Synthesis of novel urethanes from a castor oil derived C22-acyloin

The synthesis of new bio-based chemical building blocks, resulting from the condensation of a renewable C-22 acyloin derived from non-edible castor oil, with mono- and bifunctional isocyanates is reported. The condensation with aliphatic mono-isocyanates was relatively straightforward, however phenyl isocyanates only resulted in low yields together with the formation of a cyclic hemi-aminal during purification. The condensation with diisocyanates was successful for the aliphatic hexamethylene diisocyanate. As for the aromatic 2,4-toluene diisocyanate, a low yield of the desired product was obtained, since a similar ring closing reaction took place. The urethanes were synthesized in order to evaluate their plasticizing and viscosity-modifying properties

Advance Care Planning in the Netherlands

The Dutch health care system fosters a strong public health sector offering accessible generalist care including generalist palliative care. General practitioners are well positioned to conduct ACP, for example, to continue or initiate conversations after hospitalization. However, research shows that ACP conversations are often ad hoc and in frail patients, ACP is often only initiated when admitted to a nursing home by elderly care physicians who are on the staff. Tools that raise awareness of triggers to initiate ACP, screening tools, information brochures, checklists and training have been developed and implemented with funding by national programs which currently focus on implementation projects rather than or in addition to, research. The programs commonly require educational deliverables, patient and public involvement and addressing diversity in patient groups. A major challenge is how to implement ACP systematically and continuously across sectors and disciplines in a way that supports a proactive yet person-centered approach rather than an approach with an exclusive focus on medical procedures. Digital solutions can support continuity of care and communication about care plans. Solutions should fit a culture that prefers trust-based, informal deliberative approaches. This may be supported by involving disciplines other than medicine, such as nursing and spiritual caregiving, and public health approaches.</p

Development of Castor oil-based chemical platform molecules

Nowadays, a lot of attention is paid to the transition to a biobased economy, in a global as well as in a regional context. , Depletion of fossil resources and the effects of climate change provide an impulse for the development of sustainable fuels and chemicals from renewable resources. In this movement, most efforts concentrate on the development of bio-energy applications such as bio-ethanol, biodiesel and thermochemical conversion of biomass. However, in the energy sector other non-biomass alternatives (e.g. wind and solar energy) are known, whereas up to now no viable alternatives are available when thinking about chemical building blocks. Therefore, it is also essential to develop new routes for the synthesis of biobased chemicals and materials derived thereof. It has indeed been proven that over its total life cycle, the renewability of the feedstock has an important influence on the environmental impact of a product. Furthermore, in the EU a specific legislation has been developed to ensure a more environmentally friendly and a more stringent safety policy concerning chemicals, namely the REACH (Registration, Evaluation and Authorization of Chemicals) regulatory framework which proclaims registration and safety testing of all produced and imported chemicals by 2018. Besides, the concept of “green chemistry” was already formulated by Paul Anastas and John Warner. They proposed 12 principles in which the use of renewable feedstocks is one of the important themes. Examples of novel platform chemicals from renewable sources are succinic acid, isosorbide, HMF (hydroxymethylfurfural), vegetal oils and glycerol.1, Recently, several research programs have been set up to stimulate the development of biobased chemical products. One of these initiatives has led to the industrial production of isosorbide, a bicyclic diol derived from sorbitol, that has superior heat-resistant properties. Isosorbide diesters can be used as good substitutes for phthalate plasticizers, as exemplified by Polysorb® ID 37. The vegetable sources for the synthesis of renewable chemicals can still be divided in two classes, the food and non-food crops. As the non-food crops do not interfere with the food supply chain they can be used for non-food applications without any ethical concern. Castor oil is an example of such a non-edible oil extracted from the seeds of the castor bean plant Ricinus communis. It grows in tropical and subtropical areas. Crude castor oil is used in many non-food applications such as polyurethanes (PUs), plasticizers and lubricants, pharmaceuticals and cosmetics, soaps, inks and paints etc. , Several commercial applications of castor oil derived chemicals are known. Recently BASF has re-launched Ultramid® BALANCE, a polyamide (PA 6,10) derived for 60% from sebacic acid produced from castor oil. It is a polymer that combines a low weight with high impact strength at low temperatures and a low water absorption. Solvay and Mitsubishi Gas Chemical Co. (MGC, Tokyo) started up a collaboration on a high-temperature PA from sebacic acid. Low moisture retention, a high crystallisation rate, excellent wear resistance and good toughness are key properties. Potential uses include reflow soldering applications, high-temperature automotive parts and sliding applications (gears). Castor-based elastomer Pebax Rnew® from Arkema was used in the soles of running shoes for increased shock absorption. Evonik Industries very recently announced the production of their VESTAMID® Terra specialty PAs for automotive applications, based on sebacic acid. About ninety percent of the fatty acid (FA) fraction in castor oil is ricinoleic acid, a monounsaturated, eighteen-carbon FA with a hydroxyl function at position twelve, a quite unique structure for a naturally occurring FA. By heating ricinoleic acid above 400 °C in the absence of oxygen, 10-undecenoic acid (UA) is obtained. UA is an interesting renewable material readily used in insecticidal, fungicidal and perfume formulations. Present applications of undecenoic acid are Athlete’s Foot remedy and Nylon 11 or Rilsan (produced by Arkema) from ω¬¬-aminoundecanoic acid which is known for its strength and silky texture. Due to its bifunctional nature, UA has many possibilities to develop sustainable applications. It has an odd number of carbon atoms, which is not observed for natural FAs. A recent review covers the literature on UA in various fields, ranging from antimicrobial activity, (natural) product synthesis, polymer production and separation technology. This thesis is focused on the fully renewable C22-acyloin condensation product from UA, further on also called 10-undecenoin, which can be obtained through a sodium promoted reductive coupling process. Besides UA, some other renewable resources have been explored as starting materials for the acyloin condensation reaction and alternative metals and solvents for acyloin condensation have been evaluated. This part of the research is described in a first chapter. 10-Undecenoin combines terminal unsaturations with an internal hydroxyketone moiety, which gives opportunities for several functionalizations. A clever synthetic strategy starting from 10-undecenoin has been developed to obtain physiologically activeTyromycin A, involving as key steps a fine-tuned chlorination reaction designed by Dr. De Buyck and a sophisticated Transition-Metal Catalyzed Atom Transfer Radical Cyclization-Functional Rearrangement strategy to convert the terminal chlorinated carboxylic acid moieties into citraconic anhydride units in an elegant way. The second chapter is dedicated to this nice piece of synthetic organic chemistry. A reactivity study of the C22-acyloin is the subject of a third chapter. Reaction with various electrophiles (isocyanates, acid chlorides, chlorinated phosphorus compounds) and alkylating agents is evaluated, as well as epoxidation of the terminal unsaturations. Sometimes unexpected side-products are formed in these trials and explanations for this have been sought. Reaction of UA with isocyanates resulting in multifunctional urea compounds constitutes a final part of this last chapter. Throughout the text, testing of some newly synthesized compounds is being described showing their potential for replacement of fossil-based counterparts in copolymerization reactions, treatment of wood panels and some of them show promising characteristics for polymer applications

Evaluation of the Initial General Ward Early Warning Score and ICU Admission, Hospital Length of Stay and Mortality

Introduction: Despite widespread implementation of the Early Warning Score (EWS) in hospitals, its effect on patient outcomes remains mostly unknown. We aimed to evaluate associations between the initial EWS and in-hospital mortality, intensive care unit (ICU) admission, and hospital length of stay (LOS).&nbsp; Methods: We performed a retrospective cohort study of adult patients admitted to a general hospital ward between July 1, 2014–December 31, 2017. Data were obtained from electronic health records (EHR). The primary outcome was in-hospital mortality. Secondary outcomes were ICU admission and hospital LOS. We categorized patients into three risk groups (low, medium or high risk of clinical deterioration) based on EWS. Descriptive analyses were used. Results: After applying inclusion and exclusion criteria, we included 53,180 patients for analysis. We found that the initial (low- vs high-risk) EWS was associated with an increased in-hospital mortality (1.5% vs 25.3%, P &lt;0.001), an increased ICU admission rate (3.1% vs 17.6%, P &lt;0.001), and an extended hospital LOS (4.0 days vs 8.0 days, P &lt;0.001). Conclusion: Our findings suggest that an initial high-risk EWS in patients admitted to a general hospital ward was associated with an increased risk of in-hospital mortality, ICU admission, and prolonged hospital LOS. Close monitoring and precise documentation of the EWS in the EHR may facilitate predicting poor outcomes in individual hospitalized patients and help to identify patients for whom timely and adequate management may improve outcomes

Evaluation of the Initial General Ward Early Warning Score and ICU Admission, Hospital Length of Stay and Mortality

Introduction: Despite widespread implementation of the Early Warning Score (EWS) in hospitals, its effect on patient outcomes remains mostly unknown. We aimed to evaluate associations between the initial EWS and in-hospital mortality, intensive care unit (ICU) admission, and hospital length of stay (LOS).&nbsp; Methods: We performed a retrospective cohort study of adult patients admitted to a general hospital ward between July 1, 2014–December 31, 2017. Data were obtained from electronic health records (EHR). The primary outcome was in-hospital mortality. Secondary outcomes were ICU admission and hospital LOS. We categorized patients into three risk groups (low, medium or high risk of clinical deterioration) based on EWS. Descriptive analyses were used. Results: After applying inclusion and exclusion criteria, we included 53,180 patients for analysis. We found that the initial (low- vs high-risk) EWS was associated with an increased in-hospital mortality (1.5% vs 25.3%, P &lt;0.001), an increased ICU admission rate (3.1% vs 17.6%, P &lt;0.001), and an extended hospital LOS (4.0 days vs 8.0 days, P &lt;0.001). Conclusion: Our findings suggest that an initial high-risk EWS in patients admitted to a general hospital ward was associated with an increased risk of in-hospital mortality, ICU admission, and prolonged hospital LOS. Close monitoring and precise documentation of the EWS in the EHR may facilitate predicting poor outcomes in individual hospitalized patients and help to identify patients for whom timely and adequate management may improve outcomes

Undecylenic acid: a valuable renewable building block on route to Tyromycin A derivatives

A key intermediate for the synthesis of Tyromycin A, a C-20 tetrachlorodicarboxylic acid, was produced in six steps starting with the dimerization of methyl 10-undecenoate which was obtained from a renewable resource, e.g. castor oil. The acyloin condensation product was then oxidized, transformed to the diene, followed by ozonization, chlorination and finally oxidation to the corresponding tetrachlorodicarboxylic acid

A new synthetic route to tyromycin A and its analogue from renewable resources

The synthesis of tyromycin A and that of the non-natural lower homologue, involving as featuring stepsa transition metal catalyzed atom transfer radical cyclization and a functional rearrangement of thepolyhalogenated 2-pyrrolidinones thus obtained, are described. Both routes use 10-undecenoic acid,a renewable source from castor oil, as starting material for the preparation of the pivotal intermediatesa,a,a0,a0-tetrachlorodicarboxylic acids