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Optimizing antimicrobial therapy to attain drug exposure that limits the emergence of resistance, effectively treats the infection, and reduces the risk of side effects is of a particular importance in critically ill patients, in whom normal functions are augmented or/and are infected with pathogens less sensitive to treatment. Achievement of these goals can be enhanced by therapeutic drug monitoring (TDM) for many antibiotics. A liquid chromatography tandem mass spectrometry (LC-MS/MS) method is presented here for simultaneous quantification of ten antimicrobials: cefazolin (CZO), cefepime (CEP), cefotaxime (CTA), ceftazidime (CTZ), ciprofloxacin (CIP), flucloxacillin (FLU), linezolid (LIN), meropenem (MER), piperacillin (PIP) and tazobactam (TAZ) in human plasma.Plasma samples were precipitated with acetonitrile and injected into the LC-MS/MS. Chromatographic separation was on a Waters Acquity BEH CThe calibration curves were linear across the tested concentration ranges (0.5-250, CZO, CEP, CTA, CTZ and FLU; 0.2-100, MER and TAZ; 0.1-50, CIP and LIN and 1-500 mg/L, PIP). The intra and inter-day imprecision was 11 %. Accuracy ranged from 95 to 114 %. CTZ and MER showed ionization suppression while CIP showed ionization enhancement, which was normalized with the use of the internal standard.An LC-MS/MS method for simultaneous quantification of ten antimicrobials in human plasma was developed for routine TDM.

Background:Radial head fractures are common elbow injuries in adults and are frequently associated with additional soft tissue and bone injuries.Methods:A literature search was performed and the authors’ personal experiences are reported.Results:Mason type I fractures are treated non-operatively with splinting and early mobilisation. The management of Mason type II injuries is less clear with evidence supporting both non-operative treatment and internal fixation. The degree of intra-articular displacement and angulation acceptable for non-operative management has yet to be conclusively defined. Similarly the treatment of type III and IV fractures remain controversial. Traditional radial head excision is associated with valgus instability and should be considered only for patients with low functional demands. Comparative studies have shown improved results from internal fixation over excision. Internal fixation should only be attempted when anatomic reduction and initiation of early motion can be achieved. Authors have reported that results from fixation are poorer and complication rates are higher if more than three fragments are present. Radial head arthroplasty aims to reconstruct the native head and is indicated when internal fixation is not feasible and in the presence of complex elbow injuries. Overstuffing of the radiocapitellar joint is a frequent technical fault and has significant adverse effects on elbow biomechanics. Modular design improves the surgeon’s ability to reconstruct the native joint. Two randomised controlled trials have shown improved clinical outcomes and lower complication rate following arthroplasty when compared to internal fixation.Conclusion:We have presented details regarding the treatment of various types of radial head fractures - further evidence, however, is still required to provide clarity over the role of these different management strategies.

Background:The elbow is the second most commonly dislocated joint in adults and up to 20% of dislocations are associated with a fracture. These injuries can be categorised into groups according to their mechanism and the structures injured.Methods:This review includes a literature search of the current evidence and personal experiences of the authors in managing these injuries.Results:All injuries are initially managed with closed reduction of the ulno-humeral joint and splinting before clinical examination and radiological evaluation. Dislocations with radial head fractures should be treated by restoring stability, with treatment choice depending on the type and size of radial head fracture. Terrible triad injuries necessitate operative treatment in almost all cases. Traditionally the LCL, MCL, coronoid and radial head were reconstructed, but there is recent evidence to support repairing of the coronoid and MCL only if the elbow is unstable after reconstruction of lateral structures. Surgical treatment of terrible triad injuries carries a high risk of complications with an average reoperation rate of 22%. Varus posteromedial rotational instability fracture-dislocations have only recently been described as having the potential to cause severe long-term problems. Cadaveric studies have reinforced the need to obtain post-reduction CT scans as the size of the coronoid fragment influences the long-term stability of the elbow. Anterior dislocation with olecranon fracture has the same treatment aims as other complex dislocations with the added need to restore the extensor mechanism.Conclusion:Complex elbow dislocations are injuries with significant risk of long-term disability. There are several case-series in the literature but few studies with sufficient patient numbers to provide evidence over level IV.

Recent literature has claimed that inhibition of the enzyme MTH1 can eradicate cancer. MTH1 is one of the "housekeeping" enzymes that are responsible for hydrolyzing damaged nucleotides in cells and thus prevent them from being incorporated into DNA. We have developed orthogonal and chemically distinct tool compounds to those published in the literature to allow us to test the hypothesis that inhibition of MTH1 has wide applicability in the treatment of cancer. Here we present the work that led to the discovery of three structurally different series of MTH1 inhibitors with excellent potency, selectivity, and proven target engagement in cells. None of these compounds elicited the reported cellular phenotype, and additional siRNA and CRISPR experiments further support these observations. Critically, the difference between the responses of our highly selective inhibitors and published tool compounds suggests that the effect reported for the latter may be due to off-target cytotoxic effects. As a result, we conclude that the role of MTH1 in carcinogenesis and utility of its inhibition is yet to be established.

One of the main aims of bone tissue engineering is to produce three-dimensional soft bone tissue constructs of acceptable clinical size and shape in bioreactors. The tissue constructs have been proposed as possible replacements for diseased or dysfunctional bones in the human body through surgical transplantations. However, because of certain restrictions to the design and operation of the bioreactors, the size of the tissue constructs attained are currently below clinical standards. We believe that understanding the fluid flow and nutrient transport behaviour in the bioreactors is critical in achieving clinically viable constructs. Nevertheless, characterization of transport behaviour in these bioreactors is not trivial. As they are very small in size and operate under stringent conditions, in-situ measurements of nutrients are almost impossible. This issue has been somewhat resolved using computational modelling in previous studies. However, there is still a lack of certainty on the suitability of bioreactors. To address this issue we systematically compare the suitability of three bioreactors for growing bone tissues using mathematical modelling tools. We show how nutrient transport may be improved in these bioreactors by varying the operating conditions and suggest which bioreactor may be best suited for operating at high cell densities in order to achieve soft bone tissues of clinical size. The governing equations defined in our mathematical frameworks are solved through finite element method. The results show that the hollow fibre membrane bioreactor (HFMB) is able to maintain higher nutrient concentration during operation at high cell densities compared to the other two bioreactors, namely suspended tube and confined profusion type bioreactor. Our results show that by varying the operating conditions nutrient transport may be enhanced and the nutrient gradient can be substantially reduced. These are consistent with previous claims suggesting that the HFMB is suited for bone tissue growth at high cell densities.

In 2004, YWCA England & Wales began a two-year action research project with young women made possible with a grant from Big Lottery Fund. The research comprised four co-operative inquiry groups of young women in different geographical locations and of different composition. Each group met regularly and inquires, together with two YWCA project workers, about safe expression of sexuality and young women's sexual health. This article gives a practical account of the initial stages of the research; explores the challenges of doing co-operative inquiry and offers recommendations for other researchers who consider using this method. Particular attention is given to the challenges of working collaboratively in a hierarchical organization. It is argued that to establish collaborative relationships within the inquiry groups, similar relationships need to be demonstrated by the organization's staff and established within the organization's structures.

Aviation passenger traffic is forecast to grow significantly over the next decade and beyond. To accommodate this growth will require investment in airport infrastructure, including terminals. These buildings represent large, lumpy investments, so it is important to provide the capacity to accommodate the forecast traffic. However, this depends on at least two factors: the accuracy of the forecast of future demand, and the process of translating these forecasts into designs. Error in either factor can be potentially catastrophic financially. Translating forecasts into designs depends on ‘rules of thumb’ formulae that convert design hour flows into area requirements for each terminal facility. This paper examines the process of translating demand forecasts into conceptual terminal designs. The basic methods used are outlined, and how they affect the conceptual terminal design process are revealed. A model for conceptual terminal design is derived, presented and validated based on a sample of UK ai...

Eggs are truly a functional food and the ability of the egg to contribute to food systems is important. The current study was undertaken to determine the changes in functional characteristics and quality factors of commercial shell eggs during 10 wk of 4°C storage. Commercially processed eggs were collected for three consecutive weeks (reps) from an in-line facility. Analyses were conducted the day after collection (0 wk) and each subsequent week. Total solids for the albumen, yolk and whole egg were determined. Functional properties were examined via preparation of angel food cakes, mayonnaise and sponge cakes. Color was also measured for both raw yolks and prepared mayonnaise. Albumen solids were fairly consistent during storage (12.2 to 12.6%). Whole egg solids remained constant. Yolk solids decreased throughout storage (48.2 to 43.2%). Angel food cake volume decreased as the egg aged. Sponge cake volumes were inconsistent throughout testing with no clearly apparent trends. Mayonnaise was tested immediately after preparation (fresh) and incubation at 50°C for 7 d. In both cases, the average force required to compress the mayonnaise decreased with egg age. Differences were detected for changes in color values (L*, a* and b*) for yolks over time, but these changes were not generally of a magnitude great enough to be seen by the human eye. Most of the measured parameters exhibited significant interactions for replicate and egg storage. These interactions show that variability exists within the testing methods and more objective methods for determining shell egg functionality need to be developed.

OBJECTIVES To determine the efficacy and safety of botulinum toxin-B (BTX-B) in two groups of patients with urodynamically proven idiopathic detrusor overactivity (IDO) or neurogenic DO (NDO) refractory to conservative treatment. METHODS This was a nonrandomized, prospective study. We diluted 5000 U of BTX-B in 20 mL of normal saline and injected it at 20 sites around the bladder, avoiding the trigone. The data collected at recruitment and 10 and 26 weeks postoperatively included number of incontinent episodes, frequency, and nocturia, King's Health Questionnaire score, and the urodynamic parameters of volume at the first overactive contraction and maximal cystometric capacity. RESULTS A total of 25 patients were recruited, 20 with IDO and 5 with NDO. Only 7 patients, all with IDO, reported symptomatic improvement at the 10-week assessment. The symptoms had returned in these 7 patients at a median of 136 days (range 106 to 151) after injection. Of the remaining 20 patients, 16 (13 with IDO and 3 with NDO) thought an initial improvement had occurred but it had worn off or was wearing off by the first assessment. Two patients (both with NDO) reported no improvement. CONCLUSIONS BTX-B had a limited duration of action, with most of its symptomatically beneficial effects wearing off by 10 weeks in most of our patients. The short duration of action for BTX-B suggests it is unlikely to gain widespread use in the treatment of DO.

We describe a method of tailoring the laser spectrum of Fabry-Perot (FP) laser diodes using a spatially varying refractive index. The cavity geometry is determined by a perturbative transmission matrix calculation of the threshold gain of the longitudinal modes and solution of the corresponding inverse problem. Single-mode FP lasers with predetermined wavelength, and two-color FP lasers with predetermined mode spacing in the terahertz region are designed and experimentally demonstrated.

Total aerobic bacteria, molds/yeasts, coliforms and pseudomonads in the air in three shell egg processing operations (in-line, off-line and mixed operations) were determined using MicroBio MB2 Air Samplers. Sites were sampled from each facility on three different days (replication) during the same week. Four air samples (1000 L each) were drawn from each sampling site on a given day. Sampling sites, included areas in or near the following on-site locations: hen house (in-line and mixed operations), farm transition room (in-line and mixed operations), egg washers, egg dryer, packer heads, post-processing cooler, nest-run cooler (off-line and mixed operations), loading dock and dry storage. Type of operation (in- line, off-line or mixed), sampling site and the interaction between operation and site had a significant effect on the number of total aerobic bacteria, molds/yeasts, coliforms and pseudomonads recovered (P < 0.05). Highest counts for total aerobic bacteria (5.9 log cfu/ml air), molds/yeasts (4.0 log cfu/ml air) and coliforms 10 10 (2.5 log cfu/ml air) were found in the hen house. Highest counts for pseudomonads were found in the hen 10 house (3.2 log cfu/ml air) and behind the egg washer (3.5 log cfu/ml air). Lowest counts for total aerobic 10 10 bacteria (2.5 log cfu/ml air) and molds/yeast (2.7 log cfu/ml air) were found in the post-processing cooler. 10 10 Few samples in the post-processing coolers, nest-run coolers, loading docks and dry storage areas tested positive for coliforms (0/36, 2/24, 1/36 and 0/36, respectively) and pseudomonads (1/36, 2/24, 5/36 and 6/36, respectively). Data gathered during this study has been useful in identifying the sources and levels of airborne contaminates in commercial shell egg processing facilities.

Self-pulsating laser diodes operating at 650 nm are required in high-density optical storage devices. By growing saturable absorbing quantum wells in the p-doped cladding layer of a laser it is possible to obtain the interplay between gain and absorption that is required for pulsation. A self-pulsating AlGaInP laser is modelled in order to gain an insight into how the distance between the active and absorber layers affects the laser output. Results indicate that the device performance can be altered significantly as the distance changes, showing that this design feature is a key parameter for optimum performance.

Self-pulsating laser diodes operating at a wavelength of 650 nm are required in optical storage devices. Pulsation can be achieved by including saturable absorbing quantum wells in the p-doped cladding layer of an AlGaInP laser. A rate equation model of this kind of device is used to analyze the power output of the pulses by varying the cavity length and the absorber quantum-well configuration. Results indicate that certain performance tradeoffs occur between the power output and other characteristics that are subject to optical storage device constraints.

We previously reported that complement-dependent haemolysis of sheep erythrocytes (E) coated with mannan (M) and sensitized with human mannan-binding lectin (MBL) via the lectin pathway in man occurs in Mg-EGTA and requires alternative pathway amplification. Calcium was required for MBL binding to E-M, but once the E-M-MBL intermediate was formed, MBL was retained and haemolysis occurred in the absence of calcium. Comparable or greater lectin pathway haemolysis in the absence of calcium was observed upon incubation of E-M-MBL in guinea-pig, rat, dog and pig sera, and was further investigated in the guinea-pig, in which titres were much higher (∼14-fold) than in man, and in contrast to humans, greater than classical pathway haemolytic activity. As in human serum, no lysis was observed in C4- or C2-deficient guinea-pig serum until purified C4 or C2, respectively, were restored. However, lectin pathway haemolytic activity in the guinea-pig did not require the alternative pathway. Removal (>98%) of factor D activity by three sequential passages through Sephadex G-75, resulting in serum which retained a normal classical pathway but no alternative pathway haemolytic activity, did not reduce the ability of guinea-pig serum to mediate haemolysis via the lectin pathway. Further, the C3-convertase formed via the lectin pathway (E-M-MBL-C4,2) lysed in C2-deficient guinea-pig but not human serum chelated with EDTA, a condition which precludes alternative pathway amplification. Thus, lectin pathway haemolysis occurs efficiently in guinea-pig serum, in the absence of calcium and without requirement for alternative pathway amplification. The guinea-pig provides a model for studying the assembly and haemolytic function of a lectin pathway which contrasts with the lectin pathway of man, and allows for comparisons that may help clarify the role of this pathway in complement biology.

The use of soil amendments to immobilize 137 Cs in the soil and/or reduce its uptake by plants was investigated. Field plots in contaminated upland areas of the British Isles (Cwm Eigiau and Corney Fell) was treated with AFCF (ammonium ferric hexacyanoferrate), bentonite, clinoptilolite and muriate of potash (potassium chloride). The 137 Cs concentration of vegetation and soil were monitored for three years after treatment. The 137 Cs concentration and transfer coefficient of vegetation from both treated and control plots exhibited a seasonal variation with peaks in early summer and were affected by plant species. Some treatments, particularly muriate of potash and clinoptilolite, produced marked reductions in the 137 Cs transfer coefficient of the bulk vegetation and individual species especially at Cwm Eigiau.

Self-pulsating laser diodes operating at a wavelength of 650 nm are attractive for high-density optical storage. The main candidate for such a device is an AlGaInP laser diode including an epitaxially integrated saturable absorber. The characteristic self-pulsation occurs due to the interplay between gain in the active region and the absorption within the structure. In the paper, we calculate the dynamics of self-pulsation in this type of AlGaInP laser diode, including a detailed description of gain and absorption within the relative sections. In particular, we identify how, by modifying the structure of the epitaxial absorber layers, we can alter the operating characteristics of these laser diodes.