Accuracy of LightCycler® SeptiFast for the detection and identification of pathogens in the blood of patients with suspected sepsis: a systematic review protocol

Background: There is growing interest in the potential utility of molecular diagnostics in improving the detection of life-threatening infection (sepsis). LightCycler® SeptiFast is a multipathogen probebased real-time PCR system targeting DNA sequences of bacteria and fungi present in blood samples within a few hours. We report here the protocol of the first systematic review of published clinical diagnostic accuracy studies of this technology when compared with blood culture in the setting of suspected sepsis. Methods/design: Data sources: the Cochrane Database of Systematic Reviews, the Database of Abstracts of Reviews of Effects (DARE), the Health Technology Assessment Database (HTA), the NHS Economic Evaluation Database (NHSEED), The Cochrane Library, MEDLINE, EMBASE, ISI Web of Science, BIOSIS Previews, MEDION and the Aggressive Research Intelligence Facility Database (ARIF). Study selection: diagnostic accuracy studies that compare the real-time PCR technology with standard culture results performed on a patient's blood sample during the management of sepsis. Data extraction: three reviewers, working independently, will determine the level of evidence, methodological quality and a standard data set relating to demographics and diagnostic accuracy metrics for each study. Statistical analysis/data synthesis: heterogeneity of studies will be investigated using a coupled forest plot of sensitivity and specificity and a scatter plot in Receiver Operator Characteristic (ROC) space. Bivariate model method will be used to estimate summary sensitivity and specificity. The authors will investigate reporting biases using funnel plots based on effective sample size and regression tests of asymmetry. Subgroup analyses are planned for adults, children and infection setting (hospital vs community) if sufficient data are uncovered. Dissemination: Recommendations will be made to the Department of Health (as part of an open-access HTA report) as to whether the real-time PCR technology has sufficient clinical diagnostic accuracy potential to move forward to efficacy testing during the provision of routine clinical care.

Buccal absorption of enalapril and lisinopril

Objective: The buccal absorption of captopril does not exhibit the classical pH/partition hypothesis, suggesting that mechanisms other than passive diffusion are involved in its absorption; animal studies have suggested that a peptide carrier-mediated transport system may be responsible for its absorption. The present study evaluated the effects of pH on octanol partitioning, and on the buccal absorption of enalapril and lisinopril, using in vitro techniques and buccal partitioning in human volunteer subjects.

Trait assembly in plant assemblages and its modulation by productivity and disturbance

Understanding how communities assemble is a key challenge in ecology. Conflicting hypotheses suggest that plant traits within communities should show divergence to reflect strategies to reduce competition or convergence to reflect strong selection for the environmental conditions operating. Further hypotheses suggest that plant traits related to productivity show convergence within communities, but those related to disturbance show divergence. Data on functional diversity (FD ) of 12 traits from 30 communities ranging from arable fields, mown and grazed grasslands to moorland and woodland were employed to test this using randomisations tests and correlation and regression analysis. No traits showed consistent significant convergence or divergence in functional diversity. When correlated to measures of the environment, the most common pattern was for functional diversity to decline (7 out of 12 traits) and the degree of convergence (7 out of 12 traits) to increase as the levels of productivity (measured as primary productivity, soil nitrogen release and vegetation C:N) and disturbance increased. Convergence or a relationship between functional diversity and the environment was not seen for a number of important traits, such as LDMC and SLA, which are considered as key predictors of ecosystem function. The analysis indicates that taking into account functional diversity within a system may be a necessary part of predicting the relationship between plant traits and ecosystem function, and that this may be of particular importance within less productive and less disturbed systems. © 2011 Springer-Verlag.

Consistency of arsenic speciation in global tobacco products with implications for health and regulation

Background: Tobacco smoke is a major risk to the health of its users and arsenic is among the components of smoke present at concentrations of toxicological concern. There are significant variations in human toxicity between inorganic and organic arsenic species and the aim of this study was to determine whether there are predictable relationships among major arsenic species in tobacco that could be useful for risk assessment.

Methods: 14 samples of tobacco were studied spanning a wide range of concentrations in samples from different geographical regions, including certified reference materials and cigarette products. Inorganic and major organic arsenic species were extracted from powdered tobacco samples by nitric acid using microwave digestion. Concentrations of arsenic species in these extracts were determined using HPLC-ICPMS.

Results: The concentrations of total inorganic arsenic species range from 144 to 3914 mu g kg(-1), while organic species dimethylarsinic acid (DMA) ranges from 21 to 176 mu g As kg(-1), and monomethylarsonic acid (MA) ranges from 30 to 116 mu g kg(-1). The percentage of species eluted compared to the total arsenic extracted ranges from 11.1 to 36.8% suggesting that some As species (possibly macro-molecules, strongly complexed or in organic forms) do not elute from the column. This low percentage of column-speciated arsenic is indicative that more complex forms of arsenic exist in the tobacco. All the analysed species correlate positively with total arsenic concentration over the whole compositional range and regression analysis indicates a consistent ratio of about 4:1 in favour of inorganic arsenic compared with MA + DMA.

Conclusions: The dominance of inorganic arsenic species among those components analysed is a marked feature of the diverse range of tobaccos selected for study. Such consistency is important in the context of a WHO expert panel recommendation to regulate tobacco crops and products using total arsenic concentration. If implemented more research would be required to develop models that accurately predict the smoker's exposure to reduced inorganic arsenic species on the basis of leaf or product concentration and product design features.

The Environmental Fate of polybrominated diphenyl ethers in western Taiwan and coastal waters: evaluation with a fugacity based model

The environmental fate of polybrominated diphenyl ethers (PBDEs), a group of flame retardants that are considered to be persistent organic pollutants (POPs), around the Zhuoshui River and Changhua County regions of Taiwan was assessed. An investigation into emissions, partitioning, and fate of selected PBDEs was conducted based on the equilibrium constant (EQC) fugacity model developed at Trent University, Canada. Emissions for congeners PBDE 47, PBDE 99, and PBDE 209 to air (4.9–92 × 10−3 kg/h), soil (0.91–17.4 × 10−3 kg/h), and water (0.21–4.04 × 10−3 kg/h), were estimated by modifying previous models on PBDE emission rates by considering both industrial and domestic rates. It was found that fugacity modeling can give a reasonable estimation of the behavior, partitioning, and concentrations of PBDE congeners in and around Taiwan. Results indicate that PBDE congeners have a high affinity for partitioning into sediments then soils. As congener number decreases, the PBDEs then partition more readily into air. As the degree of bromination increases, congeners more readily partition to sediments. Sediments may then act as a long-term source of PBDEs which can be released back into the water column due to resuspension during storm events.

Holocene vegetation change in relation to fire and volcanic events in Jilin, Northeastern China

Volatiles erupted from large-scale explosive volcanic activities have a significant impact on climate and environmental changes. As an important ecological factor, the occurrence of fire is affected by vegetation cover, and fire can feed back into both vegetation and climatic change. The causes of fire events are diverse; and can include volcanic eruptions. The amount of charcoal in sediment sequences is related to the frequency and intensity of fire, and hence under good preservation conditions fire history can be reconstructed from fossil charcoal abundance. Until now, little research on the role of fire has been carried out in northeastern China. In this study, through research on charcoal and tephra shards from Gushantun and Hanlongwan, Holocene vegetation change in relation to fire and volcanic events in Jilin, Northeastern China, was investigated. Where tephra shards are present in Gushantun it is associated with low level of both conifers and broadleaved trees, and is also associated with a pronounced charcoal peak. This suggests forest cover was greatly reduced from a fire caused by an eruption of the Tianchi volcano. We also detected one tephra layer in Hanlongwan, which also has the almost same depth with low level forest pollen values and one charcoal peak. This was caused probably by an eruption of the Jinlongdingzi volcano.

Any versus long-term prescribing of high risk medications in older people using 2012 Beers Criteria: results from three cross-sectional samples of primary care records for 2003/4, 2007/8 and 2011/12

Background: High risk medications are commonly prescribed to older US patients. Currently, less is known about high risk medication prescribing in other Western Countries, including the UK. We measured trends and correlates of high risk medication prescribing in a subset of the older UK population (community/institutionalized) to inform harm minimization efforts. Methods: Three cross-sectional samples from primary care electronic clinical records (UK Clinical Practice Research Datalink, CPRD) in fiscal years 2003/04, 2007/08 and 2011/12 were taken. This yielded a sample of 13,900 people aged 65 years or over from 504 UK general practices. High risk medications were defined by 2012 Beers Criteria adapted for the UK. Using descriptive statistical methods and regression modelling, prevalence of ‘any’ (drugs prescribed at least once per year) and ‘long-term’ (drugs prescribed all quarters of year) high risk medication prescribing and correlates were determined. Results: While polypharmacy rates have risen sharply, high risk medication prevalence has remained stable across a decade. A third of older (65+) people are exposed to high risk medications, but only half of the total prevalence was long-term (any = 38.4 % [95 % CI: 36.3, 40.5]; long-term = 17.4 % [15.9, 19.9] in 2011/12). Long-term but not any high risk medication exposure was associated with older ages (85 years or over). Women and people with higher polypharmacy burden were at greater risk of exposure; lower socio-economic status was not associated. Ten drugs/drug classes accounted for most of high risk medication prescribing in 2011/12. Conclusions: High risk medication prescribing has not increased over time against a background of increasing polypharmacy in the UK. Half of patients receiving high risk medications do so for less than a year. Reducing or optimising the use of a limited number of drugs could dramatically reduce high risk medications in older people. Further research is needed to investigate why the oldest old and women are at greater risk. Interventions to reduce high risk medications may need to target shorter and long-term use separately.

Common cancer stem cell gene variants predict colon cancer recurrence

PURPOSE: Recent evidence suggests that cancer stem cells (CSC) are responsible for key elements of colon cancer progression and recurrence. Germline variants in CSC genes may result in altered gene function and/or activity, thereby causing interindividual differences in a patient's tumor recurrence capacity and chemoresistance. We investigated germline polymorphisms in a comprehensive panel of CSC genes to predict time to tumor recurrence (TTR) in patients with stage III and high-risk stage II colon cancer.

EXPERIMENTAL DESIGN: A total of 234 patients treated with 5-fluorouracil-based chemotherapy at the University of Southern California were included in this study. Whole blood samples were analyzed for germline polymorphisms in genes that have been previously associated with colon CSC (CD44, Prominin-1, DPP4, EpCAM, ALCAM, Msi-1, ITGB1, CD24, LGR5, and ALDH1A1) by PCR-RFLP or direct DNA-sequencing.

RESULTS: The minor alleles of CD44 rs8193 C>T, ALCAM rs1157 G>A, and LGR5 rs17109924 T>C were significantly associated with increased TTR (9.4 vs. 5.4 years; HR, 0.51; 95% CI: 0.35-0.93; P = 0.022; 11.3 vs. 5.7 years; HR, 0.56; 95% CI: 0.33-0.94; P = 0.024, and 10.7 vs. 5.7 years; HR, 0.33; 95% CI: 0.12-0.90; P = 0.023, respectively) and remained significant in the multivariate analysis stratified by ethnicity. In recursive partitioning, a specific gene variant profile including LGR5 rs17109924, CD44 rs8193, and ALDH1A1 rs1342024 represented a high-risk subgroup with a median TTR of 1.7 years (HR, 6.71, 95% CI: 2.71-16.63, P < 0.001).

CONCLUSION: This is the first study identifying common germline variants in colon CSC genes as independent prognostic markers for stage III and high-risk stage II colon cancer patients.

Gender-specific genomic profiling in metastatic colorectal cancer patients treated with 5-fluorouracil and oxaliplatin

AIMS: Survival and response rates in metastatic colorectal cancer remain poor, despite advances in drug development. There is increasing evidence to suggest that gender-specific differences may contribute to poor clinical outcome. We tested the hypothesis that genomic profiling of metastatic colorectal cancer is dependent on gender.

MATERIALS & METHODS: A total of 152 patients with metastatic colorectal cancer who were treated with oxaliplatin and continuous infusion 5-fluorouracil were genotyped for 21 polymorphisms in 13 cancer-related genes by PCR. Classification and regression tree analysis tested for gender-related association of polymorphisms with overall survival, progression-free survival and tumor response.

RESULTS: Classification and regression tree analysis of all polymorphisms, age and race resulted in gender-specific predictors of overall survival, progression-free survival and tumor response. Polymorphisms in the following genes were associated with gender-specific clinical outcome: estrogen receptor β, EGF receptor, xeroderma pigmentosum group D, voltage-gated sodium channel and phospholipase A2.

CONCLUSION: Genetic profiling to predict the clinical outcome of patients with metastatic colorectal cancer may depend on gender.

Dynamic State Estimation of Power Systems with Quantization Eects: A Recursive Filter Approach

In this paper, a recursive filter algorithm is developed to deal with the state estimation problem for power systems with quantized nonlinear measurements. The measurements from both the remote terminal units and the phasor measurement unit are subject to quantizations described by a logarithmic quantizer. Attention is focused on the design of a recursive filter such that, in the simultaneous presence of nonlinear measurements and quantization effects, an upper bound for the estimation error covariance is guaranteed and subsequently minimized. Instead of using the traditional approximation methods in nonlinear estimation that simply ignore the linearization errors, we treat both the linearization and quantization errors as norm-bounded uncertainties in the algorithm development so as to improve the performance of the estimator. For the power system with such kind of introduced uncertainties, a filter is designed in the framework of robust recursive estimation, and the developed filter algorithm is tested on the IEEE benchmark power system to demonstrate its effectiveness.

Is childhood type 1 diabetes a wealth-related disease? An ecological analysis of European incidence rates

Aims/Hypothesis: To describe the epidemiology of childhood-onset Type 1 (insulin-dependent) diabetes in Europe, the EURODIAB collaborative group has established prospective, geographically-defined registers of children diagnosed under 15 years. A total of 16,362 cases were registered by 44 centres during the period 1989-1994. The registers cover a population of approximately 28 million children with most European countries represented. Methods In most centres a primary and a secondary source of ascertainment were used so that the completeness of registration could be assessed by the capture-recapture method. Ecological correlation and regression analyses were used to study the relationship between incidence and various environmental, health and economic indicators. Findings: The standardised average annual incidence rate during the period 1989-94 ranged from 3.2 cases per 100,000 per annum in the Former Yugoslavian Republic of Macedonia to 40.2 cases per 100,000 per annum in Finland. Indicators of national prosperity such as infant mortality (r= -0.64) and gross domestic product (r= 0.58) were most strongly and significantly correlated with incidence rate, and previously-reported associations with coffee consumption (r= 0.51), milk consumption (r= 0.58) and latitude (r= 0.40) were also observed. Conclusion/Interpretation: The wide variation in childhood type 1 diabetes incidence rates within Europe could be partially explained by indicators of national prosperity. These indicators could reflect differences in environmental risk factors such as nutrition or lifestyle that are important in determining a country's incidence rate.

The Apperceptive Personality Test located in personality space.

The Apperceptive Personality Test is a projective test that claims to show good psychometric properties but which has not been related to the main, Eysenckian, personality traits. This study investigated the overlap between these two tests using a sample of students. Correlational and regression analyses showed a modest degree of overlap between Extraversion, Neuroticism and some of the scales from the Apperceptive Personality Test.

Comparison of two construction algorithms for local model networks

The divide-and-conquer approach of local model (LM) networks is a common engineering approach to the identification of a complex nonlinear dynamical system. The global representation is obtained from the weighted sum of locally valid, simpler sub-models defined over small regions of the operating space. Constructing such networks requires the determination of appropriate partitioning and the parameters of the LMs. This paper focuses on the structural aspect of LM networks. It compares the computational requirements and performances of the Johansen and Foss (J&F) and LOLIMOT tree-construction algorithms. Several useful and important modifications to each algorithm are proposed. The modelling performances are evaluated using real data from a pilot plant of a pH neutralization process. Results show that while J&F achieves a more accurate nonlinear representation of the pH process, LOLIMOT requires significantly less computational effort.

Psychological processes underlying nurses' handwashing behaviour

Aim/Background Psychological models of behaviour change have been found to be useful in predicting health-related behaviour in patients but have rarely been used in relation to the health behaviour of staff. This study explored the association between a range of psychological variables and self-reported handwashing in a sample of nurses who work in a large general hospital. Method A questionnaire-based cross-sectional, correlational study was used. Questionnaires examining demographics, self-efficacy, perceived importance of handwashing, perception of risk, occupational stress and training related to handwashing were administered to an opportunity sample (n = 76) of nurses drawn from an acute hospital. ANOVAs, correlation and regression analyses were performed to determine significant covariates of handwashing behaviour. Findings There was a weak relationship between demographic variables and self-reported handwashing. The degree to which employees perceived their workplace to assist handwashing and perceived importance of handwashing were related to self-reported handwashing. Accordingly further covariates of these variables were sought. Training received and occupational stress both covaried with nurses’ perceptions of the degree to which their workplace assisted handwashing. Nurses’ beliefs regarding the transmission of infections covaried with perceived importance of handwashing. Conclusion Occupational stress was observed to reduce the perception of having a supportive employer: organisations need to facilitate handwashing and protect staff from factors that have a detrimental impact, such as work-related stress. Nurses’ perceived importance of the potential for poor handwashing practice to contribute to the transmission of infections should be highlighted in interventions.

Linking past cultural developments to palaeoenvironmental changes in Estonia

Connections between environmental and cultural changes are analysed in Estonia during the past c. 4,500 years. Records of cereal-type pollen as (agri)cultural indices are compared with high-resolution palaeohydrological and annual mean temperature reconstructions from a selection of Estonian bogs and lakes (and Lake Igelsjon in Sweden). A broad-scale comparison shows increases in the percentage of cereal-type pollen during a decreasing trend in annual mean temperatures over the past c. 4,300 years, suggesting a certain independence of agrarian activities from environmental conditions at the regional level. The first cereal-type pollen in the region is found from a period with a warm and dry climate. A slow increase in pollen of cultivated land is seen around the beginning of the late Bronze Age, a slight increase at the end of the Roman Iron Age and a significant increase at the beginning of the Middle Ages. In a few cases increases in agricultural pollen percentages occur in the periods of warming. Stagnation and regression occurs in the periods of cooling, but regression at individual sites may also be related to warmer climate episodes. The cooling at c. 400-300 cal b.p., during the 'Little Ice Age' coincides with declines in cereal-type and herb pollen curves. These may not, however, be directly related to the climate change, because they coincide with war activities in the region.