Consensus on circulatory shock and hemodynamic monitoring. Task force of the European Society of Intensive Care Medicine.

OBJECTIVE: Circulatory shock is a life-threatening syndrome resulting in multiorgan failure and a high mortality rate. The aim of this consensus is to provide support to the bedside clinician regarding the diagnosis, management and monitoring of shock. METHODS: The European Society of Intensive Care Medicine invited 12 experts to form a Task Force to update a previous consensus (Antonelli et al.: Intensive Care Med 33:575-590, 2007). The same five questions addressed in the earlier consensus were used as the outline for the literature search and review, with the aim of the Task Force to produce statements based on the available literature and evidence. These questions were: (1) What are the epidemiologic and pathophysiologic features of shock in the intensive care unit ? (2) Should we monitor preload and fluid responsiveness in shock ? (3) How and when should we monitor stroke volume or cardiac output in shock ? (4) What markers of the regional and microcirculation can be monitored, and how can cellular function be assessed in shock ? (5) What is the evidence for using hemodynamic monitoring to direct therapy in shock ? Four types of statements were used: definition, recommendation, best practice and statement of fact. RESULTS: Forty-four statements were made. The main new statements include: (1) statements on individualizing blood pressure targets; (2) statements on the assessment and prediction of fluid responsiveness; (3) statements on the use of echocardiography and hemodynamic monitoring. CONCLUSIONS: This consensus provides 44 statements that can be used at the bedside to diagnose, treat and monitor patients with shock

The plight of the sense-making ape

This is a selective review of the published literature on object-choice tasks, where participants use directional cues to find hidden objects. This literature comprises the efforts of researchers to make sense of the sense-making capacities of our nearest living relatives. This chapter is written to highlight some nonsensical conclusions that frequently emerge from this research. The data suggest that when apes are given approximately the same sense-making opportunities as we provide our children, then they will easily make sense of our social signals. The ubiquity of nonsensical contemporary scientific claims to the effect that humans are essentially--or inherently--more capable than other great apes in the understanding of simple directional cues is, itself, a testament to the power of preconceived ideas on human perception

The Expanding Fireball of Nova Delphini 2013

A classical nova occurs when material accreting onto the surface of a white dwarf in a close binary system ignites in a thermonuclear runaway. Complex structures observed in the ejecta at late stages could result from interactions with the companion during the common envelope phase. Alternatively, the explosion could be intrinsically bipolar, resulting from a localized ignition on the surface of the white dwarf or as a consequence of rotational distortion. Studying the structure of novae during the earliest phases is challenging because of the high spatial resolution needed to measure their small sizes. Here we report near-infrared interferometric measurements of the angular size of Nova Delphini 2013, starting from one day after the explosion and continuing with extensive time coverage during the first 43 days. Changes in the apparent expansion rate can be explained by an explosion model consisting of an optically thick core surrounded by a diffuse envelope. The optical depth of the ejected material changes as it expands. We detect an ellipticity in the light distribution, suggesting a prolate or bipolar structure that develops as early as the second day. Combining the angular expansion rate with radial velocity measurements, we derive a geometric distance to the nova of 4.54 +/- 0.59 kpc from the Sun.Comment: Published in Nature. 32 pages. Final version available at http://www.nature.com/nature/journal/v515/n7526/full/nature13834.htm

Susceptibility to Ebbinghaus and Muller-Lyer illusions in autistic children: a comparison of three different methods

Background Studies reporting altered susceptibility to visual illusions in autistic individuals compared to that typically developing individuals have been taken to reflect differences in perception (e.g. reduced global processing), but could instead reflect differences in higher-level decision-making strategies. Methods We measured susceptibility to two contextual illusions (Ebbinghaus, Müller-Lyer) in autistic children aged 6–14 years and typically developing children matched in age and non-verbal ability using three methods. In experiment 1, we used a new two-alternative-forced-choice method with a roving pedestal designed to minimise cognitive biases. Here, children judged which of two comparison stimuli was most similar in size to a reference stimulus. In experiments 2 and 3, we used methods previously used with autistic populations. In experiment 2, children judged whether stimuli were the ‘same’ or ‘different’, and in experiment 3, we used a method-of-adjustment task. Results Across all tasks, autistic children were equally susceptible to the Ebbinghaus illusion as typically developing children. Autistic children showed a heightened susceptibility to the Müller-Lyer illusion, but only in the method-of-adjustment task. This result may reflect differences in decisional criteria. Conclusions Our results are inconsistent with theories proposing reduced contextual integration in autism and suggest that previous reports of altered susceptibility to illusions may arise from differences in decision-making, rather than differences in perception per se. Our findings help to elucidate the underlying reasons for atypical responses to perceptual illusions in autism and call for the use of methods that reduce cognitive bias when measuring illusion susceptibility

Glycosaminoglycan Binding Facilitates Entry of a Bacterial Pathogen into Central Nervous Systems

Certain microbes invade brain microvascular endothelial cells (BMECs) to breach the blood-brain barrier (BBB) and establish central nervous system (CNS) infection. Here we use the leading meningitis pathogen group B Streptococcus (GBS) together with insect and mammalian infection models to probe a potential role of glycosaminoglycan (GAG) interactions in the pathogenesis of CNS entry. Site-directed mutagenesis of a GAG-binding domain of the surface GBS alpha C protein impeded GBS penetration of the Drosophila BBB in vivo and diminished GBS adherence to and invasion of human BMECs in vitro. Conversely, genetic impairment of GAG expression in flies or mice reduced GBS dissemination into the brain. These complementary approaches identify a role for bacterial-GAG interactions in the pathogenesis of CNS infection. Our results also highlight how the simpler yet genetically conserved Drosophila GAG pathways can provide a model organism to screen candidate molecules that can interrupt pathogen-GAG interactions for future therapeutic applications

Inhibition of PKC activity blocks the increase of ET(B )receptor expression in cerebral arteries

BACKGROUND: Previous studies have shown that there is a time-dependent upregulation of contractile endothelin B (ET(B)) receptors in middle cerebral arteries (MCA) after organ culture. This upregulation is dependent on mitogen-activated protein kinases and possibly protein kinase C (PKC). The aim of this study was to examine the effect of PKC inhibitors with different profiles on the upregulation of contractile ET(B )receptors in rat MCA. Artery segments were incubated for 24 hours at 37°C. To investigate involvement of PKC, inhibitors were added to the medium before incubation. The contractile endothelin-mediated responses were measured and real-time PCR was used to detect endothelin receptor mRNA levels. Furthermore, immunohistochemistry was used to demonstrate the ET(B )receptor protein distribution in the MCA and Western blot to measure which of the PKC subtypes that were affected by the inhibitors. RESULTS: The PKC inhibitors bisindolylmaleimide I, Ro-32-0432 and PKC inhibitor 20–28 attenuated the ET(B )receptor mediated contractions. Furthermore, Ro-32-0432 and bisindolylmaleimide I decreased ET(B )receptor mRNA levels while PKC inhibitor 20–28 reduced the amount of receptor protein on smooth muscle cells. PKC inhibitor 20–28 also decreased the protein levels of the five PKC subtypes studied (α, βI, γ, δ and ε). CONCLUSION: The results show that PKC inhibitors are able to decrease the ET(B )receptor contraction and expression in MCA smooth muscle cells following organ culture. The PKC inhibitor 20–28 affects the protein levels, while Ro-32-0432 and bisindolylmaleimide I affect the mRNA levels, suggesting differences in activity profile. Since ET(B )receptor upregulation is seen in cerebral ischemia, the results of the present study provide a way to interfere with the vascular involvement in cerebral ischemia

Association of daily tar and nicotine intake with incident myocardial infarction: Results from the population-based MONICA/KORA Augsburg Cohort Study 1984 - 2002

<p>Abstract</p> <p>Background</p> <p>Cigarette smoking has been shown to be one of the most important risk factors for cardiovascular diseases. However, little is known about cumulative effects of daily tar and nicotine intake on the risk of incident myocardial infarction (MI) so far. To bridge this gap, we conducted an analysis in a large prospective study from Southern Germany investigating associations of daily tar and nicotine intake with an incident MI event.</p> <p>Methods</p> <p>The study was based on 4,099 men and 4,197 women participating in two population-based MONICA Augsburg surveys between 1984 and 1990 and followed up within the KORA framework until 2002. During a mean follow-up of 13.3 years, a number of 307 men and 80 women developed an incident MI event. Relative risks were calculated as hazard ratios (HRs) estimated by Cox proportional hazards models adjusted for cardiovascular risk factors.</p> <p>Results</p> <p>In the present study, male regular smokers consumed on average more cigarettes per day than female regular smokers (20 versus 15) and had a higher tar and nicotine intake per day. In men, the MI risk compared to never-smokers increased with higher tar intake: HRs were 2.24 (95% CI 1.40-3.56) for 1-129 mg/day, 2.12 (95% CI 1.37-3.29) for 130-259 mg/day and 3.01 (95% CI 2.08-4.36) for ≥ 260 mg/day. In women, the corresponding associations were comparable but more pronounced for high tar intake (HR 4.67, 95% CI 1.76-12.40). Similar associations were observed for nicotine intake.</p> <p>Conclusions</p> <p>The present study based on a large population-based sample adds important evidence of cumulative effects of tar and nicotine intake on the risk of incident MI. Even low or medium tar and nicotine intake revealed substantial risk increases as compared to never-smokers. Therefore, reduction of tar and nicotine contents in cigarettes cannot be seen as a suitable public health policy in preventing myocardial infarction.</p

Effects of microperfusion in hepatic diffusion weighted imaging

Clinical hepatic diffusion weighted imaging (DWI) generally relies on mono-exponential diffusion. The aim was to demonstrate that mono-exponential diffusion in the liver is contaminated by microperfusion and that the bi-exponential model is required. Nineteen fasting healthy volunteers were examined with DWI (seven b-values) using fat suppression and respiratory triggering (1.5 T). Five different regions in the liver were analysed regarding the mono-exponentially fitted apparent diffusion coefficient (ADC), and the bi-exponential model: molecular diffusion (D (slow) ) microperfusion (D (fast) ) and the respective fractions (f (slow/fast)). Data were compared using ANOVA and Kruskal-Wallis tests. Simulations were performed by repeating our data analyses, using just the DWI series acquired with b-values approximating those of previous studies. Median mono-exponentially fitted ADCs varied significantly (P <0.001) between 1.107 and 1.423 x 10(-3) mm(2)/s for the five regions. Bi-exponential fitted D-slow varied between 0.923 and 1.062 x 10(-3) mm(2)/s without significant differences (P = 0.140). D (fast) varied significantly, between 17.8 and 46.8 x 10(-3) mm(2)/s (P <0.001). F-tests showed that the diffusion data fitted the bi-exponential model significantly better than the mono-exponential model (F > 21.4, P <0.010). These results were confirmed by the simulations. ADCs of normal liver tissue are significantly dependent on the measurement location because of substantial microperfusion contamination; therefore the bi-exponential model should be used. Diffusion weighted MR imaging helps clinicians to differentiate tumours by diffusion properties Fast moving water molecules experience microperfusion, slow molecules diffusion Hepatic diffusion should be measured by bi-exponential models to avoid microperfusion contamination Mono-exponential models are contaminated with microperfusion, resulting in apparent regional diffusion differences Bi-exponential models are necessary to measure diffusion and microperfusion in the liver

Parent-reported health care expenditures associated with autism spectrum disorders in Heilongjiang province, China

<p>Abstract</p> <p>Background</p> <p>The aim of this study was to determine the health expenses incurred by families with children with autism spectrum disorder (ASD) and those expenses' relation to total household income and expenditures.</p> <p>Methods</p> <p>In this cross-sectional study, health care expenditure data were collected through face-to-face interviews. Expenses included annual costs for clinic visits, medication, behavioral therapy, transportation, and accommodations. Health care costs as a percentage of total household income and expenditures were also determined. The participants included 290 families with ASD children who were treated at the Children Development and Behavior Research Center, Harbin Medical University, China.</p> <p>Results</p> <p>Families with ASD children from urban and rural areas had higher per-capita household expenditures by 60.8% and 74.7%, respectively, compared with provincial statistics for 2007. Behavioral therapy accounted for the largest proportion of health expenses (54.3%) for ASD children. In 19.9% of urban and 38.2% of rural families, health care costs exceeded the total annual household income. Most families (89.3% of urban families; 88.1% of rural families) in that province reported higher health care expenditures than the provincial household average.</p> <p>Conclusion</p> <p>For families with ASD children, the economic burden of health care is substantially higher than the provincial average.</p