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Nitrate fertilizer runoff poses chemical challenge for their remedial as relatively inert nitrate-oxoanions require stringent conditions for reduction. We present a novel strategy of using thiols RSH that represent biologically relevant reductants to convert nitrate to NO at a Cu(II) center under mild conditions with formation of disulfides RSSR. The bidentate b-diketiminato complex [Cl2NNF6]Cu(κ2-O2NO) engages in O-atom transfer (OAT) with various thiols (RSH) to form sulfenic acid (RSOH). Mechanistic studies indicate formation of the copper(II) nitrite complex [Cl2NNF6]Cu(κ2-O2N) upon OAT that further reacts with RSH to give S-nitrosothiols RSNO and [CuII]2(m-OH)2 en route to NO formation with [CuII]-SR intermediates. H2S, a physiologically potent agent and thiol congener, also reduces nitrate at copper(II) to NO generation, providing a lens into NO3-/H2S cross-talk in the biological milieu.

Periprosthetic joint infection (PJI) is a devastating complication in total hip and knee replacement. Its prevention is key to decrease the incidence and avoid some consequences that seriously impact patients and health systems. In view of the variety of recommendations and guidelines, we decided to conduct an expert, peer-reviewed European consensus analysis about the pre-, intra-, and postoperative prevention of PJI. A multinational group of practicing orthopedic experts developed a series of 47 consensus statements in 6 main groups of intervention, and a 2-stage Delphi approach was launched with a threshold for agreement at 75% and for very high agreement at more than 90%. A total of 306 orthopedic surgeon responses were gathered from 9 countries. Consensus was reached for 42/47 statements, 31/47 of which achieved a very high consensus. Many preoperative actions gathered strong consensus, although areas like the use of alcoholic chlorhexidine or the timing of hair removal did not attain strong consensus, despite available evidence. Intra- and postoperative actions showed more variability regarding incise drapes, skin suturing techniques, and wound follow-up. This study confirms an important consensus among orthopedic surgeons across Europe in many areas well known to contribute to the prevention of PJI; however, there are still grounds for improvement.

A case study has been developed to illustrate one way of incorporating a Quality by Design approach into formulation and process development for a small molecule, freeze-dried parenteral product. Sodium ethacrynate was chosen as the model compound. Principal degradation products of sodium ethacrynate result from hydrolysis of the unsaturated ketone in aqueous solution, and dimer formation from a Diels-Alder condensation in the freeze-dried solid state. When the drug crystallizes in a frozen solution, the eutectic melting temperature is above -5°C. Crystallization in the frozen system is affected by pH in the range of pH 6-8 and buffer concentration in the range of 5-50 mM, where higher pH and lower buffer concentration favor crystallization. Physical state of the drug is critical to solid state stability, given the relative instability of amorphous drug. Stability was shown to vary considerably over the ranges of pH and buffer concentration examined, and vial-to-vial variability in degree of crystallinity is a potential concern. The formulation design space was constructed in terms of pH and drug concentration, and assuming a constant 5 mM concentration of buffer. The process design space is constructed to take into account limitations on the process imposed by the product and by equipment capability.

The pore diffusion model is used to express the dry layer mass transfer resistance, [Formula: see text], as a function of the ratio r(e)/?, where r(e) is the effective pore radius and ? is the tortuosity factor of the dry layer. Using this model, the effective pore radius of the dry layer can be estimated from the sublimation rate and product temperature profiles measured during primary drying. Freeze-drying cycle runs were performed using the LyoStar II dryer (FTS Systems), with real-time sublimation rate profiles during freeze drying continuously measured by tunable diode laser absorption spectroscopy (TDLAS). The formulations chosen for demonstration of the proposed approach include 5% mannitol, 5% sucrose, 5% lactose, 3% mannitol plus 2% sucrose, and a parenteral nutrition formulation denoted VitaM12. The three different methods used for determination of the product resistance are: (1) Using both the sublimation rate and product temperature profiles, (2) using the sublimation rate profile alone, and (3) using the product temperate profile alone. Unlike the second and third methods, the computation procedure of first method does not need solution of the complex heat and mass transfer equations.

Expression of the mei3 gene is sufficient to induce meiosis in the fission yeast Schizosaccharomyces pombe. The mei3 gene is located 0.64 Mb from the telomere of the left arm of Sz. pombe chromosome II. We have sequenced and analysed 107 kb of DNA from the mei3 genomic region. The sequence includes 14 known genes (bag1-B, csh3, dps1, gpt1, mei3, mfm3, pac1, prp31, rpl38-1, rpn3, rti1, spa1, spm1 and ubc4) and 26 other open reading frames (ORFs) longer than 100 codons: a density of one protein-coding gene per 2.7 kb. Twenty-one of the 40 ORFs (53%) have introns. In addition there is one lone Tf1 transposon long terminal repeat (LTR), tRNATrp and tRNASer genes and a 5S rRNA gene. 14 of the novel ORFs show sequence similarities which suggest functions of their products, including a coatomer α-subunit, a catechol O-methyltransferase, protein kinase, asparagine synthetase, zinc metalloprotease, acetyltransferase, phosphatidylinositol 4-kinase, inositol polyphosphate phosphatase, GTPase-activating protein, permease, pre-mRNA splicing factor, 20S proteasome component and a thioredoxin-like protein. One predicted protein has similarity to the human Cockayne syndrome protein CSA and one with human GTPase XPA binding protein XAB1. Three ORFs are likely to code for proteins because they have sequence similarity with hypothetical proteins, three encode predicted coiled-coil proteins and four are sequence orphans. The sequence is derived from cosmid clones c4664, c119 and c557 and has been submitted to the EMBL database under Accession Nos AL591302, AL022117, AL110506 and AL023634 (part). Copyright © 2002 John Wiley & Sons, Ltd.

This study attempts to improve the delivery of health services by applying operations research techniques to hospital admission systems. Although this study applies to hospital admissions systems in general, the admission system of one ward of one hospital was chosen to be the central object in the study. A computer simulation model was formulated to examine the -results of various policies. In the model, the admission of patients is determined primarily by the scheduling of the operating theatre and secondarily by the availability of beds. The three standard priorities for hospital admissions (elective, urgent and emergent) are given separate considerations as would be the case in real life; because scheduling can be much more flexible for elective patients, while time must be set aside for emergent patients although the hospital has no advance information about them. The general results of this study led to two suggestions that would improve most existing admission systems. The first requires that the hospital set up a special class of patients, the "quickcall patients," who would be willing to be admitted for surgery on short notice. It was shown that this procedure significantly reduced the waiting time for elective surgery. The second requires that the hospital limit each physician to a fixed number of requests for elective surgery at any given time, so that the hospital need not keep extensive files. The model could be extended to examine (1) the sensitivity of the schedule to referral patients, (2) the higher utilization of the operating theatre and (3) waiting priority based on patient need and/or utility. In conclusion the simulation study indicated that these policies if implemented would significantly reduce the waiting time (29% in the model), and increase the hospital's effectiveness in assessing the order of admission for patients.