Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

Background Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide.Methods A multimethods analysis was performed as part of the GlobalSurg 3 study-a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital.Findings Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3.85 [95% CI 2.58-5.75]; p<0.0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63.0% vs 82.7%; OR 0.35 [0.23-0.53]; p<0.0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer.Interpretation Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised

Safety and efficacy of fluoxetine on functional outcome after acute stroke (AFFINITY): a randomised, double-blind, placebo-controlled trial

Background Trials of fluoxetine for recovery after stroke report conflicting results. The Assessment oF FluoxetINe In sTroke recoverY (AFFINITY) trial aimed to show if daily oral fluoxetine for 6 months after stroke improves functional outcome in an ethnically diverse population. Methods AFFINITY was a randomised, parallel-group, double-blind, placebo-controlled trial done in 43 hospital stroke units in Australia (n=29), New Zealand (four), and Vietnam (ten). Eligible patients were adults (aged ≥18 years) with a clinical diagnosis of acute stroke in the previous 2–15 days, brain imaging consistent with ischaemic or haemorrhagic stroke, and a persisting neurological deficit that produced a modified Rankin Scale (mRS) score of 1 or more. Patients were randomly assigned 1:1 via a web-based system using a minimisation algorithm to once daily, oral fluoxetine 20 mg capsules or matching placebo for 6 months. Patients, carers, investigators, and outcome assessors were masked to the treatment allocation. The primary outcome was functional status, measured by the mRS, at 6 months. The primary analysis was an ordinal logistic regression of the mRS at 6 months, adjusted for minimisation variables. Primary and safety analyses were done according to the patient's treatment allocation. The trial is registered with the Australian New Zealand Clinical Trials Registry, ACTRN12611000774921. Findings Between Jan 11, 2013, and June 30, 2019, 1280 patients were recruited in Australia (n=532), New Zealand (n=42), and Vietnam (n=706), of whom 642 were randomly assigned to fluoxetine and 638 were randomly assigned to placebo. Mean duration of trial treatment was 167 days (SD 48·1). At 6 months, mRS data were available in 624 (97%) patients in the fluoxetine group and 632 (99%) in the placebo group. The distribution of mRS categories was similar in the fluoxetine and placebo groups (adjusted common odds ratio 0·94, 95% CI 0·76–1·15; p=0·53). Compared with patients in the placebo group, patients in the fluoxetine group had more falls (20 [3%] vs seven [1%]; p=0·018), bone fractures (19 [3%] vs six [1%]; p=0·014), and epileptic seizures (ten [2%] vs two [<1%]; p=0·038) at 6 months. Interpretation Oral fluoxetine 20 mg daily for 6 months after acute stroke did not improve functional outcome and increased the risk of falls, bone fractures, and epileptic seizures. These results do not support the use of fluoxetine to improve functional outcome after stroke

Computational Studies of Small Boron Based Clusters

<w:latentstyles deflockedstate="false" defunhidewhenused="true" defsemihidden="true" defqformat="false" defpriority="99"  In this doctoral study, we carried out theoretical investigations on a series of small pure Bn and doped BnX, with n = 2-20 and X = Si, O and Li, boron clusters using quantum chemical calculations. The systematic searches for the lower-lying isomers of the clusters considered were performed using a stochastic search method which was developed by us. Where possible, the global minima were identified on the basis of theoretical results obtained by the highly accurate CCSD(T)/CBS and Gn computational methods. From geometrical features of the global minima, a growth mechanism for each series of the BnX clusters was established. The fundamental features such as chemical bonding, electronic distribution, aromaticity, were probed using the analyses of canonical molecular orbital (CMO) in combination with other indices obtained from the electron localization function (ELF), nuclear independent chemical shift (NICS) etc Quantitatively, different basic thermochemical properties of clusters such as total atomization energies, heats of formation, ionization energies, adiabatic and vertical detachment energies, binding energies and dissociation energies were calculated by using the CCSD(T)/CBS and Gn energies and compared to the available experimental data. Some general and important points emerge as follows.There is an overall good agreement between the CCSD(T)/CBS and Gn (G3B3 and G4) methods in determining the energetic properties of boron-based clusters. The difference of heats of formation at 0K obtained by these methods is in the range of 0.0 5.0 kcal/mol. Both methods also show good agreement with available experimental data. These results give us confidence that in the lack of experimental data, and also with limited computer resources, the energetic properties of boron clusters can be reliably determined by using the Gn methods (Chapter 2). Small pure boron clusters Bn with n up to 19 tend to exhibit planar and quasi-planar structures. While the B20 member has a three-dimensional tubular form, the 3D-structures found for either B9 or B14 appear to be the unexpected cases where the sizes of boron rings are not large enough to hold the planar tendency. For these two structures, the identity of the lowest-energy structures is however not definitely established yet, and this can only be done using CCSD(T)/CBS computations in the future (Chapter 3). Detachment of one electron from the neutrals tends to destabilize planar features of boron clusters, and the resulting cationic clusters Bn+ are thus favored to have three-dimensionalstructures at smaller sizes of n = 16 - 19. On the contrary, the anionic clusters Bn- with n up to 21 still exhibit planar shape. Interestingly, both B20- and B19- anionic clusters are found to exhibit aromatic andfluxional structures in which one small inner boron ring with a central B-atom is located inside one larger outer boronring. These novel features are expected to be found again for largeranionic boron clusters. Additionally, geometries of small boron clusters considered reveal that they are constructed on the basis of triangular B3 units with a classical bonding motif of three-center two-electron (3c 2e) (Chapter 3).One of the most intriguing features of small boron clusters is their aromaticity. Based on the NICS calculations, our predictions show that most, if not all, closed-shell boron clusters have an aromatic character. Interestingly, while there is a good agreement between various indices for evaluating aromatic features of small boron clusters Bn+/0/- with n &#8804; 13, the classical Hückel rule of (4N + 2) electrons is no longer valid for larger sizes. In the present work, we proposed in Chapter 4 the concept of a new type of aromaticity, termed as disk aromaticity, to interpret the bonding features of B19- and B20-. Accordingly, a cyclic cluster will be disk aromatic when its delocalized valence &#960;-electrons fully occupy the degenerate eigenstates given from the model of a particle in a circular box. This feature is also proven to be effective on other boron-carbon mixed clusters such as C5B11+/- and C6B120/2-. Additionally, the model is also successfully applied on polycyclic aromatic hydrocarbons (C24H12 and C20H10). In Chapters 5 and 6, we also determined the global minima and growth mechanism of doped boron clusters BnSi and BnLi in both anionic and neutral states. Lithium tends to donate its unique valence electron to the Bn host and thus form the ionic complexes Li&#948;+-Bn&#948;-. Consequently, thechemical bonding and aromaticity of BnLi0/- clusters are similar to those of Bn- and Bn2-, respectively. On the other hand, small silicon doped boron clusters BnSi with n &#8804; 6 are constructed in the motif where replacement of one boron atom of Bn+1 by one silicon atom. In this motif, Si however prefers a peripheral position of the ring and tends to connect with its two neighboringB-atoms forming a bridge. BnSi is built up by doping Si on the symmetry axis of the Bn host where Si is bound to B-atoms of the ring and possesses a high coordination number. As a consequence, the chemical bonding and aromaticity features of small silicon doped boron clusters BnSi0/- are similar to those Bn+1- and Bn+12-, respectively.The final project in this thesis relates to small boron oxides BnOm. The boron monoxides BnO are formed by either condensing O on a BB edge of a Bn cycle as a &#951;2-brigde or binding one BO boronyl group to a Bn-1 ring. The BO bond is particularly strong and its formation contributes to the overall stability of the new oxide. The balance between both factors is dependent on the inherent stability of the boron cycles.The boron dioxides are formed by incorporating the second O atom into the corresponding monoxides to form BO bonds. The anions BnOm- are constructed by binding the boronyl BO groups to the Bn-1 or Bn-2 rings to form the bonding motifof Bn-m(BO)m-. Interestingly, there is an analogy between geometries of the anions Bn-m(BO)m and those of corresponding Bn-mHm boron hydrides. Similar observation is found for boron trioxides B3(BO)3 in neutral, anionic and dianionic states. The dianion B3(BO)32- has high symmetry geometry in which three boronyl BO groups are bound to a triangle B3 ring. The boron oxides interestingly conserve some of the properties of theparent boron clusters such as the planarity and multiple aromaticity.Generally, the theoretical studies reported in the present thesis point out the structural formation and growth mechanism of small boron based clusters. The energetic properties were obtained with high degree of confidence by using high accuracy computational methods. These predictions will be very useful for future experimental and theoretical investigations. In further work, investigations on the larger sized clusters closing the gap between B20 and B80, and also on bulk materials based on the boron element are highly desirable. These materials are promising candidates for possible applications in hydrogen storage, captures of industrial gases (CO, CO2, NO ), and as possible catalysts for chemical reactions. Furthermore, with the presence of some good quality experimental photoelectron spectra, theoretical simulations of the photoelectron spectra on the anionic boron Bn- clusters in order to confirm their ground states open an interesting avenue for further studies on the detailed electronic structure. Different spectroscopic signatures including the vibrational (IR) spectra or the magnetic behaviors of open-shell ionic and neutral clusters also form a challenging subject of investigation where a close interaction between experiment and theory is necessary for further advancesOne of the most important contributions of this work is the introduction of the novel concept of disk aromaticity which turns out to be effective in the determination of aromatic features of polycyclic compounds. This concept needs to be applied to a larger range of heteroatomic polycyclic compounds such as, for example, the sulflower C16S8 and its hetero-derivatives. We expect that disk aromaticity would become one of the basic chemical concept and be widely used by chemists. <w:latentstyles deflockedstate="false" defunhidewhenused="true"  <w:lsdexception="" locked="false" priority="0" semihidden="false"  in="" this="" doctoral="" study,="" we="" carried="" out="" theoretical="" investigations="" on="" a="" series="" of="" small="" pure="" bn="" and="" doped="" bnx,="" with="" n="2-20" x="Si," o="" li,="" boron="" clusters="" using="" quantum="" chemical="" calculations.="" the="" systematic="" searches="" for="" lower-lying="" isomers="" considered="" were="" performed="" stochastic="" search="" method="" which="" was="" developed="" by="" us.="" where="" possible,="" global="" minima="" identified="" basis="" results="" obtained="" highly="" accurate="" ccsd(t)="" cbs="" gn="" computational="" methods. from="" geometrical="" features="" minima,="" growth="" mechanism="" each="" bnx="" established.="" fundamental="" such="" as="" bonding,="" electronic="" distribution,="" aromaticity, ="" probed="" analyses="" canonical="" molecular="" orbital="" (cmo)="" in="" combination="" other="" indices="" from="" electron="" localization="" function="" (elf),="" nuclear="" independent="" shift="" (nics)="" etc  quantitatively,="" different="" basic="" thermochemical="" properties="" total="" atomization="" energies,="" heats="" formation,="" ionization="" adiabatic="" vertical="" detachment="" binding="" energies="" dissociation="" calculated="" compared="" to="" available="" experimental="" data.="" some="" general="" important="" points="" emerge="" follows.there="" is="" an="" overall="" good="" agreement="" between="" (g3b3="" g4)="" methods="" determining="" energetic="" boron-based="" clusters.="" difference="" formation="" at="" 0k="" these="" range="" 0.0="" ="" 5.0="" kcal="" mol.="" both="" also="" show="" give="" us="" confidence="" that="" lack="" data,="" limited="" computer="" resources,="" can="" be="" reliably="" determined="" (chapter="" 2).  small="" up="" 19="" tend="" exhibit="" planar="" quasi-planar="" structures.="" while="" b20="" member="" has="" three-dimensional="" tubular="" form,="" 3d-structures="" found="" either="" b9="" or="" b14="" appear="" unexpected="" cases="" sizes="" rings="" are="" not="" large="" enough="" hold="" tendency.="" two="" structures,="" identity="" lowest-energy="" structures="" however="" definitely="" established="" yet,="" only="" done="" computations="" future="" 3). detachment="" one="" neutrals="" tends="" destabilize="" clusters,="" resulting="" cationic="" bn+="" thus="" favored="" have="" smaller="" -="" 19.="" contrary,="" anionic="" bn-="" 21="" still="" shape.="" interestingly,="" b20-="" b19-="" aromatic="" fluxional="" onesmall="" inner="" ring="" central="" b-atom="" located="" inside="" larger="" outer="" ring.="" novel="" expected="" again="" additionally,="" geometries="" reveal="" they="" constructed="" triangular="" b3="" units="" classical="" bonding="" motif="" three-center="" two-electron="" (3c="" 2e)="" 3).one="" most="" intriguing="" their="" aromaticity.="" based="" nics="" calculations,="" our="" predictions="" most,="" if="" all,="" closed-shell="" character.="" there="" various="" evaluating="" 0="" n &#8804;="" 13,="" hückel="" rule="" (4n="" +="" 2)="" electrons="" no="" longer="" valid="" sizes. computational="" studies="" clusterssummarystatus: publishe

Aromatic cage-like B-46: existence of the largest decagonal holes in stable atomic clusters

© The Royal Society of Chemistry. The most stable form of B 46 has a cage-like structure containing two hexagonal, two heptagonal and two decagonal holes. The intriguing presence of decagonal holes is a remarkable breakthrough since such large holes have never been found before for atomic clusters. This finding not only provides more insights into the growth motif of large-sized boron clusters, but also presents a new family of cage-like boron clusters containing large B N holes with N = 6-10.status: publishe

A new chiral boron cluster B44 containing nonagonal holes

The B44 cluster has a cage-like structure containing two hexagonal, two heptagonal and two nonagonal holes. The presence of nonagonal holes is a new and remarkable finding since they have never been reported before in clusters. The present work does not only identify the new chiral members, but also provide more insight into the growth motif of large-sized boron clusters.status: publishe

Aromatic cages B: unprecedented existence of octagonal holes in boron clusters

The cage-like structures containing octagonal holes are located as the lowest-lying isomers for the B. The presence of octagonal holes, which have been found for the first time, not only gives us new insight into the bonding motif, but also marks a breakthrough in the structural characteristics of boron clusters since they were never expected to be stable units for elemental clusters. These cages are composed of both delocalized σ and π electron systems that consequently make them aromatic and thermodynamically stable.status: publishe

A theoretical study on charge transport of dithiolene nickel complexes

Organic semiconducting materials play an important role in the fabrication of high performance organic electronic devices. In the present work, we theoretically designed a series of organic semiconductors based on nickel complexes. Their characteristics of charge transport were investigated using DFT computational approaches. Based on the computed results, all compounds designed are found to be excellent candidates for ambipolar organic semiconductors with low reorganization energies for both holes and electrons. The (I-V) characteristics and transmission spectra of materials show that the replacement of benzene rings by thiophene rings results in an increase of their HOMO and LUMO energy levels. HOMOs of compounds containing thiophene end-groups are likely dominant for their conductance, while LUMOs of compounds containing benzene end-groups mainly affect their conductance. The electron distribution in these frontier MOs is identified as the main reason which makes the conductance of the compounds in the first series higher than those in the later series.status: publishe

Design of novel tetra-hetero[8]circulenes: a theoretical study of electronic structure and charge transport characteristics

© 2015 The Royal Society of Chemistry. In the present work, a series of new tetra-hetero[8]circulenes were theoretically designed in which heteroatoms include O, S, Se and N. Their electronic structure and characteristics of charge transport were investigated using DFT based computational methods. Except for the compounds containing Se-atoms (3a and 3b), all remaining compounds exhibit planar and highly symmetrical structures featuring novel aromatic features: the inner eight-membered ring is anti-aromatic and the outer fused rings are aromatic. The predicted UV spectrum and reduction potential of 1a agree well with available experimental values. Following replacement of H-atoms by F-atoms, the energy levels of the frontier orbitals of 1b-4b are consistently decreased as compared to those of 1a-4a. Based on the calculated properties of electrochemistry and charge transport, the molecules 1a-4a and 4b are suggested to be good candidates for p-type semiconductors. More importantly, the molecules 1b-3b are revealed to be potential ambipolar organic semiconductors.status: publishe

Chemical Bonding and Aromaticity in Poly-heterocyclic Compounds

status: publishe