Cardiovascular effects of serotonergic agents

Serotonin (5-hydroxytryptamine, 5-HT) is a neurotransmitter which exerts its cardiovascular effects predominantly by interaction with specific 5-HT1 and 5- HT2 receptors. The effects of serotonergic agents differ between in vivo and in vitro preparations and display wide inter-species variation. It is therefore impossible to extrapolate results from animal or in vitro studies to the clinical situation. The role of these two receptors has therefore been studied in patients with suspected coronary artery disease using 3 different 5-HT1 agonists and ketanserin, a 5-HT2 antagonist. Sumatriptan and naratriptan, 5-HT1B/D receptor agonists, vasoconstrict the systemic and pulmonary circulations. Sumatriptan-induced vasoconstriction appears more pronounced in the pulmonary circulation suggesting a greater density of 5-HT1 receptors in the pulmonary compared to the systemic circulation. Although left ventricular end diastolic pressure and pulmonary artery wedge pressure rose after sumatriptan, there was no change in peak rate of left ventricular pressure rise, indicating the absence of a negative inotropic action. Naratriptan, an analogue of sumatriptan, displayed no significant effect on coronary artery diameter, a finding previously noted with sumatriptan. Eletriptan, a selective 5-HT1D agonist with less 5-HT1B activity, had little vasoconstrictor effect on the systemic, pulmonary or coronary circulation perhaps suggesting that the 5-HT1B receptor subtype mediates vasoconstriction. The effect of sumatriptan on systolic time intervals and forearm blood flow was also assessed. The results suggest that STI's are of potential use in the non-invasive assessment of 5-HT1 agonists. No significant effect on forearm blood flow was observed but plasma noradrenaline levels fell after subcutaneous sumatriptan. Ketanserin, a 5-HT2 antagonist, acted as a vasodilator in the systemic and pulmonary circulation but failed to vasodilate the coronary arteries, presumably because the patients in this study had stable angina without platelet activation and therefore had low circulating levels of serotonin

CanSat Competition: Contributing to the Development of NASA's Vision for Robotic Space Exploration

CanSat is an international student design-build-launch competition organized by the American Astronautical Society (AAS) and American Institute of Aeronautics and Astronautics (AIAA). The competition is also sponsored by the Naval Research Laboratory (NRL) and the National Aeronautics and Space Administration (NASA). The CanSat competition is designed for college, university and high school students wanting to participate in an applicable space-related competition. The objective of the CanSat competition is to complete space exploration missions by designing a specific system for a small sounding rocket payload which will follow and perform to a specific set of rules and guidelines for each year's competition. The competition encompasses a complete life-cycle of one year which includes all phases of design, integration, testing, judging and competition. The mission guidelines are based from space exploration missions and include bonus requirement options which teams may choose to participate in. The fundamental goal of the competition is to educate future engineers and scientists. This is accomplished by students applying systems engineering practices to a development project that incorporates an end-to-end life cycle, from requirements analysis, through preliminary design, integration and testing, an actual flight of the CanSat, and concluding with a post-mission debrief. This is done specifically with space related missions to bring a unique aspect of engineering and design to the competition. The competition has been progressing since its creation in 2005. The competition was originally meant to purely convey the engineering and design process to its participants, but through many experiences the competition has also undergone a learning experience with respect to systems engineering process and design. Accordin

Safety of guidewire-based measurement of fractional flow reserve and the index of microvascular resistance using intravenous adenosine in patients with acute or recent myocardial infarction

Aims: Coronary guidewire-based diagnostic assessments with hyperemia may cause iatrogenic complications. We assessed the safety of guidewire-based measurement of coronary physiology, using intravenous adenosine, in patients with an acute coronary syndrome. Methods: We prospectively enrolled invasively managed STEMI and NSTEMI patients in two simultaneously conducted studies in 6 centers (NCT01764334; NCT02072850). All of the participants underwent a diagnostic coronary guidewire study using intravenous adenosine (140 μg/kg/min) infusion for 1–2 min. The patients were prospectively assessed for the occurrence of serious adverse events (SAEs) and symptoms and invasively measured hemodynamics were also recorded. Results: 648 patients (n = 298 STEMI patients in 1 hospital; mean time to reperfusion 253 min; n = 350 NSTEMI in 6 hospitals; median time to angiography from index chest pain episode 3 (2, 5) days) were included between March 2011 and May 2013. Two NSTEMI patients (0.03% overall) experienced a coronary dissection related to the guidewire. No guidewire dissections occurred in the STEMI patients. Chest symptoms were reported in the majority (86%) of patient's symptoms during the adenosine infusion. No serious adverse events occurred during infusion of adenosine and all of the symptoms resolved after the infusion ceased. Conclusions: In this multicenter analysis, guidewire-based measurement of FFR and IMR using intravenous adenosine was safe in patients following STEMI or NSTEMI. Self-limiting symptoms were common but not associated with serious adverse events. Finally, coronary dissection in STEMI and NSTEMI patients was noted to be a rare phenomenon

Squeezed-light-enhanced atom interferometry below the standard quantum limit

We investigate the prospect of enhancing the phase sensitivity of atom interferometers in the Mach-Zehnder configuration with squeezed light. Ultimately, this enhancement is achieved by transferring the quantum state of squeezed light to one or more of the atomic input beams, thereby allowing operation below the standard quantum limit. We analyze in detail three specific schemes that utilize (1) single-mode squeezed optical vacuum (i.e., low-frequency squeezing), (2) two-mode squeezed optical vacuum (i.e., high-frequency squeezing) transferred to both atomic inputs, and (3) two-mode squeezed optical vacuum transferred to a single atomic input. Crucially, our analysis considers incomplete quantum state transfer (QST) between the optical and atomic modes, and the effects of depleting the initially prepared atomic source. Unsurprisingly, incomplete QST degrades the sensitivity in all three schemes. We show that by measuring the transmitted photons and using information recycling [Phys. Rev. Lett. 110, 053002 (2013)], the degrading effects of incomplete QST on the sensitivity can be substantially reduced. In particular, information recycling allows scheme (2) to operate at the Heisenberg limit irrespective of the QST efficiency, even when depletion is significant. Although we concentrate on Bose- condensed atomic systems, our scheme is equally applicable to ultracold thermal vapors

Microvascular resistance predicts myocardial salvage and infarct characteristics in ST-elevation myocardial infarction

<b>Background:</b> The pathophysiology of myocardial injury and repair in patients with ST‐elevation myocardial infarction is incompletely understood. We investigated the relationships among culprit artery microvascular resistance, myocardial salvage, and ventricular function.<p></p> <b>Methods and Results:</b> The index of microvascular resistance (IMR) was measured by means of a pressure‐ and temperature‐sensitive coronary guidewire in 108 patients with ST‐elevation myocardial infarction (83% male) at the end of primary percutaneous coronary intervention. Paired cardiac MRI (cardiac magnetic resonance) scans were performed early (2 days; n=108) and late (3 months; n=96) after myocardial infarction. T2‐weighted‐ and late gadolinium–enhanced cardiac magnetic resonance delineated the ischemic area at risk and infarct size, respectively. Myocardial salvage was calculated by subtracting infarct size from area at risk. Univariable and multivariable models were constructed to determine the impact of IMR on cardiac magnetic resonance–derived surrogate outcomes. The median (interquartile range) IMR was 28 (17–42) mm Hg/s. The median (interquartile range) area at risk was 32% (24%–41%) of left ventricular mass, and the myocardial salvage index was 21% (11%–43%). IMR was a significant multivariable predictor of early myocardial salvage, with a multiplicative effect of 0.87 (95% confidence interval 0.82 to 0.92) per 20% increase in IMR; P<0.001. In patients with anterior myocardial infarction, IMR was a multivariable predictor of early and late myocardial salvage, with multiplicative effects of 0.82 (95% confidence interval 0.75 to 0.90; P<0.001) and 0.92 (95% confidence interval 0.88 to 0.96; P<0.001), respectively. IMR also predicted the presence and extent of microvascular obstruction and myocardial hemorrhage.<p></p> <b>Conclusion:</b> Microvascular resistance measured during primary percutaneous coronary intervention significantly predicts myocardial salvage, infarct characteristics, and left ventricular ejection fraction in patients with ST‐elevation myocardial infarction.<p></p&gt

A randomized trial of deferred stenting versus immediate stenting to prevent no- or slow-reflow in acute ST-segment elevation myocardial infarction (DEFER-STEMI)

Objectives: The aim of this study was to assess whether deferred stenting might reduce no-reflow and salvage myocardium in primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI). Background: No-reflow is associated with adverse outcomes in STEMI. Methods: This was a prospective, single-center, randomized, controlled, proof-of-concept trial in reperfused STEMI patients with ≥1 risk factors for no-reflow. Randomization was to deferred stenting with an intention-to-stent 4 to 16 h later or conventional treatment with immediate stenting. The primary outcome was the incidence of no-/slow-reflow (Thrombolysis In Myocardial Infarction ≤2). Cardiac magnetic resonance imaging was performed 2 days and 6 months after myocardial infarction. Myocardial salvage was the final infarct size indexed to the initial area at risk. Results: Of 411 STEMI patients (March 11, 2012 to November 21, 2012), 101 patients (mean age, 60 years; 69% male) were randomized (52 to the deferred stenting group, 49 to the immediate stenting). The median (interquartile range [IQR]) time to the second procedure in the deferred stenting group was 9 h (IQR: 6 to 12 h). Fewer patients in the deferred stenting group had no-/slow-reflow (14 [29%] vs. 3 [6%]; p = 0.006), no reflow (7 [14%] vs. 1 [2%]; p = 0.052) and intraprocedural thrombotic events (16 [33%] vs. 5 [10%]; p = 0.010). Thrombolysis In Myocardial Infarction coronary flow grades at the end of PCI were higher in the deferred stenting group (p = 0.018). Recurrent STEMI occurred in 2 patients in the deferred stenting group before the second procedure. Myocardial salvage index at 6 months was greater in the deferred stenting group (68 [IQR: 54% to 82%] vs. 56 [IQR: 31% to 72%]; p = 0.031]. Conclusions: In high-risk STEMI patients, deferred stenting in primary PCI reduced no-reflow and increased myocardial salvage

Perspectives of Statistician, Microbiologist, and Clinician Stakeholders on the Use of Microbiological Outcomes in Randomised Trials of Antimicrobial Stewardship Interventions

Microbiological data are used as indicators of infection, for diagnosis, and the identification of antimicrobial resistance in trials of antimicrobial stewardship interventions. However, several problems have been identified in a recently conducted systematic review (e.g., inconsistency in reporting and oversimplified outcomes), which motivates the need to understand and improve the use of these data including analysis and reporting. We engaged key stakeholders including statisticians, clinicians from both primary and secondary care, and microbiologists. Discussions included issues identified in the systematic review and questions about the value of using microbiological data in clinical trials, perspectives on current microbiological outcomes reported in trials, and alternative statistical approaches to analyse these data. Various factors (such as unclear sample collection process, dichotomising or categorising complex microbiological data, and unclear methods of handling missing data) were identified that contributed to the low quality of the microbiological outcomes and the analysis of these outcomes in trials. Whilst not all of these factors would be easy to overcome, there is room for improvement and a need to encourage researchers to understand the impact of misusing these data. This paper discusses the experience and challenges of using microbiological outcomes in clinical trials

ST-elevation myocardial infarction due to coronary thrombus in a young patient with diabetic ketoacidosis and a new diagnosis of type-2 diabetes

The association between cardiovascular disease and diabetes is increasingly understood and shared therapeutic targets are emerging. We describe the presentation and successful management of ST-elevation myocardial infarction (STEMI) secondary to coronary thrombus in a young patient with a new diagnosis of type 2 diabetes and diabetic ketoacidosis

Predicting illness progression for children with lower respiratory infections (LRTI) presenting to primary care

Background Antibiotics are commonly prescribed for children with lower respiratory tract infections (LRTIs), fuelling antibiotic resistance, and there are few prognostic tools available to inform management. Aim To externally validate an existing prognostic model (STARWAVe) to identify children at low risk of illness progression, and if model performance was limited to develop a new internally validated prognostic model. Design and setting Prospective cohort study with a nested trial in a primary care setting. Method Children aged 6 months to 12 years presenting with uncomplicated LRTI were included in the cohort. Children were randomised to receive amoxicillin 50 mg/kg per day for 7 days or placebo, or if not randomised they participated in a parallel observational study to maximise generalisability. Baseline clinical data were used to predict adverse outcome (illness progression requiring hospital assessment). Results A total of 758 children participated (n= 432 trial, n= 326 observational). For predicting illness progression the STARWAVe prognostic model had moderate performance (area under the receiver operating characteristic [AUROC] 0.66, 95% confidence interval [CI] = 0.50 to 0.77), but a new, internally validated model (seven items: baseline severity; respiratory rate; duration of prior illness; oxygen saturation; sputum or a rattly chest; passing urine less often; and diarrhoea) had good discrimination (bootstrapped AUROC 0.83, 95% CI = 0.74 to 0.92) and calibration. A three-item model (respiratory rate; oxygen saturation; and sputum or a rattly chest) also performed well (AUROC 0.81, 95% CI = 0.70 to 0.91), as did a score (ranging from 19 to 102) derived from coefficients of the model (AUROC 0.78, 95% CI = 0.67 to 0.88): a score of &lt;70 classified 89% (n= 600/674) of children having a low risk (&lt;5%) of progression of illness. Conclusion A simple three-item prognostic score could be useful as a tool to identify children with LRTI who are at low risk of an adverse outcome and to guide clinical management.</p

Myocardial hemorrhage after acute reperfused ST-segment-elevation myocardial infarction:Relation to microvascular obstruction and prognostic significance

Background—The success of coronary reperfusion therapy in ST-segment–elevation myocardial infarction (MI) is commonly limited by failure to restore microvascular perfusion. Methods and Results—We performed a prospective cohort study in patients with reperfused ST-segment–elevation MI who underwent cardiac magnetic resonance 2 days (n=286) and 6 months (n=228) post MI. A serial imaging time-course study was also performed (n=30 participants; 4 cardiac magnetic resonance scans): 4 to 12 hours, 2 days, 10 days, and 7 months post reperfusion. Myocardial hemorrhage was taken to represent a hypointense infarct core with a T2* value of &#60;20 ms. Microvascular obstruction was assessed with late gadolinium enhancement. Adverse remodeling was defined as an increase in left ventricular end-diastolic volume ≥20% at 6 months. Cardiovascular death or heart failure events post discharge were assessed during follow-up. Two hundred forty-five patients had evaluable T2* data (mean±age, 58 [11] years; 76% men). Myocardial hemorrhage 2 days post MI was associated with clinical characteristics indicative of MI severity and inflammation. Myocardial hemorrhage was a multivariable associate of adverse remodeling (odds ratio [95% confidence interval]: 2.64 [1.07–6.49]; P=0.035). Ten (4%) patients had a cardiovascular cause of death or experienced a heart failure event post discharge, and myocardial hemorrhage, but not microvascular obstruction, was associated with this composite adverse outcome (hazard ratio, 5.89; 95% confidence interval, 1.25–27.74; P=0.025), including after adjustment for baseline left ventricular end-diastolic volume. In the serial imaging time-course study, myocardial hemorrhage occurred in 7 (23%), 13 (43%), 11 (33%), and 4 (13%) patients 4 to 12 hours, 2 days, 10 days, and 7 months post reperfusion. The amount of hemorrhage (median [interquartile range], 7.0 [4.9–7.5]; % left ventricular mass) peaked on day 2 (P&#60;0.001), whereas microvascular obstruction decreased with time post reperfusion. Conclusions—Myocardial hemorrhage and microvascular obstruction follow distinct time courses post ST-segment–elevation MI. Myocardial hemorrhage was more closely associated with adverse outcomes than microvascular obstruction