Continuous Flow Synthesis of Hexyl Laurate Using Immobilized Thermomyces Lanuginosus Lipase from Residual Babassu Mesocarp.

Brazil has one of the greatest biodiversities on the planet, where various crops play a strategic role in the country's economy. Among the highly appreciated biomasses is babassu, whose oil extraction generates residual babassu mesocarp (BM), which still needs new strategies for valorization. This work aimed to use BM as a support for the immobilization of Thermomyces lanuginosus lipase (TLL) in an 8.83 mL packed-bed reactor, followed by its application as a biocatalyst for the synthesis of hexyl laurate in an integrated process. Initially, the percolation of a solution containing 5 mg of TLL at 25 °C and flows ranging from 1.767 to 0.074 mL min-1 was investigated, where at the lowest flow rate tested (residence time of 2 h), it was possible to obtain an immobilized derivative with hydrolytic activity of 504.7 U g-1 and 31.7 % of recovered activity. Subsequent studies of treatment with n-hexane, as well as the effect of temperature on the immobilization process, were able to improve the activities of the final biocatalyst BM-TLLF, achieving a final hydrolysis activity of 7023 U g-1 and esterification activity of 430 U ⋅ g-1 against 142 U g-1 and 113.5 U g-1 respectively presented by the commercial TLIM biocatalyst. Desorption studies showed that the TL IM has 18 mg of protein per gram of support, compared to 4.92 mg presented by BM-TLL. Both biocatalysts were applied to synthesize hexyl laurate, achieving 98 % conversion at 40 °C within 2 h. Notably, BM-TLLF displayed exceptional recyclability, maintaining catalytic efficiency over 12 cycles. This reflects a productivity of 180 mg of product ⋅ h-1 U-1 of the enzyme, surpassing 46 mg h-1 U-1 obtained for TLIM. These results demonstrate the efficacy of continuous flow technology in creating a competitive and integrated process offering an exciting alternative for the valorization of residual lignocellulosic biomass.

Batch and Continuous Flow Total Synthesis of Cannabidiol.

Herein, we present a comprehensive total synthesis of cannabidiol integrating both batch and continuous flow conditions. Our approach is planned to streamline the synthesis of olivetolic acid derivatives and utilize an enantiomerically pure monoterpene moiety obtained from naturally occurring (R)-(+)-limonene by photocatalysis. Key reactions, including the synthesis of olivetolic ester and a Friedel-Crafts alkylation, are successfully adapted to continuous flow, resulting in improved yields and selectivities. This study not only offers a scalable and efficient route for cannabidiol synthesis but also contributes to the synthetic approaches to access cannabinoids (diversity synthesis), with potential applications in medicinal and industrial contexts.

3D-Printed Tumor-on-Chip for the Culture of Colorectal Cancer Microspheres: Mass Transport Characterization and Anti-Cancer Drug Assays.

Tumor-on-chips have become an effective resource in cancer research. However, their widespread use remains limited due to issues related to their practicality in fabrication and use. To address some of these limitations, we introduce a 3D-printed chip, which is large enough to host ~1 cm3 of tissue and fosters well-mixed conditions in the liquid niche, while still enabling the formation of the concentration profiles that occur in real tissues due to diffusive transport. We compared the mass transport performance in its rhomboidal culture chamber when empty, when filled with GelMA/alginate hydrogel microbeads, or when occupied with a monolithic piece of hydrogel with a central channel, allowing communication between the inlet and outlet. We show that our chip filled with hydrogel microspheres in the culture chamber promotes adequate mixing and enhanced distribution of culture media. In proof-of-concept pharmacological assays, we biofabricated hydrogel microspheres containing embedded Caco2 cells, which developed into microtumors. Microtumors cultured in the device developed throughout the 10-day culture showing >75% of viability. Microtumors subjected to 5-fluorouracil treatment displayed <20% cell survival and lower VEGF-A and E-cadherin expression than untreated controls. Overall, our tumor-on-chip device proved suitable for studying cancer biology and performing drug response assays.

Recent Advances in the Multistep Continuous Preparation of APIs and Fine Chemicals.

Over the last two decades, with the advent of continuous flow technologies, continuous processes have emerged as a major area in organic synthesis. In this context, continuous flow processes have been increasing in the preparation of Active Pharmaceutical Ingredients (APIs) and fine chemicals, such as complex synthetic intermediates, agrochemicals, and fragrances. Thus, the development of multi-step protocols has attracted special interest from the academic and industrial chemistry communities. In addition to the beneficial aspects intrinsically associated with continuous processes (e.g., waste reduction, optimal heat transfer, improved safety, and the possibility to work under harsh reaction conditions and with more dangerous reagents), these protocols also allow a rapid increase in molecular complexity. Moreover, in telescoped multi-step processes, isolation and purification steps are generally avoided or, if necessary, carried out in-line, presenting an important economy of time, solvents, reagents, and labor. Last, important synthetic strategies such as photochemical and electrochemical reactions are compatible with flow processes and are delivering relevant advances to the synthetic approaches. In this review, a general overview of the fundamentals of continuous flow processes is presented. Recent examples of multi-step continuous processes for the preparation of fine chemicals, including telescoped and end-to-end processes, are discussed, pointing out the possible advantages and/or limitations of each of these methodologies.

Continuous flow Aza-Michael reaction for preparing the fast-acting synthetic opioid drug Remifentanil

Abstract Remifentanil is a modern fentanyl analogue with ultrashort-action granted by an esterase-labile methyl propanoate chain. Here, we present the development of a continuous flow methodology for the key N-alkylation step of remifentanil preparation in a biphasic, "slug-flow" regime. We screened parameters under microwave-assisted reactions, translated conditions to flow settings, and obtained remifentanil under 15-min residence time in a 1-mL microreactor, with a space-time yield of 89 mg/mL·h and 94% yield.

Biochemical, urinary, and acid-base profile in cattle treated with maintenance enteral electrolyte solutions containing calcium propionate, propylene glycol or glycerol.

Enteral fluid therapy administered in continuous flow through the naso-ruminal route for long periods with electrolyte solutions is safe and effective in cattle. The aim of this study was to carry out a comparative assessment between maintenance enteral electrolyte solutions containing calcium propionate, propylene glycol or glycerol administered in continuous flow in cattle. Six heifers were used and the study was carried out in a 6 × 3 crossover design, in which each animal received three different treatments: enteral electrolyte solution containing calcium propionate (ESCaP), enteral electrolyte solution containing glycerol (ESGly) and enteral electrolyte solution containing propylene glycol (ESPrG). Solutions were administered at a rate of 15 mL kg-1 h-1 for 12 h. Serum and urinary biochemical assessment; urinary volume, pH, and specific gravity; and blood gas analysis were measured at 0, 3, 6, 9, 12, and 24 h. All three enteral electrolyte solutions expanded blood volume and increased urine volume without causing electrolyte imbalances. ESCaP caused mild reversible metabolic alkalosis while the most significant glycemic potential was observed in electrolyte solutions containing propylene glycol (ESPrG) and calcium propionate (ESCaP).

Ultrasound-assisted extraction of chromium from tanned leather shavings: A promising continuous flow technology for the treatment of solid waste.

In this work, a continuous flow extraction system assisted by ultrasound (US) was developed for the extraction of Cr(III) from residual tanned leather shavings. US energy was delivered into the system by a tubular applicator (clamp-on tube US applicator). The effect of the US energy was investigated at 20 kHz of frequency and electrical input power of 75, 150, 300 and 600 W. Residence time and temperature profile were also evaluated. It was observed that the internal temperature profile was affected by the presence of US and inverted in comparison with the conditions without US. In this way, the temperature profile generated by the US was reproduced by using electrical resistances in order to compare the obtained results. The US intensity was measured using a hydrophone connected to a sound pressure meter. The use of the US did not alter the dynamic behavior of the system but increased the extraction efficiency when compared to the silent condition. US power above 75 W did not lead to increased extraction efficiency, when the residence time was 30 min. However, when 60 min of residence time were employed, the optimized US power was 150 W, resulting in an extraction efficiency of 71.7 ± 0.7 %, about 28 % higher when compared to the silent condition in the same temperature and other conditions. The US energy allowed a reduction in processing time and operational temperature when compared to the silent condition with the same temperature profile. The overall energy consumption with US was similar or lower than that observed without US, showing the feasibility of the proposed extraction system.

Photochemical Csp2-H bond thiocyanation and selenocyanation of activated arenes, batch and continuous-flow approaches.

Herein, we report an eco-friendly photochemical oxidative Csp2-H thiocyanation and selenocyanation of activated arenes. The reaction proceeds under Violet LED irradiation in the presence of K2S2O8, which quickly oxidizes KSCN and KSeCN, finally producing arylthio/selenocyanates. Using this benign, atom-economic protocol, the desired chalcogenide products were obtained regioselectively, with isolated yields that range from very good to excellent. Although, mechanistic study indicates that it is difficult to distinguish between a radical to a SEAr reaction mechanism between the photo-induced formed •SCN, for the former, or NCSSCN, for the latter, to the aromatic heterocycles. The inhibition experiment together with the observed reactivity and regioselectivity, would be in agreement with the latter. The synthetic methodology designed could be successfully adapted to continuous-flow systems in a segmented-flow regime, employing the organic phase as the product reservoir. Using this setup, the advantage of the latter can be demonstrated by reducing the reaction time and improving the product yields. Similarly, the scaling up of the reaction to gram scale resulted in favorable outcomes by the flow setup, which installs the photo-flow chemistry as a powerful tool to be included into routine reaction procedures, which have great relevance for the pharmaceutical industry.

Tangential effluent inlet in a cylindrical electrocoagulation reactor containing curved electrodes, and its use in crude oil in water treatment.

A continuous electrocoagulation reactor, with curved electrodes, polarity switch, and cylindrical geometry, was used for emulsified crude oil in water separation. Apparatus novelty consists of an inlet arranged to promote a circular flow regime. The effects of flow rate (2 and 6 mL.s-1), electrical current (2 and 4 A), and distance between electrodes (1.5 and 2.5 cm) were investigated using a full factorial design and statistical analysis. Using 6 mL.s-1 flow rate, 2 A electric current and 2.5 cm electrode distance; 86% oil removal was obtained at a pH < 9.0. For this configuration, the system will process 21.6 L of oily emulsion while consuming 6.92 Wh. Oil removal increased with flow rate, a novel characteristic created by the unusual geometry of the system.

A comprehensive dynamic kinetic model for the UVC/H2O2 process: application to zinc bacitracin degradation in wastewater as a case study.

A dynamic kinetic model is presented for the UVC/H2O2-driven process. The model comprises 103 reactions, including background species, such as HCO3-/CO32-, NO2-, NO3-, SO42-, Cl-, and H2PO4-/HPO42/PO43- anions, and effluent organic matter (EfOM) was validated based on experimental data obtained for the photooxidation of the nonribosomal peptide antibiotic zinc bacitracin (Zn-Bc, 34 µmol L-1). The set of ordinary differential equations for 38 species was combined with the molar balances describing the recirculating tubular photoreactor used. Predictions for the photolytic and UVC/H2O2 processes confirmed the good agreement with experimental data, enabling the estimation of fundamental kinetic parameters, such as the direct photolysis quantum yield (Ф254 nm, Zn-Bc = 0.0143 mol Einstein-1) and the second-order rate constants for the reactions of Zn-Bc with HO•, HO2•, and O2•- radicals (2.64 × 109, 1.63 × 103, and 1.49 × 104 L mol-1 s-1, respectively). The predicted optimum process conditions correspond to [H2O2]0 = 6.8 mmol L-1 and a specific photon emission rate of 11.1 × 10-6 Einstein L-1 s-1. Zn-Bc photooxidation was significantly impacted by wastewater constituents, particularly EfOM and HCO3-/CO32- (i.e., alkalinity), resulting in a degradation rate about 32% lower compared to that obtained in deionized water. In particular, EfOM acts as a strong radical scavenger and inner filter. In addition, simulations pointed out the continuous tubular photochemical reactor as the best configuration for treating Zn-Bc-containing wastewater. This study hence provides a comprehensive modeling approach, especially useful for predicting the effect of complex water matrices on the performance of the UVC/H2O2 treatment process.

Response of bioaerosol cells to photocatalytic inactivation with ZnO and TiO2 impregnated onto Perlite and Poraver carriers.

Bioaerosols are airborne microorganisms that cause infectious sickness, respiratory and chronic health issues. They have become a latent threat, particularly in indoor environment. Photocatalysis is a promising process to inactivate completely bioaerosols from air. However, in systems treating a continuous air flow, catalysts can be partially lost in the gaseous effluent. To avoid such phenomenon, supporting materials can be used to fix catalysts. In the present work, four photocatalytic systems using Perlite or Poraver glass beads impregnated with ZnO or TiO2 were tested. The inactivation mechanism of bioaerosols and the cytotoxic effect of the catalysts to bioaerosols were studied. The plug flow photocatalytic reactor treated a bioaerosol flow of 460 × 1 06 cells/m3 air with a residence time of 5.7 s. Flow Cytometry (FC) was used to quantify and characterize bioaerosols in terms of dead, injured and live cells. The most efficient system was ZnO/Perlite with 72% inactivation of bioaerosols, maintaining such inactivation during 7.5 h due to the higher water retention capacity of Perlite (2.8 mL/gPerlite) in comparison with Poraver (1.5 mL/gPerlite). However, a global balance showed that TiO2/Poraver system triggered the highest level of cytotoxicity to bioaerosols retained on the support after 96 h with 95% of dead cells. SEM and FC analyses showed that the mechanism of inactivation with ZnO was based on membrane damage, morphological cell changes and cell lysis; whereas only membrane damage and cell lysis were involved with TiO2. Overall, results highlighted that photocatalytic technologies can completely inactivate bioaerosols in indoor environments. ELECTRONIC SUPPLEMENTARY MATERIAL: Supplementary material is available in the online version of this article at 10.1007/s11783-020-1335-9 and is accessible for authorized users.

Gastrointestinal Bleeding as a Complication in Continuous Flow Ventricular Assist Devices: A Systematic Review With Meta-Analysis.

BACKGROUND: The use of ventricular assist devices (VADs) has become predominant in this era of medicine. It is commonly used as a bridge to transplant, recovery and as a destination therapy for patients with severe heart failure, who are not responsive to maximum optimal management or ineligible for transplant. However, several complications are known to occur with the use of these devices. In this research, we will compare gastrointestinal bleeding in patients who used centrifugal flow versus axial flow VADs. We hope that the result of this meta-analysis and the review presented provide adequate information to future researchers, physicians and other healthcare professionals who are interested in this topic. METHODS: Published articles evaluated for inclusion were obtained from MEDLINE (PubMed), Cochrane, EBSCO, clinicaltrials.gov, and international clinical trials registry. This research was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Procured articles were reviewed by two independent reviewers. Only randomized control trials and observational studies were used. Quality assessment was done with Cochrane Collaboration's tool (RoB.2 with visualization through robviz) and Newcastle-Ottawa Scale (NOS). Data analysis was carried out with the use of R data analysis tool (version 4.0.0; release date: April 24th, 2020). RESULTS: At the end of this meta-analysis, the occurrence of gastrointestinal bleeding was not significantly different between both groups; with odds ratio (OR): 0.81; 95% confidence interval (CI): 0.65 - 1.00; P value = 0.05. Between-study variance (Tau-squared) was zero (0), standard error (SE) = 0.06. The degree of heterogeneity measured with I-squared statistic was 0% (minimal). Egger's regression test was not statistically significant, P = 0.93. Symmetry of distribution was observed on the funnel plot. Trim and fill analysis showed no missing studies on the left; SE = 1.68. CONCLUSIONS: The result obtained from this research indicates that the occurrence of gastrointestinal bleeding is not significantly different in both groups of patients, irrespective of the type of continuous flow VAD used. Although, the study sample used in this meta-analysis was limited.

Performance of a continuous stirred tank bioreactor employing an immobilized actinobacteria mixed culture for the removal of organophosphorus pesticides.

In this study, we evaluated polyurethane foam (PF), volcanic rock (VR), and a modified plastic cap (MPC) as supports for the immobilization of organophosphorus (OP) pesticide-degrading actinobacterial strains. The colonization and activity of four streptomycetes were favoured by PF, which was selected as the carrier to use in a continuous stirred tank bioreactor (CSTR) that can be operated at increasing inflows of a pesticide mixture that contains the insecticides chlorpyrifos (CP) and diazinon (DZ). Our results demonstrate that the CSTR can be operated at flow rates of 10 and 40 mL h-1 with greater than 85% removal of the pesticides in the short term. A significant decrease in the efficiency of CP removal was observed at the highest inflows into the reactor. The CP and DZ loading rates in the bioreactor ranged from 0.44 to 1.68 mg L-1 h-1 and from 0.50 to 2.17 mg L-1 h-1, respectively. Although the treated wastewater exhibited moderate toxicity for Raphanus sativus, a bioreactor inoculated with a mixed culture formed by Streptomyces spp. strains AC5, AC9, GA11 and ISP13 may provide an effective biotechnological strategy for the reduction of OP pesticide residues produced during agronomic and manufacturing practices and therefore prevent environmental pesticidal pollution.

A Mild, Fast, and Scalable Synthesis of Substituted α-Acyloxy Ketones via Multicomponent Reaction Using a Continuous Flow Approach.

A continuous flow approach for the synthesis of α-acyloxy ketone derivatives from the corresponding arylglyoxals, isocyanides, and carboxylic acids is described. The target products were obtained in excellent yields in short residence times and with high purities via the first transcription of the microwave-to-flow paradigm to the isocyanide-based Passerini reaction. Furthermore, this methodology allowed a 10-fold scale-up using the same experimental conditions initially established.

Nisin penetration and efficacy against Staphylococcus aureus biofilms under continuous-flow conditions.

Biofilms may enhance the tolerance of bacterial pathogens to disinfectants, biocides and other stressors by restricting the penetration of antimicrobials into the matrix-enclosed cell aggregates, which contributes to the recalcitrance of biofilm-associated infections. In this work, we performed real-time monitoring of the penetration of nisin into the interior of Staphylococcus aureus biofilms under continuous flow and compared the efficacy of this lantibiotic against planktonic and sessile cells of S. aureus. Biofilms were grown in Center for Disease Control (CDC) reactors and the spatial and temporal effects of nisin action on S. aureus cells were monitored by real-time confocal microscopy. Under continuous flow, nisin caused loss of membrane integrity of sessile cells and reached the bottom of the biofilms within ~20 min of exposure. Viability analysis using propidium iodide staining indicated that nisin was bactericidal against S. aureus biofilm cells. Time-kill assays showed that S. aureus viability reduced 6.71 and 1.64 log c.f.u. ml-1 for homogenized planktonic cells in exponential and stationary phase, respectively. For the homogenized and intact S. aureus CDC biofilms, mean viability decreased 1.25 and 0.50 log c.f.u. ml-1, respectively. Our results demonstrate the kinetics of biofilm killing by nisin under continuous-flow conditions, and shows that alterations in the physiology of S. aureus cells contribute to variations in sensitivity to the lantibiotic. The approach developed here could be useful to evaluate the antibiofilm efficacy of other bacteriocins either independently or in combination with other antimicrobials.

Impact of Concomitant Mitral Valve Surgery With LVAD Placement: Systematic Review and Meta-Analysis.

The aim of this systematic review and meta-analysis was to evaluate the outcomes of concomitant mitral valve surgery for significant preexisting mitral regurgitation (MR) in patients undergoing continuous-flow left ventricular assist device (CF-LVAD) implantation. Electronic search was performed to identify all studies in the English literature examining concurrent mitral valve surgery in patients with CF-LVAD implantation. Identified articles were systematically assessed for inclusion and exclusion criteria. Of 2319 studies identified, 8 studies were included. Among 445 patients with moderate to severe or severe MR, 113 (25.4%) patients received concurrent mitral valvular intervention during CF-LVAD implantation. There were no significant differences in cardiopulmonary bypass time (MR Surgery 154 min vs. no MR Surgery 119 min, P = 0.64) or hospital length of stay (MR Surgery 21 days vs. no MR Surgery 18 days, P = 0.93). On follow-up, there were no significant differences in freedom from greater than moderate MR (MR Surgery 100% vs. no MR Surgery 74%, P = 0.12) or left ventricular end-diastolic diameter (MR Surgery: 60 mm vs. no MR Surgery 65 mm, P = 0.51). Survival was comparable at 6-months (MR Surgery 77% vs. no MR Surgery 81%, P = 0.75), 1-year (MR Surgery 72% vs. no MR Surgery 80%, P = 0.36), and 2-years of follow-up (MR Surgery 65% vs. no MR Surgery 70%, P = 0.56). The results of our systematic review and meta-analysis of 8 studies consisting of 445 patients demonstrates that the addition of mitral valve intervention to CF-LVAD implantation appears to be safe with comparable survival to those undergoing CF-LVAD implantation alone. Large prospective randomized clinical trials are needed to elucidate whether concomitant mitral valve intervention during CF-LVAD implantation in patients with severe MR is necessary.

Novel system configuration with activated sludge like-geometry to develop aerobic granular biomass under continuous flow.

A novel continuous flow system with "flat geometry" composed by two completely mixed aerobic tanks in series and a settler was used to promote the formation of aerobic granular sludge. Making similarities of this system with a typical sequencing batch reactor (SBR), for aerobic granules cultivation, the value of the tank 1/tank 2 vol ratio and the biomass recirculation rate would correspond with the feast/famine length ratio and the length of the operational cycle, respectively, while the settler upflow liquid velocity imposed would be related to the settling time. From the three experiments performed the best results were obtained when the tank 1/tank 2 vol ratio was of 0.28, the sludge recycling ratio of 0.25 and the settler upflow velocity of 2.5 m/h. At these conditions the aggregates had settling velocities between 29 and 113 m/h, sludge volume index at 10 min (SVI10) of 70 mL/g TSS and diameters between 1.0 and 5.0 mm.

Preclinical performance of a pediatric mechanical circulatory support device: The PediaFlow ventricular assist device.

OBJECTIVES: The PediaFlow (HeartWare International, Inc, Framingham, Mass) is a miniature, implantable, rotodynamic, fully magnetically levitated, continuous-flow pediatric ventricular assist device. The fourth-generation PediaFlow was evaluated in vitro and in vivo to characterize performance and biocompatibility. METHODS: Supported by 2 National Heart, Lung, and Blood Institute contract initiatives to address the limited options available for pediatric patients with congenital or acquired cardiac disease, the PediaFlow was developed with the intent to provide chronic cardiac support for infants as small as 3 kg. The University of Pittsburgh-led Consortium evaluated fourth-generation PediaFlow prototypes both in vitro and within a preclinical ovine model (n = 11). The latter experiments led to multiple redesigns of the inflow cannula and outflow graft, resulting in the implantable design represented in the most recent implants (n = 2). RESULTS: With more than a decade of extensive computational and experimental efforts spanning 4 device iterations, the AA battery-sized fourth-generation PediaFlow has an operating range of 0.5 to 1.5 L/min with minimal hemolysis in vitro and excellent hemocompatibility (eg, minimal hemolysis and platelet activation) in vivo. The pump and finalized accompanying implantable components demonstrated preclinical hemodynamics suitable for the intended pediatric application for up to 60 days. CONCLUSIONS: Designated a Humanitarian Use Device for "mechanical circulatory support in neonates, infants, and toddlers weighing up to 20 kg as a bridge to transplant, a bridge to other therapeutic intervention such as surgery, or as a bridge to recovery" by the Food and Drug Administration, these initial results document the biocompatibility and potential of the fourth-generation PediaFlow design to provide chronic pediatric cardiac support.

Predicting Long Term Outcome in Patients Treated With Continuous Flow Left Ventricular Assist Device: The Penn-Columbia Risk Score.

BACKGROUND: Predicting which patients are unlikely to benefit from continuous flow left ventricular assist device (LVAD) treatment is crucial for the identification of appropriate patients. Previously developed scoring systems are limited to past eras of device or restricted to specific devices. Our objective was to create a risk model for patients treated with continuous flow LVAD based on the preimplant variables. METHODS AND RESULTS: We performed a retrospective analysis of all patients implanted with a continuous flow LVAD between 2006 and 2014 at the University of Pennsylvania and included a total of 210 patients (male 78%; mean age, 56±15; mean follow-up, 465±486 days). From all plausible preoperative covariates, we performed univariate Cox regression analysis for covariates affecting the odds of 1-year survival following implantation (P<0.2). These variables were included in a multivariable model and dropped if significance rose above P=0.2. From this base model, we performed step-wise forward and backward selection for other covariates that improved power by minimizing Akaike Information Criteria while maximizing the Harrell Concordance Index. We then used Kaplan-Meier curves, the log-rank test, and Cox proportional hazard models to assess internal validity of the scoring system and its ability to stratify survival. A final optimized model was identified based on clinical and echocardiographic parameters preceding LVAD implantation. One-year mortality was significantly higher in patients with higher risk scores (hazard ratio, 1.38; P=0.004). This hazard ratio represents the multiplied risk of death for every increase of 1 point in the risk score. The risk score was validated in a separate patient cohort of 260 patients at Columbia University, which confirmed the prognostic utility of this risk score (P=0.0237). CONCLUSION: We present a novel risk score and its validation for prediction of long-term survival in patients with current types of continuous flow LVAD support.

Studies on the dynamic resolution of Crizotinib intermediate.

Crizotinib is an anti-cancer agent approved for treatment of non-small cell lung carcinoma. Retrosynthetic analysis revels 1-(2,6-dichloro-3-fluorophenyl)ethanol as an important intermediate, which can be made available by different biocatalytic approaches. Herein we report our results on the kinetic and dynamic resolution towards the desired chiral intermediate for Crizotinib synthesis. The results obtained show that very good conversions and high selectivity could be obtained for the kinetic resolution (45% conv. and E>200) while dynamic kinetic resolution under continuous-flow conditions afforded the desired product in 57% conversion and 98% e.e.