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

Chemo-, regio-, and diastereoselectivity preferences in the reaction of a sulfur ylide with a dienal and an enone

Mechanistic insights into an interesting class of reaction between sulfur ylides with (i) a dienal, and (ii) an enone, obtained by using density functional theory, is reported. The kinetic and thermodynamic factors responsible for chemo-, regio-, and diastereoselectivities are established by identifying all key transition states and intermediates along the reaction pathway for 1,2-, 1,4-, and 1,6-modes of attack of dimethylsulfonium benzylide to 5-phenylpenta-2,4-dienal. The reaction profiles for 1,2- and 1,4-modes of addition are also evaluated for the reaction between dimethylsulfonium benzylide and pent-3-en-2-one. Our results show that the final outcome of the reaction with both these substrates would be decided by the interplay between kinetic and thermodynamic factors. It is found that the addition of a semi-stabilized ylide to conjugated carbonyl compounds prefers to proceed through a 1,4( conjugate) pathway under thermodynamic conditions, which is in accordance with the available experimental reports. However, the formation of epoxides via a 1,2-(direct) addition pathway is computed to be equally competitive, which could be the favored pathway under kinetic conditions. Even though the lower barrier for the initial addition step is kinetically advantageous for the direct (or 1,2-) addition pathway, the higher energy of the betaine intermediates-as well as the reversibility of the accompanying elementary step-may disfavor product formation in this route. Thus, high diastereoselectivity in favor of 2,3-trans cyclopropanecarbaldehyde is predicted in the case of the dienal, using the most favored conjugate addition (1,4-addition) pathway. Along similar lines, ylide addition to the enone is identified to exhibit a preference toward conjugate addition over direct (1,2-) addition. The importance of transition state analysis in delineating the controlling factors towards product distribution and diastereoselectivity is established

Enantio- and Diastereoselectivities in Chiral Sulfur Ylide Promoted Asymmetric Aziridination Reactions

Density functional theory investigation on the factors controlling enantio- and diastereoselection in asymmetric aziridination reaction by the addition of chiral bicyclic sulfur ylides to substituted aldimines is presented. Hi-fi levels of enantioselection are predicted toward the formation of (2S,3S)-cis and (2R,3S)-trans aziridines by the addition of stabilized ylide (R = COMe) respectively to SO(2)Me and CO(2)Me protected aldimines. Similarly, high %ee is predicted for the formation of (2S,3R)-cis aziridines from semistabilized (R = Ph) ylide. Moderate to high levels of diastereoselectivity is noticed as well. The present study highlights that a correct prediction oil extent of enantioselection requires the knowledge of the activation barriers for elementary steps beyond the initial addition step. In the case of stabilized ylides the ring-closure (or elimination Of Sulfur compound) is found to be crucial in controlling enantio- and diastereoselection. A cumulative effect of electronic as well as other weak interactions is identified as factors contributing to the relative energies of transition states leading to enantio- and diastereomeric products for the stabilized ylide addition to aldimines. On the contrary, steric control appears quite dominant With semistabilized ylide addition. With the smallest substituent on ylide (R = Me), high enantioselectivity is predicted for the formation of (2R,3R)-trans aziridines although the %de in this case is found to be very low

Density functional theory investigations on sulfur ylide promoted cyclopropanation reactions: insights on mechanism and diastereoselection issues

[graphics] The mechanism and diastereoselectivity of synthetically useful sulfur ylide promoted cyclopropanation reactions have been studied using the density functional theory method. Addition of different substituted ylides (Me2S+CH-R) to enone ((E)-pent-3-en-2-one, MeHCCH-COMe) has been investigated. The nature of the substituent on the ylidic carbon brings about subtle changes in the reaction profile. The stabilized (R = COMe) and semistabilized (R = Ph) ylides follow a cisoid addition mode, leading to 1,2-trans and 1,2-cis cyclopropanes, respectively, via syn and anti betaine intermediates. The simplest and highly reactive model ylide (R = H) prefers a transoid addition mode. Diastereoselectivity is controlled by the barrier for cisoid-transoid rotation in the case of stabilized ylides, whereas the initial electrophilic addition is found to be the diastereoselectivity-determining step for semistabilized ylides. High selectivity toward trans cyclopropanes with stabilized ylides are predicted on the basis of the relative activation energies of diastereomeric torsional transition states. The energy differences between these transition states could be rationalized with the help of weak intramolecular as well as other stereoelectronic interactions

Mixed-valent metals bridged by a radical ligand: Fact or fiction based on structure-oxidation state correlations

Electron-rich Ru(acaC)(2) (acac(-) = 2,4-pentanedionato) binds to the pi electron-deficient bis-chelate ligands L, L = 2,2'-azobispyridine (abpy) or azobis(5-chloropyrimidine) (abcp), with considerable transfer of negative charge. The compounds studied, (abpy)Ru(acac)(2) (1), meso-(mu-abpy)[Ru(acaC)(2)](2) (2), rac-(mu-abpy)[Ru(acac)(2)](2) (3), and (mu-abcp)[Ru(acac)(2)](2) (4), were calculated by DFT to assess the degree of this metal-to-ligand electron shift. The calculated and experimental structures of 2 and 3 both yield about 1.35 angstrom for the length of the central N-N bond which suggests a monoanion character of the bridging ligand. The NBO analysis confirms this interpretation, and TD-DFT calculations reproduce the observed intense long-wavelength absorptions. While mononuclear 1 is calculated with a lower net ruthenium-to-abpy charge shift as illustrated by the computed 1.30 angstrom for d(N-N), compound 4 with the stronger pi accepting abcp bridge is calculated with a slightly lengthened N-N distance relative to that of 2. The formulation of the dinuclear systems with monoanionic bridging ligands implies an obviously valence-averaged (RuRuII)-Ru-III mixed-valent state for the neutral molecules. Mixed valency in conjunction with an anion radical bridging ligand had been discussed before in the discussion of MLCT excited states of symmetrically dinuclear coordination compounds. Whereas 1 still exhibits a conventional electrochemical and spectroelectrochemical behavior with metal centered oxidation and two ligand-based one-electron reduction waves, the two one-electron oxidation and two one-electron reduction processes for each of the dinuclear compounds Ru-2.5(L*(-))Ru-2.5 reveal more unusual features via EPR and UV-vis-NIR spectroelectrochemistry. In spite of intense near-infrared absorptions, the EPR results show that the first reduction leads to Ru-II(L*(-))Ru-II species, with an increased metal contribution for system 4*(-). The second reduction to Ru-II(L2-)Ru-II causes the disappearance of the NIR band. One-electron oxidation of the Ru-2.5(L*(-)) Ru-2.5 species produces a metal-centered spin for which the alternatives Ru-III(L-0)Ru-II or Ru-III(L*(-))Ru-III can be formulated: The absence of NIR bands as common for mixed-valent species with intervalence charge transfer (IVCT) absorption favors the second alternative. The second one-electron oxidation is likely to produce a dication with Ru-III(L-0)Ru-III formulation. The usefulness and limitations of the increasingly popular structure/oxidation state correlations for complexes with noninnocent ligands is being discussed

Valence-state distribution in the ruthenium o-quinonoid systems [Ru(trpy)(Cl)(L-1)](+) and [Ru(trpy)(Cl)(L-2)](+) (L-1 = o-iminobenzoquinone, L-2 = o-diiminobenzoquinone; trpy=2,2 ': 6 ',2 ''-terpyridine)

Valence-state distributions in the ruthenium quinonoid (L) frameworks of [Ru(trpy)(Cl)(L-1))ClO4 (1-ClO4) and [Ru(trpy)-(CI) (L-2)]ClO4 (2-ClO4) (L-1 = o-iminobenzoquinone, L-2 = o-diiminobenzoquinone, and trpy = 2,2':6',2"-terpyridine) have been examined by structural, spectroelectrochemical, and density functional studies. The structural data, in corroboration with the DFT-calculated bond lengths, suggest that the primary valence formulation of 1(+) and 21 is a spin-coupled singlet configuration of [Ru-III(trpy)(Cl)(L-Sq)](+) with a minority contribution from diamagnetic [Ru-II(trpy)(Cl)(L-Q)](+). Consequently, the closely spaced successive two oxidation processes of 1(+) and 2(+) can be assigned to Ru-III -> Ru-IV and L-Sq -> L-Q, which involve the HOMO and HOMO-3 levels, respectively. The one-electron-oxidized species 1(2+) and 2(2+) display sharp EPR signals with g values of 2.011 and 2.014 at 77 K, respectively. The free radical EPR signal (g approximate to 2.0) of the one-electron-reduced species I or 2 signifies the preferential involvement of the ruthenium-based orbitals in the first reduction process to yield [Ru-II(trpy)(Cl)(L-Sq)], although the LUMO is calculated to be a mixture of d pi(Ru) (approximate to 24 %) and pi * (L) (approximate to 70 %). The subsequent second (1(-)/2(-)) and third (1(2-)/2(2-)) reduction steps in each case are associated simply with the terpyridyl-based orbitals (>= 90 %). The lowest energy charge-transfer transitions of 1(+) and 2(+) at 556 and 509 nm are predicted to be HOMO -> LUMO+1 and HOMO-1 -> LUMO+1 transitions, respectively. In the successive oxidations 1(+)/2(+) -> 1(2+)/2(2+) -> 1(3+)/2(3+) the lowest energy charge-transfer transitions undergo a blue shift with a substantial reduction in intensity. The lowest energy charge-transfer transitions, however, are red shifted with a reduction in intensity on going from (1(+)/2(+)) to 1/2. The origin of the transitions in the 1(2+)/2(2+) and 1/2 systems is predicted by TDDFT analysis. ((c) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007

Offsetting the problem of charge trapping in white polymer light-emitting diodes using a fluorenone-based luminogen

In this study, we propose a strategy to offset charge trapping and to enhance the confinement of excitons in the emissive layer of white electroluminescent copolymer using a luminogen with aggregation-induced emission enhancement (AIEE). The fluorenone-based luminogen, 2,7-bis(9H-fluoren-9-one-2yl)-9,9-dihexylfluorene (FF) that exhibited yellow emission with AIEE property is copolymerized with 9,9-dihexylfluorene in different compositions to tune the emission color. White-light emission is demonstrated in a copolymer FF-0.25, which contained 0.25% of FF in the polymer backbone. Interestingly, the copolymers exhibited enhanced emission upon aggregation in thin film, even in low FF composition. OLEDs fabricated from the copolymer FF-0.25 elicited a white electroluminescence with Commission Internationale de l'Eclairage (CIE) coordinates of 0.30, 0.31 with a power efficiency of 4.12 lm W<SUP>−1</SUP>. FF-0.25 showed very low charge trapping compared to other white emitting single polymer OLEDs reported to date. The reduced charge carrier trapping is attributed to the positioning of energy levels in the copolymer that resulted in almost equal electron- and hole-injection barriers. A theoretical investigation on the copolymers of FF revealed the presence of an ambipolar property and low exciton binding energy implicit of efficient formation and confinement of excitons within the emissive layer. The system represents the first ambipolar white electroluminescent polymer designed by using an AIEE luminogen

2,5-dioxido-1,4-benzoquinonediimine (h2l2-), a hydrogen-bonding noninnocent bridging ligand related to aminated topaquinone: different oxidation state distributions in complexes [{(bpy)(2)ru}(2)(mu-h2l)](n) (n=0,+,2+,3+,4+) and [{(acac)(2)ru}(2)(mu-h2l)](m) (m=2-,-,0,+,2+)

The symmetrically dinuclear title compounds were isolated as diamagnetic [(bpy)(2)Ru(mu-H2L)Ru(bpy)(2)]- (ClO4)(2) (1-(ClO4)(2)) and as paramagnetic [(acac)(2)Ru(mu-H2L)Ru(acac)(2)] (2) complexes (bpy = 2,2'-bipyridine; acac(-) -, acetylacetonate = 2,4-pentanedionato; H2L=2,5-dioxido-1,4-benzoquinonediimine). The crystal structure of 2(.)2H(2)O reveals an intricate hydrogen-bonding network: Two symmetry-related molecules 2 are closely connected through two NH(H2L2-)O-...- (acac-) interactions, while the oxygen atoms of H2L2- of two such pairs are bridged by an (H2O)(1) cluster at half-occupancy. The cluster consists of cyclic (H2O)(6) arrangements with the remaining two exo-H2O molecules connecting two opposite sides of the cyclo-(H2O)(6) cluster, and oxido oxygen atoms forming hydrogen bonds with the molecules of 2. Weak antiferromagnetic coupling of the two ruthenium(ill) centers in 2 was established by using SQUID magnetometry and EPR spectroscopy. Geometry optimization by means of DFT calculations was carried out for 1(2+) and 2 in their singlet and triplet ground states, respectively. The nature of low-energy electronic transitions was explored by using time-dependent DFT methods. Five redox states were reversibly accessible for each of the complexes; all odd-electron intermediates exhibit comproportionation constants K-c > 10(8). UV-visible-NIR spectroelectrochemistry and EPR spectroscopy of the electrogenerated paramagnetic intermediates were used to ascertain the oxidation-state distribution. In general, the complexes 1(n+) prefer the ruthenium(ii) configuration with electron transfer occurring largely at the bridging ligand (mu-H2Ln-), as evident from radical-type EPR spectra for 1(3+) and 1(+). Higher metal oxidation states (111, iv) appear to be favored by the complexes 2(m); intense long-wavelength absorption bands and Ru-III-type EPR signals suggest mixed-valent dimetal configurations of the paramagnetic intermediates 2(+) and 2(-)

A solution processable fluorene–fluorenone oligomer with aggregation induced emission enhancement

Herein, we report a novel solution processable fluorenone based small molecule with an Aggregation Induced Emission Enhancement (AIEE) property. In contrast to previous reports, the presence of the fluorenone moiety in FF triggers the AIEE property