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Traditional automotive proton exchange membrane fuel cell (PEMFC) endurance testing relies on the fuel cell (FC) dynamic load cycle (FC‐DLC) protocol, which inadequately reflects real‐world driving conditions. To address this limitation the "Investigations on degradation mechanisms and Definition of protocols for PEM Fuel cells Accelerated Stress Testing" (ID‐FAST) consortium defined the new representative "ID‐FAST driving load cycle," a novel approach capturing the load distribution, transitions, temperature variations, and humidity fluctuations experienced by FCs in real‐world operation. We demonstrate the ID‐FAST driving cycle itself and the integration into a realistic durability test program for FC test benches and present the resulting test data. Furthermore, we showcase its implementation within an accelerated stress testing (AST) protocol, highlighting its potential to significantly reduce testing time by accelerating degradation. Additionally, a novel method for highly dynamic humidity adjustment within test benches is introduced. By overcoming limitations of existing methods and incorporating the ID‐FAST driving cycle, this work paves the way for a new era of efficient and realistic FC endurance testing, ultimately contributing to the development of more robust and durable automotive FC stacks. [ABSTRACT FROM AUTHOR]

Mountain social‐ecological systems (MtSES) are vital to humanity, providing ecosystem services to over half the planet's human population. Despite their importance, there has been no global assessment of threats to MtSES, even as they face unprecedented challenges to their sustainability. With survey data from 57 MtSES sites worldwide, we test a conceptual model of the types and scales of stressors and ecosystem services in MtSES and explore their distinct configurations according to their primary economic orientation and land use. We find that MtSES worldwide are experiencing both gradual and abrupt climatic, economic, and governance changes, with policies made by outsiders as the most ubiquitous challenge. Mountains that support primarily subsistence‐oriented livelihoods, especially agropastoral systems, deliver abundant services but are also most at risk. Moreover, transitions from subsistence‐ to market‐oriented economies are often accompanied by increased physical connectedness, reduced diversity of cross‐scale ecosystem services, lowered importance of local knowledge, and shifting vulnerabilities to threats. Addressing the complex challenges facing MtSES and catalyzing transformations to MtSES sustainability will require cross‐scale partnerships among researchers, stakeholders, and decision makers to jointly identify desired futures and adaptation pathways, assess trade‐offs in prioritizing ecosystem services, and share best practices for sustainability. These transdisciplinary approaches will allow local stakeholders, researchers, and practitioners to jointly address MtSES knowledge gaps while simultaneously focusing on critical issues of poverty and food security. Plain Language Summary: Mountain ecosystems and the human communities that inhabit them deliver critical resources—such as fresh water and timber—to over half the planet's human population. Despite their importance, there has been no global assessment of threats to mountain systems, even as they face unprecedented challenges to their sustainability. With survey data from 57 mountain sites worldwide, we test our understanding of the types of stresses that are threatening mountain systems as well as the resources and benefits that come from mountains. We find that mountain systems worldwide are experiencing both gradual and abrupt climatic, economic, and governance changes. One of the most ubiquitous challenges facing mountain systems is that policies directly affecting mountain systems are being made by those living outside of the mountains themselves. Mountains that support primarily subsistence‐oriented livelihoods in the developing world, especially mixed agriculture and animal husbandry systems, deliver abundant services but are also most at risk. Addressing the complex challenges facing mountain systems will require partnerships among researchers, stakeholders, and decision makers to jointly identify the types of futures they desire and the actions to achieve these. This approach will address knowledge gaps in mountains while simultaneously focusing on critical issues of poverty and food security. Key Points: Mountain social‐ecological systems (MtSES) worldwide face climatic, economic, and governance threats; policies made by outsiders are a critical challengeMountains that support subsistence‐oriented livelihoods deliver abundant cross‐scale ecosystems services, but these MtSES are also most threatenedAddressing threats to MtSES requires the united effort of policymakers, land users, scientists, and practitioners at local to global scales [ABSTRACT FROM AUTHOR]

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Abstract: Current trends in aircraft design are to increase the economic efficiency by integrating different features in multifunctional materials. One strategy is to embed resistance heater elements between glass‐fibre epoxy layers in (heated) fibre metal laminates and to use them as anti or de‐icing devices in leading edges of wings. Heated glass fibre reinforced aluminium (GLARE) is an example of such a multifunctional material where heating functionality was added to the (certified) structural feature of GLARE. As heated fibre metal laminates are an innovative and rather new material, the possible (local) effects of embedded heating on the stress–strain state have not yet been investigated. This research couples experimental characterisation of heated GLARE surface behaviour and numerical modelling analysis to investigate the surface and the through‐the‐thickness strain‐stress state and temperature distributions due to the embedded heating. For the experimental part, the surface strains and the temperatures of a developed specimen were measured in a slow heating regime (temperature increase from 22.7 to 39.4 °C within 120 s) using, respectively, a developed shearography instrument and thermocouples with an infrared camera. Then a numerical model of heated GLARE was developed and verified with experimental results. Further, the numerical model was used to predict strains, stresses, and temperatures during a temperature increase similar to that used for de‐icing in a real operation (temperature increase from −25 to 86.7 °C within 4.8 s). [ABSTRACT FROM AUTHOR]

We present a higher order discretization scheme for the compressible Euler and Navier-Stokes equations with immersed boundaries. Our approach makes use of a discontinuous Galerkin discretization in a domain that is implicitly defined by means of a level set function. The zero iso-contour of this level set function is considered as an additional domain boundary where we weakly enforce boundary conditions in the same manner as in boundary-fitted cells. In order to retain the full order of convergence of the scheme, it is crucial to perform volume and surface integrals in boundary cells with high accuracy. This is achieved using a linear moment-fitting strategy. Moreover, we apply a non-intrusive cell-agglomeration technique that averts problems with very small and ill-shaped cuts. The robustness, accuracy, and convergence properties of the scheme are assessed in several two-dimensional test cases for the steady compressible Euler and Navier-Stokes equations. Approximation orders range from 0 to 4, even though the approach directly generalizes to even higher orders. In all test cases with a sufficiently smooth solution, the experimental order of convergence matches the expected rate for discontinuous Galerkin schemes. Copyright © 2016 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Over the last decade, single stranded oligonucleotides (ON) have gained increased attention as a new drug modality. Because the assessment of genotoxicity risk during early development of pharmaceuticals is essential, we evaluated the potential of locked nucleic acids (LNA)-ONs to induce DNA damage in L5178Y tk+/− cells both with the mouse lymphoma assay (MLA) and the micronucleus test (MNT). Further, the MLA was performed to assess gene and chromosome mutation over 3 and 24h (± metabolic activation). In addition, the MNT was performed to assess, in addition, a potential aneugenic liability. None of the experiments demonstrated a genotoxic effect for the five tested LNA-ONs. We further show data from four proprietary LNA-ONs tested in standard genotoxicity assays in vitro and partially in vivo, which were all negative. In addition, cellular and nuclear uptake of LNA-ONs in L5178Y tk+/− cells was demonstrated. Based on the results presented here as well as in the literature about other representatives of this class, we consider LNA-ONs as generally not DNA reactive and question whether genotoxicity testing of this class of ONs should be required. This is in line with recent recommendation made by the OSWG that extensively assessed the genotoxicity of oligonucleotides. Environ. Mol. Mutagen. 58:112-121, 2017. © 2017 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Background: Fluid restriction (FR), the first-line treatment for hyponatraemia due to the syndrome of inappropriate antidiuresis (SIAD), often does not lead to successful correction of hyponatraemia. Therefore, predictive markers of treatment response are desirable. We evaluated routinely measured serum (s) and urine (u) parameters, s-copeptin and s-mid-regional pro-atrial natriuretic peptide (s-MR-proANP), as possible predictors of FR response.Methods: In this prospective observational study, we included patients with profound hyponatraemia (s-sodium <125 mmol L-1 ) due to SIAD. Patients were classified as FR responders (increase in s-sodium concentration of >3 mmol L-1 within 24 h) or nonresponders (increase of ≤3 mmol L-1 within 24 h). Initial laboratory parameters were compared between groups with logistic regression analysis.Results: Of 106 SIAD patients analysed, 82 underwent treatment with FR; 48 (59%) patients showed a successful response to FR and 34 (41%) were considered nonresponders. High levels of u-sodium and u-osmolality were significantly associated with nonresponse to FR [odds ratio (OR) 15.0, 95% confidence interval (CI) 2.4-95.8, P = 0.004 and OR 34.8, 95% CI 1.2-1038.8, P = 0.041, respectively). The association of u-sodium and nonresponse remained significant also after adjustment for diuretic use. Lower levels of s-MR-proANP were associated with nonresponse (OR 0.03, 95% CI 0.003-0.3, P = 0.004), whereas s-copeptin was not significantly associated with response to FR.Conclusion: Easily measured laboratory parameters, especially u-sodium, correlate with therapeutic response and identify patients most likely to fail to respond to FR. Measurement of these parameters may facilitate early treatment choice in patients with SIAD. [ABSTRACT FROM AUTHOR]

In this work, we present a high-order discontinuous Galerkin method (DGM) for simulating variable density flows at low Mach numbers. The corresponding low Mach number equations are an approximation of the compressible Navier-Stokes equations in the limit of zero Mach number. To the best of the authors'y knowledge, it is the first time that the DGM is applied to the low Mach number equations. The mixed-order formulation is applied for spatial discretization. For steady cases, we apply the semi-implicit method for pressure-linked equation (SIMPLE) algorithm to solve the non-linear system in a segregated manner. For unsteady cases, the solver is implicit in time using backward differentiation formulae, and the SIMPLE algorithm is applied to solve the non-linear system in each time step. Numerical results for the following three test cases are shown: Couette flow with a vertical temperature gradient, natural convection in a square cavity, and unsteady natural convection in a tall cavity. Considering a fixed number of degrees of freedom, the results demonstrate the benefits of using higher approximation orders. Copyright © 2015 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Background Hyponatraemia is common and its differential diagnosis and consequent therapy management is challenging. The differential diagnosis is mainly based on the routine clinical assessment of volume status, which is often misleading. Mid-regional pro-atrial natriuretic peptide ( MR-pro ANP) is associated with extracellular and cardiac fluid volume. Methods A total of 227 consecutive patients admitted to the emergency department with profound hypo-osmolar hyponatraemia (Na < 125 mmol L−1) were included in this prospective multicentre observational study conducted in two tertiary centres in Switzerland. A standardized diagnostic evaluation of the underlying cause of hyponatraemia was performed, and an expert panel carefully evaluated volaemic status using clinical criteria. MR-pro ANP levels were compared between patients with hyponatraemia of different aetiologies and for assessment of volume status. Results MR-pro ANP levels were higher in patients with hypervolaemic hyponatraemia compared to patients with hypovolaemic or euvolaemic hyponatraemia ( P = 0.0002). The area under the curve ( AUC) to predict an excess of extracellular fluid volume, compared to euvolaemia, was 0.73 [95% confidence interval ( CI) 0.62-0.84]. Additionally, in multivariate analysis, MR-pro ANP remained an independent predictor of excess extracellular fluid volume after adjustment for congestive heart failure ( P = 0.012). MR-pro ANP predicted the syndrome of inappropriate antidiuresis ( SIAD) versus hypovolaemic and hypervolaemic hyponatraemia with an AUC of 0.77 (95% CI 0.69-0.84). Conclusion MR-pro ANP is associated with extracellular fluid volume in patients with hyponatraemia and remains an independent predictor of hypervolaemia after adjustment for congestive heart failure. MR-pro ANP may be a marker for discrimination between the SIAD and hypovolaemic or hypervolaemic hyponatraemia. [ABSTRACT FROM AUTHOR]

Background and Objectives Bacterial contamination represents the major infectious hazard associated with transfusion of platelet concentrates ( PCs). As bacterial screening of PCs is not mandatory in Germany, the Bacti Flow flow cytometry test has been introduced as a rapid detection method to increase product safety. Materials and Methods During a period of 25 months, a total of 34 631 PCs (26 411 pooled and 8220 apheresis-derived PCs) were tested at the end of day 3 of their shelf life using the Bacti Flow system. PCs initially reactive in Bacti Flow testing and expired PCs not reactive in Bacti Flow on day 3 were also investigated by the Bac T/ ALERT system and by microbiological cultivation in order to identify the contaminating bacterial species and to confirm reactive Bacti Flow results. Results Two hundred and twenty-eight PCs (0·7%) had an initially reactive result, 24 of them remained reactive in a second test run. Out of these reproducible reactive Bacti Flow results, 12 could not be verified by parallel Bac T/ ALERT culturing, resulting in a confirmed false-positive rate of 0·03%. The bacterial species were identified as S. aureus, S. epidermidis, S. dysgalactiae ssp. equisimilis and B. cereus. In 10 out of 9017 expired PCs (0·11%), a confirmed-positive result was obtained in the Bac T/ ALERT system which had a negative result in the Bacti Flow system. Conclusion Testing of PCs by Bacti Flow was successfully implemented in our blood donation service and proved sufficient as a rapid and reliable screening method. False reactive results are in an acceptable range since the transfusion of 12 bacterially contaminated PCs was prevented. [ABSTRACT FROM AUTHOR]

Reduced glutamic acid decarboxylase ( GAD)67 expression may be causally involved in the development of social withdrawal in neuropsychiatric states such as autism, schizophrenia and bipolar disorder. In this study, we report disturbance of social behavior in male GAD67 haplodeficient mice. GAD67+/− mice, compared to GAD67+/+ littermates, show reduced sociability and decreased intermale aggression, but normal nest building and urine marking behavior, as well as unchanged locomotor activity and anxiety-like behavior. Moreover, the mutants display a reduced sensitivity to both social and non-social odors, indicating a disturbance in the detection and/or processing of socially relevant olfactory stimuli. Indeed, we observed reduced activation of the lateral septum, medial preoptic area, bed nucleus of the stria terminalis, medial and cortical amygdala upon exposure of GAD67+/− mice to social interaction paradigm, as indicated by c-Fos immunohistochemistry. These data suggest a disturbance of stimulus processing in the brain circuitry controlling social behavior in GAD67+/− mice, which may provide a useful model for studying the impact of a reduced GAD67 expression on alterations of social behavior related to neuropsychiatric disorders. [ABSTRACT FROM AUTHOR]

SUMMARY We introduce a new method for the numerical integration over curved surfaces and volumes defined by a level set function. The method is based on the solution of a small linear system based on a simplified variant of the moment-fitting equations. Numerical experiments suggest that the accuracy of the resulting quadrature rules exceeds the accuracy of traditional methods by orders of magnitude. Using moments up to an order of p, the measured experimental orders of convergence exceed h p. Consequently, their construction is very efficient because only coarse computational grids are required. The conceptual simplicity allows for the application on very general grid types, which is demonstrated by numerical experiments on quadrilateral, triangular and hexahedral grids. Copyright © 2013 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Objectives There are limited data on treatment effect in early and drug-naïve Parkinson's disease ( PD) outside of clinical trials. We sought to review the treatment effects on motor symptoms in early, unselected PD patients. Methods We included 183 drug-naïve patients from a longitudinal cohort ( The Norwegian Park West study). At the time of diagnosis, motor symptoms were assessed and rated. Treatment was unrestricted, aimed at treating each patient optimally. Patients were reassessed after 12 months, and then grouped according to treatment: No dopaminergic treatment ( NDT), dopamine agonists ( DA) or levodopa. All strategies could be combined with monoamine oxidase B inhibitors. Results In general, the chosen treatment was coherent with current practice. During follow-up, patients given NDT ( n = 40) had unaltered clinical motor symptoms, as opposed to improvement in the DA- and levodopa-treated patients ( n = 140). The overall improvement in these two groups was fairly similar, but axial symptoms did not improve in levodopa-treated patients as opposed to the younger DA-treated patients. Conclusions Twelve months after the diagnosis, motor symptoms in approximately one-fifth of PD patients remained clinically stable. Tremor, bradykinesia and rigidity improved in the dopaminergic-treated patients. Axial symptoms were more treatment resistant, and the different symptomatic effects found between treatment strategies may be age related. [ABSTRACT FROM AUTHOR]

Objectives Autonomic symptoms are present in early stages of Parkinson's disease (PD), but evidence on how they are influenced by dopaminergic treatment remains unclear. The aim of this study was to investigate the impact of dopaminergic treatment on autonomic symptoms in early PD in a population-based cohort. Methods A total of 171 drug-naive patients with PD were investigated at diagnosis and 12 months later. Orthostatic blood pressure was measured, and autonomic symptoms were assessed by a preliminary version of the Movement Disorders Society-sponsored new version of the Unified Parkinson's Disease Rating Scale (range 0-4). Results In the 82% using dopaminergic treatment after 1 year, constipation and orthostatic blood pressure drop increased. There was a tendency towards increased orthostatic dizziness and urinary dysfunction. Dysphagia scores were reduced, and this was associated with higher levodopa-equivalent daily dose. Conclusions Dopaminergic treatment during the first year after initiation seems to have only a minor impact on autonomic symptoms in early PD. It may increase constipation and orthostatic dizziness, while dysphagia can improve. Autonomic symptoms remained mild after 1 year of dopaminergic treatment. [ABSTRACT FROM AUTHOR]

SUMMARY We present a simple, tree-based approach for the numerical integration over volumes and surfaces defined by the zero iso-contour of a level set function. The work is motivated by a variant of the discontinuous Galerkin method that is characterized by discontinuous enrichments of the polynomial basis. Although numerical results suggest that the presently achieved accuracy is comparable with methods based on discretized delta functions and on the geometric reconstruction of the interface, the presented approach is conceptually simpler and applicable to almost arbitrary grid types, which we demonstrate by means of numerical experiments on triangular, quadrilateral, tetrahedral and hexahedral meshes. Copyright © 2012 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Background The anti-inflammatory peptide, adrenomedullin ( AM), and its cognate receptor are expressed in lung tissue, but its pathophysiological significance in airway inflammation is unknown. Objectives This study investigated whether allergen-induced airway inflammation involves an impaired local AM response. Methods Airway AM expression was measured in acute and chronically sensitized mice following allergen inhalation and in airway epithelial cells of asthmatic and nonasthmatic patients. The effects of AM on experimental allergen-induced airway inflammation and of AM on lung epithelial repair in vitro were investigated. Results Adrenomedullin m RNA levels were significantly ( P < 0.05) reduced in acute ovalbumin ( OVA)-sensitized mice after OVA challenge, by over 60% at 24 h and for up to 6 days. Similarly, reduced AM expression was observed in two models of chronic allergen-induced inflammation, OVA- and house dust mite-sensitized mice. The reduced AM expression was restricted to airway epithelial and endothelial cells, while AM expression in alveolar macrophages was unaltered. Intranasal AM completely attenuated the OVA-induced airway hyperresponsiveness and mucosal plasma leakage but had no effect on inflammatory cells or cytokines. The effects of inhaled AM were reversed by pre-inhalation of the putative AM receptor antagonist, AM(22-52). AM m RNA levels were significantly ( P < 0.05) lower in human asthmatic airway epithelial samples than in nonasthmatic controls. In vitro, AM dose-dependently (10−11-10−7 M) accelerated experimental wound healing in human and mouse lung epithelial cell monolayers and stimulated epithelial cell migration. Conclusion Adrenomedullin suppression in TH 2-related inflammation is of pathophysiological significance and represents loss of a factor that maintains tissue integrity during inflammation. [ABSTRACT FROM AUTHOR]

Conventional approaches to natural resource management are increasingly challenged by environmental problems that are embedded in highly complex systems with profound uncertainties. These so-called social-ecological systems (SESs) are characterized by strong links between the social and the ecological system and multiple interactions across spatial and temporal scales. New approaches are needed to manage those tightly coupled systems; however, basic understanding of their nonlinear behavior is still missing. Modeling is a traditional tool in natural resource management to study complex, dynamic systems. There is a long tradition of SES modeling, but the approach is now being more widely recognized in other fields, such as ecological and economic modeling, where issues such as nonlinear ecological dynamics and complex human decision making are receiving more attention. SES modeling is maturing as a discipline in its own right, incorporating ideas from other interdisciplinary fields such as resilience or complex systems research. In this paper, we provide an overview of the emergence and state of the art of this cross-cutting field. Our analysis reveals the substantial potential of SES models to address issues that are of utmost importance for managing complex human-environment relationships, such as: (i) the implications of ecological and social structure for resource management, (ii) uncertainty in natural and social systems and ways to address it, (iii) the role of coevolutionary processes in the dynamics of SESs, and (iv) the implications of microscale human decision making for sustainable resource management and conservation. The complexity of SESs and the lack of a common analytical framework, however, also pose significant challenges for this emerging field. There are clear research needs with respect to: (i) approaches that go beyond rather simple specifications of human decision making, (ii) development of coping strategies to deal with (irreducible) uncertainties, (iii) more explicit modeling of feedbacks between the social and ecological systems, and (iv) a conceptual and methodological framework for analyzing and modeling SESs. We provide ideas for tackling some of these challenges and indicate potential key focal areas for SES modeling in the future. [ABSTRACT FROM AUTHOR]

Isothermal microcalorimeters (IMC) are highly sensitive instruments that allow the measurement of heat flow in the microwatt range. Due to their detection of minute thermal heat, IMC techniques have been used in numerous biological applications, including the study of fermentation processes, pharmaceutical development, and cell metabolism. In this work, with the ultimate goal of establishing a rapid and real-time method to predict the proliferative capacity of human articular chondrocytes (HAC), we explored to use of IMC to characterize one of the crucial steps within the process of cartilage tissue engineering, namely the in vitro expansion of HAC. We first established an IMC-based model for the real-time monitoring of heat flow generated by HAC during proliferation. Profiles of the heat and heat flow curves obtained were consistent with those previously shown for other cell types. The average heat flow per HAC was determined to be 22.0 ± 5.3 pW. We next demonstrated that HAC proliferation within the IMC-based model was similar to proliferation under standard culture conditions, verifying its relevance for simulating the typical cell culture application. HAC growth and HAC heat over time appeared correlated for cells derived from particular donors. However, based on the results from 12 independent donors, no predictive correlation could be established between the growth rate and the heat increase rate of HAC. This was likely due to variability in the biological function of HAC derived from different donors, combined with the complexity of tightly couple metabolic processes beyond proliferation. In conclusion, IMC appears to be a promising technique to characterize cell proliferation. However, studies with more reproducible cell sources (e.g., cell lines) could be used before adding the complexity associated with primary human cells. Biotechnol. Bioeng. 2011;108: 3019-3024. © 2011 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Aim To investigate the correlation between geometric parameters of severely compromised root filled (RCT) pre-molar teeth with irregular root canals and their fracture resistance. The null hypothesis tested was that the fracture resistance of root filled teeth is not influenced by: (i) the adhesive surface of the post-space preparation (APS), (ii) the coronal tooth surface (AA), (iii) the amount of resin cement (VC) and (iv) the Young's modulus of the specimens. Methodology A total of 48 noncarious human pre-molar teeth with irregular root canals were decoronated, root filled and adhesively restored with post-retained direct composite crowns. After thermomechanical loading (1 200 000×, 5-50° C), static load was applied until failure. The geometric parameters of the tooth were evaluated by microcomputed tomography (μCT) using impressions taken after post-space preparation. Linear regression analyses were performed to correlate the geometric parameters of the specimens with their fracture resistance. Results The amount of resin cement (VC) comprised up to 88% of the entire post-space (mean 67%) and had no impact on the maximal load (P = 0.88). The latter was significantly influenced by post-space preparation (P = 0.003). Conclusions Amongst the geometric parameters tested, the surface area in the root canal had the greatest impact on fracture resistance of root filled premolars restored with posts and composite crowns, whilst the fit of the post was less important. [ABSTRACT FROM AUTHOR]

With 4 figures and 1 table Plant height is an important trait for breeding and as fitness criterion in natural populations of rye (Secale cereale L.). Our objectives were to investigate the inheritance of plant height in rye introgression libraries and estimate the covariation between per se and testcross performance. Two introgression libraries containing each of 40 BC2S3 candidate introgression lines (pre‐ILs) were tested at five locations in two years for per se and testcross performance. Donor population was the Iranian primitive rye accession Altevogt 14160. Plant height of the donor population was 145 ± 3.6 cm as population and 152 ± 2.9 and 132 ± 2.8 cm when crossed to the two testers, respectively. Pre‐ILs were much closer to the recurrent parent, but still most of them exceeded the recurrent parent in per se performance. Estimates of the genotypic variance were significant (P = 0.01) for both per se and testcross performance. Entry‐mean heritabilities were high in both libraries (0.97 and 0.94, respectively). Donor chromosome segments (DCS) of 59 of 72 pre‐ILs had a significant (P = 0.05) effect on plant height compared to the recurrent parent. For the testcrosses, 10 pre‐ILs still contributed DCS with significantly (P = 0.05) taller effects. Genotypic correlations between pre‐ILs per se and as testcrosses were moderate for the two testers. In conclusion, plant height per se has a complex inheritance with many loci spread across the entire genome. Hybrid breeding, however, facilitates the use of genetic resources because the tallness is less pronounced in the testcrosses. [ABSTRACT FROM AUTHOR]

Neidert S, Katan M, Schuetz P, Fluri F, Ernst A, Bingisser R, Kappos L, Engelter ST, Steck A, Müller B, Christ-Crain M (University Hospital Basel, Basel, Switzerland; SphingoTec GmbH, Borgsorf, Germany; Kantonsspital Aarau, Aarau, Switzerland) Anterior pituitary axis hormones and outcome in acute ischaemic stroke. J Intern Med 2011; : 420-432. Early and accurate prediction of outcome in acute stroke is important and influences risk-optimized therapeutic strategies. Endocrine alterations of the hypothalamic-pituitary axis are amongst the first measurable alterations after cerebral ischaemia. We therefore evaluated the prognostic value of cortisol, triiodothyronine (T3), free thyroxine (fT4), thyroid-stimulating hormone (TSH) and growth hormone (GH) in patients with an acute ischaemic stroke. In an observational study including 281 patients with ischaemic stroke, anterior pituitary axis hormones (i.e. cortisol, T3, fT4, TSH and GH) were simultaneously assessed to determine their value to predict functional outcome and mortality within 90 days and 1 year. In receiver operating characteristic curve analysis, the prognostic accuracy of cortisol was higher compared to all measured hormones and was in the range of the National Institutes of Health Stroke Scale (NIHSS). Cortisol was an independent prognostic marker of functional outcome and death [odds ratio (OR) 1.0 (1.0-1.01) and 1.62 (1.37-1.92), respectively, P < 0.0002 for both, adjusted for age and the NIHSS] in patients with ischaemic stroke, but added no significant additional predictive value to the clinical NIHSS score. Cortisol is an independent prognostic marker for death and functional outcome within 90 days and 1 year in patients with ischaemic stroke. By contrast, other anterior pituitary axis hormones such as peripheral thyroid hormones and GH are only of minor value to predict outcome in stroke. [ABSTRACT FROM AUTHOR]

With 5 figures and 6 tables Early generation plant breeding trials are often laid out in unreplicated designs with replicated checks. This study compares the systematic arrangement of check plots to an allocation, which has two or more different arrangements of check plots within blocks. Four uniformity trials were overlaid with augmented designs, which differed in block size, number and type of checks. Another aim was to compare different spatial models and a baseline model, which did not consider spatial trend. Model fit was assessed using the average empirical variance (EMP) for each arrangement. For three of the four uniformity trials the lowest EMP was found for the arrangement of check plots with different defined distributions of checks within blocks. The systematic arrangement was superior only in one uniformity trial. We propose therefore to allocate checks with different arrangements within blocks. The comparison of the spatial models showed that the linear variance model, the AR(1) model, and the spherical model, all assuming a nugget, were the most promising candidates. A further gain in precision could be detected by a two‐dimensional analysis. [ABSTRACT FROM AUTHOR]

Tysnes O-B, Müller B, Larsen JP. Are dysautonomic and sensory symptoms present in early Parkinson’s disease? Acta Neurol Scand: 2010: 122 (Suppl. 190): 72–77. © 2010 John Wiley & Sons A/S. Parkinson’s disease (PD) occurs with an annual incidence of 13/100.000, is slightly more frequent in men and is characterized by the motor symptoms tremor, rigidity, bradykinesia and postural instability. In addition, non-motor symptoms have been increasingly connected to the disease although already described in James Parkinson’s ‘Essay on the shaking palsy’ from 1817. The motor symptoms in PD are related to the degeneration of dopaminergic cells in the substantia nigra (SN). These symptoms respond well to dopaminergic substitution. It is much more unclear whether non-motor symptoms like dysautonomia, insomnia, day-time sleepiness, fatigue, pain and neuropsychiatric symptoms respond to levodopa. Autonomic symptoms include dizziness because of orthostatic hypotension, constipation, nausea, voiding symptoms and increased sweating. Such symptoms as well as sensory symptoms like hyposmia and pain are very frequently reported in PD and seem to occur early in the disease process. Braak proposed a sequential model of neuropathology in PD starting with affection of the olfactory bulb and the autonomic innervation of the heart and gut. Affection of SN is seen from Braak stage 3, and limbic and cortical structures are affected in the later stages of the disease. Currently, the evidence for sensory and autonomic involvement in PD is reviewed with special focus on the early phase of the disease. [ABSTRACT FROM AUTHOR]

To evaluate the effect of metformin on basal and insulin-induced glucose uptake in subcutaneous and visceral preadipocyte-derived adipocytes from obese and non-obese patients, preadipocytes were obtained from subcutaneous and visceral fat depots during abdominal surgery. Differentiation efficiency was evaluated by measurement of intracellular triglyceride accumulation. Preadipocyte-derived adipocytes were treated with metformin (1 mM) for 24 h with or without the addition of insulin (100 nM) for 20 min and glucose uptake was measured. In cells from each donor, intracellular triglyceride accumulation was more abundant in subcutaneous preadipocyte-derived adipocytes than in visceral preadipocyte-derived adipocytes (p < 0.001). Insulin stimulated glucose uptake in subcutaneous preadipocyte-derived adipocytes from both non-obese and obese patients (p < 0.001 vs. basal). In visceral preadipocyte-derived adipocytes, insulin did not increase basal glucose uptake. In subcutaneous preadipocyte-derived adipocytes from non-obese and obese patients, metformin alone increased glucose uptake to 2.7 ± 0.2 (p < 0.001) and 2.1 ± 0.1 fold (p < 0.001) respectively. Metformin increased glucose uptake in visceral preadipocyte-derived adipocytes from non-obese (1.7 ± 0.1 fold vs. basal, p < 0.001) and obese (2.0 ± 0.2 fold vs. basal, p < 0.001) patients. Combined treatment with metformin and insulin increased glucose uptake in subcutaneous preadipocyte-derived adipocytes from both non-obese and obese patients (p < 0.001 vs. insulin alone). In preadipocyte-derived adipocytes glucose uptake is induced by metformin independent of the fat depot origin of the preadipocytes (subcutaneous or visceral) and the obesity state of the patients (non-obese or obese). In adipocytes, metformin seems to induce glucose uptake independent of insulin suggesting an alternative mechanism of action of this drug. [ABSTRACT FROM AUTHOR]

The combination of osmium tetroxide staining and high-resolution tomographic imaging using monochromatic X rays allows visualizing cellular structures of the human inner ear, that is, the organ of Corti, the stria vascularis and further soft tissues of the membranous labyrinth, in three-dimensional space with isotropic micrometre resolution. This approach permits to follow the course of nerve fibre bundles in a major part of the specimen and reveals the detailed three-dimensional arrangement of individual ganglion cells with distinct nuclei by means of X-ray tomography for the first time. The non-destructive neuron cell counting in a selected volume of 125 μm × 800 μm × 600 μm = 0.06 mm3 gives rise to the estimate that 2000 ganglion cells are present along 1 mm organ of Corti. [ABSTRACT FROM AUTHOR]

Background Until now, it remains elusive which strategy – antithyroid drug withdrawal or increased radioiodine target doses – should be preferred to avoid the detrimental effect of antithyroid drugs in high- and low-dose radioiodine therapy, respectively. Methods We explored the effects of carbimazole on the 1-year post-radioiodine success and hypothyroidism rates by continuous dose–effect models, whereas success was defined as elimination of hyperthyroidism. Euthyroidism rates with and without carbimazole were calculated by numerical integration of the area between success and hypothyroidism curves. Target dose amplification factors for equal chance of success with and without carbimazole were calculated using logistic regression. Results Two hundred and twenty-eight patients were included in this study. Radioiodine target doses between 33 and 839 Gy were applied. Overall, the euthyroidism rates were 16·5% and 64·8%, while the hypothyroidism rates were 37·6% and 14·8% in Graves’ disease and toxic nodular goitre, respectively. The success rate with simultaneous carbimazole (median dose 15 mg day−1; range 2·5–60 mg day−1) was reduced over the entire target dose range in Graves’ disease and toxic nodular goitre. The areas between curves for euthyroidism without and with simultaneous carbimazole were 127 and 43 Gy in Graves’ disease and 178 and 128 Gy in toxic nodular goitre. The estimated radioiodine target dose amplification factor was 5·5 for Graves’ disease and 3·0 for toxic nodular goitre. Conclusions Simultaneous carbimazole reduces the euthyroidism rate, the aim of low-dose radioiodine therapy, over the entire target dose range in both Graves’ disease and toxic nodular goitre. Therefore, antithyroid drug discontinuation should be preferred in low-dose radioiodine therapy. Conversely, escalation of the target dose should be preferred in high-dose radioiodine therapy. [ABSTRACT FROM AUTHOR]

Aim: To determine the changes in adiponectin multimers upon marked weight loss. Methods: Plasma samples were obtained preoperatively and 3, 6, 12 and 24 months after surgery from 12 obese subjects undergoing weight loss–inducing bariatric surgery. Seven non-operated obese subjects served as controls. Plasma levels of adiponectin multimers were determined by protease digestion and Enzyme-Linked ImmunoSorbent Assay (ELISA) detection. In addition, adiponectin multimers were assessed by western blotting. Results: In patients with weight loss after surgery but not in controls, total adiponectin and high molecular weight (HMW) adiponectin steadily increased during the observation period. Twenty-four months after surgery, the increase in total and HMW adiponectin was 2.2 ± 0.46 and 1.4 ± 0.3 μg/ml, respectively. In contrast, plasma concentrations of middle and low molecular weight adiponectin remained unchanged. Conclusions: The increase in plasma adiponectin levels observed 24 months after bariatric surgery depended on continuous weight loss and was completely attributable to the HMW complex. [ABSTRACT FROM AUTHOR]

Background Plasma lipids can be affected by acute illnesses. The present study attempts to characterize the impact of infectious disease on plasma lipids in critical illness. It also aims to determine the value of plasma lipid routine measurements in the diagnosis of infection in critical illness in comparison to markers of infection and acute phase reactants. Materials and methods An observational study was carried out in 101 critically ill patients admitted consecutively to a medical intensive care unit in a university medical centre. Levels of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), and additional variables were measured in blood samples taken on the day of admission. Results In critically ill patients significantly lower levels of HDL-C and TC were found in infectious disease patients compared to non-infectious disease patients ( P < 0·001). No significant differences in levels of TG were found between infectious and non-infectious disease patients. Using receiver operating characteristic (ROC) curve analysis, the area under the curve (AUC) value for HDL-C and TC in the diagnosis of infection was 0·791 ( P < 0·001) and 0·730 ( P < 0·001), respectively. At a cutoff value for HDL-C of ≤ 0·78 mmol L−1, a sensitivity of 71·7% and a specificity of 86·0% were recorded. The AUC value of HDL-C was significantly ( P < 0·001) inferior to procalcitonin (AUC: 0·967, P < 0·001) and non-significantly inferior to C-reactive protein (CRP) (AUC: 0·874, P < 0·001). HDL-C correlated with albumin ( r = 0·7, P < 0·001) and CRP ( r = –0·54, P < 0·001), but not with the Acute Physiology and Chronic Health Evaluation II score. There was no significant difference between the plasma lipid concentrations in survivors and non-survivors. Conclusion In critically ill infected patients, HDL-C and TC levels are lower than in non-infected critically ill patients. In this study the diagnostic accuracy of CRP is not better than the one of HDL-C. The diagnostic accuracy of procalcitonin is superior to HDL-C. [ABSTRACT FROM AUTHOR]

Background Vasopressin has haemodynamic as well as osmoregulatory effects, and reflects the individual stress response. Copeptin is cosynthesized with vasopressin, directly mirroring vasopressin levels, but is more stable in plasma and serum. Both levels are increased in patients with septic shock. Lower respiratory tract infections (LRTI) are a precursor of sepsis. Thus, we investigated circulating levels and the prognostic use of copeptin for the severity and outcome in patients with LRTI. Materials and methods Five hundred and forty-five consecutive patients with LRTI and 50 healthy controls were evaluated. Serum copeptin levels were measured with a new chemiluminescens sandwich immunoassay. Results Of the 545 patients, 373 had community-acquired pneumonia (CAP), 60 acute exacerbations of chronic obstructive pulmonary disease (COPD), 59 acute bronchitis, 13 exacerbations of asthma and 40 other final diagnoses. Copeptin levels were significantly higher in patients with LRTI as compared to controls ( P < 0·001) with highest levels in patients with CAP. Copeptin levels increased with increasing severity of CAP, as classified by the pneumonia severity index (PSI) ( P < 0·001). In patients who died, copeptin levels on admission were significantly higher as compared to levels in survivors [70·0 (28·8–149·0) vs. 24·3 (10·8–43·8) pmol L−1, P < 0·001]. The area under the receiver operating curve (AUC) for survival was 0·75 for copeptin, which was significantly higher as compared to C-reactive protein (AUC 0·61, P = 0·01), leukocyte count (AUC 0·59, P = 0·01) and similar to procalcitonin (AUC 0·68, P = 0·21). Conclusions Copeptin levels are increased with increasing severity of LRTI namely in patients with CAP and unfavourable outcome. Copeptin levels, as a novel biomarker, might be a useful tool in the risk stratification of patients with LRTI. [ABSTRACT FROM AUTHOR]

Objective. To analyse the mid region of plasma N-terminal pro-atrial natriuretic peptide (MR-proANP) levels in patients with lower respiratory tract infections to evaluate its prognostic use for the severity of disease and outcome. Design. Prospective observational study. Setting. Emergency department of a university hospital. Subjects. A total of 545 consecutive patients with lower respiratory tract infections and 50 healthy controls. Interventions. MR-proANP was measured in serum from all patients using a new sandwich immunoassay. Results. MR-proANP levels (median [IQR], in pmol L−1) were significantly higher in patients with lower respiratory tract infections when compared with controls (138.0 [74.1–279.0] vs. 72.7 [62.5–89.5], P < 0.001), with highest levels in patients with community-acquired pneumonia (CAP). MR-proANP, but not C-reactive protein (CRP) levels, gradually increased with increasing severity of CAP, classified according to the pneumonia severity index (PSI) score ( P < 0.001). On admission, MR-proANP levels were significantly higher in nonsurvivors when compared with survivors (293.0 [154.0–633.0] vs. 129.0 [71.4–255.0], P < 0.001). In a receiver operating characteristic (ROC) analysis for the prediction of survival of patients with CAP the area under the ROC curve (AUC) for MR-proANP was 0.69, similar when compared with the PSI (AUC 0.74, P = 0.31), and better when compared with other biomarkers, i.e. procalcitonin (AUC 0.57, P = 0.08), CRP (AUC 0.52, P = 0.02), and leucocyte count (AUC 0.56, P = 0.07). Conclusions. MR-proANP levels are increased in lower respiratory tract infections, especially in CAP. Together with other clinical, radiographic and laboratory findings, MR-proANP levels might be helpful for the risk stratification in CAP. [ABSTRACT FROM AUTHOR]

Background Restoration of near-euglycaemia by intensive insulin therapy results in decreased serum levels of inflammatory mediators. The authors investigated whether the anti-inflammatory effect of insulin was independent of its glucose-lowering action and if this effect was intact in insulin-resistant women with the polycystic ovary syndrome (PCOS) characterized by low-grade chronic inflammation. Materials and methods Blood was drawn on the third and sixth days after progestin-induced withdrawal bleeding in 20 young non-diabetic women with PCOS and once between the third and sixth days of the menstrual cycle in 21 age-matched lean healthy control women during a 75-g oral glucose tolerance test (oGTT). Serum insulin, glucose and tumour necrosis factor alpha (TNF-α) concentrations were measured after 0, 30, 60, 90 and 120 min. Results The increase in insulin and glucose concentrations during the oGTT was significantly more pronounced in patients with PCOS (one patient with impaired fasting glucose, one patient with impaired glucose tolerance, three patients with both) compared with healthy controls. The TNF-α serum concentrations decreased in patients with PCOS (mean of both days, P = 0·004). In patients and in controls, there was an inverse correlation between the serum concentrations of insulin and of TNF-α during oGTT (for patients, a mean of both days, P = 0·009; for controls, P = 0·047), but not between the serum concentrations of glucose and TNF-α. Conclusions The decrease in TNF-α concentrations during oGTT and the inverse correlation between endogenous hyperinsulinaemia and serum TNF-α concentrations suggested an anti-inflammatory effect of moderately-high insulin concentrations. This occurred despite the presence of moderate hyperglycaemia. These findings also demonstrated a preserved responsiveness of inflammatory mediators to insulin in PCOS. [ABSTRACT FROM AUTHOR]

Chronic obstructive pulmonary disease (COPD) is a major health problem. The disease is driven by abnormal inflammatory reactions in response to inhaled particles and fumes. Therefore, inflammatory mediators are postulated to be of distinct importance. In the present case–control study, we investigated interleukin (IL)-promoter polymorphisms known to correlate with altered transcription levels of their gene products in patients with COPD. We analyzed tumor necrosis factor-alpha (TNF-α)-308, TNF-β-intron1-252, IL-6-174, IL-10-819, and IL-10-1082 polymorphisms in 469 individuals using restriction fragment length polymorphism-based converted polymerase chain reaction. The study population consisted of 113 patients with COPD based on chronic bronchitis, divided into subgroups by severity (I°–III°), 113 matched hospitalized individuals suffering from severe coronary heart disease without pulmonary disease (age-, sex-, and smoking-matched control group), and 243 healthy individuals (population control group). The matched analysis showed no significant differences in genotype distribution of all tested polymorphisms between the matched controls and the COPD patients. However, comparison with the population controls revealed significant differences in IL-10-1082 A/G genotype frequencies (P = 0.0247 for the whole COPD group,P = 0.009 for smokers only), with the genotypes carrying the G allele more common in the COPD cases[odds ratio (OR) = 1.66, 95% confidence interval (CI) 1.01–2.75;P = 0.046]. Interestingly, this shift toward more G alleles was even more pronounced in the matched control group (OR = 2.55, 95% CI 1.47–4.41;P = 0.0007), suggesting both presented groups share corresponding underlying mechanisms. The IL-10-1082_G allele is known to correlate with altered IL-10 levels. Therefore, it might be associated with altered or abnormal inflammatory response, a mechanism that could be postulated to be important in both chronic bronchitis and coronary heart disease. [ABSTRACT FROM AUTHOR]

High iodine uptake levels are widely accepted as a condition for successful treatment with radioiodine (RAI). However, the existing data are controversial and the correlation of pretherapeutic RAI uptake level and outcome of RAI therapy has not yet been quantified. The aim of this study was to analyze the influence of RAI uptake on the outcome after RAI treatment and to estimate uptake-dependent success rates. We retrospectively analyzed 229 patients (m = 53, f = 176; age 64 ± 14 years) suffering from toxic adenoma, multinodular goitre or Graves’ disease, respectively. Clinical status and T3, fT4 and TSH levels were assessed 3, 6, 12 and 18 months after treatment. Successful treatment was defined as loss of hyperthyroidism 18 months after radioiodine therapy. Logistic regression was used to assess the relation between the maximum iodine uptake and the rate of success and hypothyroidism, respectively, after RAI treatment. Overall, patients presented with pretherapeutic RAI uptake values between 17% and 100%. Eighteen months after RAI treatment, an euthyroid state was achieved in 136 patients (60%), hypothyroidism occurred in 47 patients (20%) and 46 patients (20%) remained hyperthyroid. The patients with the lowest pretherapeutic RAI uptakes showed the highest success rates. The overall success rate significantly decreased from 92% at low RAI uptakes to 57% at high uptakes ( P = 0·002). This effect was found in the patients suffering from multinodular goitre as well as in the patients with Graves’ disease. In contrast to the current opinion, our results provide evidence that the pretherapeutic iodine uptake level and post-therapeutic outcome are inversely correlated. Eur J Clin Invest 2004; 34 (5): 365 –370 [ABSTRACT FROM AUTHOR]

Abstract Background The estimated prevalence of endogenous subclinical hyperthyroidism varies from 4% to 6% and a basal thyroid stimulating hormone (TSH) level < 0·5 mU L-1 may be associated with increased mortality in subjects over 60 years of age who are not on thyroid medication. Exogenous TSH suppression is a mainstay in the treatment of thyroid cancer. Because of recent concerns about potential adverse effects, especially of endogenous TSH suppression on bone, the cardiovascular system and cognitive functions, subclinical hyperthyroidism obtained new clinical importance. We therefore re-evaluated the diagnostic value of basal and thyrotrop in TRH-stimulated serum TSH measurements using TSH assays with different sensitivities. Materials and methods A total of 805 oral and nasal TRH stimulation tests were performed on 409 ambulatory subjects with low basal serum TSH concentrations of less than 0·1 mIU L-1 . Basal serum TSH was measured either using a second generation assay (functional sensitivity > 0·03 mIU L-1 ) or two third generation assays (functional sensitivity 0·01 mIU L-1 and 0·007 mU L-1 , respectively). Serum TSH concentration was determined before and 3 h after oral administration of 40 mg of TRH and before and 30 min after nasal administration of 2 mg of TRH. Results In the oral testing group, the basal TSH levels measured by the different TSH assays were 0·06 ± 0·03, 0·04 ± 0·02 and 0·03 ± 0·02, respectively, whereas the peak TSH levels were 0·4 ± 0·6, 0·4 ± 0·6 and 0·3 ± 0·5 in the patients with subclinical hyperthyroidism. In overt hyperthyroidism, the basal TSH levels were 0·06 ± 0·02, 0·03 ± 0·02 and 0·03 ± 0·02, whereas the peak TSH levels were 0·19 ± 0·3, 0·16 ± 0·3 and 0·15 ± 0·2,... [ABSTRACT FROM AUTHOR]

Slab break-off is a plate-tectonic process which does not only return lithospheric material into the deeper mantle, but also has severe effects on surface movements and seismic hazard: slab-pull induced seismicity is reduced when the subducted slab decouples from the overlying crust. In the Vrancea region (SE Carpathians), strong earthquakes frequently occur at intermediate depths (70-180 km) in a laterally small volume, while the crust shows low but distributed seismicity. The stress pattern shows similar partitioning with vertical extension in the slab and no preferred orientation in the overlying crust. Both features indicate a decoupling between slab and overlying crust, either by slab break-off or delamination. However, the strong vertical elongation of the slab requires that the upper end of the slab is fixed vertically. Thus, a 'soft' coupling is assumed that is strong enough to enable elongation of the slab, but weak enough to inhibit 'quasi-static' stress transfer to the overlying crust. [ABSTRACT FROM AUTHOR]

Inhalation of nitrogen dioxide (NO2) is known to alter the composition of the bronchoalveolar lavage (BAL) and to impair the surfactant metabolism of type II pneumocytes. However, information is sparse as to whether application of the widely used antioxidant N-acetylcysteine (NAC) is capable of preventing or reducing these alterations. The aim of the study was to investigate if in vivo administration of NAC to NO2-inhaling rats protected BAL parameters and physiology of type II pneumocytes from impairment. For this purpose, rats were exposed to 720 p.p.m. h-1 NO2, that was applied continuously, intermittently or repeatedly. During inhalation one group of rats received saline and the other group received NAC antioxidant (200 mg kg-1, intraperitoneally) once a day. The BAL protein and phospholipid content increased most in the continuously and repeatedly NO2-exposed rats when compared to the controls, while the intermittent exposure did not change these parameters. Application of NAC led to a marked decrease of the protein elevation for the continuously and intermittently exposed groups, but exhibited no influence on the BAL phospholipid. Surprisingly, all NO2 exposure modes elevated the glutathione content (reduced and oxidized) in the BAL. Application of NAC clearly decreased the content of both forms of glutathione in the continuously and the repeatedly NO2-exposed groups. Phospholipid synthesis, measured by choline uptake into type II cells, was increased most after continuous NO2 inhalation. The NAC reduced this increase moderately. Whereas choline uptake by type II cells was obviously stimulated by NO2, the stimulated secretion of phosphatidylcholine from these cells was decreased by this oxidant. Only continuous exposure reduced this activity markedly. The NAC clearly restored the impaired secretion activity in the cells from the continuously... [ABSTRACT FROM AUTHOR]

The influence of thyroid failure on haemostasis is controversial, both hypocoagulable and hypercoagulable states have been reported. Since both subclinical and overt hypothyroidism have been associated with atherosclerosis, a hypercoagulable state in addition might represent a risk factor for thromboembolic disease. We investigated various haemostatic variables in 42 women with subclinical hypothyroidism and compared them to 66 euthyroid controls. Prothrombin time, activated partial thromboplastin time, fibrinogen, factor VII activity (FVII:C), factor VII antigen (FVII:Ag), factor VIII activity, von Willebrand factor (vWF), antithrombin III, heparin cofactor II, protein C, protein S, plasminogen, antiplasmin, plasminogen activator inhibitor and tissue plasminogen activator, as well as common lipid variables, were measured. Factor VII:C (P < 0·02) and the ratio FVII:C/FVII:Ag (P < 0·01) were significantly increased in subclinical hypothyroid patients compared to the control group. Both parameters remained higher in hypothyroid patients after exclusion of 18 women on oestrogen replacement therapy. No differences were found between the groups with respect to vWF or the other haemostatic and lipid variables tested. Patients with subclinical hypothyroidism had significantly higher levels of FVII:C. The greater increase in FVII:C compared to that of FVII:Ag, as shown by the increase in their ratio, might reflect the presence of activated FVIIa. This might mean a hypercoagulable state, which could contribute to the increased prevalence of coronary heart disease reported in such patients. A hypercoagulable state might be another argument in favour of thyroxine replacement treatment in subclinical hypothyroidism, especially in patients with additional risk factors for vascular disease. [ABSTRACT FROM AUTHOR]