Antibiotic prophylaxis is associated with subsequent resistant infections in children with an initial extended-spectrum-cephalosporin-resistant Enterobacteriaceae infection

ABSTRACT The objective of this study was to assess the association between previous antibiotic use, particularly long-term prophylaxis, and the occurrence of subsequent resistant infections in children with index infections due to extended-spectrum-cephalosporin-resistant Enterobacteriaceae . We also investigated the concordance of the index and subsequent isolates. Extended-spectrum-cephalosporin-resistant Escherichia coli and Klebsiella spp. isolated from normally sterile sites of patients aged &lt;22 years were collected along with associated clinical data from four freestanding pediatric centers. Subsequent isolates were categorized as concordant if the species, resistance determinants, and fumC-fimH ( E. coli ) or tonB ( Klebsiella pneumoniae ) type were identical to those of the index isolate. In total, 323 patients had 396 resistant isolates; 45 (14%) patients had ≥1 subsequent resistant infection, totaling 73 subsequent resistant isolates. The median time between the index and first subsequent infections was 123 (interquartile range, 43 to 225) days. In multivariable Cox proportional hazards analyses, patients were 2.07 times as likely to have a subsequent resistant infection (95% confidence interval, 1.11 to 3.87) if they received prophylaxis in the 30 days prior to the index infection. In 26 (58%) patients, all subsequent isolates were concordant with their index isolate, and 7 (16%) additional patients had at least 1 concordant subsequent isolate. In 12 of 17 (71%) patients with E. coli sequence type 131 (ST131)-associated type 40-30, all subsequent isolates were concordant. Subsequent extended-spectrum-cephalosporin-resistant infections are relatively frequent and are most commonly due to bacterial strains concordant with the index isolate. Further study is needed to assess the role prophylaxis plays in these resistant infections. </jats:p

The Efficient Consumer Form Contract: Law and Economics Meet the Real World

Law and economics has been hailed by its supporters as the only intellectually valid means for analyzing legal issues. Its critics have dismissed law and economics as amoral and biased against the poor. Ironically, each side in this frequently acrimonious debate has much to offer those in the opposing camp. This Article reflects a modest attempt to bridge the chasm. One need not believe that money is everything in order to believe that the effect a given legal rule has on total societal wealth is relevant in decisionmaking. But this admission does not consign one to a legal world where the wealthy win as a matter of right and legal rulings are sold to the highest bidder. It may be surprising to the detractors of law and economics, but the proper application of principles of economic analysis need not lead to anti-poor results. If all relevant factors are considered, the concerns of fairness and of efficiency may coincide more often than partisans of either side in this debate have cared to admit. This article shows how a proper application of the principles of law and economics to the puzzle of interpreting consumer form contracts leads to a nuanced result that protects both parties to the transaction

Default, Foreclosure, and Strategic Renegotiation

Locum AB har i uppdrag av Stockholms läns landsting att förvalta vårdens fastigheter. För att underlätta för sina hyresgäster erbjuder Locum Facility Management-tjänster dit bland annat vaktmästeri och andra kringaktiviteter ingår. För att vara förberedda på och kunna anpassa sig efter hur deras hyresgästers behov har förändrats över tid vill de utföra en kartläggning över vilka arbetsuppgifter som deras upphandlade entreprenörer gör i dagsläget och ifall det går att effektivisera dessa. Detta ledde till denna rapport- Värdeflödeskartläggning över vaktmästeritjänsteleveransen vid Rosenlunds sjukhus och Mariamottagningarna, där en värdeflödeskartläggning genomförs för att kartlägga vilka arbetsuppgifter som utförs av vaktmästerientreprenören, om det går att identifiera några slöserier inom detta system och ifall dessa eventuella slöserier i går att eliminera eller minska. En värdeflödeskartläggning är ett verktyg där en verksamhets värdeflöden kartläggs med utgångspunkt med hur det ser ut i nuläget, och med ett framtaget framtida målläge med en uppfattning om hur det går att tänka sig att det borde fungera i framtiden. Med dessa som grund analyseras sedan nuläget för att identifiera slöserier, och utifrån dessa observationer och med målläget som utgångspunkt kan sedan en handlingsplan tas fram med syftet att eliminera dessa slöserier. Denna rapports fokus ligger främst på att kartlägga nuläget, och därefter analysera huruvida dessa slöserier går att minska. Rapporten ger en bild av vilka arbetsuppgifter som utförs av vaktmästerientreprenören i dagsläget, och hur dessa arbetsuppgifter utförs. Kartläggningen av vaktmästeritjänsteleveransen visade också att det fanns slöserier, men att dessa till största del berodde på anledningar som låg utanför entreprenörens kontroll. De enskilt största slöserierna som identifierades var väntan på hiss på Rosenlunds sjukhus och att vaktmästaren på Mariamottagningarna var tvungen att gå och hämta samt lämna post som skickades från hyresgästerna på ett postkontor. Rapporten ger förslag på hur dessa slöserier skulle kunna elimineras. Detta innebär att den tid som skulle kunna frigöras då skulle kunna läggas på att utföra andra arbetsuppgifter som adderar värde för hyresgästerna. I de nämnda fallen skulle dessa slöserier kunna elimineras genom förskjutna arbetstider så att aktiviteter som kräver hiss inte utförs då det är högt tryck på hissarna, samt att posten levereras och hämtas från Mariamottagningarna. Med den värdeflödeskartläggning som gjorts över nuläget på de båda vårdenheterna har beställaren av rapporten en möjlig grund att utgå ifrån för framtida arbete med att kunna erbjuda sina hyresgäster en bättre service och möjligheter till att bedriva sin verksamhet med bästa möjliga förutsättningar. Denna rapport visar också att det är möjligt att tillämpa en värdeflödeskartläggning på ett system där processerna kan variera sett över olika dagar. Detta då de modeller över hur värdeflödeskartläggningar inom administration och tjänster hittills till mestadels utförts på standardiserade stödjande processer inom tillverkningsindustrin

Repositioning the Catalytic Triad Aspartic Acid of Haloalkane Dehalogenase: Effects on Stability, Kinetics, and Structure

Haloalkane dehalogenase (DhlA) catalyzes the hydrolysis of haloalkanes via an alkyl-enzyme intermediate. The covalent intermediate, which is formed by nucleophilic substitution with Asp124, is hydrolyzed by a water molecule that is activated by His289. The role of Asp260, which is the third member of the catalytic triad, was studied by site-directed mutagenesis. Mutation of Asp260 to asparagine resulted in a catalytically inactive D260N mutant, which demonstrates that the triad acid Asp260 is essential for dehalogenase activity. Furthermore, Asp260 has an important structural role, since the D260N enzyme accumulated mainly in inclusion bodies during expression, and neither substrate nor product could bind in the active-site cavity. Activity for brominated substrates was restored to D260N by replacing Asn148 with an aspartic or glutamic acid. Both double mutants D260N+N148D and D260N+N148E had a 10-fold reduced kcat and 40-fold higher Km values for 1,2-dibromoethane compared to the wild-type enzyme. Pre-steady-state kinetic analysis of the D260N+N148E double mutant showed that the decrease in kcat was mainly caused by a 220-fold reduction of the rate of carbon-bromine bond cleavage and a 10-fold decrease in the rate of hydrolysis of the alkyl-enzyme intermediate. On the other hand, bromide was released 12-fold faster and via a different pathway than in the wild-type enzyme. Molecular modeling of the mutant showed that Glu148 indeed could take over the interaction with His289 and that there was a change in charge distribution in the tunnel region that connects the active site with the solvent. On the basis of primary structure similarity between DhlA and other α/β-hydrolase fold dehalogenases, we propose that a conserved acidic residue at the equivalent position of Asn148 in DhlA is the third catalytic triad residue in the latter enzymes.

Settlement Agreements, Legal Information and the Mistake of Law Rule in Contract

The extent of the doctrine of contractual mistake of law is evaluated in light of the Court of Appeal’s decision in Brennan v Bolt Burdon through the lens of economic efficiency, the associated incentivization of productive information acquisition and contractual risk allocation. The Brennan court’s decision limits the relief available for claims of mistake grounded in unanticipated changes in the law to mistakes involving exceptional errors. In so doing it acknowledges the risk inherent in accepting contractual settlement offers as a matter of commercial risk taking which can be offset through express contractual limitation, subject to public policy concerns. The article considers the effects of such contractual risk allocation as well as the cost of dispelling ignorance to recommend a clarification of the scope of the mistake of law. This rule is based upon the gains to be achieved from the underlying contract to the contractual parties as well advantages to society engendered by the dissemination of information about the law itself