In the mind's eye : thought-pictures and ethereal presences

"The fascination with dreams and states of inwardness in the Victorian era derived part of its character from models of mind, descending from classical philosophy and from seventeenth-century interpretations of the tradition, but these ideas are enmeshed with theories of optics and the increasing potential vision of optical devices. So a double pulse runs rhythmically through time: optics expand and channel vision, amplifying the mind’s own processes; at the same time visionary ambitions make optics work to serve their needs, which include the apprehension of spirits existing out of range of ordinary physical faculties.

Communities of fate: magical writing and contemporary fabulism

Prophecies or curses often open a myth or fairy tale, and the story sub-sequently unfolds in accordance with what they have announced. Classical tragicmyth, for example about Oedipus or Dido, takes place in this form of predestinedtime and includes such speech acts; the plots of fairy tales, especially the storiesofThe Thousand and One Nights, also frequently turn on spells and oracles. Thisfatalism, as it has been called, has been generally criticized and often associatedwith passivity and superstition, both perceived as“oriental.”Can these narrativedevices be looked at in a different light? And do the stories themselves act as mag-ical writing, with purposes of preventing harm and averting danger? Writers ofcontemporary“world literature”are increasingly turning to myth and fable be-cause the forms offer them ways of commenting, Cassandra-like, on the fate oftheir countries and communities

The Pinwill Sisters

This study of the Pinwill Sisters traces their woodcarving designs across Cornwall and Devon, emphasizing their place as part of a wider aesthetic revolution. It addresses in particular the skill and craft of Violet Pinwill (1874–1957), studying her artistry alongside other woodcarvers such as Grinling Gibbons (1648–1721), as well as artists later into the twentieth century (Barbara Hepworth and John Skeaping)

Activity of OP0595-β-lactam combination against Gram-negative bacteria with extended-spectrum, AmpC and carbapenem-hydrolysing β-lactama

Background: OP0595 is a diazabicyclooctane that (i) acts as a PBP2-ctive antibacterial, (ii) inhibits Class A and C β-lactamases and (iii), like mecillinam, gives β-lactamase-independent potentiation of β-lactams targeting other PBPs. We tested its behaviour against β-lactam-resistant Enterobacteriaceae and non-fermenters. Methods: Organisms were UK clinical isolates; MICs were determined by CLSI agar dilution for OP0595 alone or combined at 1–4 mg/L with aztreonam, biapenem, cefepime or piperacillin. Results: MICs of OP0595 for Escherichia coli, Enterobacter, Citrobacter and Klebsiella spp. were mostly 1–4 mg/L but values >4 mg/L were seen for minorities of isolates irrespective of other resistances, and for 50%–60% of those with ertapenem resistance involving porin loss plus ESBL or AmpC activity. OP0595 MICs for Serratia, Proteeae and non-fermenters mostly were >4 mg/L. When its MIC was ≤4 mg/L, OP0595's antibacterial activity dominated combination activity. For ‘OP0595-resistant’ (MIC >4 mg/L) isolates with Class A or C β-lactamases OP0595 achieved strong potentiation of substrate β-lactams, contingent on β-lactamase inhibition. β-Lactamase-independent potentiation was evident with aztreonam, cefepime and piperacillin—less so for biapenem—for many OP0595-resistant Enterobacteriaceae with Class B carbapenemases, which are not inhibited by OP0595. OP0595 acted solely as a β-lactamase inhibitor for non-fermenters. Conclusions: OP0595 inhibited Enterobacteriaceae, not non-fermenters; its combinations had broad activity versus Enterobacteriaceae, largely contingent on OP0595's antibacterial activity but also on inhibition of Class A and C β-lactamases and on the β-lactam-enhancer effect, which allowed activity against many OP0595-resistant metallo-β-lactamase-producing Enterobacteriaceae. For non-fermenters OP0595 acted only as a β-lactamase inhibitor

In vitro activity of cefepime/zidebactam (WCK 5222) against Gram-negative bacteria

Background: Diazabicyclooctanes (DBOs) inhibit class A, class C and some class D β-lactamases. A few also bind PBP2, conferring direct antibacterial activity and a β-lactamase-independent ‘enhancer' effect, potentiating β-lactams targeting PBP3. We tested a novel DBO, zidebactam, combined with cefepime. Methods: CLSI agar dilution MICs were determined with cefepime/zidebactam in a chequerboard format. Bactericidal activity was also measured. Results: Zidebactam MICs were ≤2 mg/L (mostly 0.12–0.5 mg/L) for most Escherichia coli, Klebsiella, Citrobacter and Enterobacter spp., but were >32 mg/L for Proteeae, most Serratia and a few E. coli, Klebsiella and Enterobacter/Citrobacter. The antibacterial activity of zidebactam dominated chequerboard studies for Enterobacteriaceae, but potentiation of cefepime was apparent for zidebactam-resistant isolates with class A and C enzymes, illustrating β-lactamase inhibition. Overall, cefepime/zidebactam inhibited almost all Enterobacteriaceae with AmpC, ESBL, K1, KPC and OXA-48-like β-lactamases at 1 + 1 mg/L and also 29 of 35 isolates with metallo-carbapenemases, including several resistant to zidebactam alone. Zidebactam MICs for 36 of 50 Pseudomonas aeruginosa were 4–16 mg/L, and the majority of AmpC, metallo-β-lactamase-producing and cystic fibrosis isolates were susceptible to cefepime/zidebactam at 8 + 8 mg/L. Zidebactam MICs for Acinetobacter baumannii and Stenotrophomonas maltophilia were >32 mg/L; potentiation of cefepime was frequent for S. maltophilia, but minimal for A. baumannii. Kill curve results largely supported MICs. Conclusion: Zidebactam represents a second triple-action DBO following RG6080, with lower MICs for Enterobacteriaceae and P. aeruginosa. Clinical evaluation of cefepime/zidebactam must critically evaluate the reliance that can be placed on this direct antibacterial activity and on the enhancer effect as well as β-lactamase inhibition

Potential of high-dose cefepime/tazobactam against multi-resistant Gram-negative pathogens

Background: Early β-lactamase inhibitors were combined with established penicillins, but different combinations may be more appropriate to counter current β-lactamase threats, with development facilitated by the US Generating Antibiotic Incentives Now (GAIN) Act. Cefepime/tazobactam is especially attractive, combining an AmpC-stable cephalosporin with a clinically established inhibitor, active against ESBLs and suitable for high-dose administration. Methods: Organisms (n = 563) were clinical isolates submitted to the UK national reference laboratory. MICs were determined by CLSI agar dilution with tazobactam at 4 mg/L and, for a subset, at 8 mg/L. Results: Cefepime/tazobactam 8 + 4 mg/L achieved coverage of 96%–100% of Enterobacteriaceae with penicillinases, AmpC, ESBL, K1 or OXA-48 β-lactamases. Even at 1 + 4 mg/L, the combination inhibited >94% of isolates with penicillinases, AmpC enzymes or ESBLs. Most Enterobacteriaceae with KPC and NDM carbapenemase were resistant at current cefepime breakpoints but 80% of those with VIM types were susceptible at 8 + 4 mg/L. Tazobactam did little to potentiate cefepime against non-fermenter groups, though gains were seen against AmpC-producing Acinetobacter spp. and Stenotrophomonas maltophilia. Increasing the tazobactam concentration to 8 mg/L gave further small increases in activity against Enterobacteriaceae groups. Conclusions: High-dose cefepime/tazobactam, justifying an 8 + 4 or 8 + 8 mg/L breakpoint, can achieve a carbapenem-like spectrum, with some additional coverage of OXA-48 (and maybe VIM) Enterobacteriaceae. Clinical evaluation is warranted