Sepsis guidelines recommend obtaining blood cultures before starting anti-infective therapy in patients with sepsis. However, little is known of how antibiotic treatment before sampling affects ...bacterial growth. The aim of this study was to compare the results of blood cultures drawn before and during antibiotic therapy.
Prospective clinical cohort study of septic patients. Adult intensive care unit patients with two or three blood culture sets at the beginning of sepsis between 2010 and 2017 were included. Patients with blood culture samples obtained before antibiotic therapy were compared with patients with samples taken during antibiotic therapy. Blood culture positivity, defined as presence of a microbiological pathogen, was compared between the groups. Logistic regression was performed to adjust the impact of different factors with respect to blood culture positivity.
In total, 559 patients with 1364 blood culture sets at the beginning of sepsis were analysed. Blood culture positivity was 50.6% (78/154) among patients with sepsis who did not receive antibiotics and only 27.7% (112/405) in those who were already receiving antibiotics (p <0.001). Logistic regression revealed antibiotic therapy as an independent factor for less pathogen identification (odds ratio 0.4; 95% CI 0.3–0.6). Gram-positive pathogens (28.3% (111/392) versus 11.9% (116/972); p <0.001) and also Gram-negative pathogens (16.3% (64/392) versus 9.3% (90/972); p <0.001) were more frequent in blood culture sets drawn before antibiotic therapy compared with sets obtained during antibiotic therapy.
Obtaining blood cultures during antibiotic therapy is associated with a significant loss of pathogen detection. This strongly emphasizes the current recommendation to obtain blood cultures before antibiotic administration in patients with sepsis.
We present a comprehensive new global QCD analysis of polarized inclusive deep-inelastic scattering, including the latest high-precision data on longitudinal and transverse polarization asymmetries ...from Jefferson Lab and elsewhere. The analysis is performed using a new iterative Monte Carlo fitting technique which generates stable fits to polarized parton distribution functions (PDFs) with statistically rigorous uncertainties. Inclusion of the Jefferson Lab data leads to a reduction in the PDF errors for the valence and sea quarks, as well as in the gluon polarization uncertainty at x> or =0.1. The study also provides the first determination of the flavor-separated twist-3 PDFs and the d sub(2) moment of the nucleon within a global PDF analysis.
Intrinsic activity of the brain during resting-state is not random and is currently discussed as a neural reflection of self-referential processing. Self-reference is typically reduced in ...schizophrenia as a disorder of the self while extensive self-attribution of, eg, negative thoughts is characteristic for major depression. However, a quantitative meta-analysis targeting the resting-state brain activity in both disorders is lacking. Here, we predict primarily abnormal resting-state activity in brain regions related to self-referential processing. By means of activation likelihood estimation (ALE) on functional magnetic resonance imaging and positron emission tomography studies, we investigated concurrence of hyperactivation and hypoactivation in resting-state measurements of schizophrenic and depressed patients compared with healthy controls. We found hypoactivation in ventromedial prefrontal cortex (vmPFC), left hippocampus, posterior cingulate cortex, lower precueus and the precuneus, and hyperactivation in bilateral lingual gyrus of schizophrenic patients. In major depression, we found hyperactivation in vmPFC, left ventral striatum, and left thalamus and hypoactivation in left postcentral gyrus, left fusiform gyrus, and left insula. An overall ALE analysis confirmed the proximity of hypoactivation in schizophrenia and hyperactivation in major depression in the vmPFC.The opposing resting-state activity in vmPFC for the 2 disorders is in line with the different expression of dysfunctional self-reference as core characteristics of schizophrenia and major depression. The vmPFC has previously been identified as a crucial area for self-referential processing and may represent a target to increase the diagnostic validity of resting-state activity for disorders with dysfunctions of the self.
Halting global biodiversity loss is central to the Convention on Biological Diversity and United Nations Sustainable Development Goals, but success to date has been very limited. A critical ...determinant of success in achieving these goals is the financing that is committed to maintaining biodiversity; however, financing decisions are hindered by considerable uncertainty over the likely impact of any conservation investment. For greater effectiveness, we need an evidence-based model that shows how conservation spending quantitatively reduces the rate of biodiversity loss. Here we demonstrate such a model, and empirically quantify how conservation investment reduced biodiversity loss in 109 countries (signatories to the Convention on Biological Diversity and Sustainable Development Goals), by a median average of 29% per country between 1996 and 2008. We also show that biodiversity changes in signatory countries can be predicted with high accuracy, using a dual model that balances the effects of conservation investment against those of economic, agricultural and population growth (human development pressures). Decision-makers can use this model to forecast the improvement that any proposed biodiversity budget would achieve under various scenarios of human development pressure, and then compare these forecasts to any chosen policy target. We find that the impact of spending decreases as human development pressures grow, which implies that funding may need to increase over time. The model offers a flexible tool for balancing the Sustainable Development Goals of human development and maintaining biodiversity, by predicting the dynamic changes in conservation finance that will be needed as human development proceeds.
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•Systematic study of protein phase behaviour in a droplet-based microreactor.•Numerical prediction of droplet sizes in a flow-focusing geometry.•Parametric study to quantify the ...influence of the droplet volume on nucleation.•Parametric study of the influence of the droplet volume on the phase diagram limits.
This work reports a cheap and easy-to-use droplet-based microfluidic platform for the study of protein crystallization, offering the possibility to characterize the protein phase behaviour, and the effect of volumetric and interfacial phenomena on the crystallization mechanism. We conducted a parametric study supported by comparison with literature data, to quantify the influence of the droplet volume on the thermodynamic (solubility data) and kinetic (metastability data) parameters, using lysozyme as a model protein. Experiments were performed in a tubular microreactor at low Capillary numbers (4.1 × 10−5–2.3 × 10−4), resulting in a broad range of droplet sizes. The droplet formation in a flow-focusing geometry was also numerically studied using CFD and a correlation for the droplet size was developed. Subsequently, the lysozyme phase behaviour and the possible mechanisms associated with the nucleation process were evaluated. While crystallization in small volume droplets is usually characterized by a low nucleation probability and correspondingly low number of crystals, we did not observe this in our experiments. A potential explanation for this is the complex and stochastic mechanism of nucleation, including the competition between monomers and oligomers in solution.
We address liquid–liquid mass transfer between immiscible liquids using the system 1-butanol and water, with succinic acid as the mass transfer component. Using this system we evaluate the influence ...of two-phase flow transitions from Taylor flow to stratified flow and further to dispersed flow at elevated flow rates. In addition, we address the scale-up behavior of mass transfer coefficients and the extraction efficiency by using reactors on the micro- and the milli-scale. Flow imaging enables us to identify the different flow regimes and to connect them to the trends observed in mass transfer, and the obtained results highlight the dependence of mass transfer on flow patterns. Furthermore, the results show that on the milli-scale fluid–structure interactions are driving the phase dispersion and interfacial mass transfer, and such a reactor design ensures straightforward scalability from the micro- to the milli-scale.
•The scalability of mass transfer in liquid–liquid flow is addressed.•The obtained results highlight the dependence of mass transfer on the two-phase flow patterns.•On the milli-scale fluid–structure interactions are driving the interfacial mass transfer.•Reactor designs promoting fluid–structure interaction ensure straightforward scalability from the micro- to the milli-scale.
Inadequate funding levels are a major impediment to effective global biodiversity conservation and are likely associated with recent failures to meet United Nations biodiversity targets. Some ...countries are more severely underfunded than others and therefore represent urgent financial priorities. However, attempts to identify these highly underfunded countries have been hampered for decades by poor and incomplete data on actual spending, coupled with uncertainty and lack of consensus over the relative size of spending gaps. Here, we assemble a global database of annual conservation spending. We then develop a statistical model that explains 86% of variation in conservation expenditures, and use this to identify countries where funding is robustly below expected levels. The 40 most severely underfunded countries contain 32% of all threatened mammalian diversity and include neighbors in some of the world’s most biodiversity-rich areas (Sundaland, Wallacea, and Near Oceania). However, very modest increases in international assistance would achieve a large improvement in the relative adequacy of global conservation finance. Our results could therefore be quickly applied to limit immediate biodiversity losses at relatively little cost.
Video gaming is a highly pervasive activity, providing a multitude of complex cognitive and motor demands. Gaming can be seen as an intense training of several skills. Associated cerebral structural ...plasticity induced has not been investigated so far. Comparing a control with a video gaming training group that was trained for 2 months for at least 30 min per day with a platformer game, we found significant gray matter (GM) increase in right hippocampal formation (HC), right dorsolateral prefrontal cortex (DLPFC) and bilateral cerebellum in the training group. The HC increase correlated with changes from egocentric to allocentric navigation strategy. GM increases in HC and DLPFC correlated with participants' desire for video gaming, evidence suggesting a predictive role of desire in volume change. Video game training augments GM in brain areas crucial for spatial navigation, strategic planning, working memory and motor performance going along with evidence for behavioral changes of navigation strategy. The presented video game training could therefore be used to counteract known risk factors for mental disease such as smaller hippocampus and prefrontal cortex volume in, for example, post-traumatic stress disorder, schizophrenia and neurodegenerative disease.
There is growing evidence that beta-blockade may reduce mortality in selected patients with sepsis. However, it is unclear if a pre-existing, chronic oral beta-blocker therapy should be continued or ...discontinued during the acute phase of severe sepsis and septic shock.
The present secondary analysis of a prospective observational single centre trial compared patient and treatment characteristics, length of stay and mortality rates between adult patients with severe sepsis or septic shock, in whom chronic beta-blocker therapy was continued or discontinued, respectively. The acute phase was defined as the period ranging from two days before to three days after disease onset. Multivariable Cox regression analysis was performed to compare survival outcomes in patients with pre-existing chronic beta-blockade.
A total of 296 patients with severe sepsis or septic shock and pre-existing, chronic oral beta-blocker therapy were included. Chronic beta-blocker medication was discontinued during the acute phase of sepsis in 129 patients and continued in 167 patients. Continuation of beta-blocker therapy was significantly associated with decreased hospital (P=0.03), 28-day (P=0.04) and 90-day mortality rates (40.7% vs 52.7%; P=0.046) in contrast to beta-blocker cessation. The differences in survival functions were validated by a Log-rank test (P=0.01). Multivariable analysis identified the continuation of chronic beta-blocker therapy as an independent predictor of improved survival rates (HR = 0.67, 95%-CI (0.48, 0.95), P=0.03).
Continuing pre-existing chronic beta-blockade might be associated with decreased mortality rates up to 90 days in septic patients.
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•Well-structured porous medium as a scale-up approach in a milli-scale reactor.•CFD simulations to characterize the flow features within the micro-pores.•Orientation of the ...micro-pores significantly influences the fluid heterogeneity.
Despite the many advantages of micro-reactors their application in industry is still limited due to their low throughput. To address this issue, micro-scale porous media are used as inserts in milli-scale tubular reactors. In this work, six different well-structured porous media (WSPM) consisting of cylindrical rods with an outer diameter of 250 μm are characterized with computational fluid dynamics (CFD). The individual WSPM differ in the rotation of rod layers around the main flow direction, and the orientation of rod layers against the flow direction. The simulation results show that changing the rod layer orientation influences the flow heterogeneity, while the rod layer rotation affects the pore alignment resulting in connected fluid paths. Scalar transport simulations reveal that the WSPM result in a considerable mixing enhancement. This study underlines the potential of integrating WSPM in milli-scale reactors as scale-up approach, and how their geometry affects mixing.
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