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Cellular polypropylene (PP) films were treated with sulfur hexafluoride (SF6) gas in order to study the SF6 penetration behaviour and optimize the electric charging conditions. There were differences in the penetration of SF6 for different cellular PP materials, depending on the microscopic properties, which manifest themselves in the voided structure as well as in the mechanical stiffnesses of the cellular films. The penetration of SF6 after long-term pressure treatment is confirmed in strongly inflated cellular PP films with a low mechanical stiffness of about 1 MPa. No SF6 penetration occurs for slightly inflated cellular PP films with smaller void sizes and higher mechanical stiffnesses of around 5.8 MPa. The observed thickness variations, the higher charging fields during corona charging because of SF6 penetration and the SF6 environment, as well as the resulting electromechanical properties are discussed
The Great Nebula in Carina provides an exceptional view into the violent massive star formation and feedback that typifies giant H II regions and starburst galaxies. We have mapped the Carina star-forming complex in X-rays, using archival Chandra data and a mosaic of 20 new 60 ks pointings using the Chandra X-ray Observatory's Advanced CCD Imaging Spectrometer, as a testbed for understanding recent and ongoing star formation and to probe Carina's regions of bright diffuse X-ray emission. This study has yielded a catalog of properties of > 14,000 X-ray point sources;> 9800 of them have multiwavelength counterparts. Using Chandra's unsurpassed X-ray spatial resolution, we have separated these point sources from the extensive, spatially-complex diffuse emission that pervades the region; X-ray properties of this diffuse emission suggest that it traces feedback from Carina's massive stars. In this introductory paper, we motivate the survey design, describe the Chandra observations, and present some simple results, providing a foundation for the 15 papers that follow in this special issue and that present detailed catalogs, methods, and science results.
In this article, we discuss the notions of experts and expertise in resource discovery in the context of collaborative tagging systems. We propose that the level of expertise of a user with respect to a particular topic is mainly determined by two factors. First, an expert should possess a high-quality collection of resources, while the quality of a Web resource in turn depends on the expertise of the users who have assigned tags to it, forming a mutual reinforcement relationship. Second, an expert should be one who tends to identify interesting or useful resources before other users discover them, thus bringing these resources to the attention of the community of users. We propose a graph-based algorithm, SPEAR (spamming-resistant expertise analysis and ranking), which implements the above ideas for ranking users in a folksonomy. Our experiments show that our assumptions on expertise in resource discovery, and SPEAR as an implementation of these ideas, allow us to promote experts and demote spammers at the same time, with performance significantly better than the original hypertext-induced topic search algorithm and simple statistical measures currently used in most collaborative tagging systems.
Basement-cored uplift provinces are often characterized by high-angle reverse faulting along preexisting crustal heterogeneities, which may greatly affect the mechanics of deformation and the coupling between erosion and orogenic structure. Herein we construct a coupled deformation-erosion model to understand the mechanics and erosion of mountain belts in which the spatial distribution of deformation is largely influenced by the presence of preexisting high-angle faults. In this case, deformation is accommodated along, and topography is built above, these structures. This topographic loading leads to increasing lithostatic stresses beneath these regions. As a result, active deformation may migrate to frictionally stronger structures in adjacent regions where lithostatic loading is lower. The migration of deformation to such nearby structures depends on the Hubbert-Rubey pore fluid pressure ratio of the crust (lambda), the orientations of the frictionally weaker and stronger preexisting faults (beta(1) and beta(2), respectively), the friction coefficients (mu(b1) and mu(b2)) and Hubbert-Rubey fluid-pressure ratios (lambda(b1) and lambda(b2)) of these faults, and the surface slope of the topography above the frictionally weaker structure (alpha), assuming zero surface slope above the frictionally stronger structure. In general, we found that for a given alpha and beta(1), as mu(b1) increases lambda=lambda(b1)=lambda(b2) increases, and beta(2) decreases, the value of mu(b2) required to force deformation to migrate increases. However, as erosional processes lead to decreasing surface slopes, deformation will be inhibited from migrating to frictionally stronger structures in adjacent regions. Our model results may help to explain some aspects of the deformation observed and the possible correlation between precipitation and the migration of deformation within these tectonic provinces
Tectonic and climatic control on evolution of rift lakes in the Central Kenya Rift, East Africa
(2009)
The long-term histories of the neighboring Nakuru-Elmenteita and Naivasha lake basins in the Central Kenya Rift illustrate the relative importance of tectonic versus climatic effects on rift-lake evolution and the formation of disparate sedimentary environments. Although modem climate conditions in the Central Kenya Rift are very similar for these basins, hydrology and hydrochemistry of present-day lakes Nakuru, Elmenteita and Naivasha contrast dramatically due to tectonically controlled differences in basin geometries, catchment size, and fluvial processes. In this study, we use eighteen C-14 and Ar-40/Ar-39 dated fluvio-lacustrine sedimentary sections to unravel the spatiotemporal evolution of the lake basins in response to tectonic and climatic influences. We reconstruct paleoclimatic and ecological trends recorded in these basins based on fossil diatom assemblages and geologic field mapping. Our study shows a tendency towards increasing alkalinity and shrinkage of water bodies in both lake basins during the last million years. Ongoing volcano-tectonic segmentation of the lake basins, as well as reorganization of upstream drainage networks have led to contrasting hydrologic regimes with adjacent alkaline and freshwater conditions. During extreme wet periods in the past, such as during the early Holocene climate optimum, lake levels were high and all basins evolved toward freshwater systems. During drier periods some of these lakes revert back to alkaline conditions, while others maintain freshwater characteristics. Our results have important implications for the use and interpretation of lake sediment as climate archives in tectonically active regions and emphasize the need to deconvolve lacustrine records with respect to tectonics versus climatic forcing mechanisms.
Shallow lithological structure across the Dead Sea Transform derived from geophysical experiments
(2011)
In the framework of the DEad SEa Rift Transect (DESERT) project a 150 km magnetotelluric profile consisting of 154 sites was carried out across the Dead Sea Transform. The resistivity model presented shows conductive structures in the western section of the study area terminating abruptly at the Arava Fault. For a more detailed analysis we performed a joint interpretation of the resistivity model with a P wave velocity model from a partially coincident seismic experiment. The technique used is a statistical correlation of resistivity and velocity values in parameter space. Regions of high probability of a coexisting pair of values for the two parameters are mapped back into the spatial domain, illustrating the geographical location of lithological classes. In this study, four regions of enhanced probability have been identified, and are remapped as four lithological classes. This technique confirms the Arava Fault marks the boundary of a highly conductive lithological class down to a depth of similar to 3 km. That the fault acts as an impermeable barrier to fluid flow is unusual for large fault zone, which often exhibit a fault zone characterized by high conductivity and low seismic velocity. At greater depths it is possible to resolve the Precambrian basement into two classes characterized by vastly different resistivity values but similar seismic velocities. The boundary between these classes is approximately coincident with the Al Quweira Fault, with higher resistivities observed east of the fault. This is interpreted as evidence for the original deformation along the DST originally taking place at the Al Quweira Fault, before being shifted to the Arava Fault.
Although quantitative isotope data from speleothems has been used to evaluate isotope-enabled model simulations, currently no consensus exists regarding the most appropriate methodology through which to achieve this. A number of modelling groups will be running isotope-enabled palaeoclimate simulations in the framework of the Coupled Model Intercomparison Project Phase 6, so it is timely to evaluate different approaches to using the speleothem data for data–model comparisons. Here, we illustrate this using 456 globally distributed speleothem δ18O records from an updated version of the Speleothem Isotopes Synthesis and Analysis (SISAL) database and palaeoclimate simulations generated using the ECHAM5-wiso isotope-enabled atmospheric circulation model. We show that the SISAL records reproduce the first-order spatial patterns of isotopic variability in the modern day, strongly supporting the application of this dataset for evaluating model-derived isotope variability into the past. However, the discontinuous nature of many speleothem records complicates the process of procuring large numbers of records if data–model comparisons are made using the traditional approach of comparing anomalies between a control period and a given palaeoclimate experiment. To circumvent this issue, we illustrate techniques through which the absolute isotope values during any time period could be used for model evaluation. Specifically, we show that speleothem isotope records allow an assessment of a model's ability to simulate spatial isotopic trends. Our analyses provide a protocol for using speleothem isotope data for model evaluation, including screening the observations to take into account the impact of speleothem mineralogy on δ18O values, the optimum period for the modern observational baseline and the selection of an appropriate time window for creating means of the isotope data for palaeo-time-slices.
Utilising a reconstructed ancestral mitochondrial genome of a clade to design hybridisation capture baits can provide the opportunity for recovering mitochondrial sequences from all its descendent and even sister lineages. This approach is useful for taxa with no extant close relatives, as is often the case for rare or extinct species, and is a viable approach for the analysis of historical museum specimens. Asiatic linsangs (genus Prionodon) exemplify this situation, being rare Southeast Asian carnivores for which little molecular data is available. Using ancestral capture we recover partial mitochondrial genome sequences for seven banded linsangs (P. linsang) from historical specimens, representing the first intraspecific genetic dataset for this species. We additionally assemble a high quality mitogenome for the banded linsang using shotgun sequencing for time-calibrated phylogenetic analysis. This reveals a deep divergence between the two Asiatic linsang species (P. linsang, P. pardicolor), with an estimated divergence of ~12 million years (Ma). Although our sample size precludes any robust interpretation of the population structure of the banded linsang, we recover two distinct matrilines with an estimated tMRCA of ~1 Ma. Our results can be used as a basis for further investigation of the Asiatic linsangs, and further demonstrate the utility of ancestral capture for studying divergent taxa without close relatives.
Forecasting and early warning systems are important investments to protect lives, properties, and livelihood. While early warning systems are frequently used to predict the magnitude, location, and timing of potentially damaging events, these systems rarely provide impact estimates, such as the expected amount and distribution of physical damage, human consequences, disruption of services, or financial loss. Complementing early warning systems with impact forecasts has a twofold advantage: It would provide decision makers with richer information to take informed decisions about emergency measures and focus the attention of different disciplines on a common target. This would allow capitalizing on synergies between different disciplines and boosting the development of multihazard early warning systems. This review discusses the state of the art in impact forecasting for a wide range of natural hazards. We outline the added value of impact-based warnings compared to hazard forecasting for the emergency phase, indicate challenges and pitfalls, and synthesize the review results across hazard types most relevant for Europe.
Utilising a reconstructed ancestral mitochondrial genome of a clade to design hybridisation capture baits can provide the opportunity for recovering mitochondrial sequences from all its descendent and even sister lineages. This approach is useful for taxa with no extant close relatives, as is often the case for rare or extinct species, and is a viable approach for the analysis of historical museum specimens. Asiatic linsangs (genus Prionodon) exemplify this situation, being rare Southeast Asian carnivores for which little molecular data is available. Using ancestral capture we recover partial mitochondrial genome sequences for seven banded linsangs (P. linsang) from historical specimens, representing the first intraspecific genetic dataset for this species. We additionally assemble a high quality mitogenome for the banded linsang using shotgun sequencing for time-calibrated phylogenetic analysis. This reveals a deep divergence between the two Asiatic linsang species (P. linsang, P. pardicolor), with an estimated divergence of ~12 million years (Ma). Although our sample size precludes any robust interpretation of the population structure of the banded linsang, we recover two distinct matrilines with an estimated tMRCA of ~1 Ma. Our results can be used as a basis for further investigation of the Asiatic linsangs, and further demonstrate the utility of ancestral capture for studying divergent taxa without close relatives.
5-Jahres-Verlauf der LRS
(2017)
Fragestellung: Untersucht wird der Verlauf von Kindern mit Lese-Rechtschreibstörungen (LRS) über gut 5 Jahre unter Berücksichtigung des Einflusses des Geschlechts der Betroffenen. Außerdem werden Auswirkungen der LRS auf das spätere Schriftsprachniveau und den Schulerfolg überprüft. Methodik: Eingangs wurden 995 Schüler zwischen 6 und 16 Jahren untersucht. Ein Teil dieser Kinder ist nach 43 sowie 63 Monaten nachuntersucht worden. Eine LRS wurde diagnostiziert, wenn für das Lesen bzw. Rechtschreiben das doppelte Diskrepanzkriterium von 1.5 Standardabweichungen zur nonverbalen Intelligenz und dem Mittelwert der Klassenstufe erfüllt war und gleichzeitig keine Minderbegabung vorlag. Ergebnisse: Die LRS weist über einen Zeitraum von 63 Monaten eine hohe Störungspersistenz von knapp 70 % auf. Der 5-Jahres-Verlauf der mittleren Lese- und Rechtschreibleistungen wurde nicht vom Geschlecht beeinflusst. Trotz durchschnittlicher Intelligenz blieben die LRS-Schüler in der Schriftsprache mindestens eine Standardabweichung hinter durchschnittlich und etwa 0.5 Standardabweichungseinheiten hinter unterdurchschnittlich intelligenten Kindern zurück. Der Schulerfolg der LRS-Schüler glich dem unterdurchschnittlich intelligenter Kinder und fiel deutlich schlechter aus als bei durchschnittlich intelligenten Kontrollkindern. Schlussfolgerungen: Eine LRS stellt ein erhebliches Entwicklungsrisiko dar, was frühzeitige Diagnostik- und Therapiemaßnahmen erfordert. Dafür sind reliable und im Hinblick auf die resultierenden Prävalenzraten sinnvolle, allgemein anerkannte Diagnosekriterien essenziell.
Animal-associated microbial communities can play major roles in the physiology, development, ecology, and evolution of their hosts, but the study of their diversity has yet focused on a limited number of host species. In this study, we used high-throughput sequencing of partial sequences of the bacterial 16S rRNA gene to assess the diversity of the gut-inhabiting bacterial communities of 212 specimens of tropical anuran amphibians from Brazil and Madagascar. The core gut-associated bacterial communities among tadpoles from two different continents strongly overlapped, with eight highly represented operational taxonomic units (OTUs) in common. In contrast, the core communities of adults and tadpoles from Brazil were less similar with only one shared OTU. This suggests a community turnover at metamorphosis. Bacterial diversity was higher in tadpoles compared to adults. Distinct differences in composition and diversity occurred among gut bacterial communities of conspecific tadpoles from different water bodies and after experimental fasting for 8 days, demonstrating the influence of both environmental factors and food on the community structure. Communities from syntopic tadpoles clustered by host species both in Madagascar and Brazil, and the Malagasy tadpoles also had species-specific isotope signatures. We recommend future studies to analyze the turnover of anuran gut bacterial communities at metamorphosis, compare the tadpole core communities with those of other aquatic organisms, and assess the possible function of the gut microbiota as a reservoir for protective bacteria on the amphibian skin.
Mental disorders are among the greatest medical and social challenges facing us. They can occur at all stages of life and are among the most important commonly occurring diseases. In Germany 28 % of the population suffer from a mental disorder every year, while the lifetime risk of suffering from a mental disorder is almost 50 %. Mental disorders cause great suffering for those affected and their social network. Quantitatively speaking, they can be considered to be among those diseases creating the greatest burden for society due to reduced productivity, absence from work and premature retirement. The Federal Ministry of Education and Research is funding a new research network from 2015 to 2019 with up to 35 million euros to investigate mental disorders in order to devise and develop better therapeutic measures and strategies for this population by means of basic and translational clinical research. This is the result of a competitive call for research proposals entitled research network for mental diseases. It is a nationwide network of nine consortia with up to ten psychiatric and clinical psychology partner institutions from largely university-based research facilities for adults and/or children and adolescents. Furthermore, three cross-consortia platform projects will seek to identify shared causes of diseases and new diagnostic modalities for anxiety disorders, attention deficit hyperactivity disorders (ADHS), autism, bipolar disorders, depression, schizophrenia and psychotic disorders as well as substance-related and addictive disorders. The spectrum of therapeutic approaches to be examined ranges from innovative pharmacological and psychotherapeutic treatment to novel brain stimulation procedures. In light of the enormous burden such diseases represent for society as a whole, a sustainable improvement in the financial support for those researching mental disorders seems essential. This network aims to become a nucleus for long overdue and sustained support for a German center for mental disorders.
Purpose: Postoperative cognitive dysfunction (POCD) appears in up to 30% of patients suffering from postoperative delirium (POD). Both are associated with higher mortality and postoperative complications, prolonged hospital stays, and increased costs. Multi-modal models with pre-admission risk reduction counselling, perioperative monitoring, and training of multidisciplinary patient care providers have been shown to decrease the prevalence of both. The aim of our study is to understand how far those measures are known and implemented in routine care and to detect potential gaps in the current practice regarding risk communication and information flow between involved caregivers for patients at risk for POD/POCD. Patients and Methods: As part of a multicenter study, seven semi-structured focus group (FG) discussions with nurses and physicians from tertiary care hospitals (surgery, anesthesiology, and orthopedics, n=31) and general practitioners (GPs) in private practice (n=7) were performed. Transcribed discussions were analyzed using qualitative content analysis. Results: POD is present above all in the daily work of nurses, whereas physicians do not perceive it as a relevant problem. Physicians report that no regular risk assessment or risk communication was performed prior to elective surgery. Information about POD often gets lost during hand-offs and is not regularly reported in discharge letters. Thus, persisting cognitive dysfunction is often missed. The importance of standardized documentation and continuous education concerning risks, screening, and treatment was emphasized. The often-suggested pre-OP medication adjustment was seen as less important; in contrast, avoiding withdrawal was regarded as far more important. Conclusion: Altogether, it seems that standards and available best practice concepts are rarely implemented. In contrast to physicians, nurses are highly aware of delirium and ask for standardized procedures and more responsibility. Therefore, raising awareness regarding risks, screening tools, and effective preventive measures for POD/POCD seems an urgent goal. Nurses should have a central role in coordination and care of POD to prevent the risk for POCD.
Background: First rank symptoms (FRS) of schizophrenia have been used for decades for diagnostic purposes. In the new version of the DSM-5, the American Psychiatric Association (APA) has abolished any further reference to FRS of schizophrenia and treats them like any other "criterion A' symptom (e.g. any kind of hallucination or delusion) with regard to their diagnostic implication. The ICD-10 is currently under revision and may follow suit. In this review, we discuss central points of criticism that are directed against the continuous use of first rank symptoms (FRS) to diagnose schizophrenia.
Stress plays a key role in modulating addictive behavior and can cause relapse following periods of abstinence. Common effects of stress and alcohol on the dopaminergic system have been suggested, although the precise mechanisms are unclear. Here, we investigated 20 detoxified alcohol-dependent patients and 19 matched healthy controls and assessed striatal D2/D3 availability using [F-18]-fallypride positron emission tomography and stressful life events. We found a strong association between striatal D2/D3 availability and stress in patients, but not in healthy controls. Interestingly, we found increased D2/D3 receptor availability in patients with higher stress levels. This mirrors complex interactions between stress and alcohol intake in animal studies and emphasizes the importance to investigate stress exposure in neurobiological studies of addiction.
Rapid decline of glomerular filtration rate estimated from creatinine (eGFRcrea) is associated with severe clinical endpoints. In contrast to cross-sectionally assessed eGFRcrea, the genetic basis for rapid eGFRcrea decline is largely unknown. To help define this, we meta-analyzed 42 genome-wide association studies from the Chronic Kidney Diseases Genetics Consortium and United Kingdom Biobank to identify genetic loci for rapid eGFRcrea decline. Two definitions of eGFRcrea decline were used: 3 mL/min/1.73m(2)/year or more ("Rapid3"; encompassing 34,874 cases, 107,090 controls) and eGFRcrea decline 25% or more and eGFRcrea under 60 mL/min/1.73m(2) at follow-up among those with eGFRcrea 60 mL/min/1.73m(2) or more at baseline ("CKDi25"; encompassing 19,901 cases, 175,244 controls). Seven independent variants were identified across six loci for Rapid3 and/or CKDi25: consisting of five variants at four loci with genome-wide significance (near UMOD-PDILT (2), PRKAG2, WDR72, OR2S2) and two variants among 265 known eGFRcrea variants (near GATM, LARP4B). All these loci were novel for Rapid3 and/or CKDi25 and our bioinformatic follow-up prioritized variants and genes underneath these loci. The OR2S2 locus is novel for any eGFRcrea trait including interesting candidates. For the five genome-wide significant lead variants, we found supporting effects for annual change in blood urea nitrogen or cystatin-based eGFR, but not for GATM or (LARP4B). Individuals at high compared to those at low genetic risk (8-14 vs. 0-5 adverse alleles) had a 1.20-fold increased risk of acute kidney injury (95% confidence interval 1.08-1.33). Thus, our identified loci for rapid kidney function decline may help prioritize therapeutic targets and identify mechanisms and individuals at risk for sustained deterioration of kidney function.
Rapid decline of glomerular filtration rate estimated from creatinine (eGFRcrea) is associated with severe clinical endpoints. In contrast to cross-sectionally assessed eGFRcrea, the genetic basis for rapid eGFRcrea decline is largely unknown. To help define this, we meta-analyzed 42 genome-wide association studies from the Chronic Kidney Diseases Genetics Consortium and United Kingdom Biobank to identify genetic loci for rapid eGFRcrea decline. Two definitions of eGFRcrea decline were used: 3 mL/min/1.73m(2)/year or more ("Rapid3"; encompassing 34,874 cases, 107,090 controls) and eGFRcrea decline 25% or more and eGFRcrea under 60 mL/min/1.73m(2) at follow-up among those with eGFRcrea 60 mL/min/1.73m(2) or more at baseline ("CKDi25"; encompassing 19,901 cases, 175,244 controls). Seven independent variants were identified across six loci for Rapid3 and/or CKDi25: consisting of five variants at four loci with genome-wide significance (near UMOD-PDILT (2), PRKAG2, WDR72, OR2S2) and two variants among 265 known eGFRcrea variants (near GATM, LARP4B). All these loci were novel for Rapid3 and/or CKDi25 and our bioinformatic follow-up prioritized variants and genes underneath these loci. The OR2S2 locus is novel for any eGFRcrea trait including interesting candidates. For the five genome-wide significant lead variants, we found supporting effects for annual change in blood urea nitrogen or cystatin-based eGFR, but not for GATM or (LARP4B). Individuals at high compared to those at low genetic risk (8-14 vs. 0-5 adverse alleles) had a 1.20-fold increased risk of acute kidney injury (95% confidence interval 1.08-1.33). Thus, our identified loci for rapid kidney function decline may help prioritize therapeutic targets and identify mechanisms and individuals at risk for sustained deterioration of kidney function.
Objectives. Recent work suggests that a genetic variation associated with increased dopamine metabolism in the prefrontal cortex (catechol-O-methyltransferase Val158Met; COMT) amplifies age-related changes in working memory performance. Research on younger adults indicates that the influence of dopamine-related genetic polymorphisms on working memory performance increases when testing the cognitive limits through training. To date, this has not been studied in older adults. Method. Here we investigate the effect of COMT genotype on plasticity in working memory in a sample of 14 younger (aged 24-30 years) and 25 older (aged 60-75 years) healthy adults. Participants underwent adaptive training in the n-back working memory task over 12 sessions under increasing difficulty conditions. Results. Both younger and older adults exhibited sizeable behavioral plasticity through training (P < .001), which was larger in younger as compared to older adults (P < .001). Age-related differences were qualified by an interaction with COMT genotype (P < .001), and this interaction was due to decreased behavioral plasticity in older adults carrying the Val/Val genotype, while there was no effect of genotype in younger adults. Discussion. Our findings indicate that age-related changes in plasticity in working memory are critically affected by genetic variation in prefrontal dopamine metabolism.
Triaxial high temperature (900 °C) deformation experiments were conducted at constant strain rate in a Paterson-type deformation apparatus on cylinders of Carrara marble with two right or left stepping, non-overlapping weak inclusions of Solnhofen limestone, oriented at 45° to the cylinders’ longitudinal axes. Applying different values of confinement (30, 50, 100 and 300 MPa) we induced various amounts of brittle deformation in the marble matrix and investigated the effect of brittle precursors on the initiation and development of heterogeneity-induced high temperature shear zones.
Viscosity contrast between the matrix and the inclusions induces local stress concentration at the tips of these latter. The initial arrangement of the inclusions results in either an overpressured (contractional) or underpressured (extensional) domain in the step-over region of the sample. At low confinement (30 and 50 MPa) abundant brittle deformation is observed, but the spatial distribution of microfractures is dependent on the kinematics of the step-over region: microcracks occur either along the shearing plane between inclusions (in extensional bridge samples), or broadly distributed outside the step-over region (contractional bridge samples). Accordingly, ductile deformation localizes along the inclusions plane in the extensional bridge samples as opposed to distributing over large areas of the matrix in the contractional bridge samples. If microcracking is suppressed (high confinement), strain is accommodated by viscous creep and strain progressively de-localizes in extensional bridge samples. Our experiments demonstrate that brittle precursors enhance the degree of localization in the ductile deformation regime, but only if the interaction of pre-existing heterogeneities induces an extensional mean stress regime in between.
Background Uptake of self-testing and self-management of oral coagulation has remained inconsistent, despite good evidence of their effectiveness. To clarify the value of self-monitoring of oral anticoagulation, we did a meta-analysis of individual patient data addressing several important gaps in the evidence, including an estimate of the effect on time to death, first major haemorrhage, and thromboembolism.
Methods We searched Ovid versions of Embase (1980-2009) and Medline (1966-2009), limiting searches to randomised trials with a maximally sensitive strategy. We approached all authors of included trials and requested individual patient data: primary outcomes were time to death, first major haemorrhage, and first thromboembolic event. We did prespecified subgroup analyses according to age, type of control-group care (anticoagulation-clinic care vs primary care), self-testing alone versus self-management, and sex. We analysed patients with mechanical heart valves or atrial fibrillation separately. We used a random-effect model method to calculate pooled hazard ratios and did tests for interaction and heterogeneity, and calculated a time-specific number needed to treat.
Findings Of 1357 abstracts, we included 11 trials with data for 6417 participants and 12 800 person-years of follow-up. We reported a significant reduction in thromboembolic events in the self-monitoring group (hazard ratio 0.51; 95% CI 0.31-0.85) but not for major haemorrhagic events (0.88, 0.74-1.06) or death (0.82, 0.62-1.09). Participants younger than 55 years showed a striking reduction in thrombotic events (hazard ratio 0.33, 95% CI 0.17-0.66), as did participants with mechanical heart valve (0.52, 0.35-0.77). Analysis of major outcomes in the very elderly (age >= 85 years, n=99) showed no significant adverse effects of the intervention for all outcomes.
Interpretation Our analysis showed that self-monitoring and self-management of oral coagulation is a safe option for suitable patients of all ages. Patients should also be offered the option to self-manage their disease with suitable health-care support as back-up.