Real-time automatic image-based slice tracking of gadolinium-filled balloon wedge catheter during MR-guided cardiac catheterization: A proof-of-concept study.

PURPOSE: MR-guided cardiac catheterization procedures currently use passive tracking approaches to follow a gadolinium-filled catheter balloon during catheter navigation. This requires frequent manual tracking and repositioning of the imaging slice during navigation. In this study, a novel framework for automatic real-time catheter tracking during MR-guided cardiac catheterization is presented. METHODS: The proposed framework includes two imaging modes (Calibration and Runtime). The sequence starts in Calibration mode, in which the 3D catheter coordinates are determined using a stack of 10-20 contiguous saturated slices combined with real-time image processing. The sequence then automatically switches to Runtime mode, where three contiguous slices (acquired with partial saturation), initially centered on the catheter balloon using the Calibration feedback, are acquired continuously. The 3D catheter balloon coordinates are estimated in real time from each Runtime slice stack using image processing. Each Runtime stack is repositioned to maintain the catheter balloon in the central slice based on the prior Runtime feedback. The sequence switches back to Calibration mode if the catheter is not detected. This framework was evaluated in a heart phantom and 3 patients undergoing MR-guided cardiac catheterization. Catheter detection accuracy and rate of catheter visibility were evaluated. RESULTS: The automatic detection accuracy for the catheter balloon during the Calibration/Runtime mode was 100%/95% in phantom and 100%/97 ± 3% in patients. During Runtime, the catheter was visible in 82% and 98 ± 2% of the real-time measurements in the phantom and patients, respectively. CONCLUSION: The proposed framework enabled real-time continuous automatic tracking of a gadolinium-filled catheter balloon during MR-guided cardiac catheterization.

Model Predictive Control (MPC) of a Countercurrent Flow Plate Heat Exchanger in a Virtual Environment.

This research proposes advanced model-based control strategies for a countercurrent flow plate heat exchanger in a virtual environment. A virtual environment with visual and auditory effects is designed, which requires a mathematical model describing the real dynamics of the process; this allows parallel fluid movement in different directions with hot and cold temperatures at the outlet, incorporating control monitoring interfaces as communication links between the virtual heat exchanger and control applications. A multivariable and non-linear process like the plate and countercurrent flow heat exchanger requires analysis in the controller design; therefore, this work proposes and compares two control strategies to identify the best-performing one. The first controller is based on the inverse model of the plant, with linear algebra techniques and numerical methods; the second controller is a model predictive control (MPC), which presents optimal control actions that minimize the steady-state errors and aggressive variations in the actuators, respecting the temperature constraints and the operating limits, incorporating a predictive model of the plant. The controllers are tested for different setpoint changes and disturbances, determining that they are not overshot and that the MPC controller has the shortest settling time and lowest steady-state error.

Retrospective motion correction through multi-average k-space data elimination (REMAKE) for free-breathing cardiac cine imaging.

PURPOSE: To develop a motion-robust reconstruction technique for free-breathing cine imaging with multiple averages. METHOD: Retrospective motion correction through multiple average k-space data elimination (REMAKE) was developed using iterative removal of k-space segments (from individual k-space samples) that contribute most to motion corruption while combining any remaining segments across multiple signal averages. A variant of REMAKE, termed REMAKE+, was developed to address any losses in SNR due to k-space information removal. With REMAKE+, multiple reconstructions using different initial conditions were performed, co-registered, and averaged. Both techniques were validated against clinical "standard" signal averaging reconstruction in a static phantom (with simulated motion) and 15 patients undergoing free-breathing cine imaging with multiple averages. Quantitative analysis of myocardial sharpness, blood/myocardial SNR, myocardial-blood contrast-to-noise ratio (CNR), as well as subjective assessment of image quality and rate of diagnostic quality images were performed. RESULTS: In phantom, motion artifacts using "standard" (RMS error [RMSE]: 2.2 ± 0.5) were substantially reduced using REMAKE/REMAKE+ (RMSE: 1.5 ± 0.4/1.0 ± 0.4, p < 0.01). In patients, REMAKE/REMAKE+ led to higher myocardial sharpness (0.79 ± 0.09/0.79 ± 0.1 vs. 0.74 ± 0.12 for "standard", p = 0.004/0.04), higher image quality (1.8 ± 0.2/1.9 ± 0.2 vs. 1.6 ± 0.4 for "standard", p = 0.02/0.008), and a higher rate of diagnostic quality images (99%/100% vs. 94% for "standard"). Blood/myocardial SNR for "standard" (94 ± 30/33 ± 10) was higher vs. REMAKE (80 ± 25/28 ± 8, p = 0.002/0.005) and tended to be lower vs. REMAKE+ (105 ± 33/36 ± 12, p = 0.02/0.06). Myocardial-blood CNR for "standard" (61 ± 22) was higher vs. REMAKE (53 ± 19, p = 0.003) and lower vs. REMAKE+ (69 ± 24, p = 0.007). CONCLUSIONS: Compared to "standard" signal averaging reconstruction, REMAKE and REMAKE+ provide improved myocardial sharpness, image quality, and rate of diagnostic quality images.

Decision aids for localized prostate cancer treatment choice: Systematic review and meta-analysis.

Patients who are diagnosed with localized prostate cancer need to make critical treatment decisions that are sensitive to their values and preferences. The role of decision aids in facilitating these decisions is unknown. The authors conducted a systematic review of randomized trials of decision aids for localized prostate cancer. Teams of 2 reviewers independently identified, selected, and abstracted data from 14 eligible trials (n = 3377 men), of which 10 were conducted in North America. Of these, 11 trials compared decision aids with usual care, and 3 trials compared decision aids with other decision aids. Two trials suggested a modest positive impact on decisional regret. Results across studies varied widely for decisional conflict (4 studies), satisfaction with decision (2 studies), and knowledge (2 studies). No impact on treatment choices was observed (6 studies). In conclusion, scant evidence at high risk of bias suggests the variable impact of existing decision aids on a limited set of decisional processes and outcomes. Because current decision aids provide information but do not directly facilitate shared decision making, subsequent efforts would benefit from user-centered design of decision aids that promote shared decision making.

Pharmacologic Management of Chronic Obstructive Pulmonary Disease. An Official American Thoracic Society Clinical Practice Guideline.

Background: This document provides clinical recommendations for the pharmacologic treatment of chronic obstructive pulmonary disease (COPD). It represents a collaborative effort on the part of a panel of expert COPD clinicians and researchers along with a team of methodologists under the guidance of the American Thoracic Society.Methods: Comprehensive evidence syntheses were performed on all relevant studies that addressed the clinical questions and critical patient-centered outcomes agreed upon by the panel of experts. The evidence was appraised, rated, and graded, and recommendations were formulated using the Grading of Recommendations, Assessment, Development, and Evaluation approach.Results: After weighing the quality of evidence and balancing the desirable and undesirable effects, the guideline panel made the following recommendations: 1) a strong recommendation for the use of long-acting ß2-agonist (LABA)/long-acting muscarinic antagonist (LAMA) combination therapy over LABA or LAMA monotherapy in patients with COPD and dyspnea or exercise intolerance; 2) a conditional recommendation for the use of triple therapy with inhaled corticosteroids (ICS)/LABA/LAMA over dual therapy with LABA/LAMA in patients with COPD and dyspnea or exercise intolerance who have experienced one or more exacerbations in the past year; 3) a conditional recommendation for ICS withdrawal for patients with COPD receiving triple therapy (ICS/LABA/LAMA) if the patient has had no exacerbations in the past year; 4) no recommendation for or against ICS as an additive therapy to long-acting bronchodilators in patients with COPD and blood eosinophilia, except for those patients with a history of one or more exacerbations in the past year requiring antibiotics or oral steroids or hospitalization, for whom ICS is conditionally recommended as an additive therapy; 5) a conditional recommendation against the use of maintenance oral corticosteroids in patients with COPD and a history of severe and frequent exacerbations; and 6) a conditional recommendation for opioid-based therapy in patients with COPD who experience advanced refractory dyspnea despite otherwise optimal therapy.Conclusions: The task force made recommendations regarding the pharmacologic treatment of COPD based on currently available evidence. Additional research in populations that are underrepresented in clinical trials is needed, including studies in patients with COPD 80 years of age and older, those with multiple chronic health conditions, and those with a codiagnosis of COPD and asthma.

The clinical effectiveness of Eye-Search therapy for patients with hemianopia, neglect or hemianopia and neglect.

We investigated the clinical effectiveness of Eye-Search, a web-based therapy app designed to improve visual search times, in a large group of patients with either hemianopia, neglect or both hemianopia and neglect. A prospective, interventional cohort design was used. For the main, impairment-based outcome measure (average visual search time), the within-subject control was affected vs. unaffected side. Four hundred and twenty-six participants who fitted the inclusion criteria completed all 4 time points (1200 therapy trials). We found a significant three-way interaction between therapy, side and group. Eye-Search therapy improved search times to the affected visual field of patients with either hemianopia alone or neglect and hemianopia, but not those with neglect alone. Effect sizes were moderate to large and consistent with previous studies. We found a similar significant interaction between therapy and group for the patient-reported outcome measure "finding things" that most closely matched the impairment-based outcome (visual search). Eye-Search therapy improves both impairment-based and patient-reported outcome measures related to visual search in patients with hemianopia alone or hemianopia and neglect.

Surviving Sepsis Campaign: Guidelines on the Management of Critically Ill Adults with Coronavirus Disease 2019 (COVID-19).

BACKGROUND: The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of a rapidly spreading illness, Coronavirus Disease 2019 (COVID-19), affecting thousands of people around the world. Urgent guidance for clinicians caring for the sickest of these patients is needed. METHODS: We formed a panel of 36 experts from 12 countries. All panel members completed the World Health Organization conflict of interest disclosure form. The panel proposed 53 questions that are relevant to the management of COVID-19 in the ICU. We searched the literature for direct and indirect evidence on the management of COVID-19 in critically ill patients in the ICU. We identified relevant and recent systematic reviews on most questions relating to supportive care. We assessed the certainty in the evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach, then generated recommendations based on the balance between benefit and harm, resource and cost implications, equity, and feasibility. Recommendations were either strong or weak, or in the form of best practice recommendations. RESULTS: The Surviving Sepsis Campaign COVID-19 panel issued 54 statements, of which four are best practice statements, nine are strong recommendations, and 35 are weak recommendations. No recommendation was provided for six questions. The topics were: 1) infection control, 2) laboratory diagnosis and specimens, 3) hemodynamic support, 4) ventilatory support, and 5) COVID-19 therapy. CONCLUSION: The Surviving Sepsis Campaign COVID-19 panel issued several recommendations to help support healthcare workers caring for critically ill ICU patients with COVID-19. When available, we will provide new evidence in further releases of these guidelines.

Multifaceted highly targeted sequential multidrug treatment of early ambulatory high-risk SARS-CoV-2 infection (COVID-19).

The SARS-CoV-2 virus spreading across the world has led to surges of COVID-19 illness, hospitalizations, and death. The complex and multifaceted pathophysiology of life-threatening COVID-19 illness including viral mediated organ damage, cytokine storm, and thrombosis warrants early interventions to address all components of the devastating illness. In countries where therapeutic nihilism is prevalent, patients endure escalating symptoms and without early treatment can succumb to delayed in-hospital care and death. Prompt early initiation of sequenced multidrug therapy (SMDT) is a widely and currently available solution to stem the tide of hospitalizations and death. A multipronged therapeutic approach includes 1) adjuvant nutraceuticals, 2) combination intracellular anti-infective therapy, 3) inhaled/oral corticosteroids, 4) antiplatelet agents/anticoagulants, 5) supportive care including supplemental oxygen, monitoring, and telemedicine. Randomized trials of individual, novel oral therapies have not delivered tools for physicians to combat the pandemic in practice. No single therapeutic option thus far has been entirely effective and therefore a combination is required at this time. An urgent immediate pivot from single drug to SMDT regimens should be employed as a critical strategy to deal with the large numbers of acute COVID-19 patients with the aim of reducing the intensity and duration of symptoms and avoiding hospitalization and death.

Demonstrations of Cooperative Perception: Safety and Robustness in Connected and Automated Vehicle Operations.

Cooperative perception, or collective perception (CP), is an emerging and promising technology for intelligent transportation systems (ITS). It enables an ITS station (ITS-S) to share its local perception information with others by means of vehicle-to-X (V2X) communication, thereby achieving improved efficiency and safety in road transportation. In this paper, we present our recent progress on the development of a connected and automated vehicle (CAV) and intelligent roadside unit (IRSU). The main contribution of the work lies in investigating and demonstrating the use of CP service within intelligent infrastructure to improve awareness of vulnerable road users (VRU) and thus safety for CAVs in various traffic scenarios. We demonstrate in experiments that a connected vehicle (CV) can "see" a pedestrian around the corners. More importantly, we demonstrate how CAVs can autonomously and safely interact with walking and running pedestrians, relying only on the CP information from the IRSU through vehicle-to-infrastructure (V2I) communication. This is one of the first demonstrations of urban vehicle automation using only CP information. We also address in the paper the handling of collective perception messages (CPMs) received from the IRSU, and passing them through a pipeline of CP information coordinate transformation with uncertainty, multiple road user tracking, and eventually path planning/decision-making within the CAV. The experimental results were obtained with manually driven CV, fully autonomous CAV, and an IRSU retrofitted with vision and laser sensors and a road user tracking system.

Clinical Practice Guidelines by the Infectious Diseases Society of America: 2018 Update on Diagnosis, Treatment, Chemoprophylaxis, and Institutional Outbreak Management of Seasonal Influenzaa.

These clinical practice guidelines are an update of the guidelines published by the Infectious Diseases Society of America (IDSA) in 2009, prior to the 2009 H1N1 influenza pandemic. This document addresses new information regarding diagnostic testing, treatment and chemoprophylaxis with antiviral medications, and issues related to institutional outbreak management for seasonal influenza. It is intended for use by primary care clinicians, obstetricians, emergency medicine providers, hospitalists, laboratorians, and infectious disease specialists, as well as other clinicians managing patients with suspected or laboratory-confirmed influenza. The guidelines consider the care of children and adults, including special populations such as pregnant and postpartum women and immunocompromised patients.

Transfusion of fresher vs older red blood cells in hospitalized patients: a systematic review and meta-analysis.

The impact of transfusing fresher vs older red blood cells (RBCs) on patient-important outcomes remains controversial. Two recently published large trials have provided new evidence. We summarized results of randomized trials evaluating the impact of the age of transfused RBCs. We searched MEDLINE, EMBASE, CINAHL, the Cochrane Database for Systematic Reviews, and Cochrane CENTRAL for randomized controlled trials enrolling patients who were transfused fresher vs older RBCs and reported outcomes of death, adverse events, and infection. Independently and in duplicate, reviewers determined eligibility, risk of bias, and abstracted data. We conducted random effects meta-analyses and rated certainty (quality or confidence) of evidence using the GRADE approach. Of 12 trials that enrolled 5229 participants, 6 compared fresher RBCs with older RBCs and 6 compared fresher RBCs with current standard practice. There was little or no impact of fresher vs older RBCs on mortality (relative risk [RR], 1.04; 95% confidence interval [CI], 0.94-1.14; P = .45; I(2) = 0%, moderate certainty evidence) or on adverse events (RR, 1.02; 95% CI, 0.91-1.14; P = .74; I(2) = 0%, low certainty evidence). Fresher RBCs appeared to increase the risk of nosocomial infection (RR, 1.09; 95% CI, 1.00-1.18; P = .04; I(2) = 0%, risk difference 4.3%, low certainty evidence). Current evidence provides moderate certainty that use of fresher RBCs does not influence mortality, and low certainty that it does not influence adverse events but could possibly increase infection rates. The existing evidence provides no support for changing practices toward fresher RBC transfusion.

The correlation between retrograde leak point pressure and 24-hour pad weight.

AIM: To assess the correlation between retrograde leak point pressure (RLPP) and 24-hr pad weight (24PW) in men with post-prostatectomy incontinence. METHODS: We performed RLPP and 24PW measurements on 61 patients with a history of post-prostatectomy stress urinary incontinence (SUI). We examined the relationship of RLPP and 24PW. We also reviewed the urodynamic and clinical data of these patients to explain our findings. RESULTS: The mean age was 70 years (SD ± 7.4, range: 51-87). The mean RLPP was 36.8 cmH2 O (SD ± 15.3, range: 9-76), the mean 24PW was 499 g (±677 g, range: 16.5-3,177 g). There was a good and significant negative correlation between RLPP and 24PW (r = 0.56, P < 0.01). RLPP was able to differentiate between cases of mild/moderate (<400 g) and severe (≥400 g) incontinence. Patients with RLPP <30 cmH2 O had significantly higher 24PW (mean 825 g, median 768 g) when compared with patients with RLPP >30 cmH2 O (mean 257.8 g, median 100 g, P < 0.01). CONCLUSIONS: RLPP could be used as an objective and potentially more reliable substitute to pad weight to objectify and stratify SUI in post-prostatectomy patients. Neurourol. Urodynam. 36:1119-1123, 2017. © 2016 Wiley Periodicals, Inc.

Corticosteroid Therapy for Patients Hospitalized With Community-Acquired Pneumonia: A Systematic Review and Meta-analysis.

BACKGROUND: Community-acquired pneumonia (CAP) is common and often severe. PURPOSE: To examine the effect of adjunctive corticosteroid therapy on mortality, morbidity, and duration of hospitalization in patients with CAP. DATA SOURCES: MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials through 24 May 2015. STUDY SELECTION: Randomized trials of systemic corticosteroids in hospitalized adults with CAP. DATA EXTRACTION: Two reviewers independently extracted study data and assessed risk of bias. Quality of evidence was assessed with the Grading of Recommendations Assessment, Development, and Evaluation system by consensus among the authors. DATA SYNTHESIS: The median age was typically in the 60s, and approximately 60% of patients were male. Adjunctive corticosteroids were associated with possible reductions in all-cause mortality (12 trials; 1974 patients; risk ratio [RR], 0.67 [95% CI, 0.45 to 1.01]; risk difference [RD], 2.8%; moderate certainty), need for mechanical ventilation (5 trials; 1060 patients; RR, 0.45 [CI, 0.26 to 0.79]; RD, 5.0%; moderate certainty), and the acute respiratory distress syndrome (4 trials; 945 patients; RR, 0.24 [CI, 0.10 to 0.56]; RD, 6.2%; moderate certainty). They also decreased time to clinical stability (5 trials; 1180 patients; mean difference, -1.22 days [CI, -2.08 to -0.35 days]; high certainty) and duration of hospitalization (6 trials; 1499 patients; mean difference, -1.00 day [CI, -1.79 to -0.21 days]; high certainty). Adjunctive corticosteroids increased frequency of hyperglycemia requiring treatment (6 trials; 1534 patients; RR, 1.49 [CI, 1.01 to 2.19]; RD, 3.5%; high certainty) but did not increase frequency of gastrointestinal hemorrhage. LIMITATIONS: There were few events and trials for many outcomes. Trials often excluded patients at high risk for adverse events. CONCLUSION: For hospitalized adults with CAP, systemic corticosteroid therapy may reduce mortality by approximately 3%, need for mechanical ventilation by approximately 5%, and hospital stay by approximately 1 day. PRIMARY FUNDING SOURCE: None.

Complexes of Trypanosoma cruzi sterol 14α-demethylase (CYP51) with two pyridine-based drug candidates for Chagas disease: structural basis for pathogen selectivity.

Chagas disease, caused by the eukaryotic (protozoan) parasite Trypanosoma cruzi, is an alarming emerging global health problem with no clinical drugs available to treat the chronic stage. Azole inhibitors of sterol 14α-demethylase (CYP51) were proven effective against Chagas, and antifungal drugs posaconazole and ravuconazole have entered clinical trials in Spain, Bolivia, and Argentina. Here we present the x-ray structures of T. cruzi CYP51 in complexes with two alternative drug candidates, pyridine derivatives (S)-(4-chlorophenyl)-1-(4-(4-(trifluoromethyl)phenyl)-piperazin-1-yl)-2-(pyridin-3-yl)ethanone (UDO; Protein Data Bank code 3ZG2) and N-[4-(trifluoromethyl)phenyl]-N-[1-[5-(trifluoromethyl)-2-pyridyl]-4-piperi-dyl]pyridin-3-amine (UDD; Protein Data Bank code 3ZG3). These compounds have been developed by the Drugs for Neglected Diseases initiative (DNDi) and are highly promising antichagasic agents in both cellular and in vivo experiments. The binding parameters and inhibitory effects on sterol 14α-demethylase activity in reconstituted enzyme reactions confirmed UDO and UDD as potent and selective T. cruzi CYP51 inhibitors. Comparative analysis of the pyridine- and azole-bound CYP51 structures uncovered the features that make UDO and UDD T. cruzi CYP51-specific. The structures suggest that although a precise fit between the shape of the inhibitor molecules and T. cruzi CYP51 active site topology underlies their high inhibitory potency, a longer coordination bond between the catalytic heme iron and the pyridine nitrogen implies a weaker influence of pyridines on the iron reduction potential, which may be the basis for the observed selectivity of these compounds toward the target enzyme versus other cytochrome P450s, including human drug-metabolizing P450s. These findings may pave the way for the development of novel CYP51-targeted drugs with optimized metabolic properties that are very much needed for the treatment of human infections caused by eukaryotic microbial pathogens.

Plasticity of human auditory-evoked fields induced by shock conditioning and contingency reversal.

We used magnetoencephalography (MEG) to assess plasticity of human auditory cortex induced by classical conditioning and contingency reversal. Participants listened to random sequences of high or low tones. A first baseline phase presented these without further associations. In phase 2, one of the frequencies (CS(+)) was paired with shock on half its occurrences, whereas the other frequency (CS(-)) was not. In phase 3, the contingency assigning CS(+) and CS(-) was reversed. Conditioned pupil dilation was observed in phase 2 but extinguished in phase 3. MEG revealed that, during phase-2 initial conditioning, the P1m, N1m, and P2m auditory components, measured from sensors over auditory temporal cortex, came to distinguish between CS(+) and CS(-). After contingency reversal in phase 3, the later P2m component rapidly reversed its selectivity (unlike the pupil response) but the earlier P1m did not, whereas N1m showed some new learning but not reversal. These results confirm plasticity of human auditory responses due to classical conditioning, but go further in revealing distinct constraints on different levels of the auditory hierarchy. The later P2m component can reverse affiliation immediately in accord with an updated expectancy after contingency reversal, whereas the earlier auditory components cannot. These findings indicate distinct cognitive and emotional influences on auditory processing.

Withdrawn: A systematic review of autopsy findings in deaths after COVID-19 vaccination.

This Article-in-Press has been withdrawn at the request of the Editors-in-Chief. Members of the scientific community raised concerns about this Article-in-Press following its posting online. The concerns encompassed. • Inappropriate citation of references. • Inappropriate design of methodology. • Errors, misrepresentation, and lack of factual support for the conclusions. • Failure to recognise and cite disconfirming evidence. The concerns were shared with the authors, who prepared a response and submitted a revised manuscript for consideration by the journal. In consideration of the extent of the concerns raised and the responses from the authors, the journal sent the revised manuscript to two independent peer-reviewers. The peer-reviewers concluded that the revised manuscript did not sufficiently address the concerns raised by the community and that it was not suitable for publication in the journal. The authors disagree with this withdrawal and dispute the grounds for it. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/policies/article-withdrawal.

Fast reconstruction of SMS bSSFP myocardial perfusion images using noise map estimation network (NoiseMapNet): a head-to-head comparison with parallel imaging and iterative reconstruction.

Background: Simultaneous multi-slice (SMS) bSSFP imaging enables stress myocardial perfusion imaging with high spatial resolution and increased spatial coverage. Standard parallel imaging techniques (e.g., TGRAPPA) can be used for image reconstruction but result in high noise level. Alternatively, iterative reconstruction techniques based on temporal regularization (ITER) improve image quality but are associated with reduced temporal signal fidelity and long computation time limiting their online use. The aim is to develop an image reconstruction technique for SMS-bSSFP myocardial perfusion imaging combining parallel imaging and image-based denoising using a novel noise map estimation network (NoiseMapNet), which preserves both sharpness and temporal signal profiles and that has low computational cost. Methods: The proposed reconstruction of SMS images consists of a standard temporal parallel imaging reconstruction (TGRAPPA) with motion correction (MOCO) followed by image denoising using NoiseMapNet. NoiseMapNet is a deep learning network based on a 2D Unet architecture and aims to predict a noise map from an input noisy image, which is then subtracted from the noisy image to generate the denoised image. This approach was evaluated in 17 patients who underwent stress perfusion imaging using a SMS-bSSFP sequence. Images were reconstructed with (a) TGRAPPA with MOCO (thereafter referred to as TGRAPPA), (b) iterative reconstruction with integrated motion compensation (ITER), and (c) proposed NoiseMapNet-based reconstruction. Normalized mean squared error (NMSE) with respect to TGRAPPA, myocardial sharpness, image quality, perceived SNR (pSNR), and number of diagnostic segments were evaluated. Results: NMSE of NoiseMapNet was lower than using ITER for both myocardium (0.045 ± 0.021 vs. 0.172 ± 0.041, p < 0.001) and left ventricular blood pool (0.025 ± 0.014 vs. 0.069 ± 0.020, p < 0.001). There were no significant differences between all methods for myocardial sharpness (p = 0.77) and number of diagnostic segments (p = 0.36). ITER led to higher image quality than NoiseMapNet/TGRAPPA (2.7 ± 0.4 vs. 1.8 ± 0.4/1.3 ± 0.6, p < 0.001) and higher pSNR than NoiseMapNet/TGRAPPA (3.0 ± 0.0 vs. 2.0 ± 0.0/1.3 ± 0.6, p < 0.001). Importantly, NoiseMapNet yielded higher pSNR (p < 0.001) and image quality (p < 0.008) than TGRAPPA. Computation time of NoiseMapNet was only 20s for one entire dataset. Conclusion: NoiseMapNet-based reconstruction enables fast SMS image reconstruction for stress myocardial perfusion imaging while preserving sharpness and temporal signal profiles.

Design, structure-activity relationship and in vivo efficacy of piperazine analogues of fenarimol as inhibitors of Trypanosoma cruzi.

A scaffold hopping exercise undertaken to expand the structural diversity of the fenarimol series of anti-Trypanosoma cruzi (T. cruzi) compounds led to preparation of simple 1-[phenyl(pyridin-3-yl)methyl]piperazinyl analogues of fenarimol which were investigated for their ability to inhibit T. cruzi in vitro in a whole organism assay. A range of compounds bearing amide, sulfonamide, carbamate/carbonate and aryl moieties exhibited low nM activities and two analogues were further studied for in vivo efficacy in a mouse model of T. cruzi infection. One compound, the citrate salt of 37, was efficacious in a mouse model of acute T. cruzi infection after once daily oral dosing at 20, 50 and 100 mg/kg for 5 days.