Isothiourea-catalysed enantioselective radical conjugate addition under batch and flow conditions

Financial support was provided by the Spanish Government (RTI2018-095038-B-I00), “Comunidad de Madrid” for European Structural Funds (S2018/NMT-4367) and proyectos sinergicos I+D (Y2020/NMT-6469). J. A. F.-S. thanks the Spanish Government for a Ramón y Cajal contract. The research leading to these results has received funding from the EaSI-CAT centre for Doctoral Training (M.T.W) and Carlsberg Foundation (M.J.).The photocatalytic generation of α-amino radicals is combined with chiral isothiourea derived α,β-unsaturated acyl ammonium intermediates. The reaction proceeds via a [3+2] radical-polar crossover mechanism to generate γ-lactams in good yields and enantioselectivities. The enantioselective radical conjugate addition was carried out under batch and flow conditions.Publisher PDFPeer reviewe

Rigidity of conformal functionals on spheres

In this paper we investigate the nature of stationary points of functionals on the space of Riemannian metrics on a smooth compact manifold. Special cases are spectral invariants associated with Laplace or Dirac operators such as functional determinants, and the total Q-curvature. When the functional is invariant under conformal changes of the metric, and the manifold is the standard n-sphere, we apply methods from representation theory to give a universal form of the Hessian of the functional at a stationary point. This reveals a very strong rigidity in the local structure of any such functional. As a corollary this gives a new proof of the results of K. Okikiolu (Ann. Math., 2001) on local maxima and minima for the determinant of the conformal Laplacian, and we obtain results of the same type in general examples.Comment: 29 page

Individualised perioperative blood pressure and fluid therapy in oesophagectomy:study protocol for a randomised clinical trial

INTRODUCTION: Oesophagectomy is the mainstay of curative treatment for oesophageal cancer, but it is associated with a high risk of major complications. Goal-directed fluid therapy and individualised blood pressure management may prevent complications after surgery. Extending goal-directed fluid therapy after surgery and applying an individual blood pressure target may have substantial benefit in oesophagectomy. This is a protocol for a clinical trial implementing a novel haemodynamic protocol from the start of anaesthesia to the next day with the patient’s own night-time blood pressure as the lower threshold.METHODS: This is a single-centre, single-blind, randomised, clinical trial. Oesophagectomy patients are randomised 1:1 for either perioperative haemodynamic management according to a goal-directed fluid therapy protocol with an individual target blood pressure or for standard care. The primary endpoint is the total burden of morbidity and mortality assessed by the Comprehensive Complication Index 30 days after surgery. Secondary endpoints are complications, reoperations, fluid and vasopressor dosage and quality of life at 90 days after surgery.CONCLUSIONS: The results from this trial provide an objective and easy-to-follow algorithm for fluid administration, which may improve patient-centred outcomes in oesophagectomy patients.</p