Measurement latency significantly contributes to reduced heart rate measurement accuracy in wearable devices.

The purpose of this study was to determine the extent to which measurement latency has significance for the accuracy of heart rate (HR) measured by wearable devices during physical activities. Thirty participants (15 female) aged 18-50 years (mean 24.8, 6.3 SD years) with weight ranging from 53-87 kg (mean 70.5, 9.4 SD kg) participated in this cross-sectional study. Participants completed three submaximal exercise conditions; cycling, treadmill walking/running and rapid arm movements. During the exercises, HR was concurrently measured using the Polar H10 (PL), the Apple Watch 2 (AW) and the Garmin Forerunner 235 (GF). Measurement latency significantly affected the discrepancy in HR measures and measurement latency accounted for 15% (GF) and 2% (AW) of the explained discrepancy in HR between the criterion measure PL and the GF and AW. However, the findings also showed that the magnitude of HR measurement latency differed notably among the two wearable devices and measurement latency was greatly influenced not only by type but also by the intensity of exercise. These findings contribute to our understanding of wearable device HR measures discrepancy and this knowledge may be of assistance when electing to use wearable devices to monitor physical exertion in different contexts.

[COPD symptom screening can identify patients who require palliation].

This study developed and tested a collaboration model to improve the quality of palliative care for all patients with life-threatening illness who require palliation. Journal audit was performed on 79 in-hospital patients. European Organisation for Research and Treatment of Cancer, Quality of Life Question-naire (EORTC-QLQ-C15-PAL) symptom screening was found to be applicable to all patients with life-threatening illness. It was found important to document the patients' wishes for the end of life care and furthermore the electronic correspondence was found to contain relevant and sufficient information for the continuity of care.

On the origin of the stereoselectivity in organocatalysed reactions with trimethylsilyl-protected diarylprolinol.

The origin of the enantioselectivity in the TMS-protected (TMS=trimethylsilyl) prolinol-catalysed alpha-heteroatom functionalisation of aldehydes has been investigated by using density functional theory calculations. Eight different reaction paths have been considered which are based on four different conformers of the TMS-protected prolinol-enamine intermediate. Optimisation of the enamine structures gave two intermediates with nearly the same energy. These intermediates both have an E configuration at the C==C bond and the double bond is positioned anti or syn, relative to the 2-substituent in the pyrrolidine ring. For the four intermediates, the chiral TMS-protected-diaryl substituent effectively shields one of the faces of the reacting C==C bond in the enamine intermediate. A number of transition states have been calculated for the enantioselective fluorination by N-fluorobenzenesulfonimide (NFSI) and based on the transition-state energies it has been found that the enantioselectivity depends on the orientation of the C==C bond, being anti or syn, relative to the 2-substituent on the pyrrolidine ring, rather than the approach of the electrophilic fluorine to the face of the reacting carbon atom in the enamine which is less shielded relative to the face with the highest shielding. The calculated enantiomeric excess of 96 % ee (ee=enantiomeric excess) for the fluorination reaction corresponds well with the experimentally found enantiomeric excess-97 % ee. The transition state for the alpha-amination reaction with the same type of intermediate has also been calculated by using diethyl azodicarboxylate as the amination reagent. The implication of the intermediate structures on the stereoselection of alpha-functionalisation of aldehydes is discussed.

Organocatalytic asymmetric direct phosphonylation of alpha,beta-unsaturated aldehydes: mechanism, scope, and application in synthesis.

The first direct organocatalytic enantioselective phosphonylation of alpha,beta-unsaturated aldehydes with phosphite, in combination with a Brønsted acid and a nucleophile, is presented. Mechanistic investigations have revealed that the first step in the catalytic process, after the formation of the iminium intermediate, is the addition of phosphite to the beta-carbon atom, leading to the phosphonium ion-enamine intermediate. The rate-determining step for the reaction is the transformation of P(III) to P(V), which occurs via a nucleophilic SN2-type dealkylation, and a screening of various nucleophiles shows that soft nucleophiles in combination with a Brønsted acid improve the reaction rate and enantioselectivity. The reaction conditions developed show that the use of 2-[bis(3,5-bistrifluoromethylphenyl)trimethylsilanoxymethyl]pyrrolidine as the catalyst and tri-iso-propyl phosphite as the phosphonylation reagent, in the presence of stoichiometric amount of benzoic acid and sodium iodide, gave the beta-phosphonylation of aromatic and aliphatic alpha,beta-unsaturated aldehydes in good yields and enantioselectivities. The products formed by this new reaction have been used for the synthesis of a number of biologically important compounds, such as optically active hydroxyl phosphonate esters, phosphonic acids, and especially glutamic acid and fosmidomycin precursors, of which the two latter are showing important properties for the treatment of central nervous system diseases and as anti-malarial compounds, respectively. DFT calculations have been applied to explain the approach of the phosphite to the reactive carbon atom in the iminium intermediate in order to account for the observed absolute enantioselectivity in the reaction.

A general organocatalyst for direct alpha-functionalization of aldehydes: stereoselective C-C, C-N, C-F, C-Br, and C-S bond-forming reactions. Scope and mechanistic insights.

The development of a general organocatalyst for the alpha-functionalization of aldehydes, via an enamine intermediate, is presented. Based on optically active alpha,alpha-diarylprolinol silyl ethers, the scope and applications of this catalyst for the stereogenic formation of C-C, C-N, C-F, C-Br, and C-S bonds are outlined. The reactions all proceed in good to high yields and with excellent enantioselectivities. Furthermore, we will present mechanistic insight into the reaction course applying nonlinear effect studies, kinetic resolution, and computational investigations leading to an understanding of the properties of the alpha,alpha-diarylprolinol silyl ether catalysts.

Mechanistic investigation of the 2,5-diphenylpyrrolidine-catalyzed enantioselective alpha-chlorination of aldehydes.

The mechanism for the 2,5-diphenylpyrrolidine-catalyzed enantioselective alpha-chlorination of aldehydes with electrophilic halogenation reagents has been investigated by using experimental and computational methods. These studies have led us to propose a mechanism for the reaction that proceeds through an initial N-chlorination of the chiral catalyst-substrate complex, followed by a 1,3-sigmatropic shift of the chlorine atom to the enamine carbon atom. The suggested reaction course is different from previously proposed mechanisms for organocatalytic enamine reactions, in which the carbon-electrophile bond is formed directly. Furthermore, the rate-determining step in the overall reaction was determined and the presence of nonlinear effects was probed.

Catalytic asymmetric addition of beta-keto phosphonates to an activated imine--formation of optically active functionalized phosphonate alpha-amino acid derivatives.

The direct stereoselective addition of an activated imine to beta-keto phosphonates in the presence of chiral Lewis acid complexes is developed. The evaluation of different activated imines shows that an N-tosyl-alpha-imino ester adds in a diastereo- and enantioselective fashion to beta-keto phosphonates activated by especially chiral copper(II)-bisoxazoline complexes. An evaluation of Lewis acids, chiral ligands and reaction conditions, such as solvent, bases and other additives, shows that high yields, moderate diastereoselectivity and good enantioselectivity are obtained. The scope of the reaction is demonstrated for the reaction of beta-keto phosphonates and finally, the mechanism for the catalytic stereoselective step is presented.

Direct catalytic asymmetric mannich reactions of malonates and beta-keto esters.

The first catalytic asymmetric direct Mannich reaction of malonates and beta-keto esters has been developed. Malonates react with an activated N-tosyl-alpha-imino ester catalyzed by chiral tert-butyl-bisoxazoline/Cu(OTf)(2) to give the Mannich adducts in high yields and with up to 96% ee. These reactions create a chiral quaternary carbon center and it is demonstrated that this new direct Mannich reactions provides for example a new synthetic procedure for the formation of optically active beta-carboxylic ester alpha-amino acid derivatives. A series of different beta-keto esters with various ester substituents has been screened as substrates for the catalytic asymmetric direct Mannich reaction and it was found that the best results in terms of yield, diastereo- and enantioselectivity were obtained when tert-butyl esters of beta-keto esters were used as the substrate. The reaction of different beta-keto tert-butyl esters with the N-tosyl-alpha-imino ester gave the Mannich adducts in high yields, diastereo- and enantioselectivities (up to 95% ee) in the presence of chiral tert-butyl-bisoxazoline/Cu(OTf)(2) as the catalyst. To expand the synthetic utility of this direct Mannich reaction a diastereoselective decarboxylation reaction was developed for the Mannich adducts leading to a new synthetic approach to attractive optically active beta-keto alpha-amino acid derivatives. Based on the stereochemical outcome of the reactions, various approaches of the N-tosyl-alpha-imino ester to the chiral bisoxazoline/Cu(II)-substrate intermediate are discussed.