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Introduction The use of recreational substances in a sexual context (sex-linked substance use) is common among young adults, with up to a third indicating that that they used alcohol, cannabis, or both during their recent partnered sexual activity (Willis et al., 2021; Herbenick et al., 2018). Sex-linked substance use (SLSU) is associated with a variety of positive and negative clinical outcomes including increased sexual pleasure, but also greater risk for condomless sex. Expectations of how one will behave and feel during sex while under the influence have been shown to predict SLSU habits. Contextual factors like relationship status may contribute to these expectancies, with studies finding that young women who are casually dating have more positive sexual expectancies of alcohol compared to women who are not dating or are in a long-term relationship (e.g., Patrick et al., 2014; Pedersen et al., 2009). Given the relationship between SLSU, relationship status, and sexual expectancies, it is likely that other contextual factors of a relationship, like partnered sexual desire, may play a role in sexual outcomes of women’s substance use. However, little is known about how partnered sexual desire is related to either substance sex-related expectancies in college-aged women. Objective To investigate how relationship status and partnered sexual desire is related to differences in alcohol and drug sexual expectancies and SLSU. Methods We surveyed 512 women (mean age 20.09, SD = 1.56) in the Midwestern US. Participants completed the Brief Comprehensive Expectancies of Alcohol and Drug scales, assessing their alcohol and drug expectancies, including sex-related expectancies (e.g., “to be a better lover” and to “enjoy sex more”); the Sexual Desire Inventory, assessing partnered and solitary sexual desire; and reported their relationship status, frequency of SLSU, and demographics. Using independent sample t-tests and multivariate general linear models, we examined how relationship status and partnered & solitary sexual desire interacted to predict differences in alcohol and drug sex-related expectancies and SLSU. Results Contrary to previous research findings, relationship status alone was not related to either alcohol or drug sex-related expectancies or SLSU. However, there was a marginally significant interaction between relationship status and sexual expectancies in predicting women’s SLSU. Specifically, the association between more positive sexual expectancies and higher frequency of SLSU was relatively stronger in partnered women. Moreover, regardless of relationship status, women who reported higher levels of partner desire reported more positive sexual alcohol and drug expectancies. Additionally, women who reported more positive sexual alcohol and drug expectancies reported more frequent SLSU. In contrast, solitary sexual desire was not a significant predictor of either substance-related sexual expectancies. Conclusions Our results indicate that partnership and partnered desire may interact with alcohol and drug sexual expectancies to predict women’s SLSU. These findings question the predominant assumption that women’s use of substances in sexual settings is primarily in casual sexual contexts and points to the need for targeted interventions to address the functions of SLSU in the context of women’s long-term relationships. Clinically, these findings reinforce the value of including our patient’s partner when addressing sexual dysfunction secondary to substance use. Disclosure No

Vascular compliance is considered both a cause and a consequence of cardiovascular disease and a significant factor in the mid- and long-term patency of vascular grafts. However, the biomechanical effects of localised changes in compliance, such as during plaque development or after bypass grafting and stenting, cannot be satisfactorily studied with the available medical imaging technologies or surgical simulation materials. To address this unmet need, we developed a coupledsilico-vitroplatform which allows for the validation of numerical fluid-structure interaction (FSI) results as a numerical model and physical prototype. This numerical one-way and two-way FSI study is based on a three-dimensional computer model of an idealised femoral artery which is validated against patient measurements derived from the literature. The numerical results are then compared with experimental values collected from compliant arterial phantoms. Phantoms within a compliance range of 1.4 - 68.0%/100mmHg were fabricatedviaadditive manufacturing and silicone casting, then mechanically characterisedviaring tensile testing and optical analysis under direct pressurisation with differences in measured compliance ranging between 10 - 20% for the two methods. One-way FSI coupling underestimated arterial wall compliance by up to 14.71% compared to two-way FSI modelling. Overall, Smooth-On Solaris matched the compliance range of the numerical andin vivopatient models most closely out of the tested silicone materials. Our approach is promising for vascular applications where mechanical compliance is especially important, such as the study of diseases which commonly affect arterial wall stiffness, such as atherosclerosis, and the model-based design, surgical training, and optimisation of vascular prostheses.

Recent studies using convection-permitting (CP) climate simulations have demonstrated a step-change in the representation of heavy rainfall and rainfall characteristics (frequency-intensity) compared to coarser resolution Global and Regional Climate models. The goal of this study is to better understand what explains the weaker frequency of precipitation in the CP ensemble by assessing the triggering process of precipitation in the different ensembles of regional climate simulations available over Europe. We focus on the statistical relationship between tropospheric temperature, humidity and precipitation to understand how the frequency of precipitation over Europe and the Mediterranean is impacted by model resolution and the representation of convection (parameterized vs. explicit). We employ a multi-model data-set with three different resolutions (0.44°, 0.11° and 0.0275°) produced in the context of the MED-CORDEX, EURO-CORDEX and the CORDEX Flagship Pilot Study "Convective Phenomena over Europe and the Mediterranean" (FPSCONV). The multi-variate approach is applied to all model ensembles, and to several surface stations where the integrated water vapor (IWV) is derived from Global Positioning System (GPS) measurements. The results show that all model ensembles capture the temperature dependence of the critical value of IWV (IWVcv), above which an increase in precipitation frequency occurs, but the differences between the models in terms of the value of IWVcv, and the probability of its being exceeded, can be large at higher temperatures. The lower frequency of precipitation in convection-permitting simulations is not only explained by higher temperatures but also by a higher IWVcv necessary to trigger precipitation at similar temperatures, and a lower probability to exceed this critical value. The spread between models in simulating IWVcv and the probability of exceeding IWVcv is reduced over land in the ensemble of models with explicit convection, especially at high temperatures, when the convective fraction of total precipitation becomes more important and the influence of the representation of entrainment in models thus becomes more important. Over lowlands, both model resolution and convection representation affect precipitation triggering while over mountainous areas, resolution has the highest impact due to orography-induced triggering processes. Over the sea, since lifting is produced by large-scale convergence, the probability to exceed IWVcv does not depend on temperature, and the model resolution does not have a clear impact on the results.

Invasive species management can be challenging or even impossible, especially in aquatic environments. To determine if the tropical origins of an invasive species affected where it could be targeted, we constructed a study to compare winter behavior of a tropical, invasive species to a temperate weather, native species in Louisiana. The winter activity and cold tolerance of ten invasive Rio Grande Cichlids, Herichthys cyanoguttatus and ten native bluegill, Lepomis macrochirus was observed using an outdoor pond with a dual antenna PIT tag array and an artificial culvert created inside of the pond. All fishes had PIT tags injected into their lateral musculature. Both species were active at temperatures below 10°C and all twenty fish survived temperatures as low as 7°C. Even though the invasive H. cyanoguttatus is a member of a tropical family of fishes, activity and even feeding behavior of both species was similar up to 13°C; but H. cyanoguttatus individuals were more active than L. macrochirus at higher temperatures. Both species appeared to use the culvert during cold fronts, demonstrating that the behavior of both species during cold weather were remarkably similar. This study illustrates the thermal tolerance abilities of H. cyanoguttatus in New Orleans and also demonstrates their potential for invading other cold-water habitats. Significance Statement This article is the first to investigate the simultaneous examination of overwintering behavior of a temperate native species of fish and an invasive tropical species of fish. Its application to invasive species management has unique usefulness not previously published. It is also unique in its examination of overwintering fish behavior in general, using a mesocosm PIT tag array.

Processing of end-of-life products (EoL) containing rare earth elements (REE) has gained increasing importance in recent years with the aim of avoiding supply risks. In addition, circular economy renders complete recirculation of technology metals mandatory. Fluorescent lamp wastes are an important source for REE recovery since they contain significant amounts, up to 55 wt%, of Y and Eu in red phosphors. For these purposes, solid-state chlorination (SSC) is an economically attractive alternative to wet acid leaching treatment, which profits from a considerable reduction of chemicals consumption and process costs. Chlorination takes place with dry HCl(g) produced from thermal decomposition of NH4Cl(s), not only converting the REE content of the Hg-free phosphor waste into water soluble REE metal chlorides, but also avoiding the implications of aqueous complex chemistry of REE. To establish an industrial process viable on a commercial scale, the SSC process has been optimized by (i) using a design of experiment (DOE) varying temperature, residence time, and gNH4Cl/gsolid ratio and (ii) improved leaching of the chlorinated metals with an organic mixture selective for REE. As a result, 95.7% of the Y and 92.2% of the Eu were selectively recovered at 295.9 °C, 67 min and a ratio of 1.27 gNH4Cl/gsolid, followed by quantitative selective leaching of the REE. Owed to its low chemicals consumption and operation costs, the current process allows for valorizing lamp waste even when raw material prices are low.

Introduction While most parents and healthcare providers understand the importance of educating young people about their emerging sexuality, about 20% of parents and 65% of providers never talk about sex with their children/young patients. Little prior research has asked young people directly what they perceive to be the greatest barriers to sexuality communication. Objective To center the voices of emerging adults in their perceived barriers to sexuality communication in the patient-provider and parent-child context. Methods Using data from a survey of 1193 young adults (mean age = 19.23, 72% female), we applied concept mapping to a corpus of over 2,400 qualitative responses to two questions: 1) What, if anything, makes it difficult to talk to your parents about sexuality or your sexual health? 2) What, if anything, makes it difficult to talk to your doctors, therapists, or mental health professionals about sexuality or your sexual health? These data were split into single-concept statements and grouped by similarity by seven researchers of varying demographic and academic backgrounds. Conceptual groupings were derived statistically via multidimensional scaling (MDS) and hierarchical cluster analyses. We then explored how perceived barrier clusters differed across demographic and cultural factors, including socioeconomic status, gender and sexual minority status, race and acculturation, religion and religiosity. Results MDS and cluster analyses revealed a best-fit solution of 8 conceptual groups for perceived barriers talking about sexuality with healthcare providers, but only 4 groups of barriers in talking with parents. That is, young people's descriptions of barriers in talking to healthcare providers were discrete, specific, and shared across participants when considering difficulties talking to clinicians about sex, but more diffuse and idiosyncratic when considering talking to their parents. Younger participants were more likely to endorse awkwardness across contexts. Those with lower parental SES were more likely to perceive mismatch with their provider's communication style or demeanor. Gender typicality and sexual orientation were generally associated with resilience and relative lack of barriers to communication across contexts. Those more assimilated to their heritage/home culture, and Evangelical Christians, were more likely to identify shame as a barrier in talking to parents, but not providers. Conclusions Our findings suggest greater specificity and agreement among young people as to what makes it difficult to talk to healthcare providers about their sexuality. A common qualitative theme was recognition of the need to talk to healthcare providers about sex, but not one's parents. Thus, young people may be ready to jump directly into interventions to build skills to talk to providers, but may need to be convinced of the benefits of open communication about sexuality with their parents to get them on board. Moreover, as barriers differed across identity groups, these findings reinforce the need to tailor sexual health communication to patient characteristics. Disclosure No

The increase in computational resources has enabled the emergence of multi-model ensembles of convection-permitting regional climate model (CPRCM) simulations at very high horizontal resolutions. An example is the CORDEX Flagship Pilot Study on “Convective phenomena at high resolution over Europe and the Mediterranean”, a set of kilometre-scale simulations over an extended Alpine domain. This first-of-its-kind multi-model ensemble, forced by the ERA-Interim reanalysis, can be considered a benchmark dataset. This study uses a recently proposed metric to determine the added value of all the available Flagship Pilot Study hindcast kilometre-scale simulations for maximum and minimum temperature. The analysis is performed using state-of-the-art gridded and station observations as ground truth. This approach directly assesses the added value between the high-resolution CPRCMs against their driving global simulations and coarser resolution RCM counterparts. Overall, models display some modest gains, but also considerable shortcomings are exhibited. In part, these deficiencies can be attributed to the assimilation of temperature observations into ERA-Interim. Although the gains for the use of kilometre-scale resolution for temperature are limited, the improvement of the spatial representation of local atmospheric circulations and land–atmosphere interactions can ultimately lead to gains, particularly in coastal areas. The added value of km-scale simulations to describe temperature over complex orography: the CORDEX FPS-Convection multi-model ensemble runs over the Alps publishedVersion

A realistic representation of the stable atmospheric boundary layer in numerical weather prediction (NWP) and climate models is still a challenge. We study the evolution of a stable boundary layer over snow-covered sea ice in Bothnian Bay during wintertime in 2018. We perform high-resolution model experiments with the Weather Research and Forecasting model in its single-column model configuration and its default mesoscale configuration to assess which physical processes are essential to predict near-surface variables correctly. We evaluate our model runs against the unique observational dataset collected during ISOBAR18, which combines novel, upper-air measurements by an uncrewed aircraft system with wind lidar, sodar, and conventional meteorological mast data. By analysing surface fluxes in the single-column model, we demonstrate how the atmospheric cooling at the ground can be modelled more realistically than in the mesoscale set-up. We show that surface albedo and sea-ice thickness are essential for the surface energy balance in the model, and we demonstrate how the surface fluxes in the mesoscale downscaling with default settings are subject to strong biases. We also show that the ERA5 reanalysis is not capable of representing the observed surface meteorology in the stable atmospheric boundary layer. Our study illustrates the importance of surface albedo and sea-ice thickness for NWP models. Though a seasonal snow albedo is already in use in many NWP settings, the routine inclusion of sea-ice thickness, in particular, would be a great step forward for weather forecasts and regional climate simulations. publishedVersion

Introduction There is a substantial residual risk in patients with chronic coronary syndrome (CCS). Risk scores could be useful tools to allocate intensified secondary preventive medications to address this residual risk. Whether their predictive value can be improved by addition of angiographic scores of the extent of coronary artery disease (CAD) is unknown. Purpose To test and compare the predictive value of three externally developed risk scores for CAD and to investigate the effect of addition of SYNTAX and Gensini scores. Methods We tested the TIMI risk score for secondary prevention (TRS 2°P), a risk score derived from the INVEST study, and the ABC-CHD model (see references 1–3) in 1280 patients with CCS from a contemporary observational CAD cohort ongoing since 2015 with a median follow-up of 3.6 years. In a second step we added SYNTAX and Gensini scores to the models. The endpoints tested were cardiovascular death and major adverse cardiovascular events (MACE), consisting of cardiovascular death, myocardial infarction and ischemic stroke. Results All investigated scores yielded continuously increasing event rates for MACE and cardiovascular death with increasing score points obtained. As an example Figure 1 displays 3-year rates for cardiovascular death and MACE against the points obtained in the TRS 2°P, whilst also displaying the distribution of patients amongst the risk categories. The three scores showed modest predictive value for occurrence of cardiovascular death (c-indices 0.60, 0.64, 0.70 for TRS 2°P, INVEST score, ABC-CHD score, respectively). Addition of both SYNTAX and Gensini scores to the models yielded c-indices of 0.66, 0.69 and 0.70 respectively (Figure 2a). Similar predictive values were observed for the occurrence of MACE (c-indices 0.59, 0.60, 0.64 for TRS 2°P, INVEST score, ABC-CHD score, respectively) as well after addition of both SYNTAX and Gensini scores (c-indices 0.62, 0.63, 0.64, see Figure 2b). Conclusion (I) Currently available risk scores are modestly predictive for the occurence of cardiovascular events in patients with CCS. (II) Addition of Gensini and SYNTAX scores improves their predictive value particularly in weaker risk scores. Funding Acknowledgement Type of funding sources: None. Figure 1Figure 2a (left) and 2b (right)

Background High-sensitivity Troponin T and I (hsTnT/I) concentration is independently associated with coronary artery disease (CAD) severity and cardiovascular outcome. Here we explored whether hsTnT/I blood levels add predictive information irrespective of CAD severity and further confounders in unselected stable patients with angiographically characterized CAD. Methods Between 2015 and 2020, 3,012 patients undergoing coronary angiography were included in the observational Hamburg INTERCATH study. In 2,209 consecutive patients Troponin levels were quantified for hsTnT (Roche Diagnostics Elecsys) and hsTnI (Abbott Diagnostics ARCHITECT STAT). Patients presenting with acute coronary syndromes and heart transplant recipients were excluded, leaving 1,841 patients for analyses. CAD severity was graded according to the Gensini score. Major adverse cardiac events (MACE) as a composite of cardiovascular death, stroke, myocardial infarction, and coronary revascularization were defined as endpoint. Kaplan-Meier analyses stratified by hsTnT/I quartiles were performed. Multivariable Cox models were computed for the association of hsTnT/I with MACE adjusting for age, gender, arterial hypertension, hyperlipoproteinemia, smoking, diabetes mellitus, body-mass index, eGFR and Gensini Score. Results Mean age was 68.5±10.9 years (27.9% female). 81.1% were diagnosed with CAD by coronary angiography. Gensini score was 21.0±30.2. Median follow-up time was 4.42 years. hsTnT quartiles differentiated MACE across all categories (Figure 1A). For hsTnI, cardiovascular risk was differentiated between the lowest and highest quartiles as well as the 1st and 2nd quartile particularly beyond 24 months of follow-up (Figure 1B). However, MACE after 3 years was not associated with hsTnT after adjustment for classical cardiovascular risk factors and CAD severity (Figure 1C), whereas the hazard of MACE was increased in the 3rd and 4th hsTnI quartiles compared to the 1st quartile (HR 1.3, IQR 1.1–1.6 for both categories; Figure 1D). Conclusion Increasing hsTn concentration was related to intermediate term cardiovascular outcome in unselected stable patients. Only hsTnI concentration remained as independent predictor after testing for most possible confounders, including CAD severity. This data underpins the role of hsTnI in outcome prediction. Funding Acknowledgement Type of funding sources: None.

Introduction A majority of women who use Selective Serotonin Reuptake Inhibitors (SSRIs) experience iatrogenic sexual dysfunction – primarily decreased arousal and desire (Lorenz et al., 2016). Experiencing SSRI-linked sexual side effects predicts decreased medication satisfaction and adherence, but few psychosocial factors have been identified that may increase risk of experiencing SSRI-linked side effects. Objective To describe characteristics of young women who report experiencing sexual versus non-sexual side effects linked with SSRI use. Methods 818 emerging adult women (mean age = 19.7, SD = 2.5) in the Southeastern and Midwestern United States reported their lifetime history of medication use (including SSRIs), mental health, unwanted sexual activity, and age of sexual debut. Those who reported ever using an SSRI medication indicated if they had ever experienced any of 20 possible SSRI-related effects, including sexual effects (e.g., desire changes, problems becoming aroused, problems having an orgasm, and increased pain during sex) and 16 non-sexual effects (e.g., weight gain, insomnia, emotional dulling). Linear logistic regression examined psychosocial predictors of reporting sexual versus non-sexual SSRI-linked side effects. Results 187 women (22.9% of sample) reported ever using an SSRI to manage mental health. Among the women who reported lifetime SSRI use, 89 (47.6%) reported experiencing at least one non-sexual side effect, while 45 (24.1%) reported experiencing at least one sexual side effect. Of those who reported that they experienced non-sexual side effects, 45 (50.6%) also reported one or more sexual effect. Every respondent who reported experiencing sexual effects also reported nonsexual effects – that is, nobody reported sexual side effects in the absence of nonsexual side effects. Respondents were 3.8x more likely to report sexual side effects if they ever experienced unwanted sex, p = .005; while mental health disorder history did not significantly predict sexual side effect reporting, p = .226. On the other hand, unwanted sexual experiences did not contribute to models predicting non-sexual effect reporting, p = .236; whereas mental health disorder history was a significant factor, linked with 1.76x increased odds for each positive screening of three possible psychiatric diagnoses, p = .016. Respondents’ age of sexual debut did not significantly contribute to predictions of sexual or non-sexual effects, ps = .813 and .709. Conclusions Among this sample of young women who used SSRIs, sexual and nonsexual side effect reporting was not unilaterally distributed; while non-sexual effects sometimes occurred independently from sexual effects, sexual effects always occurred in the presence of non-sexual effects. This finding raises important questions about whether sexual side effects might be mediated by other secondary effects, like fatigue or emotional dulling. Further, women's unwanted sexual experiences uniquely predicted increased likelihood of reporting sexual effects, whereas their mental health disorder history uniquely predicted increased odds of reporting non-sexual effects. Future directions include testing how patient-provider communication influences patient perception of side effects and how various unwanted sexual experiences (forced and coerced) may differentially impact women's risk of experiencing SSRI-linked side effects. Disclosure No

Introduction Introduction: While most clinicians know it is important to tailor sexual healthcare for their sexual minority patients, it can be complicated to assess who identifies with a sexual minority label, as engaging in same-sex behavior or having same-sex attractions does not always lead to an identity as a sexual minority1. Prior work suggests that people who have same-sex attractions or behaviors but identify as heterosexual have different healthcare needs than people who identify as sexual minorities2. Given this, and recent data showing that 1 in 6 young Americans identify with non-heterosexual orientation labels3, it is important to understand what drives discrepancies between young people's attractions and sexual identity label. Objective Objective: To determine characteristics that predict discordance between young women's sexual orientation label and reported sexual attractions. Methods Methods: 440 young, Midwestern women (age M = 20.6, SD = 1.53) completed a survey battery that assessed their sexual orientation – using both orientation labels and numeric attraction scales – as well as their sexual function (Female Sexual Function Index), sexual desire (Sexual Desire Inventory), sexual sensation seeking (Sexual Sensation Seeking Scale), sexual excitation and inhibition (Sexual Excitation and Inhibition Inventory), and their mental health (Patient Health Questionnaire-9 and Generalized Anxiety Disorder-7). The numeric attraction scale scored participant's attractions to men, women, and non-binary people from 0 – 100. To assess concordance, participant's chosen sexual orientation labels were compared to their numeric attraction scores. Results Results: Desire for solitary sexual experiences increased the likelihood of participants indicating identity labels that did not match their reported patterns of attraction (effect size = - .044, z = -2.69, p = .007); these results remained significant when controlling the influence of other sexuality measures (sexual function, sexual sensation seeking, sexual excitation and inhibition). Further, neither depression scores nor anxiety scores were related to the likelihood of identity/attraction concordance. Conclusions Conclusions: Desire for solitary sex seems to uniquely predict dissonance between one's stated sexual orientation label and experiencing sexual attraction patterns that may be better encapsulated by another label. A sizeable portion of our sample were in relationships with men, which may be a more salient consideration than attraction patterns when choosing an orientation label. If replicated, these findings suggest that assessing sexual desire patterns may help identify patients whose identity/attraction discordance lead to unique sexual health needs. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: Good Clean Love

Introduction The recently updated ESC guidelines on the management of dyslipidaemias recommend a more intense LDL-cholesterol (LDL-C) reduction. For patients with atherosclerotic cardiovascular disease (ASCVD) the LDL-C goal has been revised to ≤55 mg/dl with a concomitant class IA upgrade for cost intensive PCSK9 inhibitors. Purpose We aim to quantify the need for PCSK9 inhibitors to achieve the revised LDL-C target compared to former ESC recommendations in ASCVD patients Methods We included all patients with ASCVD (angiographically documented coronary artery disease, history of peripheral artery disease or stroke) from an observational cohort study ongoing since 2015. A simulation treatment algorithm adding sequentially a high intensity statin, ezetimibe and a PCSK9 inhibitor in case of a missed treatment target was applied with consideration of both partial and total statin intolerance. The need for PCSK9 inhibitors was calculated for 3 recommendations: 1. LDL-C treatment target ≤55 mg/dl (ESC 2019 Guidelines), 2. LDL-C treatment target ≤70 mg/dl (ESC 2016 Guidelines) and 3. risk-based use of PCSK9 inhibitors restricted to patients with a residual LDL-C >140 mg/dl or >100 mg/dl with clinical/angiographic risk factors (ESC consensus update 2017). Results We included 1936 patients (mean age 69 years, 74% male). Median LDL-C at inclusion was 86 mg/dl, with 60% of patients taking lipid lowering medication (55% statin only, 4% statin + ezetimibe, 1% ezetimibe only). Table 1 shows the distribution of medications required to meet recommendations 1–3. After simulated stepwise intensification of lipid lowering therapy 99% of patients achieved the revised LDL-C target of ≤55 mg/dl, with a need of 23.5% for a PCSK9 inhibitor. For the former LDL-C target of ≤70 mg/dl the need for PCSK9 inhibitors was 10.5%. Restricting the use of PCSK9 inhibitors to the highest risk patients according to the ESC 2017 consensus statement reduced the need for PCSK9 inhibition to only 1.4% with slightly fewer patients achieving their LDL-C target (78% for ≤55 mg/dl and 91% for ≤70 mg/dl respectively). Conclusion The revised LDL-C treatment goals substantially increase the projected need for PCSK9 inhibitors with an unclear health economic impact. Identification of ASCVD patients with a reasonable benefit/cost-ratio of PCSK9 inhibition remains to be investigated urgently. Funding Acknowledgement Type of funding source: None

Introduction Modifiable lifestyle risk factors (modRF) of coronary artery disease (CAD) such as smoking, lack of physical activity (PA) and poor diet are associated with high inflammatory burden. An optimisation of modRF might significantly affect the target population for pharmacological anti-inflammatory treatment (AIT) as determined by a hsCRP ≥2 mg/l. Aim To analyse the influence of modRF on hsCRP in a contemporary CAD cohort and model the effect of modRF optimisation on hsCRP in a target population with high inflammatory burden. Methods We included all patients with angiographically documented CAD from an observational cohort study ongoing since 2015 and excluded patients with recent myocardial infarction, malignancy, infectious disease, and immunosuppressive medication. ModRF were assessed by questionnaire at enrolment. Lack of PA was defined as PA Results Of the 1003 patients (mean age 69 years, 72% male) included, 48% (N=479) had a hsCRP ≥2 mg/l. HsCRP increased with the incremental number of modRF (median hsCRP-values for 0–3 modRF: 1.1, 1.6, 2.1, 2.7 mg/l, p12, and smoking (Table 1). Recalculation of hsCRP levels identified 21% (N=102/479) of patients with hsCRP ≥2 mg/l who could achieve a hsCRP Table 1. Linear regression results Univariate Multivariate exp(β) (95% CI) p-value exp(β) (95% CI) p-value PA ≥1.5 h/week 0.63 (0.54, 0.72) 12 0.74 (0.65, 0.86) Conclusion Modifiable lifestyle risk factors are independently associated with hsCRP levels in CAD patients. A relevant portion of patients with high inflammatory burden might achieve a hsCRP

The present study aims to enhance the design of future cockpits by supporting pilots in their monitoring and control of autonomous wingmen. In our scenario, autonomous wingmen are F-16 aircraft that can fly autonomously; a real capability currently under development by industry partners. These autonomous fighter aircraft exist to enhance mission effectiveness by reducing the risk of harm to humans, increasing sensor coverage, providing access to more environments, and decreasing cost. However, the method and systems used for interaction between pilots and the autonomous systems are still under development and an active area of research. In collaboration with industry partners, we are assessing different control input devices for supervisory control of autonomous fighter aircraft in a flight simulator. In this simulator, 60 participants will fly various mission types with autonomous wingmen using one of three different types of controllers: Microsoft Sidewinder, F-35 Hands on Throttle and Stick (HOTAS), and a wrist-mounted computer gaming keypad. Pilots will interact with their autonomous wingmen for brief periods of time through calling “plays” that initiate the unmanned aircraft to conduct a task in combat scenarios. Physiological data will be collected via electroencephalogram (EEG), electrocardiogram (ECG), and galvanic skin response (GSR). Eye movements and behavioral measures of reliance on the autonomous wingmen and usage of each of the aforementioned controllers will also be collected. These data, in addition to survey responses, will inform design recommendations for optimal interaction with autonomous wingmen.

An NH4Cl-catalyzed ethoxy ethyl deprotection was developed for the synthesis of merestinib, a MET inhibitor. Alternative reactor technologies using temperatures above the solvent boiling point are combined with this mild catalyst to promote the deprotection reaction. The reaction is optimized for flow and has been used to synthesize over 100 kg of the target compound. The generality of the reaction conditions is also demonstrated with other compounds and protecting groups.

An appropriate experimental approach is described from which information can be obtained on the amounts of radiotoxic polonium isotopes 208-210Po produced in a lead spallation target during an irradiation period of 16 months from 2000 to 2001. Lead samples from a central position near the beam entry were dissolved and spontaneous deposition of polonium on silver discs was used to prepare thin layer samples for α-counting. The evaluated results show a good correlation to the gradient of the proton beam profile.

Laser-based shock experiments have been conducted in thin Si and Cu crystals at pressures above the published Hugoniot Elastic Limit (HEL) for these materials. In situ x-ray diffraction has been used to directly measure the response of the shocked lattice during shock loading. Static film and x-ray streak cameras recorded x rays diffracted from lattice planes both parallel and perpendicular to the shock direction. In addition, experiments were conducted using a wide-angle detector to record x rays diffracted from multiple lattice planes simultaneously. These data showed uniaxial compression of Si (100) along the shock direction and three-dimensional compression of Cu (100). In the case of the Si diffraction, there was a multiple wave structure observed. This is evaluated to determine whether there is a phase transition occurring on the time scale of the experiments, or the HEL is much higher than previously reported. Results of the measurements are presented. (C) 2003 American Institute of Physics.

The process of new drug development is both time and cost intensive. Therefore, all test systems, in particular during the pre-clinical phase, have to provide reliable results to minimize the risk of failure at a later stage of drug development. However, current pre-clinical studies are mainly performed using experimental animals and in vitro cell culture models, which both are not able to reliably emulate human physiology. As a consequence, the common test procedures may be one reason for late-stage drug failures. Hence, improved test systems are needed, which mimic the diverse and dynamic human physiology and are well controllable and suitable for high-throughput screening.

Microfluidics could not be thought about without advances in micro- and nanofabrication. Following an approach that has been adapted from microelectronics fabrication is carried out in a cleanroom environment using monocrystalline silicon as base material. It typically involves mask-based photolithography, dry and wet etching and thin film deposition. Glass can be used as an alternative or in combination with silicon and allows optical access to the fluid in the microdevices. A different approach using the so-called soft lithography and PDMS (polydimethylsiloxane) material has found widespread applications because it is relatively cheap and easy to use. In most cases the manipulation of fluids at microscales takes place in closed volumes or channels. Several bonding techniques have been developed allowing closure by a lid which in many cases can be transparent. Recently, maskless techniques like inkjet- or 3D-printing, laser micromachining, and microelectrical discharge machining get more and more attention.

The palladium-catalyzed decarboxylative cross-coupling of aminothiophene carboxylate and 1-bromo-4-chlorobenzene to produce 3-amino-2-(4-chlorophenyl)thiophene (2) is described. The cross-coupling proceeds under relatively mild conditions using catalytic Pd(0) and TBAB. Through use of a mixed-solvent system of DMF and NMP, it was possible to operate the cross-coupling system at 80 °C. An assessment of carbon dioxide liberation, which provides insight into the reaction operating parameters, is also discussed.

Routes to (2-chlorophenyl)[2-(phenylsulfonyl)pyridin-3-yl]methanone, 1, an intermediate in the manufacture of NK1-II inhibitor LY686017 are described which produce 1 in >75% yield and 95% purity. A highly selective telescoped ortho lithation/condensation/oxidation process was developed and successfully scaled to the clinical pilot plant to produce 25 kg of 1. For the pilot-plant campaign, the lithiation step was developed to operate at −50 °C using commercial lithium diisopropylamide (LDA), and the oxidation step employed catalytic TEMPO as the primary and NaOCl as the terminal oxidant. After completion of the pilot-plant campaign second-generation approaches to 1 were developed to improve process greenness where the lithiation and condensation step were operated as warm as −10 °C, the highly efficient AZADO catalyst was used as a substitute for TEMPO in the Anelli−Montanari oxidation, and process mass intensity was reduced 25%.

The pelvic subcutaneous cross-over internal fixator is a minimally invasive technique for the fixation of instable anterior pelvic ring fractures. A USS-II-VAS screw is anchored bilaterally in the supra-acetabular region of the os ileum by a mini-incision approach. An angled fixation rod is inserted subcutaneously and after successful closed reduction attached to the screws forming a locking internal fixation. In a retrospective study of the clinical and radiological outcomes of 19 patients after an average follow-up of 2.54 years, results were excellent and good in 31.6%, moderate in 63.2% and poor in 5.3%. Complications were one wound infection, one loosening of the VAS screw and seven temporary lesions of the lateral femoral cutaneous nerve. The main benefits are a simple surgical technique preventing damage to soft tissue, a low risk of neurovascular lesions and the avoidance of pin infections. Moreover patients with multiple trauma profit from a shorter time of surgery and greater comfort allowing a prone position. The new procedure combines the advantages of internal osteosynthesis and a minimally invasive technique, providing early mobilization under full-weight bearing for instable pelvic fractures.

The shared governance literature contains numerous examples of how to design and implement nursing shared governance models. However, there is a major gap between design/implementation and a change in culture. A change in nursing culture will support viability of this governance model. The authors detail the steps taken by a shared governance transition team to help a large nursing organization make changes in governance process and perception as well as to incorporate a maintenance plan.

Raman scattering experiments on stoichiometric, Mott-insulating LaTiO_{3} over a wide range of excitation energies reveal a broad electronic continuum which is featureless in the paramagnetic state, but develops a gap of ~800 cm^{-1} upon cooling below the Néel temperature T_{N}=146 K. In the antiferromagnetic state, the spectral weight below the gap is transferred to well-defined spectral features due to spin and orbital excitations. Low-energy phonons exhibit pronounced Fano anomalies indicative of strong interaction with the electron system for TT_{N}, but become sharp and symmetric for TT_{N}. The electronic continuum and the marked renormalization of the phonon lifetime by the onset of magnetic order are highly unusual for Mott insulators and indicate liquidlike correlations between spins and orbitals.

In the most recent measurements of the reaction ${e}^{+}{e}^{\ensuremath{-}}\ensuremath{\rightarrow}p\overline{p}$ by the BABAR collaboration, new structures have been found with unknown origin. We examine a possible relation of the most distinct peak to the recently observed $\ensuremath{\phi}(2170)$. Alternatively, we analyze possible explanations due to the nucleon $\overline{\mathrm{\ensuremath{\Delta}}}$ and $\mathrm{\ensuremath{\Delta}}\overline{\mathrm{\ensuremath{\Delta}}}$ thresholds. The latter could explain a periodicity found in the data.

We calculate the two-photon exchange corrections to electron-proton scattering with nucleon and $\Delta$ intermediate states. The results show a dependence on the elastic nucleon and nucleon-$\Delta$-transition form factors used as input which leads to significant changes compared to previous calculations. We discuss the relevance of these corrections and apply them to the most recent and precise data set and world data from electron-proton scattering. Using this, we show how the form factor extraction from these data is influenced by the subsequent inclusion of physical constraints. The determination of the proton charge radius from scattering data is shown to be dominated by the enforcement of a realistic spectral function. Additionally, the third Zemach moment from the resulting form factors is calculated. The obtained radius and Zemach moment are shown to be consistent with Lamb shift measurements in muonic hydrogen., Comment: minor changes, added references, version to appear in PRD

The high energy density of pulsed lasers can be used to generate shockless loading in solids to high pressures and compressions but low temperatures. [J. Edwards, K.T. Lorenz, B.A. Remington, S. Pollaine, J. Colvin, D. Braun, B.F. Lasinski, D. Reisman, J.M. McNaney, J.A. Greenough, R.Wallace, H. Louis, D. Kalantar, Laser-driven plasma loader for shockless compression and acceleration of samples in the solid state, Phys. Rev. Lett. 92 (2004) 075002.] We have used the Omega laser to extend the capabilities of this technique to multi-Mbar pressures and compressions approaching a factor of 2 in aluminum foils. The energy from a 3.7 ns laser pulse is used to drive a strong shock through a 200 μm polystyrene disc. The disc material unloads from a high-pressure state and expands across a 300 μm vacuum gap where it stagnates against the sample to produce a smooth, monotonically increasing load with rise times from a few to ∼20 ns. Ramped compression waves having peak pressures of 14–200 GPa (0.14–2.0 Mbar) and peak compressions ρ / ρ 0 of 1.1–2.0 were generated in the aluminum samples using laser pulse energies of 400 J to 2 kJ. Wave profiles from a series of successively thicker targets loaded to 120 GPa show the evolution of the high-pressure compression wave within the sample. The initial loading in the sample is shockless, and develops into a shock at a depth of 20–25 μm. We compare these wave profiles with hydrodynamic simulations from which we extract material temperatures and plastic strain rates behind the compression wave. Limitations and future prospects for this new shockless loading technique are discussed.

We demonstrate the recently developed technique of laser driven isentropic compression (ICE) for dynamically compressing Al samples at high laoding rates close to the room temperature isentrope and up to peak stresses above 100GPa. Upon analysis of the unloading profiles from a multi-stepped Al/LiF target a continuous path through Stress-Density space may be calculated. For materials with phase transformations ramp compression techniques reveals the location of equilibrium phase boundaries and provide information on the kinetics of the lattice re-ordering.

Establishing appropriate impurity specifications for active pharmaceutical ingredient (API) starting materials is an important component of the commercialization and registration of an API. Multiple sources and routes of manufacture of starting materials and the capability of the API synthetic process for tolerating impurities introduced with starting materials must be understood. A strategy for purity method development and use test evaluation of starting materials to aid in establishing quality requirements is described. Phenyl methyl amino propanol (PMAP), a starting material that may be used for fluoxetine hydrochloride and atomoxetine hydrochloride, is used to illustrate the quality evaluation strategy. Knowledge of actual and potential synthetic routes was used to predict potential impurities and guide purity method development. Multiple analytical methods that were semi-orthogonal in the nature of impurity retention (ion-pairing, ion interaction and hydrophilic interaction chromatographic modes) along with use tests were investigated.

Recent development of a laser-based experimental platform allows loading materials to high pressures in the solid state while controlling both strain rate and peak pressure. The drive utilizes momentum transfer from a plasma generated by the introduction of a strong shock in a reservoir of low-Z material. This study looks at the response of a commercial aluminum alloy (6061-T6) subjected to pressures of 18 and 40 GPa at strain rates of 107/s and 5 × 107/s, respectively. It was found that the depth of the crater formed on the sample surface is a good indicator of the general yield behavior of the material and that a relatively simple strength model prevails under the loading conditions considered here. Metallographic examination of recovered samples showed no evidence of shear-band formation or significant melting due to plasma-surface interactions. Crystal plasticity-based calculations were used to assess the effects of material texture. Lack of shear-band formation during the laser-based drive is rationalized by considering the strain gradient as compared to grain size and texture.

Solid-state dynamics experiments at very high pressures and strain rates are becoming possible with high-power laser facilities, albeit over brief intervals of time and spatially small scales. To achieve extreme pressures in the solid state requires that the sample be kept cool, with T-sample < T-melt. To this end, a shockless, plasma-piston "drive" has been developed on the Omega laser, and a staged shock drive was demonstrated on the Nova laser. To characterize the drive, velocity interferometer measurements allow the high pressures of 10 to 200 GPa (0.1 to 2 Mbar) and strain rates of 10(6) to 10(8) s(-1) to be determined. Solid-state strength in the sample is inferred at these high pressures using the Rayleigh-Taylor (RT) instability as a "diagnostic." Lattice response and phase can be inferred for single-crystal samples from time-resolved X-ray diffraction. Temperature and compression in polycrystalline samples can be deduced from extended X-ray absorption fine-structure (EXAFS) measurements. Deformation mechanisms and residual melt depth can be identified by examining recovered samples. We will briefly review this new area of laser-based materials-dynamics research, then present a path forward for carrying these solid-state experiments to much higher pressures, P > 10(3) GPa (10 Mbar), on the National Ignition Facility (NIF) laser at Lawrence Livermore National Laboratory.

Laser-based shock experiments have been conducted in thin Si and Cu crystals at pressures above the Hugoniot elastic limit. In these experiments, static film and x-ray streak cameras recorded x rays diffracted from lattice planes both parallel and perpendicular to the shock direction. These data, showed uniaxial compression of Si(100) along the shock direction and three.-dimensional compression of Cu(100). In the case of the Si diffraction, there was a multiple wave structure observed, which may be due to a one-dimensional phase transition or a time variation in the shock pressure. A new film-based detector has been developed for these in situ dynamic diffraction experiments. This large-angle detector consists of three film cassettes that are positioned to record x rays diffracted from a shocked crystal anywhere within a full pi steradian. It records x rays that are diffracted from multiple lattice planes both parallel and at oblique angles with respect to the shock direction. It is a time-integrating measurement, but time-resolved data may be recorded using a short duration laser pulse to create the diffraction source x rays. This new instrument,has been fielded at the OMEGA and Janus lasers to study single-crystal materials shock compressed by direct laser irradiation. In these experiments, a multiple wave structure was observed on many different lattice planes in Si. These data provide information on, the structure under compression. (C) 2003 American Institute of Physics.

The palladium-catalysed decarboxylative cross-coupling of heterocyclic aromatic carboxylates and aryl halides is described. The cross-coupling proceeds under relatively mild conditions using catalytic Pd(0) and tetrabutylammonium bromide (TBAB). Utilizing a mixed solvent system consisting of N,N-dimethylformamide (DMF) and N-methyl-2-pyrrolidone (NMP), the cross-coupling system operated at temperatures ranging from 80 to 140 °C.

Barbara T. Lorenz is a cardiothoracic nurse practitioner and Kathleen M. Coyte is a critical care clinical nurse specialist at the James A. Haley Veterans Hospital in Tampa, Fla. nated cardiac surgery for more than 2 decades. Initial reports described success with minimally invasive direct coronary artery bypass graft (CABG) surgery in which the left internal mammary artery was used to bypass the left anterior descending artery via a small anterior thoracotomy. Since then, rapid developments in surgical techniques enabled offpump surgery to be performed through a median sternotomy for patients with multivessel coronary artery disease. The offbypass technique has regained popularity as cardiac surgeons attempt to decrease the risks of surgical revascularization by eliminating the adverse effects of CPB. In this article, we provide an overview of the adverse effects of CPB, a review of the literature in which the outcomes of onand off-bypass procedures are compared, and a discussion of nursing implications related to this emerging practice trend. majority of the literature credits Kolessov, from the former Soviet Union, with performing the initial off-bypass surgery in 1964, when he reported his experience in anastomosing the internal mammary artery to the left anterior descending artery on a beating heart. Later in the United States, Favaloro (in 1968) and Garrett et al (in 1973) presented their experiences with the use of saphenous vein grafts as additional conduits. Despite these favorable initial results in the surgical treatment of coronary artery disease, the introduction and refinement of cardiopulmonary bypass (CPB, also referred to as the “heartlung machine”) in the 1960s offered a more widely acceptable alternative to coronary revascularization. The CPB machine and cardioplegic arrest provided surgeons with a motionless target and a bloodless environment in which to accomplish a safe operation. Graft patency rates after this type of surgery are excellent. This preferred practice domiM any critical care nurses in current practice are unaware that s u r g i c a l c o r o n a r y revascularization, in its infancy, was first performed on a beating heart. The To receive CE credit for this article, visit the American Association of CriticalCare Nurses’ (AACN) Web site at http://www.aacn.org, click on "Education" and select “Continuing Education,” or call AACN’s Fax on Demand at (800) 222-6329 and request item No. 1150. Online

We show that in previous analyses of electron-proton scattering, the uncertainties in the statistical procedure to extract the proton charge radius are underestimated. Using a fit function based on a conformal mapping, we can describe the scattering data with high precision and extract a radius value in agreement with the one obtained from muonic hydrogen., minor changes, matches the accepted version

State selective differential cross sections for rotationally inelastic scattering of NO (Ji=0.5, 1.5, F1→Jf=2.5–12.5, F1 and Jf=1.5–9.5, F2) from He and D2 measured by crossed molecular beam product imaging are reported. The differential cross sections were extracted from the data images using a new basis image iterative fitting technique. The images typically exhibit a single broad rotational rainbow maximum that shifts from the forward to the backward scattering direction with increasing ΔJ. The angle of the rainbow maximum was lower at a given ΔJ for D2 than for He as a collision partner. At a collision energy of ∼500 cm−1, primarily the repulsive part of the potential surface is probed, which can be modeled with a two-dimensional hard ellipse potential. This model for rotationally inelastic scattering is shown to qualitatively match the experimental differential cross sections. A more advanced correlated electron pair approximation potential energy surface for NO+He does not give substantially better ...

Human parvovirus B19 can persist in immunocompromised patients and may produce severe clinical illness. In this retrospective study the incidence of B19-associated infections in bone marrow transplant patients was investigated. During 1 year 60 patients received bone marrow grafts (eight autografts and 52 allogeneic transplantations). In case of early onset, atypical or steroid-resistant erythrodermia the patients' blood and/or tissue specimens were screened for B19 infection by polymerase chain reaction (PCR). Additionally, specimens of patients with severe organ failure were tested. A total of 64 PCRs was performed in 27 patients. Seven patients with erythrodermia and one with vulvovaginitis proved to be PCR positive. In patients with organ failure B19 DNA was detected in the myocardium and liver. The incidence of B19 infections in this cohort was 15% and the B19-associated mortality rate 7%. In conclusion, parvovirus B19-associated infections may be more common in immunocompromised patients than previously anticipated.

The obese Zucker rat represents a model of obesity combined with insulin resistance and hyperlipidaemia, which over a period of several months develops spontaneous glomerulosclerosis. The present study addressed the question as to whether glomerular sclerosis was associated with alterations in the degradation of matrix components. In the early phase (up to 6 months) glomeruli from obese rats displayed increased total collagen content (+ 64 %) and decreased gelatinolytic activity (− 34 %) as compared to lean control animals. This decline in glomerular gelatinolytic activity was due to a reduction in gelatinase B [matrix metalloproteinase (MMP)-9]. Glomerular MMP-9 mRNA was reduced 4.6 ± 0.6-fold (n = 3; p < 0.05), MMP-9 protein was not detectable by Western blotting and MMP-9 activity was considerably suppressed in gelatin zymograms. MMP-2, in terms of mRNA expression and activity, was unchanged. Tissue inhibitor of metalloproteinases (TIMP)-1 mRNA expression, TIMP-1 protein (immunohistochemistry) and TIMP-1 activity (reverse zymography) were enhanced in glomeruli from obese rats, while TIMP-2 mRNA remained unchanged. Moreover, mRNA for the α1 IV collagen chain was 2.1 ± 0.8-fold higher in glomeruli isolated from obese animals (n = 3; p < 0.05). These findings indicate that matrix expansion in glomeruli from obese Zucker rats is due to both enhanced synthesis of matrix components as well as reduced degradation by matrix metalloproteinases. Apparently the latter effect is based on a reduction in MMP-9 and up-regulation of its inhibitor TIMP-1. [Diabetologia (1997) 40: 1035–1043]