Paleo‐temperature gradients for Site 768 are determined by modelling organic maturities. It is found that the measured maturity of the organic matter cannot be attributed to the present‐day thermal gradient of 130°C/KM. From a comparison between modelled and measured maturities a high paleogradient of 250°C/KM is derived.
The cyclocondensation reaction between N,N-bis(2-aminoethyl)-2-phenylethylamine and 2,6-diformylpyridine in the presence of a barium template gave an unexpected 18-membered macrocyclic product in which a ring contraction at one side-arm has occurred to produce an imidazolidine ring.
Purpose: We examined whether the change of the logistic organ dysfunction score (LOD) between the first and the fourth day in the intensive care unit (ICU) could be predictive of death in the ICU. The LOD could then be used to help make decisions concerning therapeutic limitations (TL). Methods: One hundred fifty-four patients were included. Exclusion criteria were: discharge from the ICU or TL before the 72 nd hr. Ninety-three patients remained for evaluation. The LOD was calculated on the day of admission (LOD1) and between the 72 nd and 96 th hr (LOD4). The ΔLOD = LOD4 – LOD1 index was calculated for survivors and non-survivors; sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated. Results: Sixteen patients died in the ICU, they had a higher ΔLOD (0 vs -2; P = 0.0046) than the survivors. After logistic regression, a high ΔLOD was associated with a higher risk of death in the ICU independent of the initial severity of disease. The PPV concerning death in the ICU was 0.66 for a ΔLOD ≥ 4 cut-off. The NPV was 0.89 for a cut-off of ≥ 1. Conclusion: ΔLOD appears to be a predictor of death in the ICU, independent of the initial severity of disease. The PPV is not high enough to assist with making individual TL decisions. The NPV can help to identify patients at low risk of death. The ΔLOD deserves to be evaluated in a population exhibiting greater severity of disease. Objectif : Verifier si le changement de score logistique de dysfonction organique (LDO) entre le premier et le quatrieme jour a l’unite des soins intensifs (USI) peut etre predicteur d’un deces a l’USI. Le LDO pourrait alors etre utilise pour aider a prendre des decisions concernant les limites therapeutiques (LT).
Introduction: Zinc-dependent histone deacetylases (HDAC) inhibitors represent an important class of biologically active compounds with four of them approved by the FDA. A wide range of molecules has been reported for applications in several human diseases.Area covered: This review covers recent efforts in the synthesis and applications of HDAC inhibitors from 2013-2017.Expert opinion: HDAC inhibitors represent an important class of biologically active compounds for single or combination therapies. The current synthetic methodologies are oriented towards selective HDAC isoforms to achieve better therapeutic effects. Among the recent patents available, most of them focus on HDAC6 selective inhibitors. Beside this search for isoform selectivity, the quest for zinc binding groups with better pharmacokinetic properties and high potency against HDACs only motivates medicinal chemists, as well as the design of inhibitors targeting HDACs and at the same time another biological target. If the major applications are for anticancer activity, one can note the emerging applications in neurological or metabolic disorders or for the stimulation of the immune system.
