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We perform a stability analysis on a discrete analogue of a known, continuous model of mutualism. We illustrate how the introduction of delays affects the asymptotic stability of the system's positive nontrivial equilibrium point. In the second part of the paper we explore the insights that the model can provide when it is used in relation to interacting financial markets. We also note the limitations of such an approach. [ABSTRACT FROM AUTHOR]

Graphical abstract Abstract Osteoporosis and bone fractures occur at higher frequency in patients with inflammatory bowel disease (IBD), and decreased bone mass is observed in animal models of colitis. Another consistent feature of colitis is increased serotonin (5-HT) availability in the intestinal mucosa. Since gut-derived 5-HT can decrease bone mass, via activation of 5-HT 1B receptors on pre-osteoblasts, we tested the hypothesis that 5-HT contributes to bone loss in colitis. Colitis was chronically induced in mice by adding dextran sodium sulfate (DSS) to their drinking water for 21 days. At day 21, circulating 5-HT levels were elevated in DSS-inflamed mice. Micro-computed tomography of femurs showed a decrease in trabecular bone volume fraction, formation, and surface area, due largely to decreased trabecular numbers in DSS-treated mice. The colitis-induced loss of trabecular bone was significantly suppressed in mice treated with the 5-HT synthesis inhibitor, p-chloro-DL-phenylalanine (PCPA; 300 mg/kg/day IP daily), and in mice treated with the 5-HT 1B receptor antagonist GR55562 (1 mg/Kg/day SC daily). The 5-HT reuptake transporter (SERT) is critical for moving 5-HT from the interstitial space into enterocytes and from serum into platelets. Mice lacking SERT exhibited significant deficits in trabecular bone mass that are similar to those observed in DSS-inflamed mice, and these deficits were not extensively worsened by DSS-induced colitis in the SERT−/− mice. Taken together, findings from both the DSS and SERT−/− mouse models support a contributing role for 5-HT as a significant factor in bone loss induced by colitis. [ABSTRACT FROM AUTHOR]

We introduce delay dynamics to an ordinary differential equation model of tumour growth based upon von Bertalanffy's growth model, a model which has received little attention in comparison to other models, such as Gompertz, Greenspan and logistic models. Using existing, previously published data sets we show that our delay model can perform better than delay models based on a Gompertz, Greenspan or logistic formulation. We look for replication of the oscillatory behaviour in the data, as well as a low error value (via a Least-Squares approach) when comparing. We provide the necessary analysis to show that a unique, continuous, solution exists for our model equation and consider the qualitative behaviour of a solution near a point of equilibrium. [ABSTRACT FROM AUTHOR]

Nebulized antimicrobial agents are increasingly administered for treatment of respiratory infections in mechanically ventilated (MV) patients. A structured online questionnaire assessing the indications, dosages and recent patterns of use for nebulized antimicrobial agents in MV patients was developed. The questionnaire was distributed worldwide and completed by 192 intensive care units. The most common indications for using nebulized antimicrobial agent were ventilator-associated tracheobronchitis (VAT; 58/87), ventilator-associated pneumonia (VAP; 56/87) and management of multidrug-resistant, Gram-negative (67/87) bacilli in the respiratory tract. The most common prescribed nebulized agents were colistin methanesulfonate and sulfate (36/87, 41.3% and 24/87, 27.5%), tobramycin (32/87, 36.7%) and amikacin (23/87, 26.4%). Colistin methanesulfonate, amikacin and tobramycin daily doses for VAP were significantly higher than for VAT (p < 0.05). Combination of parenteral and nebulized antibiotics occurred in 50 (86%) of 58 prescriptions for VAP and 36 (64.2%) of 56 of prescriptions for VAT. The use of nebulized antimicrobial agents in MV patients is common. There is marked heterogeneity in clinical practice, with significantly different in use between patients with VAP and VAT. Randomized controlled clinical trials and international guidance on indications, dosing and antibiotic combinations to improve clinical outcomes are urgently required. [ABSTRACT FROM AUTHOR]

Abstract: The aims of this study were to describe the variability in protein binding of teicoplanin in critically ill patients as well as the number of patients achieving therapeutic target concentrations. This report is part of the multinational pharmacokinetic DALI Study. Patients were sampled on a single day, with blood samples taken both at the midpoint and the end of the dosing interval. Total and unbound teicoplanin concentrations were assayed using validated chromatographic methods. The lower therapeutic range of teicoplanin was defined as total trough concentrations from 10 to 20mg/L and the higher range as 10–30mg/L. Thirteen critically ill patients were available for analysis. The following are the median (interquartile range) total and free concentrations (mg/L): midpoint, total 13.6 (11.2–26.0) and free 1.5 (0.7–2.5); trough, total 11.9 (10.2–22.7) and free 1.8 (0.6–2.6). The percentage free teicoplanin for the mid-dose and trough time points was 6.9% (4.5–15.6%) and 8.2% (5.5–16.4%), respectively. The correlation between total and free antibiotic concentrations was moderate for both the midpoint (ρ =0.79, P =0.0021) and trough (ρ =0.63, P =0.027). Only 42% and 58% of patients were in the lower and higher therapeutic ranges, respectively. In conclusion, use of standard dosing for teicoplanin leads to inappropriate concentrations in a high proportion of critically ill patients. Variability in teicoplanin protein binding is very high, placing significant doubt on the validity of total concentrations for therapeutic drug monitoring in critically ill patients. [Copyright &y& Elsevier]

Abstract: Strong periodic stimuli such as bright flashing lights evoke nonlinear responses in the brain and interact nonlinearly with ongoing cortical activity, but the underlying mechanisms for these phenomena are poorly understood at present. The dominant features of these experimentally observed dynamics are reproduced by the dynamics of a quantitative neural field model subject to periodic drive. Model power spectra over a range of drive frequencies show agreement with multiple features of experimental measurements, exhibiting nonlinear effects including entrainment over a range of frequencies around the natural alpha frequency f α , subharmonic entrainment near 2f α , and harmonic generation. Further analysis of the driven dynamics as a function of the drive parameters reveals rich nonlinear dynamics that is predicted to be observable in future experiments at high drive amplitude, including period doubling, bistable phase-locking, hysteresis, wave mixing, and chaos indicated by positive Lyapunov exponents. Moreover, photosensitive seizures are predicted for physiologically realistic model parameters yielding bistability between healthy and seizure dynamics. These results demonstrate the applicability of neural field models to the new regime of periodically driven nonlinear dynamics, enabling interpretation of experimental data in terms of specific generating mechanisms and providing new tests of the theory. [Copyright &y& Elsevier]

Abstract: Dynamical properties of epileptic seizures are investigated using a recent compact continuum model for electric activity of the brain. Large amplitude limit cycles resembling electroencephalograms during epilepsy emerge when the system loses linear stability. Seizures that are confined to an onset area, or spread synchronously to other areas via spatial coupling, are studied and argued to be associated with clinical partial and secondarily generalized seizures, respectively. Suppression of such seizures is also demonstrated, which implies potential for future clinical applications. [Copyright &y& Elsevier]

Abstract: In a mid-continental North American grassland, solute concentrations in shallow, limestone-hosted groundwater and adjacent surface water cycle annually and have increased steadily over the 15-year study period, 1991–2005, inclusive. Modeled groundwater CO2, verified by measurements of recent samples, increased from 10−2.05 atm to 10−1.94 atm, about a 20% increase, from 1991 to 2005. The measured groundwater alkalinity and alkaline-earth element concentrations also increased over that time period. We propose that carbonate minerals dissolve in response to lowered pH that occurs during an annual carbonate-mineral saturation cycle. The cycle starts with low saturation during late summer and autumn when dissolved CO2 is high. As dissolved CO2 decreases in the spring and early summer, carbonates become oversaturated, but oversaturation does not exceed the threshold for precipitation. We propose that groundwater is a CO2 sink through weathering of limestone: soil-generated CO2 is transformed to alkalinity through dissolution of calcite or dolomite. The annual cycle and long-term increase in shallow groundwater CO2 is similar to, but greater than, atmospheric CO2. [Copyright &y& Elsevier]

Abstract: A field trial was carried out in West Java to investigate the potential for control of fasciolosis of antagonism between larvae of Fasciola gigantica and Echinostoma revolutum in Lymnaea rubiginosa. The trial was undertaken in 26 farmers’ irrigated rice fields, each chosen because it was adjacent to a cattle pen the effluent from which flowed into or was used as fertiliser in the rice field. Fourteen of the fields chosen at random were retained as controls and received no treatment while in 12, faeces from 5 to 15 ducks containing eggs of E. revolutum were introduced to the rice from a duck pen located over the effluent drain from the cattle pen before it emptied into the adjacent rice field, or at the site bovine faeces was added to the field as fertiliser. After harvest significantly fewer L. rubiginosa were found infected with F. gigantica in fields where duck and cattle dung entered the field together than in control fields, supporting a conclusion that this method of biological control would reduce the infectivity of rice fields fertilised with bovine dung (which are those with the highest potential for being a source of infection with F. gigantica). Positive features of using dung from ducks infected with E. revolutum to control F. gigantica are the minimum additional work and disruption to existing farming practices required to implement the scheme, the common natural infection with E. revolutum in village ducks, and effectiveness of dung from 5 to 15 ducks, a number commonly kept by farmers. [Copyright &y& Elsevier]

Objectives: To test the hypotheses that, compared with conventional outpatient consultations, joint teleconsultation (virtual outreach) would incur no increased costs to the NHS, reduce costs to patients, and reduce absences from work by patients and their carers. Design: Cost consequences study alongside randomised controlled trial. Setting: Two hospitals in London and Shrewsbury and 29 general practices in inner London and Wales. Participants: 3170 patients identified; 2094 eligible for inclusion and willing to participate. 1051 randomised to virtual outreach and 1043 to standard outpatient appointments. Main outcome measures: NHS costs, patient costs, health status (SF-12), time spent attending index consultation, patient satisfaction. Results: Overall six month costs were greater for the virtual outreach consultations (£724 per patient) than for conventional outpatient appointments (£625): difference in means £99 ($162; €138) (95% confidence interval £10 to £187, P=0.03). If the analysis is restricted to resource items deemed "attributable" to the index consultation, six month costs were still greater for virtual outreach: difference in means £108 (£73 to £142, P < 0.0001). In both analyses the index consultation accounted for the excess cost. Savings to patients in terms of costs and time occurred in both centres: difference in mean total patient cost £8 (£5 to £10, P < 0.0001). Loss of productive time was less in the virtual outreach group: difference in mean cost £11 (£10 to £12, P < 0.0001). Conclusion: The main hypothesis that virtual outreach would be cost neutral is rejected, but the hypotheses that costs to patients and losses in productivity would be lower are supported. [ABSTRACT FROM AUTHOR]

Focuses on the economic impact of prompt intervention in a nationwide outbreak of salmonellosis in Great Britain. Contamination of chocolate with Salmonella napoli; Rate of return on an investment in public health surveillance; Cost effectiveness of the collaboration between public health authorities and the industry.

Estimates the cost and benefits of chemoprophylaxis against travel acquired malaria, typhoid fever and hepatitis A in Great Britain. Analysis on the epidemiological and economic data of the country; Increase in the incidence of imported malaria; Effectiveness of chemoprophylaxis. INSET: Public health implications.

India's National Gas Hydrate Program Expedition 2 (NGHP-02) completed an ambitious pressure coring program as part of their effort to evaluate gas hydrate in coarse-grained reservoirs in the Bay of Bengal. The 75 successful pressure cores were used to measure gas hydrate saturation, examine the morphology of the gas hydrate at in situ conditions, and to provide samples for further laboratory work. Pressure core quality was assessed via pressure-temperature records and X-ray computed tomographic reconstructions of cores. Gas hydrate saturations were measured by using the gas from quantitative degassing experiments in methane mass balance calculations. Gas hydrate morphology was determined from X-ray computed tomographic reconstructions, P-wave velocity, and gamma density measured under pressure using PCATS, the Pressure Core Analysis and Transfer System. Gas hydrate saturations reached 65–85% in the pores of sandy reservoir sediments, and were near full saturation in gravelly sediments. Clayey interlayers between reservoir sediments had gas hydrate saturations near 10%, with no evidence of gas hydrate veins in X-ray computed tomographic (CT) reconstructions. Veins of gas hydrate were visible in X-ray images of clayey non-reservoir sediments; at some locations the full complement of gas hydrate was contained in X-ray-resolveable veins, but in others the veins only accounted for part of the total gas hydrate burden in the sediment, implying that some gas hydrate was finely distributed in the pore space or in veins below the resolution of the X-ray CT data. At one location low-density, biosilica-rich silty clays hosted pore-filling gas hydrate at saturations of 45%, with only slightly elevated P-wave velocities. Gas hydrate saturation and morphology from all the pressure cores are presented here and placed into geological context. • Pressure core quality must be critically examined before using data. • Gas hydrate saturations reached 65–85% in the pores of sandy reservoir sediments. • Clayey interlayers between reservoir sediments had hydrate saturations near 10%. • Visible veins did not contain all the gas hydrate in many clayey samples. • Low-density biosilica-rich silty clays contained 45% pore-filling gas hydrate. [ABSTRACT FROM AUTHOR]

Describes extensions to the sliding interleaved kY (SLINKY) technique to eliminate the slab boundary artifact from multi-slab magnetic resonance angiography. Overlapping thin slab acquisitions for addressing the residual errors in the implementation of SLINKY; Sliding interleaved projection reconstruction (SLIPR); Fast spin-echo SLIPR.

Focuses on the unexplained loss of form in athletes due to viral infection. Increase of titres of antibodies against Coxsackie B or Epstein-Barr virus; Abnormality of white blood cells; Identification of excessive intracellular acidosis of skeletal muscles.

Treatment of infectious diseases is becoming increasingly challenging with the emergence of less-susceptible organisms that are poorly responsive to existing antibiotic therapies, and the unpredictable pharmacokinetic alterations arising from complex pathophysiologic changes in some patient populations. In view of this fact, there has been a progressive work on novel dose optimization strategies to renew the utility of forgotten old antibiotics and to improve the efficacy of those currently in use. This review summarizes the different approaches of optimization of antibiotic dosing regimens and the special patient populations which may benefit most from these approaches. The existing methods are based on monitoring of antibiotic concentrations and/or use of clinical covariates. Measured concentrations can be correlated with predefined pharmacokinetic/pharmacodynamic targets to guide clinicians in predicting the necessary dose adjustment. Dosing nomograms are also available to relate observed concentrations or clinical covariates (e.g. creatinine clearance) with optimal dosing. More precise dose prediction based on observed covariates is possible through the application of population pharmacokinetic models. However, the most accurate estimation of individualized dosing requirements is achieved through Bayesian forecasting which utilizes both measured concentration and clinical covariates. Various software programs are emerging to ease clinical application. Whilst more studies are warranted to clarify the clinical outcomes associated with the different dose optimization approaches, severely ill patients in the course of marked infections and/or inflammation including those with sepsis, septic shock, severe trauma, burns injury, major surgery, febrile neutropenia, cystic fibrosis, organ dysfunction and obesity are those groups which may benefit most from individualized dosing. [ABSTRACT FROM AUTHOR]

Abstract: It is well established that exposure to ozone (O3) may impair vegetative growth and reproductive development in plants, although the consequences for yield depend on the effectiveness of the compensatory processes induced. This study examined the effects of exposing the terminal inflorescence of Brassica campestris L. to 100ppb O3 for 6hd−1 on four consecutive days during early flowering while the vegetative organs received charcoal-filtered air. The ordered predictability of development in B. campestris is ideal for studies of the impact of abiotic stress factors such as O3 on reproductive development and seed production. Effects on reproductive development and seed yield characteristics were determined for floral sites exposed at different developmental stages. Flower and pod numbers on the terminal raceme were unaffected by exposure, but effects on pod length varied depending on the developmental stage of floral sites during exposure. Increased ovule abortion and precocious seed germination in the pods of O3-treated plants reduced mature seed number pod−1. Although the individual weight of mature seeds was slightly greater in O3-treated plants, seed yield pod−1 and seed yield plant−1 were reduced due to the lower seed number pod−1. Seed from O3-treated plants germinated more rapidly than control seed irrespective of the stage of floral development during exposure. The results show that exposure to realistic O3 episodes during the early stages of flowering significantly reduced seed yield without impairing the vigour of the seeds produced. The physiological origins of these effects are discussed. [Copyright &y& Elsevier]

Abstract: Exposure to ozone (O3) affects both vegetative and reproductive growth in plants, although consequences for seed yield depend on the efficacy of compensatory reproductive processes. This study examined whether the limited compensatory capacity of species with determinate reproductive strategies influences seed production following exposure. The first flowering spike (Spike 1) of Plantago major L. populations which exhibit contrasting sensitivity of vegetative growth to chronic O3 exposure was exposed, while the leaves and second spike (Spike 2) received charcoal-filtered air. Exposure of Spike 1 during flowering influenced seed number capsule−1 on both spikes, even though Spike 2 was not exposed. Responses varied between populations, position on the spike and plant age at the start of exposure; the greater impact on capsules located on the upper section of the spike suggests they were more responsive. Compensatory increases in seed number capsule−1 in the middle and upper sections of Spikes 1 and 2 generally precluded significant effects on seed number spike−1; individual seed weight was largely unaffected. However, the combined seed weight of Spikes 1 and 2 was increased by 19% in the two O3-resistant populations following exposure to 120ppb O3 on 9 successive days, suggesting that they over-compensated for injury, but was reduced by 21% in the most sensitive population. Compensatory reproductive responses and their possible implications for biomass production, biodiversity and carbon sequestration in natural communities in temperate regions are discussed. [Copyright &y& Elsevier]

Abstract: This study estimated the cost-effectiveness of infant rotavirus vaccination with Rotarix™ in the UK, taking into account community rotavirus infections that do not present to the healthcare system. A Markov model compared the costs and outcomes of vaccination versus no vaccination in a hypothetical birth cohort of children followed over a lifetime, from a societal perspective and the perspective of the National Health Service (NHS). The model estimated costs and quality-adjusted life-years (QALYs) lost due to death, hospitalisation, general practitioner (GP) consultation, emergency attendance and calls to NHS Direct for rotavirus infection in children aged <5 years. Time lost from work and parents’ travel costs were also included in the societal perspective. The base case cost-effectiveness ratio for vaccination compared with no vaccination was £23,298/QALY from the NHS perspective and £11,459 from the societal perspective. In sensitivity analysis, the most important parameters were hospitalisation cost and number of GP consultations. Addition of Rotarix™ to the paediatric vaccination schedule would be a cost-effective policy option in the UK at the threshold range (£20,000–30,000/QALY) currently adopted by the National Institute for Health and Clinical Excellence. [Copyright &y& Elsevier]

Therapeutic drug monitoring (TDM) is a tool to personalize and optimize dosing by measuring the drug concentration and subsequently adjusting the dose to reach a target concentration or exposure. The evidence to support TDM is however often ranked as expert opinion. Limitations in study design and sample size have hampered definitive conclusions of the potential added value of TDM. We aim to give expert opinion and discuss the main points and limitations of available data from antibiotic TDM trials and emphasize key elements for consideration in design of future clinical studies to quantify the benefits of TDM. The sources were peer-reviewed publications, guidelines and expert opinions from the field of TDM. This review focuses on key aspects of antimicrobial TDM study design: describing the rationale for a TDM study, assessing the exposure of a drug, assessing susceptibility of pathogens and selecting appropriate clinical endpoints. Moreover we provide guidance on appropriate study design. This is an overview of different aspects relevant for the conduct of a TDM study. We believe that this paper will help researchers and clinicians to design and conduct high-quality TDM studies. [ABSTRACT FROM AUTHOR]

• Elimination of piperacillin (PIP) is saturable at therapeutic concentrations. • Same dose continuous PIP results in lower exposure compared with intermittent PIP. • Intermittent vs continuous PIP trials may be biased towards intermittent PIP. The study aimed to evaluate saturation of piperacillin elimination in critically ill adult patients. Seventeen critically ill adult patients received continuous and intermittent infusion of piperacillin/tazobactam. Piperacillin plasma concentrations (n = 217) were analysed using population pharmacokinetic (PopPK) modelling. Post-hoc simulations were performed to evaluate the type I error rate associated with the study. Unseen data were used to validate the final model. The mean error (ME) and root mean square error (RMSE) were calculated as a measure of bias and imprecision, respectively. A PopPK model with parallel linear and non-linear elimination best fitted the data. The median and 95% confidence interval (CI) for the model parameters drug clearance (CL), volume of central compartment (V), volume of peripheral compartment (V p) and intercompartmental clearance (Q) were 9 (7.69–11) L/h, 6.18 (4.93–11.2) L, 11.17 (7.26–12) L and 15.61 (12.66–23.8) L/h, respectively. The Michaelis–Menten constant (K m) and the maximum elimination rate for Michaelis–Menten elimination (V max) were estimated without population variability in the model to avoid overfitting and inflation of the type I error rate. The population estimates for K m and V max were 37.09 mg/L and 353.57 mg/h, respectively. The bias (ME) was –20.8 (95% CI –26.2 to –15.4) mg/L, whilst imprecision (RMSE) was 49.2 (95% CI 41.2–56) mg/L. In conclusion, piperacillin elimination is (partially) saturable. Moreover, the population estimate for K m lies within the therapeutic window and therefore saturation of elimination should be accounted for when defining optimum dosing regimens for piperacillin in critically ill patients. [ABSTRACT FROM AUTHOR]

Nebulized antibiotics have an established role in patients with cystic fibrosis or bronchiectasis. Their potential benefit to treat respiratory infections in mechanically ventilated patients is receiving increasing interest. In this consensus statement of the European Society of Clinical Microbiology and Infectious Diseases, the body of evidence of the therapeutic utility of aerosolized antibiotics in mechanically ventilated patients was reviewed and resulted in the following recommendations: Vibrating-mesh nebulizers should be preferred to jet or ultrasonic nebulizers. To decrease turbulence and limit circuit and tracheobronchial deposition, we recommend: (a) the use of specifically designed respiratory circuits avoiding sharp angles and characterized by smooth inner surfaces, (b) the use of specific ventilator settings during nebulization including use of a volume controlled mode using constant inspiratory flow, tidal volume 8 mL/kg, respiratory frequency 12 to 15 bpm, inspiratory:expiratory ratio 50%, inspiratory pause 20% and positive end-expiratory pressure 5 to 10 cm H 2 O and (c) the administration of a short-acting sedative agent if coordination between the patient and the ventilator is not obtained, to avoid patient's flow triggering and episodes of peak decelerating inspiratory flow. A filter should be inserted on the expiratory limb to protect the ventilator flow device and changed between each nebulization to avoid expiratory flow obstruction. A heat and moisture exchanger and/or conventional heated humidifier should be stopped during the nebulization period to avoid a massive loss of aerosolized particles through trapping and condensation. If these technical requirements are not followed, there is a high risk of treatment failure and adverse events in mechanically ventilated patients receiving nebulized antibiotics for pneumonia. [ABSTRACT FROM AUTHOR]

With an established role in cystic fibrosis and bronchiectasis, nebulized antibiotics are increasingly being used to treat respiratory infections in critically ill invasively mechanically ventilated adult patients. Although there is limited evidence describing their efficacy and safety, in an era when there is a need for new strategies to enhance antibiotic effectiveness because of a shortage of new agents and increases in antibiotic resistance, the potential of nebulization of antibiotics to optimize therapy is considered of high interest, particularly in patients infected with multidrug-resistant pathogens. This Position Paper of the European Society of Clinical Microbiology and Infectious Diseases provides recommendations based on the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology regarding the use of nebulized antibiotics in invasively mechanically ventilated adults, based on a systematic review and meta-analysis of the existing literature (last search July 2016). Overall, the panel recommends avoiding the use of nebulized antibiotics in clinical practice, due to a weak level of evidence of their efficacy and the high potential for underestimated risks of adverse events (particularly, respiratory complications). Higher-quality evidence is urgently needed to inform clinical practice. Priorities of future research are detailed in the second part of the Position Paper as guidance for researchers in this field. In particular, the panel identified an urgent need for randomized clinical trials of nebulized antibiotic therapy as part of a substitution approach to treatment of pneumonia due to multidrug-resistant pathogens. [ABSTRACT FROM AUTHOR]

Details of the energy (food) requirements of wild herbivores are essential for understanding their role in ecosystems generally, and for evaluating their potential impact on co-occurring domestic herbivores, as in the case for Australia’s largest grazing herbivores, the marsupial kangaroos, which co-exist with domestic livestock, particularly the wool breed Merino sheep. Using the doubly labelled water method we compared the field metabolic rate (FMR) of the western grey kangaroo ( Macropus fuliginosus melanops ) with that of the merino sheep, grazed sympatrically in a large naturally-vegetated enclosure. We combined our FMR studies with fine-scale GPS-monitoring to reveal important and significant impacts of daily movement patterns on the energetics of western grey kangaroos, but not the sheep. The daily FMR was substantially higher for kangaroos with longer daily movements. These individuals elevated their FMRs relative to predicted basal or minimal metabolic rates (i.e. FMR:BMR) by 4–5 times that expected for mature, non-reproductive mammals. Notably, those kangaroos that exhibited FMR:BMRs typical of mammals generally (around 2–3 times) had daily energy requirements around 6245 kJ. This level of energy expenditure was less than one third of that of the domestic sheep (22,799 kJ d −1 ). Even when compared on a common body mass of 35 kg, the western grey kangaroo energy expenditure was only 0.46 that of the merino sheep. Moreover, for typically-sized mature females kangaroos (25 kg), which make the bulk of kangaroo populations, the comparative energy requirement was just 0.31 that of a mature, non-breeding merino ewe. [ABSTRACT FROM AUTHOR]

Describes to use of depth buffer segmentation algorithm for segmentation and display of blood vessels from images obtained with magnetic resonance angiography. Basis of the algorithm; Results of patient studies using the algorithm; Nature of the algorithm.

The impact of decreased serum albumin concentrations on free antibiotic concentrations in non-critically ill patients is poorly described. This study aimed to describe the pharmacokinetics of a high-dose regimen of teicoplanin, a highly protein-bound antibiotic, in non-critically ill patients with hypoalbuminaemia. Ten patients with chronic bone sepsis and decreased serum albumin concentrations (<35 g/L) receiving teicoplanin 12 mg/kg 12-hourly intravenously for 48 h followed by 12 mg/kg once daily were enrolled. Surgical debridement was performed on Day 3. Samples of venous blood were collected pre-infusion and post-infusion during the first 4 days of therapy. Total and free teicoplanin concentrations were assayed using validated chromatographic methods. The median serum albumin concentration for the cohort was 18 (IQR 15–24) g/L. After 48 h, the median (IQR) free trough ( f C min ) and total trough ( t C min ) concentrations were 2.90 (2.67–3.47) mg/L and 15.54 (10.28–19.12) mg/L, respectively, although trough concentrations declined thereafter. Clearance of the free concentrations was significantly high relative to the total fraction at 38.6 (IQR 29.9–47.8) L/h and 7.0 (IQR 6.8–9.8) L/h, respectively ( P < 0.001). Multiple linear regression analysis demonstrated that whereas total teicoplanin concentration did not impact on free concentrations ( P = 0.174), albumin concentration did ( P < 0.001). This study confirms the significant impact of hypoalbuminaemia on free concentrations of teicoplanin in non-critically ill patients, similar to that in critically ill patients. Furthermore, the poor correlation with total teicoplanin concentration suggests that therapeutic drug monitoring of free concentrations should be used in these patients. [ABSTRACT FROM AUTHOR]

Linezolid is a valuable treatment option for central nervous system (CNS) infections caused by multidrug-resistant Gram-positive micro-organisms. Data regarding its penetration into the CNS have shown wide variability. The aim of this study was to describe the population pharmacokinetics of linezolid in plasma and cerebrospinal fluid (CSF) in critically ill patients with external CSF drainage and proven or suspected CNS infections. This was an observational pharmacokinetic (PK) study in 11 critically ill patients with proven or suspected CNS infection receiving linezolid. Serial blood and CSF samples were taken and were subject to population PK analysis. The median (interquartile range) of AUC 0–12 h was 47.6 (17.9–58.6) mg h/L in plasma and 21.1 (18.8–30.4) mg h/L in CSF, with a median CSF/plasma ratio of 0.77. At pre-dose at steady state, a strong positive correlation was observed between linezolid concentrations in CSF and plasma (Spearman's rho = 0.758; P = 0.011). For a minimum inhibitory concentration (MIC) of 2 mg/L, the median AUC 0–24 h /MIC values in plasma and CSF were <80 in all patients. A three-compartment linear model was found to be most appropriate. The mean value for linezolid clearance was 16.6 L/h and mean volume of distribution was 101.3 L. No covariate relationships could be supported on any of the parameters. Linezolid demonstrated good penetration into the CNS but high interindividual PK variability. Administration of higher than standard doses of linezolid and therapeutic drug monitoring should therefore be considered as options to optimise linezolid dosing in critically ill patients with CNS infections. [ABSTRACT FROM AUTHOR]

Abstract: Time-lapse borehole radar was used to monitor a sandy aquifer with dielectric property changes hypothesized to result from biomass growth and biodegradation of hydrocarbons. A blend of gasoline and ethanol was released below the water table at Canadian Forces Base (CFB) Borden, Canada, and a source of oxygen was used for cyclic stimulation of microbial activity over a period of two years. A dense grid of fourteen borehole ground-penetrating radar (GPR) pairs monitoring the bioactive region showed 200MHz radar wave velocity changes of ±4% and signal attenuation changes of ±25% during three cycles of variable biostimulation. GPR signal changes correlated spatially and temporally to independent measurements of groundwater velocity flow changes and geochemical variations that occurred in response to microbial activity. Greater relative changes in radar wave velocity of propagation were observed in the region of enhanced bacterial stimulation, adjacent to the oxygen release wells, and along the path of the hydrocarbon plume where biomass growth was the greatest. In the zone of maximum biological activity, radar wave velocity decreased during two cycles of enhanced biostimulation, whereas it increased during the intervening period of low-level biostimulation. Monitored regions at the fringe of the plume and farther down-gradient of the oxygen source, where biostimulation was less or absent, exhibited GPR signal changes of lesser magnitude and consistency. Spatial and temporal variabilities of GPR observations indicate a high degree of transient heterogeneity within the relatively homogeneous Borden aquifer as a result of hydrocarbon biodegradation. Mechanisms postulated to cause the dielectric property changes observed in the radar data are biogenic gas formation, mineral dissolution/precipitation, and direct biomass growth. Geochemical data, in-situ groundwater velocity measurements and biomass quantification suggest biomass formation in the pore space as a plausible mechanism for the changes observed in the aquifer. Therefore, at 200MHz frequency, biomass formation is observed to cause a decrease of EM wave velocity of propagation suggesting an increase of the bulk dielectric constant of the water saturated medium. This finding is in agreement with published laboratory-scale GPR monitoring of microbial growth in porous media. This study shows that time-lapse GPR along with supporting biogeochemical observations can be used for monitoring of biological activity at the field scale. [Copyright &y& Elsevier]

Abstract: Three projects involving point velocity probes (PVPs) illustrate the advantages of direct groundwater velocity measurements. In the first, a glacial till and outwash aquifer was characterized using conventional methods and multilevel PVPs for designing a bioremediation program. The PVPs revealed a highly conductive zone that dominated the transport of injected substances. These findings were later confirmed with a natural gradient tracer test. In the second, PVPs were used to map a groundwater velocity field around a dipole recirculation well. The PVPs showed higher than expected velocities near the well, assuming homogeneity in the aquifer, leading to improved representations of the aquifer heterogeneity in a 3D flow model, and an improved match between the modelled and experimental tracer breakthrough curves. In the third study, PVPs detected subtle changes in aquifer permeability downgradient of a biostimulation experiment. The changes were apparently reversible once the oxygen source was depleted, but in locations where the oxygen source lingered, velocities remained low. PVPs can be a useful addition to the hydrogeologist''s toolbox, because they can be constructed inexpensively, they provide data in support of models, and they can provide information on flow in unprecedented detail. [Copyright &y& Elsevier]

Ceftriaxone is a broad-spectrum cephalosporin that may be one option to treat methicillin-susceptible Staphylococcus aureus (MSSA). Although MSSA may be susceptible to ceftriaxone, the minimum inhibitory concentration (MIC) is generally two- to four-fold higher than other susceptible bacterial pathogens. This study aimed to explore the pharmacodynamics of ceftriaxone against MSSA and to determine the likely optimal dose. A hollow-fibre infection model was used with one clinical MSSA isolate (MIC = 4 mg/L) at an initial inoculum of 1 × 106 CFU/mL. Ceftriaxone dosing regimens of 1 g once and twice daily and 2 g once and twice daily were simulated. Ceftriaxone 1 g dosing regimens did not substantially impact bacterial killing within the first 12 h. Conversely, when administered as a 2 g dose either once or twice daily, an approximate 1-log 10 bacterial reduction was observed where it plateaued for up to 96 h. No resistance was identified. Only a high ceftriaxone dose of 2 g twice daily achieves bacterial killing and sustained inhibition of bacterial growth. Ceftriaxone at routinely used doses is unsuitable for the treatment of MSSA infections and alternative agents should be preferentially used. [ABSTRACT FROM AUTHOR]

Abstract: The identification of alpha rhythm in the human electroencephalogram (EEG) is generally a laborious task involving visual inspection of the spectrum. Moreover the occurrence of multiple alpha rhythms is often overlooked. This paper seeks to automate the process of identifying alpha peaks and quantifying their frequency, amplitude and width as a function of position on the scalp. Experimental EEG was fitted with parameterized spectra spanning the alpha range, with results categorized by multi-site criteria into three distinct classes: no distinguishable alpha peak, a single alpha peak, and two alpha peaks. The technique avoids visual bias, integrates spatial information, and is automated. We show that multiple alpha peaks are a common feature of many spectra. [Copyright &y& Elsevier]

Rat bite fever is a worldwide zoonotic, non-reportable disease. This entity encompasses similar, yet distinct, disease syndromes caused by Streptobacillus moniliformis or Spirillum minus. Naturally occurring rat bite fever has not been previously described in non-human primates. This report describes two cases of non-human primate rat bite fever caused by S. moniliformis; a rhesus macaque (Macaca mullata) with valvular endocarditis, and a titi monkey (Callicebus sp.) with septic arthritis. Potential sources of infection included direct contact, and ingestion of surface water or feed contaminated with rodent feces. [ABSTRACT FROM AUTHOR]

• Activity of non-polymyxin-based combinations and potential synergy against carbapenem-resistant Acinetobacter baumannii. • Fosfomycin/sulbactam combination displayed synergy in 74% of isolates. • Meropenem/sulbactam combination displayed synergy in 56% of isolates. • Both combinations displayed bactericidal activity in time–kill assays. • Non-polymyxin-based combinations may be effective against A. baumannii. Due to limited therapeutic options, combination therapy has been used empirically to treat carbapenem-resistant Acinetobacter baumannii (CRAB). Polymyxin-based combinations have been widely studied and used in the clinical setting. However, the use of polymyxins is often limited due to nephrotoxicity and neurotoxicity. This study aimed to evaluate the activity of non-polymyxin-based combinations relative to polymyxin-based combinations and to identify potential synergistic and bactericidal two-drug non-polymyxin-based combinations against CRAB. In vitro activity of 14 two-drug combinations against 50 A. baumannii isolates was evaluated using the checkerboard method. Subsequently, the two best-performing non-polymyxin-based combinations from the checkerboard assay were explored in static time–kill experiments. Concentrations of antibiotics corresponding to the fractional inhibitory concentrations (FIC) and the highest serum concentration achievable clinically were tested. The most synergistic combinations were fosfomycin/sulbactam (synergistic against 37/50 isolates; 74%), followed by meropenem/sulbactam (synergistic against 28/50 isolates; 56%). No antagonism was observed for any combination. Both fosfomycin/sulbactam and meropenem/sulbactam combinations exhibited bactericidal and synergistic activity against both isolates at the highest clinically achievable concentrations in the time–kill experiments. The meropenem/sulbactam combination displayed synergistic and bactericidal activity against one of two strains at concentrations equal to the FIC. Non-polymyxin-based combinations such as fosfomycin/sulbactam and meropenem/sulbactam may have a role in the treatment of CRAB. Further in vivo and clinical studies are required to scrutinise these activities further. [ABSTRACT FROM AUTHOR]

Objectives To describe the population pharmacokinetics of teicoplanin in adult patients with haematological malignancies receiving higher than standard doses, and to perform Monte Carlo simulations to determine dosing regimens associated with optimal teicoplanin concentrations. Methods This was a hospital-based clinical trial (EudraCT 2013–004535–72). Nine blood samples were collected on Day 3, plus single trough samples on Days 7 and 10, and 24 and 48 hours after the last dose. Teicoplanin minimum inhibitory concentrations were determined for Gram-positive isolates from study patients. Population pharmacokinetic analyses and Monte Carlo dosing simulations were undertaken using Pmetrics. Results Thirty adult haematological malignancy patients were recruited with a mean (SD) loading dose, age, total body weight, and creatinine clearance of 9.5 (1.9) mg/kg, 63 (12) years, 69.1 (15.8) kg, and 72 (41) mL/min, respectively. A three-compartment linear pharmacokinetic model best described the teicoplanin concentration data. Covariates supported for inclusion in the final model were creatinine clearance for clearance and total body weight for volume of the central compartment. The median (IQR) area under the concentration-time curve from 48 to 72 hours (AUC 48–72h ) was 679 (319) mg.h/L. There was a strong correlation between the AUC 48–72h and trough concentration at 72 hours (Pearson correlation coefficient 0.957, p <0.001). Dosing simulations showed that administration of five loading doses at 12-hourly intervals, stratified by total body weight and creatinine clearance, increased the probability of achieving target concentrations within 72 hours. Conclusions To increase the number of patients achieving optimal teicoplanin concentrations an individualized dosing approach, based on body weight and creatinine clearance, is recommended. [ABSTRACT FROM AUTHOR]