Approaching zero : temporal effects of a restrictive antibiotic policy on hospital-acquired Clostridium difficile, extended-spectrum β-lactamase-producing coliforms and meticillin-resistant Staphylococcus aureus

A restrictive antibiotic policy banning routine use of ceftriaxone and ciprofloxacin was implemented in a 450-bed district general hospital following an educational campaign. Monthly consumption of nine antibiotics was monitored in defined daily doses (DDDs) per 1000 patient-occupied bed-days (1000 pt-bds) 9 months before until 16 months after policy introduction. Hospital-acquired Clostridium difficile, meticillin-resistant Staphylococcus aureus (MRSA) and extended-spectrum -lactamase (ESBL)- producing coliform cases per month/1000 pt-bds were identified and reviewed throughout the hospital. Between the first and final 6 months of the study, average monthly consumption of ceftriaxone reduced by 95% (from 46.213 to 2.129 DDDs/1000 pt-bds) and that for ciprofloxacin by 72.5% (109.804 to 30.205 DDDs/1000 pt-bds). Over the same periods, hospital-acquisition rates for C. difficile reduced by 77% (2.398 to 0.549 cases/1000 pt-bds), for MRSA by 25% (1.187 to 0.894 cases/1000 pt-bds) and for ESBL-producing coliforms by 17% (1.480 to 1.224 cases/1000 pt-bds). Time-lag modelling confirmed significant associations between ceftriaxone and C. difficile cases at 1 month (correlation 0.83; P < 0.005), and between ciprofloxacin and ESBL-producing coliform cases at 2 months (correlation 0.649; P = 0.002). An audit performed 3 years after the policy showed sustained reduction in C. difficile rates (0.259 cases/1000 pt-bds), with additional decreases for MRSA (0.409 cases/1000 pt-bds) and ESBL-producing coliforms (0.809 cases/1000 pt-bds). In conclusion, banning two antibiotics resulted in an immediate and profound reduction in hospital-acquired C. difficile, with possible longer-term effects on MRSA and ESBL-producing coliform rates. Antibiotic stewardship is fundamental in the control of major hospital pathogens

The Immune Landscape of Cancer

We performed an extensive immunogenomic anal-ysis of more than 10,000 tumors comprising 33diverse cancer types by utilizing data compiled byTCGA. Across cancer types, we identified six im-mune subtypes\u2014wound healing, IFN-gdominant,inflammatory, lymphocyte depleted, immunologi-cally quiet, and TGF-bdominant\u2014characterized bydifferences in macrophage or lymphocyte signa-tures, Th1:Th2 cell ratio, extent of intratumoral het-erogeneity, aneuploidy, extent of neoantigen load,overall cell proliferation, expression of immunomod-ulatory genes, and prognosis. Specific drivermutations correlated with lower (CTNNB1,NRAS,orIDH1) or higher (BRAF,TP53,orCASP8) leukocytelevels across all cancers. Multiple control modalitiesof the intracellular and extracellular networks (tran-scription, microRNAs, copy number, and epigeneticprocesses) were involved in tumor-immune cell inter-actions, both across and within immune subtypes.Our immunogenomics pipeline to characterize theseheterogeneous tumors and the resulting data areintended to serve as a resource for future targetedstudies to further advance the field

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Cyanoacetylenes and cyanoacetylides: versatile ligands in organometallic chemistry

The nitrile like lone pair of the cyanoacetylene PhCequivalent toCCequivalent toN (1) has been found to coordinate readily to the Ru(PPh3)(2)Cp fragment, to give [Ru(Nequivalent toCCequivalent toCPh)(PPh3)(2)Cp]PF6 (2) which may be considered its an "extended" derivative of the more common benzonitrile complex [Ru(Nequivalent toCPh)(PPh3)(2)Cp]PF6 (3). Reaction of 1 with [Co-2(CO)(6)(dppm)] readily forms the mu,eta(2) complex [Co-2(mu,eta(2)-PhC(2)Cequivalent toN)(CO)(4)(dppm)] (4), which reacts with [RuCl(PPh3)(2)Cp] to give the mixed metal species [{Co-2(mu,eta(2)-PhC(2)Cequivalent toN) {Ru(PPh3)(2)Cp}(CO)(4)(mu-dppm)}]PF6 (5). The eta(1)(N) bonded PhCequivalent toCCequivalent toN ligand is labile, being displaced by NCMe at ambient temperature to afford [Ru(NCMe)(PPh3)(2)Cp]PF6, or by tcne to give trans-[{Ru(PPh3)(2)Cp}(2)(mu-tcne)}][PF6](2) (9). The metallocyanoacetylide [Ru(Cequivalent toCCequivalent toN)(PPh3)(2)Cp] (6) was prepared by lithiation (BuLi) of [Ru(Cequivalent toCH)(PPh3)(2)Cp] followed by treatment with PhOCN. Coordination of the metal fragments Ru(PPh3)(2)Cp or Fe(dppe)Cp to the N terminus in 6 occurs readily to give the homo- or hetero-bimetallic cations [{Cp(PPh3)(2)Ru}(mu-Cequivalent toCCequivalent toN){ML2Cp}](+), which were isolated as the PF6 salts [ML2Cp=Ru(PPh3)(2)Cp (7); Fe(dppe)Cp (8)]. The crystal structures of 2-5, 7 and 9 are reported. The electrochemical response of these complexes suggests there are considerable electronic interactions between the heterometallic end-caps in 8 through the polarised C3N bridge

935. VACHELLIA ANEGADENSIS

Vachellia anegadensis (Britton) Seigler & Ebinger, a spiny tree endemic to the British Virgin Islands (BVI), a Caribbean UK Overseas Territory, is described and illustrated. It is one of the four known endemic plant species to occur in the BVI, an archipelago of only 153 km2. It has been assessed as Endangered (EN) based on the IUCN categories and criteria. Its botanical history and conservation status are described, and ex situ propagation discussed

Parthenogenic blastocysts cultured under in vivo conditions exhibit proliferation and differentiation expression genes similar to those of normal embryos

Parthenote embryos offer multiple possibilities in biotechnological investigation, such as stem cell research. However, there is still a dearth of knowledge of this kind of embryo. In this study, development and ploidy were analysed in parthenotes under in vitro and in vivo culture conditions. Subsequently, using real-time PCR, the expressions of factor OCT-4, Vascular Endothelial Growth Factor, Epidermal Growth Factor Receptor 3 and Transforming Growth Factor ß2 genes were analysed to compare the embryo types at the blastocyst stage. Development and implantation of parthenote embryos were described after transfer at day 10 of pregnancy. Parthenotes showed similar blastocyst development for both culture conditions and most of the parthenotes produced were diploid. However, parthenotes developed under in vivo conditions showed similar mRNA expression of OCT-4, VEGF and TGF-ß2 to 5 and 6 day old blastocysts. In contrast, parthenotes developed under in vitro conditions had altered the expression pattern of these genes, except for erbB3 mRNA. Finally, transferred parthenotes had the ability to implant but showed severe growth retardation and lesser size. This is the first demonstration of the influence of culture conditions on parthenote mRNA expression. Our study highlights the importance of culture conditions in subsequent uses of parthenotes, such as the production of stem cell lines. © 2011 Elsevier B.V.This work was supported by Generalitat Valenciana research program (Prometeo 2009-8260: 125) and by the Spanish Research Projects (CICYT AGL2008-03274). The authors thank Neil Macowan Language Services for revising the English version of the manuscript.Naturil Alfonso, C.; Saenz De Juano Ribes, MDLD.; Peñaranda, D.; Vicente Antón, JS.; Marco Jiménez, F. (2011). Parthenogenic blastocysts cultured under in vivo conditions exhibit proliferation and differentiation expression genes similar to those of normal embryos. Animal Reproduction Science. (127):222-228. https://doi.org/10.1016/j.anireprosci.2011.08.005S22222812