Extended-interval Dosing of Gentamicin for Treatment of Neonatal Sepsis in Developed and Developing Countries

Serious bacterial infections are the single most important cause of neonatal mortality in developing countries. Case-fatality rates for neonatal sepsis in developing countries are high, partly because of inadequate administration of necessary antibiotics. For the treatment of neonatal sepsis in resource-poor, high-mortality settings in developing countries where most neonatal deaths occur, simplified treatment regimens are needed. Recommended therapy for neonatal sepsis includes gentamicin, a parenteral aminoglycoside antibiotic, which has excellent activity against gram-negative bacteria, in combination with an antimicrobial with potent gram-positive activity. Traditionally, gentamicin has been administered 2–3 times daily. However, recent evidence suggests that extended-interval (i.e. ≥24 hours) dosing may be applicable to neonates. This review examines the available data from randomized and non-randomized studies of extended-interval dosing of gentamicin in neonates from both developed and developing countries. Available data on the use of gentamicin among neonates suggest that extended dosing intervals and higher doses (>4 mg/kg) confer a favourable pharmacokinetic profile, the potential for enhanced clinical efficacy and decreased toxicity at reduced cost. In conclusion, the following simplified weight-based dosing regimen for the treatment of serious neonatal infections in developing countries is recommended: 13.5 mg (absolute dose) every 24 hours for neonates of ≥2,500 g, 10 mg every 24 hours for neonates of 2,000–2,499 g, and 10 mg every 48 hours for neonates of <2,000 g

Extended-interval Dosing of Gentamicin for Treatment of Neonatal Sepsis in Developed and Developing Countries

Serious bacterial infections are the single most important cause of neonatal mortality in developing countries. Case-fatality rates for neonatal sepsis in developing countries are high, partly because of inadequate administration of necessary antibiotics. For the treatment of neonatal sepsis in resource-poor, high-mortality settings in developing countries where most neonatal deaths occur, simplified treatment regimens are needed. Recommended therapy for neonatal sepsis includes gentamicin, a parenteral aminoglycoside antibiotic, which has excellent activity against gram-negative bacteria, in combination with an antimicrobial with potent gram-positive activity. Traditionally, gentamicin has been administered 2-3 times daily. However, recent evidence suggests that extended-interval (i.e. 65 24 hours) dosing may be applicable to neonates. This review examines the available data from randomized and non-randomized studies of extended-interval dosing of gentamicin in neonates from both developed and developing countries. Available data on the use of gentamicin among neonates suggest that extended dosing intervals and higher doses (&gt;4 mg/kg) confer a favourable pharmacokinetic profile, the potential for enhanced clinical efficacy and decreased toxicity at reduced cost. In conclusion, the following simplified weight-based dosing regimen for the treatment of serious neonatal infections in developing countries is recommended: 13.5 mg (absolute dose) every 24 hours for neonates of 65 2,500 g, 10 mg every 24 hours for neonates of 2,000-2,499 g, and 10 mg every 48 hours for neonates of &lt;2,000 g

Clinical signs associated with earlier diagnosis of children with autism Spectrum disorder

Background The objective of this study is to gain new insights into the relationship between clinical signs and age at diagnosis. Method We utilize a new, large, online survey of 1743 parents of children diagnosed with ASD, and use multiple statistical approaches. These include regression analysis, factor analysis, and machine learning (regression tree). Results We find that clinical signs that most strongly predict early diagnosis are not necessarily specific to autism, but rather those that initiate the process that eventually leads to an ASD diagnosis. Given the high correlations between symptoms, only a few signs are found to be important in predicting early diagnosis. For several clinical signs we find that their presence and intensity are positively correlated with delayed diagnosis (e.g., tantrums and aggression). Even though our data are drawn from parents’ retrospective accounts, we provide evidence that parental recall bias and/or hindsight bias did not play a significant role in shaping our results. Conclusion In the subset of children without early deficits in communication, diagnosis is delayed, and this might be improved if more attention will be given to clinical signs that are not necessarily considered as ASD symptoms. Our findings also suggest that careful attention should be paid to children showing excessive tantrums or aggression, as these behaviors may interfere with an early ASD diagnoses

Plant-Associated Bacterial Degradation of Toxic Organic Compounds in Soil

A number of toxic synthetic organic compounds can contaminate environmental soil through either local (e.g., industrial) or diffuse (e.g., agricultural) contamination. Increased levels of these toxic organic compounds in the environment have been associated with human health risks including cancer. Plant-associated bacteria, such as endophytic bacteria (non-pathogenic bacteria that occur naturally in plants) and rhizospheric bacteria (bacteria that live on and near the roots of plants), have been shown to contribute to biodegradation of toxic organic compounds in contaminated soil and could have potential for improving phytoremediation. Endophytic and rhizospheric bacterial degradation of toxic organic compounds (either naturally occurring or genetically enhanced) in contaminated soil in the environment could have positive implications for human health worldwide and is the subject of this review

Remote sensing of annual terrestrial gross primary productivity from MODIS: an assessment using the FLUXNET La Thuile data set

Gross primary productivity (GPP) is the largest and most variable component of the global terrestrial carbon cycle. Repeatable and accurate monitoring of terrestrial GPP is therefore critical for quantifying dynamics in regional-to-global carbon budgets. Remote sensing provides high frequency observations of terrestrial ecosystems and is widely used to monitor and model spatiotemporal variability in ecosystem properties and processes that affect terrestrial GPP. We used data from the Moderate Resolution Imaging Spectroradiometer (MODIS) and FLUXNET to assess how well four metrics derived from remotely sensed vegetation indices (hereafter referred to as proxies) and six remote sensing-based models capture spatial and temporal variations in annual GPP. Specifically, we used the FLUXNET La Thuile data set, which includes several times more sites (144) and site years (422) than previous studies have used. Our results show that remotely sensed proxies and modeled GPP are able to capture significant spatial variation in mean annual GPP in every biome except croplands, but that the percentage of explained variance differed substantially across biomes (10–80%). The ability of remotely sensed proxies and models to explain interannual variability in GPP was even more limited. Remotely sensed proxies explained 40–60% of interannual variance in annual GPP in moisture-limited biomes, including grasslands and shrublands. However, none of the models or remotely sensed proxies explained statistically significant amounts of interannual variation in GPP in croplands, evergreen needleleaf forests, or deciduous broadleaf forests. Robust and repeatable characterization of spatiotemporal variability in carbon budgets is critically important and the carbon cycle science community is increasingly relying on remotely sensing data. Our analyses highlight the power of remote sensing-based models, but also provide bounds on the uncertainties associated with these models. Uncertainty in flux tower GPP, and difference between the footprints of MODIS pixels and flux tower measurements are acknowledged as unresolved challenges.This is the publisher’s final pdf. The published article is copyrighted by the author(s) and published by Copernicus Publications on behalf of the European Geosciences Union. The published article can be found at: http://www.biogeosciences.net/

Oral abstracts 3: RA Treatment and outcomesO13. Validation of jadas in all subtypes of juvenile idiopathic arthritis in a clinical setting

Background: Juvenile Arthritis Disease Activity Score (JADAS) is a 4 variable composite disease activity (DA) score for JIA (including active 10, 27 or 71 joint count (AJC), physician global (PGA), parent/child global (PGE) and ESR). The validity of JADAS for all ILAR subtypes in the routine clinical setting is unknown. We investigated the construct validity of JADAS in the clinical setting in all subtypes of JIA through application to a prospective inception cohort of UK children presenting with new onset inflammatory arthritis. Methods: JADAS 10, 27 and 71 were determined for all children in the Childhood Arthritis Prospective Study (CAPS) with complete data available at baseline. Correlation of JADAS 10, 27 and 71 with single DA markers was determined for all subtypes. All correlations were calculated using Spearman's rank statistic. Results: 262/1238 visits had sufficient data for calculation of JADAS (1028 (83%) AJC, 744 (60%) PGA, 843 (68%) PGE and 459 (37%) ESR). Median age at disease onset was 6.0 years (IQR 2.6-10.4) and 64% were female. Correlation between JADAS 10, 27 and 71 approached 1 for all subtypes. Median JADAS 71 was 5.3 (IQR 2.2-10.1) with a significant difference between median JADAS scores between subtypes (p < 0.01). Correlation of JADAS 71 with each single marker of DA was moderate to high in the total cohort (see Table 1). Overall, correlation with AJC, PGA and PGE was moderate to high and correlation with ESR, limited JC, parental pain and CHAQ was low to moderate in the individual subtypes. Correlation coefficients in the extended oligoarticular, rheumatoid factor negative and enthesitis related subtypes were interpreted with caution in view of low numbers. Conclusions: This study adds to the body of evidence supporting the construct validity of JADAS. JADAS correlates with other measures of DA in all ILAR subtypes in the routine clinical setting. Given the high frequency of missing ESR data, it would be useful to assess the validity of JADAS without inclusion of the ESR. Disclosure statement: All authors have declared no conflicts of interest. Table 1Spearman's correlation between JADAS 71 and single markers DA by ILAR subtype ILAR Subtype Systemic onset JIA Persistent oligo JIA Extended oligo JIA Rheumatoid factor neg JIA Rheumatoid factor pos JIA Enthesitis related JIA Psoriatic JIA Undifferentiated JIA Unknown subtype Total cohort Number of children 23 111 12 57 7 9 19 7 17 262 AJC 0.54 0.67 0.53 0.75 0.53 0.34 0.59 0.81 0.37 0.59 PGA 0.63 0.69 0.25 0.73 0.14 0.05 0.50 0.83 0.56 0.64 PGE 0.51 0.68 0.83 0.61 0.41 0.69 0.71 0.9 0.48 0.61 ESR 0.28 0.31 0.35 0.4 0.6 0.85 0.43 0.7 0.5 0.53 Limited 71 JC 0.29 0.51 0.23 0.37 0.14 -0.12 0.4 0.81 0.45 0.41 Parental pain 0.23 0.62 0.03 0.57 0.41 0.69 0.7 0.79 0.42 0.53 Childhood health assessment questionnaire 0.25 0.57 -0.07 0.36 -0.47 0.84 0.37 0.8 0.66 0.4

BHPR research: qualitative1. Complex reasoning determines patients' perception of outcome following foot surgery in rheumatoid arhtritis

Background: Foot surgery is common in patients with RA but research into surgical outcomes is limited and conceptually flawed as current outcome measures lack face validity: to date no one has asked patients what is important to them. This study aimed to determine which factors are important to patients when evaluating the success of foot surgery in RA Methods: Semi structured interviews of RA patients who had undergone foot surgery were conducted and transcribed verbatim. Thematic analysis of interviews was conducted to explore issues that were important to patients. Results: 11 RA patients (9 ♂, mean age 59, dis dur = 22yrs, mean of 3 yrs post op) with mixed experiences of foot surgery were interviewed. Patients interpreted outcome in respect to a multitude of factors, frequently positive change in one aspect contrasted with negative opinions about another. Overall, four major themes emerged. Function: Functional ability & participation in valued activities were very important to patients. Walking ability was a key concern but patients interpreted levels of activity in light of other aspects of their disease, reflecting on change in functional ability more than overall level. Positive feelings of improved mobility were often moderated by negative self perception ("I mean, I still walk like a waddling duck”). Appearance: Appearance was important to almost all patients but perhaps the most complex theme of all. Physical appearance, foot shape, and footwear were closely interlinked, yet patients saw these as distinct separate concepts. Patients need to legitimize these feelings was clear and they frequently entered into a defensive repertoire ("it's not cosmetic surgery; it's something that's more important than that, you know?”). Clinician opinion: Surgeons' post operative evaluation of the procedure was very influential. The impact of this appraisal continued to affect patients' lasting impression irrespective of how the outcome compared to their initial goals ("when he'd done it ... he said that hasn't worked as good as he'd wanted to ... but the pain has gone”). Pain: Whilst pain was important to almost all patients, it appeared to be less important than the other themes. Pain was predominately raised when it influenced other themes, such as function; many still felt the need to legitimize their foot pain in order for health professionals to take it seriously ("in the end I went to my GP because it had happened a few times and I went to an orthopaedic surgeon who was quite dismissive of it, it was like what are you complaining about”). Conclusions: Patients interpret the outcome of foot surgery using a multitude of interrelated factors, particularly functional ability, appearance and surgeons' appraisal of the procedure. While pain was often noted, this appeared less important than other factors in the overall outcome of the surgery. Future research into foot surgery should incorporate the complexity of how patients determine their outcome Disclosure statement: All authors have declared no conflicts of interes

Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.

BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700

Seasonal variation of photosynthetic model parameters and leaf area index from global Fluxnet eddy covariance data

This is the publisher’s final pdf. The published article is copyrighted by American Geophysical Union and can be found at: http://sites.agu.org/.Global vegetation models require the photosynthetic parameters, maximum carboxylation capacity (V[subscript cm]), and quantum yield (alpha) to parameterize their plant functional types (PFTs). The purpose of this work is to determine how much the scaling of the parameters from leaf to ecosystem level through a seasonally varying leaf area index (LAI) explains the parameter variation within and between PFTs. Using Fluxnet data, we simulate a seasonally variable LAI(F) for a large range of sites, comparable to the LAI[subscript M] derived from MODIS. There are discrepancies when LAI[subscript F] reach zero levels and LAI[subscript M] still provides a small positive value. We find that temperature is the most common constraint for LAI[subecript F] in 55% of the simulations, while global radiation and vapor pressure deficit are the key constraints for 18% and 27% of the simulations, respectively, while large differences in this forcing still exist when looking at specific PFTs. Despite these differences, the annual photosynthesis simulations are comparable when using LAI[subscript F] or LAI[subscript M](r² = 0.89). We investigated further the seasonal variation of ecosystem-scale parameters derived with LAI[subscript F]. V[subscript cm] has the largest seasonal variation. This holds for all vegetation types and climates. The parameter alpha is less variable. By including ecosystem-scale parameter seasonality we can explain a considerable part of the ecosystem-scale parameter variation between PFTs. The remaining unexplained leaf-scale PFT variation still needs further work, including elucidating the precise role of leaf and soil level nitrogen

Thermal optimality of net ecosystem exchange of carbon dioxide and underlying mechanisms

It is well established that individual organisms can acclimate and adapt to temperature to optimize their functioning. However, thermal optimization of ecosystems, as an assemblage of organisms, has not been examined at broad spatial and temporal scales. Here, we compiled data from 169 globally distributed sites of eddy covariance and quantified the temperature response functions of net ecosystem exchange (NEE), an ecosystem-level property, to determine whether NEE shows thermal optimality and to explore the underlying mechanisms. We found that the temperature response of NEE followed a peak curve, with the optimum temperature (corresponding to the maximum magnitude of NEE) being positively correlated with annual mean temperature over years and across sites. Shifts of the optimum temperature of NEE were mostly a result of temperature acclimation of gross primary productivity (upward shift of optimum temperature) rather than changes in the temperature sensitivity of ecosystem respiration. Ecosystem-level thermal optimality is a newly revealed ecosystem property, presumably reflecting associated evolutionary adaptation of organisms within ecosystems, and has the potential to significantly regulate ecosystemclimate change feedbacks. The thermal optimality of NEE has implications for understanding fundamental properties of ecosystems in changing environments and benchmarking global models.This is the publisher’s final pdf. The published article is copyrighted by New Phytologist Trust and can be found at: http://www.newphytologist.org/Keywords: Climate change, Temperature acclimation, Optimum temperature, Thermal optimality, Temperature adaptatio