) and non-organic sexual dysfunction (F52) had the lowest. The risk of receiving a subsequent diagnosis with a psychiatric disorder from an ICD-10 group different from that of the first-time diagnosis varied substantially among first-time diagnoses.These data provide detailed information on possible diagnostic outcomes after a first-time presentation in a psychiatric hospital. This information could help clinicians to plan relevant follow-up and inform patients and families on the degree of diagnostic uncertainty associated with receiving a first psychiatric hospital diagnosis, as well as likely and unlikely trajectories of diagnostic progression.Mental Health Services, Capital region of Denmark.For the Danish translation of the abstract see Supplementary Materials section.

Globally, coral reefs are under pressure from climate change, with concerning declines in coral abundance observed due to increasing cumulative impacts. Active intervention measures that mitigate the declines are increasingly being applied to buy time for coral reefs as the world transitions to a low-carbon economy. One such mitigation strategy is coral restoration based on large-scale coral aquaculture to provide stock for reseeding reefs, with the added potential of selecting corals that better tolerate environmental stress. Application of probiotics during production and deployment, to modulate the naturally occurring bacteria associated with corals, may confer health benefits such as disease resistance, increased environmental tolerance or improved coral nutrition. Here, we briefly describe coral associated bacteria and their role in the coral holobiont, identify probiotics traits potentially beneficial to coral, and discuss current research directions required to develop, test and verify the feasibility for probiotics to improve coral aquaculture at industrial scales.

Catalytic conversion of (ligno)cellulosic biomass at hydrothermal or pyrolysis conditions represent attractive approaches for the production of valuable oxygenated chemicals and platform molecules. Despite many efforts, there is still a knowledge gap in the fundamental phenomena occurring on the catalyst surface, considering the complexity of the reaction networks and catalyst behavior under reaction conditions. In this review, to gain a better understanding of the processes and for designing the most effective catalysts, the main reactions and possible products obtained from catalytic valorization of cellulose are discussed, focusing particularly on diols. The review illustrates how catalysts act for selective production of platform chemicals from cellulose and cellulose-derived sugars at both pyrolysis and hydrothermal conditions and systematically summarizes recent advancements of heterogeneous catalysts, with a view to structure-activity relationships for production of diols.

Objectives: The aim of this study was to assess clinical outcomes after combined pressure and flow assessment of coronary lesions. Background: Although fractional flow reserve (FFR) remains the invasive reference standard for revascularization, approximately 40% of stenoses have discordant coronary flow reserve (CFR). Optimal treatment for these disagreements remains unclear. Methods: A total of 455 subjects with 668 lesions were enrolled from 12 sites in 6 countries. Only lesions with reduced FFR and CFR underwent revascularization; all other combinations received initial medical therapy. Results: Fourteen percent of lesions had FFR ≤0.8 but CFR ≥2.0 while 23% of lesions had FFR >0.8 but CFR 0.8 and CFR ≥2.0 (6.2% event rate) exceeded the prespecified +10% noninferiority margin (P = 0.090). Target vessel failure models using both continuous FFR and continuous CFR found that only higher FFR was associated with reduced target vessel failure (Cox P = 0.007) after initial medical treatment. Central core laboratory review accepted 69.8% of all tracings with mean differences of 0.8 and CFR ≥2.0. These results do not support using invasive CFR ≥2.0 to defer revascularization for lesions with reduced FFR if the patient would otherwise be a candidate on the basis of the entire clinical scenario and treatment preference.

Objectives This study was designed to compare head-to-head fractional flow reserve (FFR) derived from coronary computed tomography angiography (CTA) (FFRCT) and cardiac magnetic resonance (CMR) stress perfusion imaging for prediction of standard-of-care–guided coronary revascularization in patients with stable chest pain and obstructive coronary artery disease by coronary CTA. Background FFRCT is a novel modality for noninvasive functional testing. The clinical utility of FFRCT compared to CMR stress perfusion imaging in symptomatic patients with coronary artery disease is unknown. Methods Prospective study of patients (n=110) with stable angina pectoris and 1 or more coronary stenosis ≥50% by coronary CTA. All patients underwent invasive coronary angiography. Revascularization was FFR-guided in stenoses ranging from 30% to 90%. FFRCT ≤0.80 in 1 or more coronary artery or a reversible perfusion defect (≥2 segments) by CMR categorized patients with ischemia. FFRCT and CMR were analyzed by core laboratories blinded for patient management. Results A total of 38 patients (35%) underwent revascularization. Per-patient diagnostic performance for identifying standard-of-care–guided revascularization, (95% confidence interval) yielded a sensitivity of 97% (86 to 100) for FFRCT versus 47% (31 to 64) for CMR, p 0.05, respectively. Conclusions In patients with stable chest pain referred to invasive coronary angiography based on coronary CTA, FFRCT and CMR yielded similar overall diagnostic accuracy. Sensitivity for prediction of revascularization was highest for FFRCT, whereas specificity was highest for CMR.

We compared 10-year clinical outcomes in diabetes and nondiabetes patients treated with Endeavor zotarolimus-eluting (ZES) or Cypher sirolimus-eluting coronary stents (SES). A total of 1,162 patients were randomized to ZES (169 with diabetes) and 1,170 patients were randomized to SES (168 with diabetes). Patients were further stratified by diabetes status at the time of inclusion. A subgroup of patients with diabetes (n = 88) underwent angiographic re-evaluation 10 months after stent implantation. End points included a combined end point of death or myocardial infarction, and the individual end points of death, myocardial infarction, and revascularization. In patients with diabetes, we found no difference in the combined end point (odds ratio [OR] 0.81, 95% confidence interval [CI] 0.53 to 1.24), death (OR 0.80, 95% CI 0.51 to 1.25), or in MI (OR 1.07, 95% CI 0.60 to 1.91). However, diabetics with ZES more frequently underwent coronary revascularization compared with SES patients (OR 1.93, 95% CI 1.05 to 3.66). In patients without diabetes, ZES and SES had similar 10-year rates of all end points (death: OR 1.13, 95% CI 0.93 to 1.39; MI: OR 0.80, 95% CI 0.61 to 1.05; revascularization: OR 0.81, 95% CI 0.61 to 1.09). Landmark analysis from 5 to 10 years showed no difference in outcomes between SES and ZES in either subgroup. In conclusion, at 10 years, SES and ZES performed similarly in patients with and without diabetes. Although coronary revascularization was more prevalent in diabetes patients with ZES, this may, in part, have been related to the angiographic follow-up that was offered to a subgroup of diabetes patients.

As direct-acting antiviral (DAA) therapy costs fall and eligibility criteria are relaxed, people who inject drugs (PWID) will increasingly become eligible for HCV treatment. Yet eligibility does not necessarily equate to access. Amidst efforts to expand treatment uptake in this population, we seek to synthesise and clarify the conceptual underpinnings of access to health care for PWID, with a view to informing research and practice. Integrating dominant frameworks of health service utilisation, care seeking processes, and ecological perspectives on health promotion, we present a comprehensive theoretical framework to understand, investigate and intervene upon barriers and facilitators to HCV care for PWID. Built upon the concept of Candidacy, the framework describes access to care as a continually negotiated product of the alignment between individuals, health professionals, and health systems. Individuals must identify themselves as candidates for services and then work to stake this claim; health professionals serve as gatekeepers, adjudicating asserted candidacies within the context of localised operating conditions; and repeated interactions build experiential knowledge and patient-practitioner relationships, influencing identification and assertion of candidacy over time. These processes occur within a complex social ecology of interdependent individual, service, system, and policy factors, on which other established theories provide guidance. There is a pressing need for a deliberate and nuanced theory of health care access to complement efforts to document the HCV ‘cascade of care’ among PWID. We offer this framework as an organising device for observational research, intervention, and implementation science to expand access to HCV care in this vulnerable population. Using practical examples from the HCV literature, we demonstrate its utility for specifying research questions and intervention targets across multiple levels of influence; describing and testing plausible effect mechanisms; and identifying potential threats to validity or barriers to research translation.

Catalytic hydropyrolysis of beech wood has been conducted in a fluid bed reactor at 450 °C with a sulfided CoMo catalyst followed by a fixed bed hydrodeoxygenation (HDO) reactor with a sulfided NiMo catalyst at hydrogen pressures between 3.0 and 35.8 bar. Using both reactors the condensable organic yield (condensed organic and C4+ in gas) varied between 18.7 and 21.5 wt% dry ash free basis (daf) and was independent of the hydrogen pressure. At 15.9 bar hydrogen or higher the condensed organic phase was essentially oxygen free (

Background Multiple barriers for accessing hepatitis C virus (HCV) treatment were identified during the interferon-based (IFN) treatment era for people who inject drugs (PWID). Whether these barriers persist since the introduction of IFN-free direct-acting antiviral (DAA) agents in Canada remains to be documented. This study examined temporal trends in HCV treatment initiation and associated factors during the transition from INF-based to all-oral DAA regimens. Methods The study population was drawn from a prospective cohort of PWID in Montreal, Canada. At three-month/one-year intervals between 2011 and 2017, participants with chronic HCV infection completed an interviewer-administered questionnaire on socio-demographic characteristics, drug use and health service utilisation, including HCV treatment. Time-updated Cox multivariate regression models, stratified by DAA + INF (2011-2013) and all-oral DAA (2014–2017) availability periods, were conducted to examine associations between time to HCV treatment initiation and associated barriers and facilitators. Results Of 308 participants (85% male, median age 42 [IQR: 33, 50]), 80 (26%) initiated HCV treatment during 915 person-years (PY). Incidence rates increased from 1.6 /100 PY (95%CI:0.9–2.6) in 2011 to 12.7 (10.6–15.1) in 2017 (p-trend = 0.0012). In multivariate analyses, visiting a primary care physician (2011–2013: aHR = 3.63[1.21–10.9]; 2014–2017: 2.52[1.10–5.77]) and frequent injection (0.23[0.05–0.99] and 0.49[0.24–0.99]) were consistently associated with treatment initiation. Participants aged >40 (2.27[1.24–4.13]), receiving opioid agonist therapy (OAT) (2.17[1.19–3.94]), and reporting prior HCV treatment (3.00[1.75–5.15]) were more likely to initiate treatment in the all-oral DAA period. Conclusion Treatment initiation increased between 2011 and 2017, but still remains low among PWID. Primary care visiting was a key facilitator regardless of the period, while engagement in OAT and health services, indicated by prior HCV treatment, increased the likelihood of treatment initiation in the DAA era. These findings suggest that access to health services is essential but not enough to scale up treatment in this population.

OBJECTIVES: To estimate the association between fetal congenital heart defects (CHDs) and measures of brain size throughout pregnancy, from the end of the first trimester to birth.STUDY DESIGN: The cohort consisted of all fetuses scanned in Western Denmark in 2012 and 2013. Anthropometric measures in fetuses with isolated CHDs diagnosed within 12 months after birth were compared with those in the fetuses without CHDs. Z-scores standardized to gestational age were calculated for first trimester biparietal diameter, second trimester head circumference, fetal weight, birthweight, head circumference, and placental weight.RESULTS: We obtained data from 63 349 pregnancies and identified 295 fetuses with isolated CHDs (major n = 145; minor n = 150). The first trimester mean biparietal diameter Z-scores were not different between those with and those without CHDs. The head circumference mean Z-score difference was -0.13 (95% CI, -0.24 to -0.01; P = .03) in the second trimester and -0.22 (95% CI, -0.35 to -0.09; P < .001) at birth. Fetuses with univentricular physiology or tetralogy of Fallot showed the most pronounced compromise in cerebral size.CONCLUSIONS: Our results suggest that the brain alterations inducing an increased risk of impaired neurodevelopment in children with CHDs begin during pregnancy. Although fetuses with univentricular physiology or tetralogy of Fallot exhibited the most pronounced compromise in cerebral size, we recommend neurodevelopmental follow-up for all children with CHDs.

Objectives The aim of this study was to compare the thin-strut biodegradable-polymer everolimus-eluting platinum-chromium stent (EES) with the biodegradable-polymer biolimus-eluting stainless-steel stent (BES). Background Currently available drug-eluting coronary stents have been refined to reduce the risk for coronary events following implantation. Methods This randomized, multicenter, all-comers, noninferiority trial was undertaken at 3 sites in western Denmark. Patients with clinical indications for percutaneous coronary intervention were eligible for inclusion. Patients were randomly assigned (1:1) to either EES or BES. The primary endpoint, target lesion failure, was a composite of safety (cardiac death and myocardial infarction not clearly attributable to a nontarget lesion) and efficacy (target lesion revascularization) at 12 months, analyzed using intention-to-treat principles. The trial was powered to assess target lesion failure noninferiority of the EES compared with the BES with a predetermined noninferiority margin of 3%. Results A total of 1,385 patients were assigned to treatment with EES and 1,369 patients to treatment with BES. The analysis showed that 55 patients (4.0%) assigned to the EES and 60 (4.4%) assigned to the BES met the primary endpoint (absolute risk difference 0.4%; upper limit of 1-sided 95% confidence interval: 1.7%; p Conclusions At 1-year follow-up, the EES was found to be noninferior to the BES with respect to target lesion failure. (Everolimus-eluting SYNERGY Stent Versus Biolimus-Eluting Biomatrix NeoFlex Stent—SORT-OUT VIII; NCT02093845)

Introduction Promoting active transport offers the potential to increase population physical activity levels. Compensation theories state that above-average physical activity in one activity is compensated in later activities; a mechanism that results in stable levels of total physical activity. Little is known about possible compensation of transport physical activity among older adults. Methods GPS (Global Positioning System) and accelerometer data collected among older adults (65+) were pooled from four cohorts in Canada, Luxembourg, and France (n=636, collected between 2012 and 2016). Physical activity was measured as total volume of physical activity for trips and non-trip activities. Robust linear regressions on person-centered data were used to test within-person associations between transport and total physical activity. Results 636 older adults – median age of 76 years, 49% women - provided accelerometer and GPS data for at least 4 days. 18% of the total volume of physical activity was related to transport. A positive association was found between physical activity during a trip and the physical activity during the next hour, among those with lower levels of regular physical activity. Negative associations - indicating partial compensation - were found between transport physical activity during a day, and both total physical activity during the next day and non-transport physical activity during the same day. No differences were found between the four study cohorts. Conclusions Transport physical activity is compensated partially by older adults during non-transport physical activity. Given the presence of compensation, we strongly recommend evaluations of transport interventions to measure and analyze both non-transport and transport physical activity.

Objectives The aim was to establish a contemporary scoring system to predict the outcome of chronic total occlusion coronary angioplasty. Background Interventional treatment of chronic total coronary occlusions (CTOs) is a developing subspecialty. Predictors of technical success or failure have been derived from datasets of modest size. A robust scoring tool could facilitate case selection and inform decision making. Methods The study analyzed data from the EuroCTO registry. This prospective database was set up in 2008 and includes >20,000 cases submitted by CTO expert operators (>50 cases/year). Derivation (n = 14,882) and validation (n = 5,745) datasets were created to develop a risk score for predicting technical failure. Results There were 14,882 patients in the derivation dataset (with 2,356 [15.5%] failures) and 5,745 in the validation dataset (with 703 [12.2%] failures). A total of 20.2% of cases were done retrogradely, and dissection re-entry was performed in 9.3% of cases. We identified 6 predictors of technical failure, collectively forming the CASTLE score (Coronary artery bypass graft history, Age (≥70 years), Stump anatomy [blunt or invisible], Tortuosity degree [severe or unseen], Length of occlusion [≥20 mm], and Extent of calcification [severe]). When each parameter was assigned a value of 1, technical failure was seen to increase from 8% with a CASTLE score of 0 to 1, to 35% with a score ≥4. The area under the curve (AUC) was similar in both the derivation (AUC: 0.66) and validation (AUC: 0.68) datasets. Conclusions The EuroCTO (CASTLE) score is derived from the largest database of CTO cases to date and offers a useful tool for predicting procedural outcome.

BACKGROUND: Impaired fetal growth may increase vulnerability towards metabolic disturbances associated with some medications. We examined whether birth weight and ponderal index modify the association between psychotropic medication and type 2 diabetes among young adults with severe psychiatric diagnosis.METHODS: A total of 36,957 individuals born in Denmark between 1973 and 1983 with a diagnosis of schizophrenia, bipolar disorder, or depression were followed from first diagnosis until 2018. Cox proportional hazard models were applied to analyse risk of type 2 diabetes with use of psychotropic medications and interactions between psychotropic medication and birth weight and ponderal index, respectively.RESULTS: During follow-up, 1575 (4.2%) individuals received a diagnosis of type 2 diabetes. Use of antipsychotic, mood stabilizing and antidepressant medications were associated with higher hazard ratios (HRs) of type 2 diabetes (HRantipsychotics 1.68 [95%CI 1.49-1.90]; HRmood stabilizing medication 1.41 [95%CI 1.25-1.59]; HRantidepressants 2.00 [95%CI 1.68-2.37]), as were a birth weight below 2500 g (HR 1.13 [95%CI 1.01-1.28]), and high ponderal index (HR 1.26 [95%CI 1.11-1.43]). The highest rates of type 2 diabetes for each psychotropic medication category were found in medication users with low birth weight or high ponderal index. However, neither birth weight nor ponderal index significantly modified the association between psychotropic medication and diabetes risk.CONCLUSION: Psychotropic medication use, birth weight, and ponderal index were risk factors for type 2 diabetes in patients with severe mental illness, but neither birth weight nor ponderal index modified the association between psychotropic medication and type 2 diabetes.

BACKGROUND: The concept of social foreground describes how adult offspring's socioeconomic resources may influence older adults' health and several studies have shown an association between socioeconomic position of adult offspring and the health of their older parents. However, little is known about the factors that generate these associations. We study 1) how adult offspring's social class is associated with physical function (PF) among older adults, 2) whether geographical closeness and contact frequency with offspring modify the association, and 3) whether intergenerational social mobility of offspring is associated with PF of older adults.METHOD: Data are obtained from the 2002 (n = 621) and 2011 (n = 931) waves of the Swedish Panel Study of Living Conditions of the Oldest Old. Multivariable linear regression models were employed and adjusted for own and partner's prior social class and offspring's age and gender.RESULTS: Compared to offspring with non-manual occupation, offsprings with manual occupation was associated with poorer PF in older adults (-0.14, CI95%:-0.28;0.00). In stratified analyses, offspring's social class was only associated with older adults' PF among those who lived geographically close. Contact frequency between the offspring and the older adults did not modify the associations. Older adults whose offspring experienced downward intergenerational social mobility were associated with the poorest PF.CONCLUSION: This study supports evidence of a relationship between social foreground and older adults' PF where geographical closeness and social mobility are important components.

Exposure from the dissolved-phase and through food-chains contributes to bioaccumulation of polycyclic aromatic hydrocarbons (PAHs) in organisms such as fishes and copepods. However, very few studies have investigated the accumulation of PAHs in corals. Information on dietary uptake contribution to PAHs accumulation in corals is especially limited. Here, we used Cavity-Ring-Down Spectroscopy (CRDS) to investigate the uptake rates and accumulation of a

Background: Clinical outcomes following coronary computed tomography–derived fractional flow reserve (FFR CT) testing in clinical practice are unknown. Objectives: This study sought to assess real-world clinical outcomes following a diagnostic strategy including first-line coronary computed tomography angiography (CTA) with selective FFR CT testing. Methods: The study reviewed the results of 3,674 consecutive patients with stable chest pain evaluated with CTA and FFR CT testing to guide downstream management in patients with intermediate stenosis (30% to 70%). The composite endpoint (all-cause death, myocardial infarction, hospitalization for unstable angina, and unplanned revascularization) was determined in 4 patient groups: 1) CTA stenosis CT >0.80, OMT, no additional testing; 3) FFR CT ≤0.80, OMT, no additional testing; and 4) FFR CT ≤0.80, OMT, and referral to invasive coronary angiography. Patients were followed for a median of 24 (range 8 to 41) months. Results: FFR CT was available in 677 patients, and the test result was negative (>0.80) in 410 (61%) patients. In 75% of the patients with FFR CT >0.80, maximum coronary stenosis was ≥50%. The cumulative incidence proportion (95% confidence interval [CI]) of the composite endpoint at the end of follow-up was comparable in groups 1 (2.8%; 95% CI: 1.4% to 4.9%) and 2 (3.9%; 95% CI: 2.0% to 6.9%) (p = 0.58) but was higher (when compared with group 1) in groups 3 (9.4%; p = 0.04) and 4 (6.6%; p = 0.08). Risk of myocardial infarction was lower in group 4 (1.3%) than in group 3 (8%; p < 0.001). Conclusions: In patients with intermediate-range coronary stenosis, FFR CT is effective in differentiating patients who do not require further diagnostic testing or intervention (FFR CT >0.80) from higher-risk patients (FFR CT ≤0.80) in whom further testing with invasive coronary angiography and possibly intervention may be needed. Further studies assessing the risk and optimal management strategy in patients undergoing first-line CTA with selective FFR CT testing are needed.

Objectives The authors sought to compare reclassification of treatment strategy following instantaneous wave-free ratio (iFR) and fractional flow reserve (FFR). Background iFR was noninferior to FFR in 2 large randomized controlled trials in guiding coronary revascularization. Reclassification of treatment strategy by FFR is well-studied, but similar reports on iFR are lacking. Methods The iFR-SWEDEHEART (Instantaneous Wave-Free Ratio Versus Fractional Flow Reserve in Patients With Stable Angina Pectoris or Acute Coronary Syndrome Trial) study randomized 2,037 participants with stable angina or acute coronary syndrome to treatment guided by iFR or FFR. Interventionalists entered the preferred treatment (optimal medical therapy [OMT], percutaneous coronary intervention [PCI], or coronary artery bypass grafting [CABG]) on the basis of coronary angiograms, and the final treatment decision was mandated by the iFR/FFR measurements. Results In the iFR/FFR (n = 1,009/n = 1,004) populations, angiogram-based treatment approaches were similar (p = 0.50) with respect to OMT (38%/35%), PCI of 1 (37%/39%), 2 (15%/16%), and 3 vessels (2%/2%) and CABG (8%/8%). iFR and FFR reclassified 40% and 41% of patients, respectively (p = 0.78). The majority of reclassifications were conversion of PCI to OMT in both the iFR/FFR groups (31.4%/29.0%). Reclassification increased with increasing number of lesions evaluated (odds ratio per evaluated lesion for FFR: 1.46 [95% confidence interval: 1.22 to 1.76] vs. iFR 1.37 [95% confidence interval: 1.18 to 1.59]). Reclassification rates for patients with 1, 2, and 3 assessed vessels were 36%, 52%, and 53% (p Conclusions Reclassification of treatment strategy of intermediate lesions was common and occurred in 40% of patients with iFR or FFR. The most frequent reclassification was conversion from PCI to OMT regardless of physiology modality. Irrespective of the physiological index reclassification of angiogram-based treatment strategy increased with the number of lesions evaluated.

BACKGROUND: Coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) are used for coronary revascularization in patients with multivessel and left main coronary artery disease. Stroke is among the most feared complications of revascularization. Due to its infrequency, studies with large numbers of patients are required to detect differences in stroke rates between CABG and PCI.OBJECTIVES: This study sought to compare rates of stroke after CABG and PCI and the impact of procedural stroke on long-term mortality.METHODS: We performed a collaborative individual patient-data pooled analysis of 11 randomized clinical trials comparing CABG with PCI using stents; ERACI II (Argentine Randomized Study: Coronary Angioplasty With Stenting Versus Coronary Bypass Surgery in Patients With Multiple Vessel Disease) (n = 450), ARTS (Arterial Revascularization Therapy Study) (n = 1,205), MASS II (Medicine, Angioplasty, or Surgery Study) (n = 408), SoS (Stent or Surgery) trial (n = 988), SYNTAX (Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery) trial (n = 1,800), PRECOMBAT (Bypass Surgery Versus Angioplasty Using Sirolimus-Eluting Stent in Patients With Left Main Coronary Artery Disease) trial (n = 600), FREEDOM (Comparison of Two Treatments for Multivessel Coronary Artery Disease in Individuals With Diabetes) trial (n = 1,900), VA CARDS (Coronary Artery Revascularization in Diabetes) (n = 198), BEST (Bypass Surgery Versus Everolimus-Eluting Stent Implantation for Multivessel Coronary Artery Disease) (n = 880), NOBLE (Percutaneous Coronary Angioplasty Versus Coronary Artery Bypass Grafting in Treatment of Unprotected Left Main Stenosis) trial (n = 1,184), and EXCEL (Evaluation of Xience Versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization) trial (n = 1,905). The 30-day and 5-year stroke rates were compared between CABG and PCI using a random effects Cox proportional hazards model, stratified by trial. The impact of stroke on 5-year mortality was explored.RESULTS: The analysis included 11,518 patients randomly assigned to PCI (n = 5,753) or CABG (n = 5,765) with a mean follow-up of 3.8 ± 1.4 years during which a total of 293 strokes occurred. At 30 days, the rate of stroke was 0.4% after PCI and 1.1% after CABG (hazard ratio [HR]: 0.33; 95% confidence interval [CI]: 0.20 to 0.53; p < 0.001). At 5-year follow-up, stroke remained significantly lower after PCI than after CABG (2.6% vs. 3.2%; HR: 0.77; 95% CI: 0.61 to 0.97; p = 0.027). Rates of stroke between 31 days and 5 years were comparable: 2.2% after PCI versus 2.1% after CABG (HR: 1.05; 95% CI: 0.80 to 1.38; p = 0.72). No significant interactions between treatment and baseline clinical or angiographic variables for the 5-year rate of stroke were present, except for diabetic patients (PCI: 2.6% vs. CABG: 4.9%) and nondiabetic patients (PCI: 2.6% vs. CABG: 2.4%) (p for interaction = 0.004). Patients who experienced a stroke within 30 days of the procedure had significantly higher 5-year mortality versus those without a stroke, both after PCI (45.7% vs. 11.1%, p < 0.001) and CABG (41.5% vs. 8.9%, p < 0.001).CONCLUSIONS: This individual patient-data pooled analysis demonstrates that 5-year stroke rates are significantly lower after PCI compared with CABG, driven by a reduced risk of stroke in the 30-day post-procedural period but a similar risk of stroke between 31 days and 5 years. The greater risk of stroke after CABG compared with PCI was confined to patients with multivessel disease and diabetes. Five-year mortality was markedly higher for patients experiencing a stroke within 30 days after revascularization.

Background Frequent injecting increases hepatitis C (HCV) acquisition risk among people who inject drugs (PWID). However, few studies have examined how temporal fluctuations in injecting frequency may effect HCV infection risk. Thus, this study examined HCV incidence according to injecting frequency trajectories followed by PWID over one year in Montreal, Canada. Methods At three-month intervals from March 2011 to June 2016, HCV-uninfected PWID (never infected or cleared infection) enrolled in the Hepatitis Cohort (HEPCO) completed interviewer-administered questionnaires and HCV testing. At each visit, participants reported the number of injecting days (0–30 days) for each of the past three months. In previous work, using group-based trajectory modeling, we identified five injecting frequency trajectories followed by participants over one year (months 1–12 of follow-up), including sporadic, infrequent, increasing, decreasing, and frequent injecting. In this study, we estimated group-specific HCV incidence (months 1–63 of follow-up) using posterior probabilities to assign participants to their most likely trajectory group. Results Of 386 participants (mean age=40, 82% male, 48% never HCV-infected), 72 acquired HCV during 893 person-years of follow-up. HCV incidence for the whole study sample was 8.1 per 100 person-years (95%CI=6.4–10.1). Trajectory group-specific HCV incidences were highest for those injecting drugs with decreasing (23.9, 14.4–37.5) or increasing frequency (16.0, 10.1–24.3), intermediate for those injecting at consistently high frequency (10.2, 5.4–17.8), and lowest for those injecting infrequently (3.9, 2.2–6.5) or sporadically (4.3, 2.2–7.6). Conclusion Results suggest that PWID at highest HCV risk are those injecting at high frequency, either transitorily (increasing, decreasing injecting) or consistently (frequent injecting). This study highlights changes in injecting frequency as a potentially important dimension to consider among the factors leading to HCV acquisition. Clinical and public health interventions tailored to PWID with different injecting frequency profiles may contribute to HCV prevention.

Background Little is known about how socioeconomic circumstances relate to injection frequencies among people who inject drugs (PWID) with diverse trajectories of injection. We aimed to characterize trajectories of injection drug use in a community-based sample of PWID over 7.5 years and to investigate the extent to which two modifiable factors reflecting socioeconomic stability—stable housing and stable income—relate to injection frequencies across distinct trajectories. Methods HEPCO is an open, prospective cohort study of PWID living in Montreal with repeated follow-up at three-month or one-year intervals. Self-reported data on injection frequency, housing and income are collected at each visit. Injection frequency was defined as the number of injection days (0–30), reported for each of the past three months. Using group-based trajectory modeling, we first estimated average trajectories of injection frequency. Then, we estimated the trajectory group-specific average shift upward or downward associated with periods of stable housing and stable income relative to periods when these conditions were unstable. Results Based on 19,527 injection frequency observations accrued by 529 participants followed over 2011–2019 (18.3% female, median age: 41), we identified five trajectories of injection frequency: three characterized by sustained injection at different frequencies (28% infrequent; 19% fluctuating; 19% frequent), one by a gradual decline (12%), and another by cessation (28%). Periods of stable housing and stable income were each independently associated with a lower injection frequency, on average, in all five trajectory groups (2.2–7.5 fewer injection days/month, depending on the factor and trajectory group). Conclusion Trajectories of injection drug use frequency were diverse and long-lasting for many PWID. Despite this diversity, socioeconomic stability was consistently associated with a lower injection frequency, emphasizing the close relationship between access to fundamental necessities and injection patterns in all PWID, irrespective of whether they are on a path to cessation or sustained injecting.

With the huge ambition to achieve a fossil fuel-free energy sector by 2050, the Danish government has targeted the building stock as a priority, offering large potential for feasible and cost-effective energy savings. Around 75% of the existing buildings in Denmark were constructed before 1979 and therefore a special focus has been directed in the recent years towards buildings’ energy renovation especially non-residential and public buildings. A comprehensive strategy for energy renovation of the existing Danish building stock was established with multiple initiatives to enhance cost-effective and energy-efficient renovation of buildings. In this context, Aarhus Municipality is investing 450 million DKK for public buildings energy renovation covering an area of about 1 million m2 and aiming to cut CO2 emissions by 40%. Thus, two daycare centers, Bogevangen 101 and Runevej 107-109, have been selected as case studies under the international research project COORDICY aiming to improve the centers energy performance implementing renovation techniques. A detailed energy model was developed for each center employing a package of Google Sketchup, Open Studio and Energy Plus energy modelling and simulation tools. The energy model was calibrated against actual meter data. Using the developed model, multiple energy management and retrofit combinations were analyzed and evaluated from both technical and economic perspectives. Conventional envelope insulation and windows upgrade were found unfavorable from the economic perspective and thus were not prioritized. It was shown that employing a retrofit package consisting of installing LED lights, implementing demand-controlled ventilation, and installing efficient equipment could lead to an overall reduction of 30.2% and 31.1% on the energy consumption in Bogevangen and Runevej respectively, improving the thermal comfort and indoor air quality with an acceptable payback period of around 3 years.

Objectives: The aim of this study was to assess calcium growth with fused grayscale intravascular ultrasound (IVUS), IVUS–virtual histology, and optical coherence tomography (OCT) from base...

Objectives This study sought to investigate the effect of post-dilatation on angiographic and intracoronary imaging parameters in the setting of primary percutaneous coronary intervention comparing the everolimus-eluting bioresorbable scaffold (BRS) with the everolimus-eluting metallic stent (EES). Background Routine post-dilatation of BRS has been suggested to improve post-procedural angiographic and subsequent device-related clinical outcomes. Methods In the ABSORB STEMI TROFI II trial, 191 patients with ST-segment elevation myocardial infarction were randomly assigned to treatment with BRS (n = 95) or EES (n = 96). Minimal lumen area and healing score as assessed by optical coherence tomography at 6 months were compared between BRS- and EES-treated patients stratified according to post-dilatation status. Results Primary percutaneous coronary intervention with post-dilatation was performed in 48 (50.5%) BRS- and 25 (25.5%) EES-treated lesions. There were no differences in baseline characteristics and post-procedural minimal lumen diameter between groups. In the BRS group, lesions with post-dilatation were associated with a trend toward a smaller minimal lumen area at 6 months (5.07 ± 1.68 mm2 vs. 5.72 ± 1.77 mm2; p = 0.09) and significantly larger angiographic late lumen loss (0.28 ± 0.34 mm vs. 0.12 ± 0.25 mm; p = 0.02), whereas no difference was observed in the EES arm (5.46 ± 2.18 mm2 vs. 5.55 ± 1.77 mm2; p = 0.85). The neointimal healing score was low and comparable between groups with and without post-dilation (BRS: 1.55 ± 2.61 vs. 1.92 ± 2.17; p = 0.48; EES: 2.50 ± 3.33 vs. 2.90 ± 4.80; p = 0.72). Conclusions In the setting of selected patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention with BRS or EES, post-dilatation did not translate into larger lumen area or improved arterial healing at follow-up. (ABSORB STEMI: The TROFI II; NCT01986803)

Objectives The aims of this study were to characterize cardiac allograft vasculopathy (CAV) phenotypes using optical coherence tomography (OCT) and to evaluate the prognostic significance of OCT-determined CAV severity. Background Intravascular OCT enables in vivo characterization of CAV microstructure after heart transplantation. Methods Sixty-two patients undergoing heart transplantation were enrolled at routine angiography from September 2013 through October 2015 and prospectively followed until censoring on May 27, 2016. Optical coherence tomographic acquisitions aimed for the longest possible pull-backs, including proximal segments of all 3 major vessels. Plaques and bright spots were analyzed by delineating circumferential borders and measuring the angulation of total circumference. Layers were contoured for absolute and relative estimates. Nonfatal CAV progression (NFCP) during follow-up was registered. NFCP included occluded vessels or severe (≥70%) new angiographic coronary stenosis or percutaneous coronary intervention. Results A total of 172 vessels were categorized as follows: no CAV, n = 111; mild to moderate CAV ( Conclusions OCT enables the detection of CAV-associated plaque compositions and allows early detection and differentiation of vessel wall disease not visible on angiography. LFP was the most prevalent plaque component, was strongly associated with NFCP, and may be associated with stepwise CAV progression caused by organizing mural thrombi. (The GRAFT Study: Evaluation of Graft Function, Rejection and Cardiac Allograft Vasculopathy in First Heart Transplant Recipients; NCT02077764)

OBJECTIVES: The goal of this study was to assess the real-world clinical utility of fractional flow reserve (FFR) derived from coronary computed tomography angiography (FFRCT) for decision-making in patients with stable coronary artery disease (CAD).BACKGROUND: FFRCT has shown promising results in identifying lesion-specific ischemia. The real-world feasibility and influence on the diagnostic work-up of FFRCT testing in patients suspected of having CAD are unknown.METHODS: We reviewed the complete diagnostic work-up of nonemergent patients referred for coronary computed tomography angiography over a 12-month period at Aarhus University Hospital, Denmark, including all patients with new-onset chest pain with no known CAD and with intermediate-range coronary lesions (lumen reduction, 30% to 70%) referred for FFRCT. The study evaluated the consequences on downstream diagnostic testing, the agreement between FFRCT and invasively measured FFR or instantaneous wave-free ratio (iFR), and the short-term clinical outcome after FFRCT testing.RESULTS: Among 1,248 patients referred for computed tomography angiography, 189 patients (mean age 59 years; 59% male) were referred for FFRCT, with a conclusive FFRCT result obtained in 185 (98%). FFRCT was ≤0.80 in 31% of patients and 10% of vessels. After FFRCT testing, invasive angiography was performed in 29%, with FFR measured in 19% and iFR in 1% of patients (with a tendency toward declining FFR-iFR guidance during the study period). FFRCT ≤0.80 correctly classified 73% (27 of 37) of patients and 70% (37 of 53) of vessels using FFR ≤0.80 or iFR ≤0.90 as the reference standard. In patients with FFRCT >0.80 being deferred from invasive coronary angiography, no adverse cardiac events occurred during a median follow-up period of 12 (range 6 to 18 months) months.CONCLUSIONS: FFRCT testing is feasible in real-world symptomatic patients with intermediate-range stenosis determined by coronary computed tomography angiography. Implementation of FFRCT for clinical decision-making may influence the downstream diagnostic workflow of patients. Patients with an FFRCT value >0.80 being deferred from invasive coronary angiography have a favorable short-term prognosis.

Photodynamic Antimicrobial Chemotherapy (PACT) has emerged as a promising method for pathogen eradication and control. PACT uses light excitation of non-toxic photosensitisers to produce singlet oxygen ( 1 O 2 ), which in turn damages and eradicates microbial cells. In the present study, a naturally luminescent Vibrio campbellii strain ISO7 ( V. campbellii ISO7) was used as a model aquaculture pathogen to test the suitability of two porphyrin compounds, the tetra-cationic TMPyP and the tetra-anionic TPPS 4 , for the treatment of aquaculture water. Initial work accurately identified the bacterial strain and confirmed its virulence towards giant tiger prawns Penaeus monodon when injected. The strain killed 100% of injected prawns within 1 to 16 h, while control prawns injected with sterile buffer remained healthy. Koch's postulates were satisfied by identification of re-isolated strains by multiplex PCR and sequencing of housekeeping genes. In separate time-course experiments, the two photosensitisers were diluted in aquaculture water seeded with the indicator bacterium and samples were irradiated for 24 h using 150 W white LED light. Luminescence assays, growth and regrowth experiments demonstrated that the cytotoxicity of generated 1 O 2 was both time- and dose-dependent, and confirmed that light or porphyrins alone were not toxic. Continuous irradiation in the presence of 20 μM cationic porphyrin for 5 h or 1 μM for 24 h achieved complete lethality of the indicator bacterium. Consistent with previous reports, the tested anionic porphyrin did not impact on the survival of the bacterium, causing only a slight decline in the luminescence signal. Photo-bleaching tests demonstrated natural degradation of both porphyrins after continuous irradiation, making them suitable as ‘self-destructive’ photosensitizers for in situ treatment of aquaculture waters, as they do not accumulate in the water.

INTRODUCTION: Mechanical circulatory support may be considered as a therapeutic option in selected patients with refractory cardiac arrest (rCA). Animal studies suggest a potential role for the Impella(®) left ventricular assist device in this setting, but so far no human data have been published.METHODS: Eight patients with rCA were treated with the Impella CP(®) device at our institution from November 2014 to October 2015. The Impella CP(®) was used at the discretion of the treating physicians in patients with rCA and pulseless electrical activity with presumed primary left ventricular failure. These patients were compared to 12 patients with cardiogenic shock also treated with the Impella device during the same period.RESULTS: All cardiac arrests were witnessed with a no-flow time of 0min, six in-hospital and two out-of-hospital. Low-flow time was 50±52min (SD). The Impella device was successfully inserted in all patients with rCA and circulation was re-established. Survival rate to hospital discharge with good neurological outcome was similar among patients with rCA and cardiogenic shock treated with the Impella device (50% vs. 58%). Major vascular complications after Impella insertion occurred more frequently among patients with rCA compared to patients with cardiogenic shock (50% vs. 0%, PCONCLUSION: Mechanical support with the Impella CP(®) device is a feasible and promising treatment option for selected patients with rCA. Further studies are warranted to determine the full potential and optimal patient selection compared to other modalities of mechanical circulatory support.

Objectives The authors sought to compare the safety and efficacy of the biocompatible durable-polymer zotarolimus-eluting stent with the biodegradable-polymer biolimus-eluting stent in unselected coronary patients. Background Biodegradable-polymer biolimus-eluting stents are superior to first-generation durable-polymer drug-eluting stents in long-term randomized all-comer trials. Long-term data comparing them to second-generation durable-polymer drug-eluting stents are lacking. Methods The study was a randomized, multicenter, all-comer, noninferiority trial in patients with chronic stable coronary artery disease or acute coronary syndromes and at least 1 coronary artery lesion requiring treatment with a drug-eluting stent. Endpoints included major adverse cardiac events (MACE), a composite of safety (cardiac death and myocardial infarction not clearly attributable to a non-target lesion) and efficacy (target lesion revascularization); the individual endpoints of MACE; all-cause mortality; any myocardial infarction; target vessel revascularization; and definite or probable stent thrombosis at 36 months. Results From March 2011 to August 2012, 2,999 patients were randomly assigned (1:1) to receive either the zotarolimus-eluting (1,502 patients) or the biolimus-eluting (1,497 patients) stent. At 3-year follow-up, MACE occurred in 128 (8.6%) patients assigned to the durable-polymer zotarolimus-eluting stent and in 144 (9.6%) assigned to the biodegradable-polymer biolimus-eluting stent (p = 0.36). Occurrence of cardiac death (2.7% vs. 3.4%), myocardial infarction not clearly attributable to a non-target lesion (2.7% vs. 2.5%), and target lesion revascularization (5.4% vs. 5.5%) did not differ significantly between the 2 groups. Definite very late stent thrombosis occurred in 6 (0.4%) patients assigned to the durable-polymer zotarolimus-eluting stent and in 10 (0.7%) assigned to the biodegradable-polymer biolimus-eluting stent (p = 0.33). Conclusions At 3-year follow-up, the durable-polymer zotarolimus-eluting stent and the biodegradable-polymer biolimus-eluting stent were similar in clinical outcome, with no significant difference in safety and efficacy outcomes, including stent thrombosis.

Recent research has shown that catalytic hydropyrolysis is a promising method for production of liquid hydrocarbon fuels from lignocellulosic biomass. However, only limited research has been conducted within this field and the process is still not well-understood. Based on the available literature and research in our laboratories we identified the most important reactions and propose a mechanistic model for catalytic hydropyrolysis of biomass. The influence of the hydrogenation catalyst on the product distribution and composition as well as deactivation of the catalyst are discussed. Catalytic hydropyrolysis is compared with other pyrolysis technologies, such as non-catalytic and catalytic fast pyrolysis and the challenges for catalytic hydropyrolysis are highlighted and discussed.

Background There are limited data on the incidence, clinical implications, and predisposing factors of transcatheter heart valve (THV) thrombosis following transcatheter aortic valve replacement (TAVR). Objectives The authors assessed the incidence, potential predictors, and clinical implications of THV thrombosis as determined by contrast-enhanced multidetector computed tomography (MDCT) after TAVR. Methods Among 460 consecutive patients who underwent TAVR with the Edwards Sapien XT or Sapien 3 (Edwards Lifesciences, Irvine, California) THV, 405 (88%) underwent MDCT in addition to transthoracic and transesophageal echocardiography 1 to 3 months post-TAVR. MDCT scans were evaluated for hypoattenuated leaflet thickening that indicated THV thrombosis. Results MDCT verified THV thrombosis in 28 of 405 (7%) patients. A total of 23 patients had subclinical THV thrombosis, whereas 5 (18%) patients experienced clinically overt obstructive THV thrombosis. THV thrombosis risk did not differ among different generations of THVs (8% vs. 6%; p = 0.42). The risk of THV thrombosis in patients who did not receive warfarin was higher compared with patients who received warfarin (10.7% vs. 1.8%; risk ratio [RR]: 6.09; 95% confidence interval [CI]: 1.86 to 19.84). A larger THV was associated with an increased risk of THV thrombosis (p = 0.03). In multivariable analysis, a 29-mm THV (RR: 2.89; 95% CI: 1.44 to 5.80) and no post-TAVR warfarin treatment (RR: 5.46; 95% CI: 1.68 to 17.7) independently predicted THV thrombosis. Treatment with warfarin effectively reverted THV thrombosis and normalized THV function in 85% of patients as documented by follow-up transesophageal echocardiography and MDCT. Conclusions Incidence of THV thrombosis in this large study was 7%. A larger THV size may predispose to THV thrombosis, whereas treatment with warfarin appears to have a protective effect. Although often subclinical, THV thrombosis may have important clinical implications.

BACKGROUND: Despite successful treatment of the culprit artery lesion by primary percutaneous coronary intervention (PCI) with stent implantation, thrombotic embolisation occurs in some cases, which impairs the prognosis of patients with ST-segment elevation myocardial infarction (STEMI). We aimed to assess the clinical outcomes of deferred stent implantation versus standard PCI in patients with STEMI.METHODS: We did this open-label, randomised controlled trial at four primary PCI centres in Denmark. Eligible patients (aged >18 years) had acute onset symptoms lasting 12 h or less, and ST-segment elevation of 0·1 mV or more in at least two or more contiguous electrocardiographic leads or newly developed left bundle branch block. Patients were randomly assigned (1:1), via an electronic web-based system with permuted block sizes of two to six, to receive either standard primary PCI with immediate stent implantation or deferred stent implantation 48 h after the index procedure if a stabilised flow could be obtained in the infarct-related artery. The primary endpoint was a composite of all-cause mortality, hospital admission for heart failure, recurrent infarction, and any unplanned revascularisation of the target vessel within 2 years' follow-up. Patients, investigators, and treating clinicians were not masked to treatment allocation. We did analysis by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01435408.FINDINGS: Between March 1, 2011, and Feb 28, 2014, we randomly assigned 1215 patients to receive either standard PCI (n=612) or deferred stent implantation (n=603). Median follow-up time was 42 months (IQR 33-49). Events comprising the primary endpoint occurred in 109 (18%) patients who had standard PCI and in 105 (17%) patients who had deferred stent implantation (hazard ratio 0·99, 95% CI 0·76-1·29; p=0·92). Procedure-related myocardial infarction, bleeding requiring transfusion or surgery, contrast-induced nephopathy, or stroke occurred in 28 (5%) patients in the conventional PCI group versus 27 (4%) patients in the deferred stent implantation group, with no significant differences between groups.INTERPRETATION: In patients with STEMI, routine deferred stent implantation did not reduce the occurrence of death, heart failure, myocardial infarction, or repeat revascularisation compared with conventional PCI. Results from ongoing randomised trials might shed further light on the concept of deferred stenting in this patient population.FUNDING: Danish Agency for Science, Technology and Innovation, and Danish Council for Strategic Research.

Users represent an often untapped source of knowledge which companies can capitalize on during different stages of the innovation process. However, identifying helpful users for innovation projects is far from trivial as these individuals are often hidden within considerably larger populations. We contribute to open and user innovation research by empirically investigating the efficiency of pyramiding and screening, two methods used to identify valuable users. Analyzing a sample of 942 children in 42 school classes, we show that pyramiding, a search process based on personal references from user to user, is significantly more efficient in identifying rare individuals than screening, even though many references are not based on close personal relations. Pyramiding's relative efficiency advantage increases with the size of the population being searched. Finally, we explore how searchers can further increase pyramiding search efficiency by using information to select promising starting points or prematurely abandoning unpromising search chains. (C) 2015 Elsevier B.V. All rights reserved.

Background Long-term safety and efficacy for everolimus-eluting stents (EES) versus those of sirolimus-eluting stents (SES) are unknown. Objectives This study compared 5-year outcomes for EES with those for SES from the SORT OUT IV (Scandinavian Organization for Randomized Trials with Clinical Outcome) trial. Methods Five-year follow-up was completed for 2,771 patients (99.9%). Primary endpoint was a composite of major adverse cardiac events (MACE), including cardiac death, myocardial infarction (MI), target vessel revascularization (TVR), and definite stent thrombosis. Results At 5-years, MACE occurred in 14.0% and 17.4% in the EES and SES groups, respectively (hazard ratio [HR]: 0.80, 95% confidence interval [CI]: 0.66 to 0.97; p = 0.02). The MACE rate did not differ significantly within the first year (HR: 0.96, 95% CI: 0.71 to 1.19; p = 0.79), but from years 1 through 5, the MACE rate was lower with EES (HR: 0.71, 95% CI: 0.55 to 0.90; p = 0.006; p interaction = 0.12). Definite stent thrombosis was lower with EES (0.4%) than with SES (2.0%; HR: 0.18, 95% CI: 0.07 to 0.46), with a lower risk of very late definite stent thrombosis in the EES group (0.2% vs. 1.4%, respectively; HR: 0.16, 95% CI: 0.05 to 0.53). When censoring the patients at the time of stent thrombosis, we found no significant differences between the 2 stent groups for MACE rates (HR: 0.89, 95% CI: 0.73 to 1.08; p = 0.23), target lesion revascularization (HR: 0.90, 95% CI: 0.64 to 1.27; p = 0.55), and MI (HR: 0.93, 95% CI: 0.64 to 1.36; p = 0.72). Conclusions At 5-year follow-up, MACE rate was significantly lower with EES- than with SES-treated patients, due largely due to a lower risk of very late definite stent thrombosis. (Randomized Clinical Comparison of the Xience V and the Cypher Coronary Stents in Non-selected Patients With Coronary Heart Disease [SORT OUT IV]; NCT00552877 )

Polycyclic aromatic hydrocarbons (PAHs) are widespread pollutants in marine ecosystems including threatened and potentially sensitive coral reefs. Lower organisms such as phytoplankton, known to bioconcentrate PAHs, could serve as potential entry points for these chemicals into higher trophic levels. Here, we present a novel method using a 13C-labelled PAH and cavity ring-down spectroscopy (CRDS) to investigate accumulation, uptake rates and trophic transfer of PAHs in corals, which are key organisms to sustain biodiversity in tropical seas. We quantified the accumulation of 13C-phenanthrene in the marine microalga Dunaliella salina, and in the coral Acropora millepora after diffusive uptake from seawater or dietary uptake via labelled D. salina. Additionally, we monitored the photophysiological health of D. salina and A. millepora during phenanthrene exposure by pulse-amplitude modulation (PAM) fluorometry. Dose-dependent accumulation of 13C-phenanthrene in the microalga showed a mean bioconcentration factor (BCF) of 2590 ± 787 L kg−1 dry weight. Corals accumulated phenanthrene from both exposure routes. While uptake of 13C-phenanthrene in corals was faster through aqueous exposure than dietary exposure, passive diffusion showed larger variability between individuals and both routes resulted in accumulation of similar concentrations of phenanthrene. The 13C-PAH labelling and analysis by CRDS proved to be a highly sensitive method. The use of stable isotopic label eliminated additional toxicity and risks by radioactive isotopic-labelling, and CRDS reduced the analytical complexity of PAH (less biomass, no extraction, fast analysis). The simultaneous, precise quantification of both carbon content and 13C/12C ratio (δ13C) enabled accurate determination of 13C-phenanthrene accumulation and uptake rate. This is the first study to provide empirical evidence for accumulation of phenanthrene in a phytoplankton-coral food chain.

Catalytic hydropyrolysis of biomass to green fuels was performed using supported, sulfided CoMo catalysts. With MgAl2O4 as support material the CoMo loading was varied between 4.1 and 12.0 wt% at constant Co/Mo atomic ratio of 0.3. Increasing the metal loading decreased the amount of oxygen in the condensed organic phase from 9.0 to 4.7 wt% on dry basis (db) and the condensable organic yield decreased from 25.2 to 22.7 wt% on dry ashfree (daf) basis, corresponding to a decrease in the carbon recovery from 39 to 37%. Using zeolite H-ZSM-5 mixed with alumina as support with a CoMo loading of 4.1 wt%, the condensed organics contained only 5.2 to 6.1 wt% db oxygen. The condensable organic yield was between 23.9 and 24.4 wt% db, and the carbon recovery was 39–40%. Thus using an acidic support can remove the oxygen without decreasing the carbon recovery. The latter was ascribed to alkylation of the aromatics when the zeolite support was used.Elemental maps of the spent catalysts were obtained using STEM-EDS, showing that the CoMo phase was mainly located as monolayer MoS2 slab structures (> 93%) on the support and indicated a high dispersion of cobalt, consistent with incorporation of Co into the MoS2 structure in the CoMoS phase. Potassium was observed on all the spent catalysts, indicating transfer of alkali metal from the biomass to the catalyst. Potassium may decrease the acidity of the catalyst over time, thus reducing the positive effect of using a more acidic support.