Preparation Initiation Research Articles

Simulation as a potential tool for successful clinical trial initiation.

Conducting clinical trials is often complex and involves many individuals from a variety of services, each with a specific role in ensuring its successful implementation. Although an experienced clinical trialist may anticipate many of the challenges, others may be unexpected and detrimental to the successful completion of a study. We describe the use of simulation during preparation for initiation of a randomized clinical trial of a new preparation of antiseizure medication in neonates with seizures. The process of identification of stakeholders and roles, scenario development, and identification of challenges are described. Lessons learned included the potential benefits of simulation exercises, simulation challenges, and challenges associated with the study itself. We posit that going through the steps of a study, rather than merely reading them from a manual of procedures, will help identify potential barriers, complexities, and contingencies that are not readily apparent and may result in fewer protocol deviations and violations.

Multi-muscle synergies in preparation for gait initiation in Parkinson’s disease

ObjectiveWe investigated changes in indices of muscle synergies prior to gait initiation and the effects of gaze shift in patients with Parkinson’s disease (PD). A long-term objective of the study is to develop a method for quantitative assessment of gait-initiation problems in PD. MethodsPD patients without clinical signs of postural instability and two control groups (age-matched and young) performed a gait initiation task in a self-paced manner, with and without a quick prior gaze shift produced by turning the head. Muscle groups with parallel scaling of activation levels (muscle modes) were identified as factors in the muscle activation space. Synergy index stabilizing center of pressure trajectory in the anterior-posterior and medio-lateral directions (indices of stability) was quantified in the muscle mode space. A drop in the synergy index in preparation to gait initiation (anticipatory synergy adjustment, ASA) was quantified. ResultsCompared to the control groups, PD patients showed significantly smaller synergy indices and ASA for both directions of the center of pressure shift. Both PD and age-matched controls, but not younger controls, showed detrimental effects of the prior gaze shift on the ASA indices. ConclusionsPD patients without clinically significant posture or gait disorders show impaired stability of the center of pressure and its diminished adjustment during gait initiation. SignificanceThe indices of stability and ASA may be useful to monitor pre-clinical gait disorders, and lower ASA may be relevant to emergence of freezing of gait in PD.

Mastering the Best Practices: A Comprehensive Look at the European Guidelines for Cardiopulmonary Bypass in Adult Cardiac Surgery.

The successful outcome of a cardiac surgery procedure is significantly dependent on the management of cardiopulmonary bypass (CPB). Even if a cardiac operation is technically well-conducted, a patient may suffer CPB-related complications that could result in severe comorbidities, reduced quality of life, or even death. However, the role of clinical perfusionists in perioperative patient care, which is critical, is often overlooked. Therefore, the European Association for Cardio-Thoracic Surgery (EACTS), the European Association of Cardiothoracic Anaesthesiology (EACTA), and the European Board of Cardiovascular Perfusion (EBCP) have agreed to develop joint clinical practice guidelines (CPGs) for CPB due to its significant impact on patient care and significant variations in practice patterns between countries. The European guidelines, based on the EACTS standardized framework for the development of CPGs, cover the entire spectrum of CPB management in adult cardiac surgery. This includes training and education of clinical perfusionists, machine hardware, disposables, preparation for initiation of CPB, a complete set of procedures during CPB to help maintain end-organ function and anticoagulation, weaning from CPB, and the gaps in evidence and future research directions. This comprehensive coverage ensures that all aspects of CPB management are addressed, providing clinicians with a standardized approach to CPB management based on the latest evidence and best practices. To ensure better integration of these evidence-based recommendations into daily practice, this review aims to provide a general understanding of guideline development and an overview of essential treatment recommendations for CPB management.

Core–Shell Copper Azide-Based Nanofiber Films Prepared by Coaxial Electrospinning for MEMS Microinitiators

The main bottleneck preventing powders from being used in a microinitiation system is the paradox between safety and detonation performance, as well as powders’ inherent brittleness and difficulty in shaping. To address this problem, we used the coaxial electrospinning technology to design and fabricate a core–shell film (CA@C–D) with low sensitivity and high energy. Electrostatic sensitivity (E50 = 5.22 mJ) and flame sensitivity (H50 = 51 cm) are both significantly lower than those of the raw copper azide (CA) material and can detonate secondary explosives. Extensive characterization and experiments show that the unusual core–shell structure of coaxial electrostatic spinning fibers is responsible for this significant improvement. This high specific surface area carbon shell wraps around the CA particles, providing double protection, while the superior thermal and electrical conductivity of the carbon material helps improve system safety and maintains the azide output performance. More importantly, it always maintains a good film structure and is simple to process, meeting the actual requirements of MEMS initiators and introducing a new scheme for the preparation of film-based initiators.

Assessing and Improving Provider Knowledge for a Cardiothoracic Intensive Care Unit Electronic Dashboard Initiative.

Electronic dashboards measure intensive care unit (ICU) performance by tracking quality indicators, especially pinpointing sub-standard metrics. This helps ICUs scrutinize and change current practices in an effort to improve failing metrics. However, its technological value is lost if end users are unaware of its importance. This results in decreased staff participation, leading to unsuccessful initiation of the dashboard. Therefore, the purpose of this project was to improve cardiothoracic ICU providers' understanding of electronic dashboards by providing an educational training bundle in preparation for an electronic dashboard initiation. A Likert survey assessing providers' knowledge, attitudes, skills, and application of electronic dashboards was conducted. Subsequently, an educational training bundle, consisting of a digital flier and laminated pamphlets, was made available to providers for four months. After bundle review, providers were assessed using the same pre-bundle Likert survey. A comparison of summated scores from pre-bundle (mean = 38.75) and post-bundle surveys (mean = 46.13) yielded an increased summated score overall (mean = 7.38, p ≤ 0.001). An educational bundle improved providers' understanding and increased their likelihood of using electronic dashboards upon its initiation. Further studies are needed to continue increasing staff participation such as providing specific education to navigate the interface for data retrieval and interpretation.

Antiretroviral therapy initiation and outcomes of hospitalized HIV-infected patients in Uganda-An evaluation of the HIV test and treat strategy.

Uganda adopted the HIV Test and Treat in 2016. There is paucity of data about its implementation among hospitalized patients. We aimed to determine the proportion of patients initiating anti-retroviral therapy (ART) during hospitalization, barriers and mortality outcome. In this mixed methods cohort study, we enrolled hospitalized patients with a recent HIV diagnosis from three public hospitals in Uganda. We collected data on clinical characteristics, ART initiation and reasons for failure to initiate ART, as well as 30 day outcomes. Healthcare workers in-depth interviews were also conducted and data analyzed by sub-themes. We enrolled 234 patients; females 140/234 (59.8%), median age 34.5 years (IQR 29-42), 195/234 (83.7%) had WHO HIV stage 3 or 4, and 74/116 (63.8%) had CD4 ≤ 200 cell/μL. The proportion who initiated ART during hospitalization was 123/234 (52.6%) (95% CI 46.0-59.1), of these 35/123 (28.5%) initiated ART on the same day of hospitalization, while 99/123 (80.5%) within a week of hospitalization. By 30 days 34/234 (14.5%) (95% CI 10.3-19.7) died. Patients residing ≥ 35 kilometers from the hospital were more likely not to initiate ART during hospitalization, [aRR = 1.39, (95% CI 1.22-1.59). Inadequate patient preparation for ART initiation and advanced HIV disease were highlighted as barriers of ART initiation during hospitalization. In this high HIV prevalence setting, only half of newly diagnosed HIV patients are initiated on ART during hospitalization. Inadequate pre-ART patient preparation and advanced HIV are barriers to rapid ART initiation among hospitalized patients in public hospitals.

Abstract 816: Cyclin c suppresses pancreatic intraepithelial neoplasm progression and neuroendocrine neoplasm development in a murine Kras model

Abstract Cyclin c is a component of the Cdk8 kinase module that plays both a positive and negative role in transcription. In addition, cellular damage induces cyclin c re-localization to the mitochondria where it stimulates fission and recruits Bax in preparation for apoptotic initiation. Previous studies revealed that cyclin c suppresses thyroid hyperplasia in a Pten knockout mouse model. In the present study, a role for cyclin c in suppressing pancreatic cancer progression was investigated in the Pdx1-Cre LSL-KrasG12D murine pancreatic cancer model. Within eight weeks, a 6-8 fold increase in the appearance of pancreatic intraepithelial neoplasia (PanIN) and acinar ductal metaplasia (ADM) lesions was observed in the KrasG12D+Ccnc-/- animals compared to KrasG12D alone. Surprisingly, high-grade neuroendocrine neoplasms (NEN) were also observed. These aggressive NEN showed mixed morphology with areas of acinar-like differentiation. High grade NEN exhibited pronounced proliferative index (Ki67), high EZH2 expression, and elevated Notch1, suggesting a connection between aberrant Notch signaling and NEN formation. Our previous studies identified a positive role for cyclin c in autophagy gene transcription. Similarly, cell lines derived from a KrasG12D+Ccnc-/- pancreas exhibited a reduction in autophagy compared to KrasG12D+Ccnc+/+ cells. Autophagic deficiency induces pancreatic cell stress and is associated with apoptosis. Consistent with this model, high caspase 3 expression was observed in early KrasG12D+Ccnc-/- NEN but not in KrasG12D+Ccnc+/+ tissues. Taken together, these results demonstrate a role for cyclin c in suppressing both progression of early PanIN and the development of high-grade NEN and suggest a model that cyclin c loss suppresses autophagy and increases apoptosis. Acknowledgements: Support was provided by NCI CCSG grant CA06927 for the FCCC Histopathology and Cell Culture Facilities, the PA Department of Health CURE fund (KSC), the Boye Foundation (RS), and the New Jersey Health Foundation (RS). Citation Format: Kathy Q. Cai, Sara E. Hanley, Andres Klein-Szanto, Kerry S. Campbell, Randy Strich. Cyclin c suppresses pancreatic intraepithelial neoplasm progression and neuroendocrine neoplasm development in a murine Kras model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 816.

Cyclin C Suppresses Pancreatic Intraepithelial Neoplasia and Neural Endocrine Neoplasia Progression in a Murine Kras Model

Cyclin C is a component of the Cdk8 kinase module that plays both a positive and negative role in transcription. In addition, cellular damage induces cyclin C re‐localization to the mitochondria where it stimulates fission and recruits Bax in preparation for apoptotic initiation. Previous studies revealed that cyclin C suppresses thyroid hyperplasia in a Pten knockout mouse model. In the present study, a role for cyclin C in suppressing pancreatic cancer progression was investigated in the LSL‐KrasG12Dmurine cancer model. Within eight weeks, a 6‐8 fold increase in the appearance of pancreatic Intraepithelial neoplasia (PanIN) and acinar ductal metaplasia (ADM) lesions were observed in the KrasG12D+; Ccnc‐/‐ animals compared to KrasG12D alone. Surprisingly, high‐grade, poorly differentiated pancreatic neuroendocrine tumors/carcinomas (PNET/PNEC) were also observed. These lesions coexisted in the pancreas with some PanIN regions possessing intermixed cells expressing PNEC markers. Our previous studies identified a positive role for cyclin C in autophagy gene transcription. Similarly, cell lines derived from a KrasG12D+; Ccnc‐/‐ pancreas exhibited a reduction in autophagy compared to KrasG12D+; Ccnc+/+ cells. Autophagic deficiency induces pancreatic cell stress and is associated with elevated apoptosis. Consistent with this model, caspase 3 activation was observed in early KrasG12D+; Ccnc‐/‐PNETs but not in KrasG12D+ tissues. In addition, KrasG12D+; Ccnc‐/‐ cells showed decreased proteasomal activity and a 30% increase in cell death compared to KrasG12D+; Ccnc+/+ cells following treatment with the proteasome inhibitor, Bortezomib. Taken together, these results demonstrate a role for cyclin C in suppressing both PDAC and PNEN cancer progression and suggest a model that its loss promotes pre‐cancerous lesions by stimulating pancreatic cell injury.

Abstract 1731: EXS21546, a non-CNS penetrant A2AR-selective antagonist for anti-cancer immunotherapy

Abstract Elevated levels of adenosine found in the tumor microenvironment have been highlighted as a potential mechanism contributing to the restricted efficacy of immune checkpoint inhibitors. While the advent of these inhibitors has brought significant benefit to patients with cancer, there is still significant unmet need even in disease indications for which these agents are approved. Adenosine has an immune-suppressive effect in tumors, and pre-clinical and early clinical evidence indicates that antagonists of the GPCR family of adenosine receptors are able to relieve that suppression and restore anti-tumor immune cell activity. EXS21546 is a non-furan, selective antagonist of the A2A receptor with low brain penetration. Using EXS21546, we show that activity at the A2A receptor is sufficient for complete restoration of T-cell function in the presence of high concentrations of adenosine analogue. Translational studies with EXS21546 have been undertaken using patient samples to better understand its activity in signaling and disease-relevant endpoints. We will present data characterizing the activity of EXS21546 ex vivo in patient-derived whole blood samples. Interrogation of primary cancer cells from pancreatic and lung cancer patients treated with EXS21546 ex vivo by phenotypic image-based screening, demonstrated that EXS21546 reduces the relative fraction of viable cancer cells while inducing an expansion of the viable CD8+ T cell fraction in the presence of high concentrations of an adenosine analogue. Together, these data indicate the potential for EXS21546 may have a role in cancer therapy. EXS21546 has completed pre-IND studies in preparation for initiation of first-in-human clinical studies. Citation Format: Andrew Payne, Pierre Fons, Isabella Alt, Joost van Ham, Christina Taubert, Andy Bell, Stephanie Versluys, Florie Bertrand, Virgile Visentin, Emilie Mirey, Emilie Pelissier, Michael Paillasse, Sabrina Pagliarusco, Gregory Vladimer, Mark Whittaker. EXS21546, a non-CNS penetrant A2AR-selective antagonist for anti-cancer immunotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1731.

Surface charge-based rational design of aspartase modifies the optimal pH for efficient β-aminobutyric acid production

β-Aminobutyric acid (BABA) can be widely used in the preparation of anti-tumor drugs, AIDS drugs, penicillin antibiotics, and plant initiators. However, the efficient, economical, and environmentally friendly production of BABA still faces challenges. Its important production enzyme, aspartase, catalyzes the substrate crotonic acid, and depends on harsh conditions, such as high temperatures and the presence of strong alkali. Here, we modified the surface charge of the enzyme to enable it to become more negatively charged (K19E, N87E, N125D, S133D, Q262E, and N451E; from −60 to −80), reducing its optimal pH from 9.0 to 8.0. The M20 enzyme showed improved specific activity (400.21 mU/mg at pH 8.0; 2.47-fold that of aspartase), and at pH 7.0, its activity increased 3-fold. The thermal stability of the enzyme was also improved. For the production of BABA, a 500 g/L whole-cell transformation was obtained with a 1.41-fold increase in yield, and the final production of BABA reached 556.1 g/L within 12 h. Our method provides a new strategy for modifying the characteristics of the enzyme through the modification of its surface charge, which also represents the first modification of the optimal pH for aspartase.

Factors Affecting Pregnant Women in Preparation of Early Breastfeeding Initiation (IMD) at Grobogan Regencys

Exclusive breastfeeding will be realized if mother start implementing Early Breastfeeding Initiation (IMD) program. The purpose of this study is to investigate factors influencing pregnant women in preparation for early breastfeeding initiation (IMD) in Grobogan regency. Study method is quantitative with cross-sectional design. Total population is 716 pregnant women with minimal of 85 sample after calculations. To anticipate drop out, 100 samples will be collected. Independent variable is the factors influencing preparation of IMD in pregnant women and dependent variable is preparation of Early Breastfeeding Initiation (IMD). Data was analyzed using multiple logistic regression. The analysis showed no significant relation between factors such as education, knowledge, attitudes, breastfeeding experience, husband/family support, participation in classes of pregnant women, the role of health workers with preparation for IMD. In contrast, the variable trust had a significance value of 0.001 <0.05. We conclude that IMD preparation of pregnant women is most influenced by trust.

Metal–interlayer–metal structured initiator containing Al/CuO reactive multilayer films that exhibits improved ignition properties

Aluminum/cupric oxide (Al/CuO) reactive multilayer films (RMFs) are widely used for micro-chip energetic initiator applications; however, there are only a few examples where they are initiated through the direct input of electrical energy. This study describes the preparation of micro-chip energetic initiators containing Al/CuO RMFs as an interlayer between two Al electrical contact pads that are prepared using an image reversal lift-off process and the magnetron sputtering technology. This design enables the direct transfer of current from the contact pads to Al/CuO RMFs, which results in fast ignition (less than 1.0 μs) and produces luminous flame ball that spread over a wide area (maximum flame area of 13.8 mm2). A metal–interlayer–metal (MIM) structured initiator will not be fired until the external voltage has exceeded the breakdown field strength of CuO layers. These initiators achieved a critical breakdown voltage (VB) of 32–50 V and a complete electrical-explosion voltage (VC) of 72–84 V. The ignition threshold rises with increasing the bilayer thicknesses of the RMFs. These characteristics of this specially structured initiator are well suited for applications in highly efficient and insensitive initiating explosive devices.

An fMRI-compatible force measurement system for the evaluation of the neural correlates of step initiation

Knowledge of brain correlates of postural control is limited by the technical difficulties in performing controlled experiments with currently available neuroimaging methods. Here we present a system that allows the measurement of anticipatory postural adjustment of human legs to be synchronized with the acquisition of functional magnetic resonance imaging data. The device is composed of Magnetic Resonance Imaging (MRI) compatible force sensors able to measure the level of force applied by both feet. We tested the device in a group of healthy young subjects and a group of elderly subjects with Parkinson’s disease using an event-related functional MRI (fMRI) experiment design. In both groups the postural behavior inside the magnetic resonance was correlated to the behavior during gait initiation outside the scanner. The system did not produce noticeable imaging artifacts in the data. Healthy young people showed brain activation patterns coherent with movement planning. Parkinson’s disease patients demonstrated an altered pattern of activation within the motor circuitry. We concluded that this force measurement system is able to index both normal and abnormal preparation for gait initiation within an fMRI experiment.

CLINICAL TRIALS IN THE PRECLINICAL TO MCI STAGES OF AD: CROSS-CULTURAL VALIDATION AND NORMATIVE STUDY OF THE TOMMORROW NEUROPSYCHOLOGICAL BATTERY

Clinical trials in preclinical Alzheimer’s disease (AD) require reliable and validated measures appropriate for the detection of subtle cognitive changes. In preparation for international site initiation in the TOMMORROW Study, a trial to delay the clinical onset of Mild Cognitive Impairment due to AD (MCI-AD), we conducted a multicultural and multilingual validation and normative study of a neurocognitive battery. The battery was culturally adapted for use in Italy, Switzerland (German language), and Russia to support the systematic application of operationalized criteria to detect MCI-AD in these countries. A total of 675 individuals comprised of 200 healthy controls [∼50/age strata/country; ages 65-88, including men and women with a range of low and high education] and 25 AD subjects from each country were recruited. Construct validity, test-retest, and alternate form reliability were assessed in healthy controls. Criterion and discriminant validity of the cognitive measures were tested in the entire sample (healthy controls and AD cases) using logistic regression, discriminant analysis, and Receiver Operating Characteristic analysis. Measure equivalence was examined in relationship to normative values from English-speaking populations in the United States. The translated and culturally adapted tests demonstrated high test-retest reliabilities as well as good construct and criterion validity. Tests performed comparably to the “gold standard” English versions with respect to direction, magnitude, and patterns of correlations and main effects. Several tests showed some cultural variability, underscoring the importance of country-specific norms. Gender influenced verbal episodic memory (women> men) and visual naming (men> women) performances in the German version. Education affected visual memory, naming, and attention measures in Italian; whereas, performance on a test of executive function (Trails B) required greater average time to completion in Russian when compared to the English language versions. The TOMMORROW neuropsychological battery has now been translated, culturally adapted, validated and normed for ages 65-88 in German, Italian, and Russian languages. The battery is in use currently in German (Switzerland & Germany) and English speaking sites participating in the trial, providing further opportunities for multilingual investigation of its utility in detecting MCI-AD and measuring change in preclinical AD.

Improving Awareness and Outcomes Related to Venous Thromboembolism.

Improving Awareness and Outcomes Related to Venous Thromboembolism.

One-Step Simple Preparation of Catalytic Initiators for Catalyst-Transfer Kumada Polymerization: Synthesis of Defect-Free Polythiophenes

Externally initiated living catalyst-transfer polymerization based on Ni(II)-catalyzed Kumada coupling of aromatic halogen-substituted Grignard monomers is an established and highly efficient method for the controlled preparation of conjugated polymers such as polythiophenes and poly(p-phenylenes). In this contribution, we report a simple preparation of external catalytic initiators for such a polymerization based on oxidative addition between a readily available Ni(0) complex Ni(dppp)2 (where dppp is 1,3-bis(diphenylphosphino)propane) and various aryl halides. As a direct challenge to previous reports and established opinion that such a reaction would be impossible, this clean and efficient oxidative addition enables simple preparation of highly reactive catalytic initiators for the catalyst-transfer polymerization. In particular, we demonstrated that polymerization of 5-halo-2-thienylmagnesium monomers initiated by these catalysts produced highly regioregular, defect-free polythiophenes and block copoly...

Effects of deep brain stimulation in the subthalamic nucleus or globus pallidus internus on step initiation in Parkinson disease

Difficulty with step initiation, called "start hesitation," is related to gait bradykinesia and is an early hallmark of gait freezing in Parkinson disease (PD). Authors of this study investigated the effects of deep brain stimulation (DBS) and levodopa on step initiation before and 6 months after DBS surgery in 29 patients with PD who were randomized to either the bilateral subthalamic nucleus (STN) or globus pallidus internus (GPi) as the DBS site. The authors measured the amplitude and duration of anticipatory postural adjustments (APAs), the feed-forward postural preparation that precedes the onset of voluntary step initiation, based on center-of-pressure displacements on a force plate. They also measured the length and velocity of the first step using a motion analysis system to study kinematics. Some of the patients (22) were from a large, multicenter, double-blind clinical trial, and all patients in the study (29, PD-DBS group) were randomized to DBS in either the bilateral STN (15 patients) or bilateral GPi (14 patients). Differences in step initiation were investigated in 2 conditions before surgery (off/on levodopa) and in 4 conditions after surgery (off/on levodopa combined with off/on DBS). Twenty-eight elderly healthy control volunteers (CTRL group) were also tested, and 9 control volunteers with PD who met the criteria for DBS (PD-C group) were tested at baseline and 6 months later. Patients in the PD-DBS group had smaller amplitudes and longer durations of APAs compared with those in the 28 healthy control volunteers in all conditions. Before surgery, APAs improved with levodopa. After surgery, the APAs were significantly worse than in the best-treatment state before surgery (DOPA condition), and responsiveness to levodopa decreased. No differences in APAs were detected between the STN and GPi groups. A comparison with PD control volunteers who did not undergo DBS surgery confirmed that a deterioration in step preparation was not related to disease progression. Step length and velocity were smaller in the PD-DBS group than in controls in all conditions. Before surgery, levodopa improved the length and velocity of the first step. Both step length and velocity were unchanged in the best-treatment state before surgery (DOPA condition) as compared with after surgery (DBS+DOPA), with only step velocity in the STN group getting worse after surgery. Six months of DBS in the STN or GPi impaired anticipatory postural preparation for step initiation, the opposite effect as with levodopa. Deep brain stimulation disrupted postural preparation more than step execution, suggesting independent motor pathways for preparation and execution of gait. Although turning the stimulators on after surgery combined with levodopa benefited the postural preparation to step, a comparison of pre- and postsurgery conditions suggests that either the surgery itself or 6 months of continuous stimulation may lead to an alteration of circuits or plastic changes that impair step initiation.

Preparation of cationic latent initiators containing imidazole group and their effects on the properties of DGEBA epoxy resin

The thermal cationic latent initiators, N-benzyl-3-methylimidazolium hexafluoroantimonate (BMH1) and N-butyl-3-methylimidazolium hexafluoroantimonate (BMH2) were synthesized and applied to the thermal cationic polymerization of diglycidyl ether of bisphenol A (DGEBA). The performance of BMH1 and BMH2 was examined by differential scanning calorimetry (DSC), which showed good thermal latent properties and excelled epoxy resin curing behavior. The morphology, thermal, mechanical, and water sorption properties of DGEBA resin cured by 1 wt% of BMH1 and BMH2 were measured by X-ray diffraction (XRD), scaming electron microscopy (SEM), thermogravimetric analysis (TGA), nanoindentation, and thin film diffusion analysis. The cured DGEBA/BMH1 system showed relatively higher thermal stability than the DGEBA/BMH2 system. The diffusion coefficient and water uptake were 14.2×10−9 cm2/s and 1.15 wt% for the DGEBA/BMH1 system and 11.5×10−9 cm2/s and 1.07 wt% for the DGEBA/BMH2 system, respectively. Therefore, DGEBA/BMH2 showed higher resistance to water sorption than DGEBA/BMH1. On the other hand, hardness and elastic modulus of DGEBA/BMH2 were higher than those of DGEBA/BMH1. This can be attributed to the difference in the end group of initiators as well as the degree of crosslinking in the cured resin network. Open image in new window

Ruthenium Olefin Metathesis Catalysts Containing Six-Membered Sulfone and Sulfonamide Chelating Rings

The preparation and X-ray structure characterization of new olefin metathesis initiators containing sulfone- and sulfonamide-substituted benzylidene ligands are described. We observed that these catalysts exhibit Ru···O(SO)R interactions, forming six-membered chelates. Tuning the electronic and steric factors of the benzylidene part as well as selecting the proper NHC ligands can have a direct impact on catalyst activity and stability, leading to promising new catalysts.

ChemInform Abstract: An Efficient One‐Pot Four‐Step Domino Reaction for the Synthesis of C2‐Substituted 3‐Methylcyclohex‐2‐enones.

An efficient one-pot four-step domino reaction of substituted β-ketoesters has been optimized giving rise to a large panel of C2-substituted 3-methylcyclohex-2-enones, an important scaffold for the preparation of various initiators for cationic or radical cyclizations. The developed methodology is quite general and applicable to a wide range of β-ketoester substrates, allowing the introduction of various functionalities at the C2 position of the 3-methylcyclohex-2-enones, in good to excellent yields.