Evaluation of appendicitis risk prediction models in adults with suspected appendicitis

Background Appendicitis is the most common general surgical emergency worldwide, but its diagnosis remains challenging. The aim of this study was to determine whether existing risk prediction models can reliably identify patients presenting to hospital in the UK with acute right iliac fossa (RIF) pain who are at low risk of appendicitis. Methods A systematic search was completed to identify all existing appendicitis risk prediction models. Models were validated using UK data from an international prospective cohort study that captured consecutive patients aged 16–45 years presenting to hospital with acute RIF in March to June 2017. The main outcome was best achievable model specificity (proportion of patients who did not have appendicitis correctly classified as low risk) whilst maintaining a failure rate below 5 per cent (proportion of patients identified as low risk who actually had appendicitis). Results Some 5345 patients across 154 UK hospitals were identified, of which two‐thirds (3613 of 5345, 67·6 per cent) were women. Women were more than twice as likely to undergo surgery with removal of a histologically normal appendix (272 of 964, 28·2 per cent) than men (120 of 993, 12·1 per cent) (relative risk 2·33, 95 per cent c.i. 1·92 to 2·84; P < 0·001). Of 15 validated risk prediction models, the Adult Appendicitis Score performed best (cut‐off score 8 or less, specificity 63·1 per cent, failure rate 3·7 per cent). The Appendicitis Inflammatory Response Score performed best for men (cut‐off score 2 or less, specificity 24·7 per cent, failure rate 2·4 per cent). Conclusion Women in the UK had a disproportionate risk of admission without surgical intervention and had high rates of normal appendicectomy. Risk prediction models to support shared decision‐making by identifying adults in the UK at low risk of appendicitis were identified

Application of MOORA & COPRAS integrated with entropy method for multi-criteria decision making in dry turning process of Nimonic C263

This article presents an integrated multi-criteria decision making using Entropy, MOORA and COPRAS methods for turning Nimonic C263. Experiments were performed under L27 Taguchi orthogonal array. Dry turning was performed and cubic boron nitride (CBN) was used to turn the alloy. The variables speed, feed and depth of cut were chosen as factors. For each experiment, the shear force component was measured during on line. The insert flank wear was measured after every experiment. The main objective of this paper is to identify the suitable trial to ensure minimum force and flank wear simultaneously. Because of the cost reduction and quality improvement, the controlling factors level should be selected appropriately. Hence, the integrated MCDM technique using MOORA, COPRAS and Entropy was chosen to determine the best experiment out of 27 experiments. Alternatives were ranked and the results were evaluated. The best experiment for minimization of force and flank wear is found to be 125 m/min, 0.055 mm/rev and 0.25 mm. The experimental test were observed with lesser deviation and confirmed that proposal found is more suitable to obtain minimum force and flank wear

Discovery of a Potent Dihydrooxadiazole Series of Non-ATP-Competitive MK2 (MAPKAPK2) Inhibitors

Inhibition of MK2 has been shown to offer advantages over that of p38 MAPK in the development of cures for inflammatory diseases such as arthritis. P38 MAPK knockout in mice was lethal, whereas MK2-null mice demonstrated strong inhibition of disease progression in collagen-induced arthritis and appeared normal and viable. However, it is challenging to develop ATP-competitive MK2 inhibitors due to high ATP binding affinity to the kinase. Non-ATP-competitive MK2 inhibitors interact and bind to the kinase in a mode independent of ATP concentration, which could provide better selectivity and cellular potency. Therefore, it is desirable to identify non-ATP-competitive MK2 inhibitors. Through structure optimization of lead compound <b>1</b>, a novel series of dihydrooxadiazoles was discovered. Additional structure–activity relationship (SAR) study of this series led to the identification of compound <b>38</b> as a non-ATP-competitive MK2 inhibitor with potent enzymatic activity and good cellular potency. The SAR, synthesis, and biological data of dihydrooxadiazole series are discussed

Ligand-Dependent Site-Selective Suzuki Cross-Coupling of 3,5-Dichloropyridazines

General methods for the highly site-selective Suzuki monocoupling of 3,5-dichloropyridazines have been discovered. By changing the ligand employed, the preferred coupling site can be switched from the 3-position to the 5-position, typically considered the less reactive C–X bond. These conditions are applicable to the coupling of a wide variety of aryl-, heteroaryl-, and vinylboronic acids with high selectivities, thus enabling the rapid construction of diverse arrays of diarylpyradazines in a modular fashion