Year in review 2007: Critical Care – shock

The research papers on shock published in Critical Care throughout 2007 are related to three major subjects: the modulation of the macrocirculation and microcirculation during shock, focusing on arginine vasopressin, erythropoietin and nitric oxide; studies on metabolic homeostasis (acid–base status, energy expenditure and gastrointestinal motility); and basic supportive measures in critical illness (fluid resuscitation and sedation, and body-temperature management). The present review summarizes the key results of these studies and provides a brief discussion in the context of the relevant scientific and clinical background

Biological Therapies in Immune-Mediated Inflammatory Diseases: Can Biosimilars Reduce Access Inequities?

Biological therapies are an effective treatment for a range of immune-mediated inflammatory diseases (IMIDs), including rheumatoid arthritis, psoriasis, and inflammatory bowel diseases. However, due to their high costs, considerable differences in their utilization exist across the world, even among the various European countries, with many countries restricting access despite professional society guideline recommendations. Adoption of biologics by healthcare providers has been particularly poor in many Central and Eastern European countries. Differences in utilization have also been observed across medical specialties, healthcare providers, and at a regional and national level. The objective of this paper is to provide an overview of the different market access policies for biologics in Europe and to investigate reasons for such differences. One of the potential solutions for providing broader access to IMID patients, where cost is the major barrier, is to encourage the use of biosimilars in place of their reference products. Biosimilars are generally less expensive alternatives to already licensed biological therapies and are approved on the basis that they are similar to the reference product in terms of quality, safety, and efficacy. Budget impact models predict considerable cost savings following the introduction of biosimilars in the next few years. These savings could be used to increase access to biologics and other innovative therapies

Solution Atomic Layer Deposition of Smooth, Continuous, Crystalline Metal-Organic Framework Thin Films

For the first time, a procedure has been established for the growth of surface-anchored metal–organic framework (SURMOF) copper(II) benzene-1,4-dicarboxylate (Cu-BDC) thin films of thickness control with single molecule accuracy. For this, we exploit the novel method solution atomic layer deposition (sALD). The sALD growth rate has been determined at 4.5 Å per cycle. The compact and dense SURMOF films grown at room temperature by sALD possess a vastly superior film thickness uniformity than those deposited by conventional solution-based techniques, such as dipping and spraying while featuring clear crystallinity from 100 nm thickness. The highly controlled layer-by-layer growth mechanism of sALD proves crucial to prevent unwanted side reactions such as Ostwald ripening or detrimental island growth, ensuring continuous Cu-BDC film coverage. This successful demonstration of sALD-grown compact continuous Cu-BDC SURMOF films is a paradigm change and provides a key advancement enabling a multitude of applications that require continuous and ultrathin coatings while maintaining tight film thickness specifications, which were previously unattainable with conventional solution-based growth methods

Solution Atomic Layer Deposition of Smooth, Continuous, Crystalline Metal–Organic Framework Thin Films

For the first time, a procedure has been established for the growth of surface-anchored metal–organic framework (SURMOF) copper(II) benzene-1,4-dicarboxylate (Cu-BDC) thin films of thickness control with single molecule accuracy. For this, we exploit the novel method solution atomic layer deposition (sALD). The sALD growth rate has been determined at 4.5 Å per cycle. The compact and dense SURMOF films grown at room temperature by sALD possess a vastly superior film thickness uniformity than those deposited by conventional solution-based techniques, such as dipping and spraying while featuring clear crystallinity from 100 nm thickness. The highly controlled layer-by-layer growth mechanism of sALD proves crucial to prevent unwanted side reactions such as Ostwald ripening or detrimental island growth, ensuring continuous Cu-BDC film coverage. This successful demonstration of sALD-grown compact continuous Cu-BDC SURMOF films is a paradigm change and provides a key advancement enabling a multitude of applications that require continuous and ultrathin coatings while maintaining tight film thickness specifications, which were previously unattainable with conventional solution-based growth methods

Using out-of-office blood pressure measurements in established cardiovascular risk scores: implications for practice

YesAbstract Background: Blood pressure (BP) measurement is increasingly carried out through home or ambulatory monitoring, yet existing cardiovascular risk scores were developed for use with measurements obtained in clinic. Aim: To describe differences in cardiovascular risk estimates obtained using ambulatory or home BP measurements instead of clinic readings. Design and setting: Secondary analysis of data from adults aged 30-84 without prior history of cardiovascular disease (CVD) in two BP monitoring studies (BP-Eth and HOMERUS). Method: The primary comparison was Framingham risk calculated using BP measured as in the Framingham study or daytime ambulatory BP measurements. The QRISK2 and SCORE risk equations were also studied. Statistical and clinical significance were determined using the Wilcoxon signed-rank test and scatter plots respectively. Results: In 442 BP-Eth patients (mean age = 58 years, 50% female) the median absolute difference in 10-year Framingham cardiovascular risk calculated using BP measured as in the Framingham study or daytime ambulatory BP measurements was 1.84% (interquartile range 0.65 to 3.63, p=0.67). Only 31/ 442 (7.0%) of patients were reclassified across the 10% risk treatment threshold. In 165 HOMERUS patients (mean age = 56 years, 46% female) the median difference in 10-year risk was 2.76% (IQR 1.19 to 6.39, p<0.001) and only 8/165 (4.8%) of patient were reclassified. Conclusion: Estimates of cardiovascular risk are similar when calculated using BP measurements obtained as in the risk score derivation study or through ambulatory monitoring. Further research is required to determine if differences in estimated risk would meaningfully influence risk score accuracy

Brexit: Neue Herausforderungen für ein neues Europa

[Einleitung ...] Mit diesem Positionspapier aus der ARL möchten wir einen Beitrag zur Debatte um die möglichen raumbezogenen Auswirkungen des Brexits leisten. Wir betrachten diese Auswirkungen aus einer eher deutschen Perspektive heraus. Das heißt: Andere raumbezogene Auswirkungen bzw. Problemlagen, wie zum Beispiel das komplizierte Verhältnis zwischen der EU, der Republik Irland und Nordirland (als Teil des VK) bleiben bewusst außen vor, weil sie den Rahmen dieses Papiers sprengen würden. Wir skizzieren dazu Entwicklungen in sieben Handlungsfeldern, die in besonderer Weise die räumliche Entwicklung beeinflussen werden. Die Betrachtung in den jeweiligen Teilkapiteln fokussiert auf das jeweilige Handlungsfeld selbst, und es werden, je nach Daten- und Informationslage, Ausblicke zur Situation nach dem Brexit vermittelt. Das Positionspapier schließt mit einer Diskussion möglicher Szenarien des zukünftigen Handelsverhältnisses zwischen VK und EU

Double-Barred Galaxies: I. A Catalog of Barred Galaxies with Stellar Secondary Bars and Inner Disks

I present a catalog of 67 barred galaxies which contain distinct, elliptical stellar structures inside their bars. Fifty of these are double-barred galaxies: a small-scale, "inner" or "secondary" bar is embedded within a large-scale, "outer" or "primary" bar. I provide homogenized measurements of the sizes, ellipticities, and orientations of both inner and outer bars, along with with global parameters for the galaxies. The other 17 are classified as "inner-disk" galaxies, where a large-scale bar harbors an inner elliptical structure which is aligned with the galaxy's outer disk. Four of the double-barred galaxies also possess inner disks, located in between the inner and outer bars. While the inner-disk classification is ad-hoc -- and undoubtedly includes some inner bars with chance alignments (five such probable cases are identified) -- there is good evidence that inner disks form a statistically distinct population, and that at least some are indeed disks rather than bars. In addition, I list 36 galaxies which may be double-barred, but for which current observations are ambiguous or incomplete, and another 23 galaxies which have been previously suggested as potentially being double-barred, but which are probably *not*. False double-bar identifications are usually due to features such as nuclear rings and spirals being misclassified as bars; I provide some illustrated examples of how this can happen.Comment: LaTeX, 25 pages, 6 EPS figures. Typos fixed and title slightly altered; accepted by Astronomy & Astrophysics. Version with full-resolution figures available at http://www.iac.es/galeria/erwin/research

Reduced proteasome activity in the aging brain results in ribosome stoichiometry loss and aggregation.

A progressive loss of protein homeostasis is characteristic of aging and a driver of neurodegeneration. To investigate this process quantitatively, we characterized proteome dynamics during brain aging in the short-lived vertebrate Nothobranchius furzeri combining transcriptomics and proteomics. We detected a progressive reduction in the correlation between protein and mRNA, mainly due to post-transcriptional mechanisms that account for over 40% of the age-regulated proteins. These changes cause a progressive loss of stoichiometry in several protein complexes, including ribosomes, which show impaired assembly/disassembly and are enriched in protein aggregates in old brains. Mechanistically, we show that reduction of proteasome activity is an early event during brain aging and is sufficient to induce proteomic signatures of aging and loss of stoichiometry in vivo. Using longitudinal transcriptomic data, we show that the magnitude of early life decline in proteasome levels is a major risk factor for mortality. Our work defines causative events in the aging process that can be targeted to prevent loss of protein homeostasis and delay the onset of age-related neurodegeneration