bluuebunny/crossref_metadata_2025 huggingface dataset:
Risk Assessment of Recurrence in Patients With Unprovoked Deep Vein Thrombosis or Pulmonary Embolism
Authors: Eichinger Sabine , Heinze Georg , Jandeck Lisanne M. , Kyrle Paul A.
Published: March 2010

Background—

Predicting the risk of recurrent venous thromboembolism (VTE) in an individual patient is often not feasible. We aimed to develop a simple risk assessment model that improves prediction of the recurrence risk.

Methods and Results—

In a prospective cohort study, 929 patients with a first unprovoked VTE were followed up for a median of 43.3 months after discontinuation of anticoagulation. We excluded patients with a strong thrombophilic defect such as a natural inhibitor deficiency, the lupus anticoagulant, and homozygous or combined defects. A total of 176 patients (18.9%) had recurrent VTE. Preselected clinical and laboratory variables (age, sex, location of VTE, body mass index, factor V Leiden, prothrombin G20210A mutation, D-dimer, and in vitro thrombin generation) were analyzed in a Cox proportional hazards model, and those variables that were significantly associated with recurrence were used to compute risk scores. Male sex (hazard ratio versus female sex 1.90, 95% confidence interval 1.31 to 2.75), proximal deep vein thrombosis (hazard ratio versus distal 2.08, 95% confidence interval 1.16 to 3.74), pulmonary embolism (hazard ratio versus distal thrombosis 2.60, 95% confidence interval 1.49 to 4.53), and elevated levels of D-dimer (hazard ratio per doubling 1.27, 95% confidence interval 1.08 to 1.51) were related to a higher recurrence risk. Using these variables, we developed a nomogram that can be used to calculate risk scores and to estimate the cumulative probability of recurrence in an individual patient. The model was cross validated, and patients were assigned to different risk categories based on their risk score. Recurrence rates corresponded well with the different risk categories.

Conclusions—

By use of a simple scoring system, the assessment of the recurrence risk in patients with a first unprovoked VTE and without strong thrombophilic defects can be improved.
Rapid Reversal of Left Ventricular Hypertrophy and Intracardiac Volume Overload in Patients With Resistant Hypertension and Hyperaldosteronism
Authors: Gaddam Krishna , Corros Cecilia , Pimenta Eduardo , Ahmed Mustafa , Denney Thomas , Aban Inmaculada , Inusah Seidu , Gupta Himanshu , Lloyd Steven G. , Oparil Suzanne , Husain Ahsan , Dell'Italia Louis J. , Calhoun David A.
Published: March 2010

We have shown previously that patients with resistant hypertension and hyperaldosteronism have increased brain natriuretic peptide suggestive of increased intravascular volume. In the present study, we tested the hypothesis that hyperaldosteronism contributes to cardiac volume overload. Thirty-seven resistant hypertensive patients with hyperaldosteronism (urinary aldosterone ≥12 μg/24 hours and plasma renin activity ≤1.0 ng/mL per hour) and 71 patients with normal aldosterone status were studied. Both groups had similar blood pressure and left ventricular mass, whereas left and right ventricular end-diastolic volumes measured by cardiac MRI were greater in high versus normal aldosterone subjects (
P
<0.05). Spironolactone treatment (19 patients in the high aldosterone group and 15 patients from the normal aldosterone group participated in the follow-up) resulted in a significant decrease in clinic systolic blood pressure, right and left ventricular end diastolic volumes, left atrial volume, left ventricular mass, and brain natriuretic peptide at 3 and 6 months of follow-up in patients with high aldosterone, whereas in those with normal aldosterone status, spironolactone decreased blood pressure and left ventricular mass without changes in ventricular or atrial volumes or plasma brain natriuretic peptide. Hyperaldosteronism causes intracardiac volume overload in patients with resistant hypertension in spite of conventional thiazide diuretic use. Mineralocorticoid receptor blockade induces rapid regression of left ventricular hypertrophy irrespective of aldosterone status. In subjects with high aldosterone, mineralocorticoid receptor blockade induces a prominent diuretic effect compared with a greater vasodilatory effect in subjects with normal aldosterone status.
Autoantibody-Mediated Angiotensin Receptor Activation Contributes to Preeclampsia Through Tumor Necrosis Factor-α Signaling
Authors: Irani Roxanna A. , Zhang Yujin , Zhou Cissy Chenyi , Blackwell Sean C. , Hicks M. John , Ramin Susan M. , Kellems Rodney E. , Xia Yang
Published: March 2010

Preeclampsia is a prevalent life-threatening hypertensive disorder of pregnancy for which the pathophysiology remains largely undefined. Recently, a circulating maternal autoantibody, the angiotensin II type I (AT
1
) receptor agonistic autoantibody (AA), has emerged as a contributor to disease features. Increased circulating maternal tumor necrosis factor α (TNF-α) is also associated with the disease; however, it is unknown whether this factor directly contributes to preeclamptic symptoms. Here we report that this autoantibody increases the proinflammatory cytokine TNF-α in the circulation of AT
1
-AA–injected pregnant mice but not in nonpregnant mice. Coinjection of AT
1
-AA with a TNF-α neutralizing antibody reduced cytokine availability in AT
1
-AA–injected pregnant mice. Moreover, TNF-α blockade in AT
1
-AA–injected pregnant mice significantly attenuated the key features of preeclampsia. Autoantibody-induced hypertension was reduced from 131±4 to 110±4 mm Hg, and proteinuria was reduced from 212±25 to 155±23 μg of albumin per milligram of creatinine (both
P
<0.05). Injection of AT
1
-AA increased the serum levels of circulating soluble fms-like tyrosine kinase 1 and soluble endoglin (34.1±5.1, 2.4±0.3 ng/mL, respectively) and coinjection with the TNF-α blocker significantly reduced their levels (21.7±3.4 and 1.2±0.4 ng/mL, respectively). Renal damage and placental abnormalities were also decreased by TNF-α blockade. Lastly, the elevated circulating TNF-α in preeclamptic patients is significantly correlated with the AT
1
-AA bioactivity in our patient cohort. Similarly, the autoantibody, through AT
1
receptor–mediated TNF-α induction, contributed to increased soluble fms-like tyrosine kinase 1, soluble endoglin secretion, and increased apoptosis in cultured human villous explants. Overall, AT
1
-AA is a novel candidate that induces TNF-α, a cytokine that may play an important pathogenic role in preeclampsia.
Spatial Variability of Sea Level Rise in Twenty-First Century Projections
Authors: Yin Jianjun , Griffies Stephen M. , Stouffer Ronald J.
Published: March 2010

A set of state-of-the-science climate models are used to investigate global sea level rise (SLR) patterns induced by ocean dynamics in twenty-first-century climate projections. The identified robust features include bipolar and bihemisphere seesaws in the basin-wide SLR, dipole patterns in the North Atlantic and North Pacific, and a beltlike pattern in the Southern Ocean. The physical and dynamical mechanisms that cause these patterns are investigated in detail using version 2.1 of the Geophysical Fluid Dynamics Laboratory (GFDL) Coupled Model (CM2.1). Under the Intergovernmental Panel on Climate Change’s (IPCC) Special Report on Emissions Scenarios (SRES) A1B scenario, the steric sea level changes relative to the global mean (the local part) in different ocean basins are attributed to differential heating and salinity changes of various ocean layers and associated physical processes. As a result of these changes, water tends to move from the ocean interior to continental shelves. In the North Atlantic, sea level rises north of the Gulf Stream but falls to the south. The dipole pattern is induced by a weakening of the meridional overturning circulation. This weakening leads to a local steric SLR east of North America, which drives more waters toward the shelf, directly impacting northeastern North America. An opposite dipole occurs in the North Pacific. The dynamic SLR east of Japan is linked to a strong steric effect in the upper ocean and a poleward expansion of the subtropical gyre. In the Southern Ocean, the beltlike pattern is dominated by the baroclinic process during the twenty-first century, while the barotropic response of sea level to wind stress anomalies is significantly delayed.
Optimal Detection of Regional Trends Using Global Data
Authors: Leroy Stephen S. , Anderson James G.
Published: March 2010

A complete accounting of model uncertainty in the optimal detection of climate signals requires normalization of the signals produced by climate models; however, there is not yet a well-defined rule for the normalization. This study seeks to discover such a rule. The authors find that, to arrive at the equations of optimal detection from a general application of Bayesian statistics to the problem of climate change, it is necessary to assume that 1) the prior probability density function (PDF) for climate change is separable into independent PDFs for sensitivity and the signals’ spatiotemporal patterns; 2) postfit residuals are due to internal variability and are normally distributed; 3) the prior PDF for sensitivity is uninformative; and 4) a continuum of climate models used to estimate model uncertainty gives a normally distributed PDF for the spatiotemporal patterns for the climate signals. This study also finds that the rule for normalization of the signals’ patterns is a simple division of model-simulated climate change in any observable quantity or set of quantities by a change in a single quantity of interest such as regionally averaged temperature or precipitation. With this normalization, optimal detection yields the most probable estimates of the underlying changes in the region of interest due to external forcings. Data outside the region of interest add information that effectively suppresses the interannual fluctuations associated with internal climate variability.
Risks of Model Weighting in Multimodel Climate Projections
Authors: Weigel Andreas P. , Knutti Reto , Liniger Mark A. , Appenzeller Christof
Published: March 2010

Multimodel combination is a pragmatic approach to estimating model uncertainties and to making climate projections more reliable. The simplest way of constructing a multimodel is to give one vote to each model (“equal weighting”), while more sophisticated approaches suggest applying model weights according to some measure of performance (“optimum weighting”). In this study, a simple conceptual model of climate change projections is introduced and applied to discuss the effects of model weighting in more generic terms. The results confirm that equally weighted multimodels on average outperform the single models, and that projection errors can in principle be further reduced by optimum weighting. However, this not only requires accurate knowledge of the single model skill, but the relative contributions of the joint model error and unpredictable noise also need to be known to avoid biased weights. If weights are applied that do not appropriately represent the true underlying uncertainties, weighted multimodels perform on average worse than equally weighted ones, which is a scenario that is not unlikely, given that at present there is no consensus on how skill-based weights can be obtained. Particularly when internal variability is large, more information may be lost by inappropriate weighting than could potentially be gained by optimum weighting. These results indicate that for many applications equal weighting may be the safer and more transparent way to combine models. However, also within the presented framework eliminating models from an ensemble can be justified if they are known to lack key mechanisms that are indispensable for meaningful climate projections.
Constrain-Thy-Neighbor Effects as a Determinant of Transnational Interest Group Cohesion
Authors: Callaghan Helen
Published: March 2010

Why does the willingness of interest groups to join forces with their peers abroad vary across issues? The present article points to cross-issue variation in the “constrain-thy-neighbor” effects of transnational law. Interest groups consider not only whether they are worse off if they themselves are subjected to a transnational law. They also consider how it affects them if the same law applies abroad. Depending on the issue, they derive advantages or disadvantages from seeing their neighbors constrained, and this affects their willingness to fight transnational legislation on that issue. To illustrate the argument, the article compares cohesion within the Union of Industrial and Employers’ Confederations of Europe (UNICE), the European peak employer federation, on two aspects of EU company law. UNICE members were divided over EU takeover directives while uniting against EU worker participation directives. Statements released by German and British UNICE members show that the divergent constrain-thy-neighbor effect associated with these issues contributed to variation in cohesion.
Dentin-derived BMP-2 and Odontoblast Differentiation
Authors: Casagrande L. , Demarco F.F. , Zhang Z. , Araujo F.B. , Shi S. , Nör J.E.
Published: March 2010

It is known that stem cells from exfoliated deciduous teeth (SHED) can be induced to differentiate into odontoblasts. However, the nature of dentin-derived morphogenic signals required for dental pulp stem cell differentiation remains unclear. The hypothesis underlying this work is that dentin-derived Bone Morphogenetic Proteins (BMP) are necessary for the differentiation of SHED into odontoblasts. We observed that SHED express markers of odontoblastic differentiation (DSPP, DMP-1, MEPE) when seeded in human tooth slice/scaffolds and cultured in vitro, or implanted subcutaneously into immunodeficient mice. In contrast, SHED cultured in deproteinized tooth slice/scaffolds, or scaffolds without a tooth slice, do not express these markers. SHED express the BMP receptors BMPR-IA, BMPR-IB, and BMPR-II. Notably, blockade of BMP-2 signaling inhibited the expression of markers of odontoblastic differentiation by SHED cultured in tooth slice/scaffolds. Collectively, this work demonstrates that dentin-derived BMP-2 is required to induce the differentiation of SHED into odontoblasts.
Demonstration of the Analgesic Efficacy and Dose‐Response of Acetylsalicylic Acid With Pseudoephedrine
Authors: Schachtel Bernard P. , Voelker Michael , Sanner Kathleen M. , Gagney Diana , Bey Mary , Schachtel Emily J. , Becka Michael
Published: March 2010

To determine acute analgesia by acetylsalicylic acid (ASA) when combined with pseudoephedrine (PSE) in patients with upper respiratory tract infection (URTI), we used the sore throat pain model to measure single‐dose effects of ASA 500 mg/PSE 30 mg, ASA 1000 mg/PSE 60 mg, and acetaminophen (APAP) 1000 mg/PSE 60 mg (serving as a positive control). Under double‐blind, randomized, placebo‐controlled conditions, 640 adult patients with confirmed acute pharyngitis and rhinosinusitis associated with URTI rated throat pain intensity and relief at intervals over 6 hours. Efficacy was demonstrated for both doses of ASA/PSE compared with placebo for all end points, including total pain relief and summed pain intensity differences, beginning at 20 minutes on both scales (all P < .05), and the efficacy of APAP/PSE compared with placebo was confirmed (P < .01). Greater differences in pain relief and intensity were also demonstrated between the higher and lower doses of ASA/PSE (P < .05), in particular, among 329 patients with severe pain, as well as between ASA 1000 mg/PSE 60 mg and APAP 1000 mg/PSE 60 mg (P < .05). No serious adverse events were reported. This study demonstrates that ASA is a well‐tolerated and effective analgesic in 500‐ and 1000‐mg doses when combined with pseudoephedrine.
Neuronal Embryonal Tumors in Fish
Authors: Kagan R. A. , Pinkerton M. E. , Kinsel M. J.
Published: March 2010

This article describes 11 cases of neuronal embryonal neoplasia in captive adult teleost fish. Neoplasms were located within 1 or both eyes of 8 fish and the skin of 3 other fish. Ocular neoplasms most often presented as unilateral or bilateral exophthalmia. Seven ocular and 1 cutaneous mass were composed of small triangular (carrot-shaped) neoplastic cells with Flexner-Wintersteiner-type rosette formation. Mass location and histologic and ultrastructural features were suggestive of retinoblastomas. One ocular mass was composed of ribbons and rosettes of neoplastic cells with multiple areas of neuronal differentiation and was diagnosed as a teratoid medulloepithelioma. A cutaneous mass from an electric eel ( Electrophorus electricus) consisted of rosettes and streams of elongate neoplastic cells. The epidermal electroreceptor (ampullary) organ was considered as an origin. Although distant metastases were not observed, neoplasms were generally locally aggressive with postexcision recurrence. There was occasional spread to or de novo occurrence within the contralateral eye.
Systemic Spironucleosis in 2 Immunodeficient Rhesus Macaques (Macaca mulatta)
Authors: Bailey C. , Kramer J. , Mejia A. , MacKey J. , Mansfield K. G. , Miller A. D.
Published: March 2010

Spironucleus spp are parasites of fish and terrestrial vertebrates, including mice and turkeys, that rarely cause extraintestinal disease. Two rhesus macaques ( Macaca mulatta) were experimentally inoculated with simian immunodeficiency virus mac251. Both progressed to simian acquired immune deficiency syndrome within 1 year of inoculation and developed systemic protozoal infections in addition to common opportunistic infections, including rhesus cytomegalovirus, rhesus lymphocryptovirus, and rhesus adenovirus. In the first case, the protozoa were associated with colitis, multifocal abdominal abscessation, and lymphadenitis. In the second case, they were one of a number of organisms associated with extensive pyogranulomatous pneumonia and colitis. Ultrastructural, molecular, and phylogenetic analysis revealed the causative organism to be a species of Spironucleus closely related to Spironucleus meleagridis of turkeys. This report is the first of extraintestinal infection with Spironucleus sp in higher mammals and expands the list of opportunistic infections found in immunocompromised rhesus macaques.
Changes of urban wetlands in Wuhan, China, from 1987 to 2005
Authors: Kai Xu  , Chunfang Kong  , Gang Liu  , Chonglong Wu  , Hongbin Deng  , Yi Zhang  , Qianlai Zhuang
Published: March 2010

Urban wetlands play a significant role in the sustainable development of the urban eco-environment. However, accelerated urbanization has caused rapid changes in urban wetland landscape patterns, which may seriously affect their functions. Based on land-use maps, TM images, and field data from the Wuhan wetlands, the spatiotemporal evolution and wetland landscape pattern were quantitatively analyzed, with reference to landscape ecology indices of diversity, fragmentation, dominance, shape, and dimension. The results showed that: (1) the natural wetland area decreased: lake wetlands and marsh wetlands decreased by 18.71% and 50.3% from 1987 to 2005, respectively; (2) artificial wetland area increased by 47.75% in Wuhan over the same period; (3) the lake wetland area of Wuhan declined due to the conversion of large lakes to smaller ones; (4) the value of the diversity index (H), evenness index (E), and fragmentation index (F) decreased, while the value of the dominance index (D) increased from 1987 to 2005; (5) the landscape shape index (LSI) and fractal dimension (FD) of the river wetlands, lake wetlands, bottomland wetlands, and marsh wetlands decreased, while the LSI and FD of the reservoir and pond wetlands increased from 1987 to 2005; and (6) natural, societal, and economic, as well as human, activities are major factors for the structural changes in the Wuhan wetland landscape, as revealed by canonical correlation analysis. Results suggest that the ecological environment of urban wetlands should be protected to maximize the services of urban wetland ecosystems in Wuhan, China.
Tendon Disorders of the Foot and Ankle, Part 3
Authors: Gluck George S. , Heckman Daniel S. , Parekh Selene G.
Published: March 2010

This article provides a review of posterior tibial tendon pathology and the authors’ preferred management. The tibialis posterior musculotendinous unit is the most powerful inverter of the foot and an important dynamic stabilizer of the arch. In the stance phase of the gait cycle, it serves as an initiator of both ankle plantar flexion and subtalar inversion. This creates a rigid midfoot by stabilizing the transverse tarsal joint, and allows for increased power generation by the gastrocsoleus complex through toe-off. Injuries to the posterior tibialis tendon include traumatic laceration and dislocation, as well as tenosynovitis and tendinopathy, which can lead to attenuation and rupture. If these injuries are not addressed, significant clinical deformity and disability can result.
Holocene hydrologic variability in temperate southeastern Australia: An example from Lake George, New South Wales
Authors: Fitzsimmons Kathryn E. , Barrows Timothy T.
Published: March 2010

Lake George is one of the largest freshwater lakes in Australia when full, and provides one of the most complete records of Quaternary sedimentation in the southeastern part of the continent. The lake is currently ephemeral, but sediments within the basin preserve evidence of multiple permanent and dry lake conditions in the past. We present an optically stimulated luminescence (OSL) chronology of recent lake shoreline sediments in order to reconstruct Holocene hydrologic variability at Lake George, providing past climatic context for the presently ephemeral lake conditions. The OSL chronology indicates three distinct periods of permanent lake conditions up to 15—18 m depth over the Holocene period, at approximately 10—8, 6—2.4 and 0.7—0.3 ka, with lower lake levels occurring in between those events. There appears to be a trend towards lake regression over this period despite relatively recent high lake levels. The chronology is broadly synchronous with comparable records of Holocene climatic variability across southeastern Australia. We also investigate the intrinsic luminescence characteristics of different sediment types as diagnostic tools, but these appear not to be appropriate in this context or form.
The role of LRP8 (ApoER2’) in the pathophysiology of the antiphospholipid syndrome
Authors: de Groot PG , Derksen RHWM , Urbanus RT
Published: March 2010

One of the greatest enigmas in thrombosis research is the observation that one can diagnose a person with a thrombotic risk with a prolongation of the clotting time. Our textbooks have taught us that prolongation of clotting correlates with a tendency to bleed. To confuse our textbook knowledge further, the same patients often have a prolonged bleeding time, a diagnostic test to detect a dysfunction in primary haemostasis. In this paper we critically review the literature that tries to explain the contradiction that exists between in-vitro diagnostic tests and the observed clinical manifestations and discuss our current opinion on how antiphospholipid antibodies can disturb the haemostatic balance.
Antiphospholipid syndrome and the brain in pediatric and adult patients
Authors: Muscal E. , Brey RL
Published: March 2010

The most common neurological manifestations of antiphospholipid syndrome (APS) in all age-groups include stroke and transient ischemic attacks due to arterial thromboses and cerebral ischemia. Antiphospholipid antibodies may cause additional non-criteria neurological impairments through vascular, neuroinflammatory and direct neuronal effects. Anti-aggregant or anticoagulant therapies are indicated for APS-related ischemic strokes. Treatment regimens for asymptomatic antibody-positive patients and those with refractory or recurrent disease remain controversial. There is scant literature on the epidemiology and therapy of neurological APS manifestations in pediatric patients. Assessments of modifiable cardiovascular and inherited thrombophilia risk factors are essential in patients with APS. There may be a role for novel neuroimaging modalities in quantifying APS-related microstructural brain damage. The clinical utility of statins, antimalarials, angiotensin-converting enzyme inhibitors, and thrombin inhibitors warrant further research.
Use of monoclonal antibodies to dissect specificity and pathogenesis of antiphospholipid antibodies
Authors: Lambrianides A. , Giles IP
Published: March 2010

Monoclonal antiphospholipid antibodies (aPL) have been utilized to dissect the relationship between their sequence, structure, binding and biological properties relevant to the pathogenesis of the antiphospholipid syndrome. In particular, sequence analysis of aPL has highlighted the clustering of certain amino acid residues in the antigen contact sites of their heavy and light chains. Therefore, these sequence motifs are likely to be important in determining aPL binding properties and their pathogenic effects. Experiments, however, using monoclonal aPL engineered to contain specific point mutations in their sequence which alter their ability to bind relevant antigens have shown that these alterations in binding are not directly mirrored by their pathogenic effects. In this review we focus on work carried out by others and ourselves using monoclonal antibodies with specific binding properties to extend our knowledge of the non-linear structure—binding—function relationship of aPL.
Antiphospholipid syndrome (Hughes syndrome): 10 clinical topics
Authors: Hughes GRV
Published: March 2010

This year in Galveston, Texas, Silvia Pierangeli hosts the 13th International Congress on Antiphospholipid Antibodies. Twenty-six years after the first antiphospholipid syndrome meeting, the number of interested colleagues has multiplied, and the subject has become more scientifically understood. So also has the clinical picture. In this short contribution, I will highlight a number of clinical observations which may, or may not, contribute to our understanding of antiphospholipid syndrome.
Proteomics in antiphospholipid syndrome: a review
Authors: Cuadrado MJ , Aguirre MA , Barbarroja N. , Khamashta MA , Lopez-Pedrera Ch
Published: March 2010

The presence of antiphospholipid antibodies (aPL) has been closely related to the development of thrombosis and complications in pregnancy. However, not all patients with aPL will develop those clinical features. The exact pathogenic mechanisms leading to thrombosis and/or pregnancy morbidity are poorly understood. Currently, biomarkers which enable one to predict the prognosis of patients with positive aPL are not readily available. Current advances in genomics and proteomics provide the opportunity to discover novel biomarkers based on changes in concentration levels or post-translational modifications of proteins and peptides. These techniques are now being applied in various areas of medicine with very promising results. This review covers recent studies that have used this approach for a better understanding of the pathogenic mechanisms involved in the development of thrombosis in patients with antiphospholipid syndrome (APS). Although, there are very few qualified biomarkers that have arisen as a result of efforts in proteomics, it is expected that these techniques will deliver biomarkers that might ultimately identify different subgroups of APS patients with various prognoses that might have implications with respect to management and prognosis. Lupus (2010) 19, 385—388.
Catastrophic antiphospholipid syndrome (CAPS): update from the ‘CAPS Registry’
Authors: Cervera R. ,   CAPS Registry Project Group
Published: March 2010

Although less than 1% of patients with the antiphospholipid syndrome (APS) develop the catastrophic variant, its potentially lethal outcome emphasizes its importance in clinical medicine today. However, the rarity of this variant makes it extraordinarily difficult to study in any systematic way. In order to put together all of the published case reports as well as the new diagnosed cases from all over the world, an international registry of patients with catastrophic APS (CAPS Registry) was created in 2000 by the European Forum on Antiphospholipid Antibodies (see http://www.med.ub.es/MIMMUN/FORUM/CAPS.HTM). Currently, it documents the entire clinical, laboratory and therapeutic data of more than 300 patients whose data has been fully registered.
Towards evidence-based treatment of thrombotic antiphospholipid syndrome
Authors: Derksen Rhwm , de Groot PG
Published: March 2010

Thrombosis in the presence of persistently positive tests for antiphospholipid antibodies is termed thrombotic antiphospholipid syndrome (APS). At present, ‘standard’ secondary thromboprophylaxis in thrombotic APS is treatment with moderate intensity oral anticoagulants for life after a first venous thrombosis and with high intensity oral anticoagulation after non-embolic ischaemic stroke. These recommendations differ from those applied in the general population, where a restricted period of anticoagulation is common practice after venous thrombosis and antiplatelet drugs are the first choice after ischaemic stroke. From an extensive literature review we conclude that the available data are insufficient to apply a different strategy for secondary thromboprophylaxis in patients with thrombotic APS than the one that holds for the general population.
Obstetric antiphospholipid syndrome: still a challenge
Authors: Levy RA , Jesús GRR , Jesús NR
Published: March 2010

Obstetric complications such as fetal death, premature delivery, preeclampsia and recurrent abortions (since chromosomal or anatomic defects have been excluded) are characteristic manifestations of antiphospholipid syndrome (APS). They can occur in patients with known APS with previous arterial or venous events in any tissue or organ, or be its first and only manifestation. Pregnancy in a patient with APS is considered high risk and the full prenatal clinical follow-up must be carried with this in mind, eliminating or minimizing concomitant thrombotic risk factors.
Antiphospholipid syndrome treatment beyond anticoagulation: are we there yet?
Authors: Pierangeli SS , Erkan D.
Published: March 2010

Persistently positive antiphospholipid antibodies in association with thromboses and/or pregnancy morbidity is the hallmark of the antiphospholipid syndrome. The management of antiphospholipid antibody-positive patients has been focused on utilizing anti-thrombotic medications such as heparin or warfarin. Given that our understanding of the molecular mechanisms of antiphospholipid antibody-mediated thrombosis has been growing, it is highly likely that the current ‘anti-thrombotic’ approach to these patients will be replaced by an ‘immunomodulatory’ approach in the near future. This review article will address the experimental and/or clinical evidence behind some of these potential ‘immunomodulatory’ approaches (tissue factor inhibition, P38 mitogen-activated protein kinase inhibition, nuclear factor-κB inhibition, platelet glycoprotein receptor inhibition, hydroxychloroquine, statins, inhibition of β2GPI and/or anti-β2GPI binding to target cells, complement inhibition, and B cell inhibition) in antiphospholipid syndrome.
Energy Harvesting from Highly Unsteady Fluid Flows using Piezoelectric Materials
Authors: Akaydin Huseyin Dogus , Elvin Niell , Andreopoulos Yiannis
Published: March 2010

In the present work we explore some aspects of energy harvesting from unsteady, turbulent fluid flow using piezoelectric generators. Turbulent flows exhibit a large degree of coherence in their spatial and temporal scales, which provides a unique opportunity for energy harvesting. The voltage generated by short, flexible piezoelectric cantilever beams placed inside turbulent boundary layers and wakes of circular cylinders at high Reynolds numbers is investigated. Matching the fluid flow’s predominant frequency with the natural frequency of the piezoelectric generator appears to maximize the piezoelectric output voltage. This voltage is also dependent on the generator’s location inside the flow field. A three-way coupled interaction simulation that takes into account the aerodynamics, structural vibration, and electrical response of the piezoelectric generator has been developed. The simulation results agree reasonably well with the experimental data paving the way of using such a tool to estimate the performance of different energy harvesting devices within unsteady flow fields.
Experimental Evaluation of a ‘Self-Sensing’ Capability of an Electromagnetic Induction System Designed for MR Dampers
Authors: Jung Hyung-Jo , Jang Dong-Doo , Koo Jeong-Hoi , Cho Sang-Won
Published: March 2010

This article presents a sensing capability of an electromagnetic induction (EMI) system that is incorporated in a vibration control system based on an MR fluid damper. The EMI system, consisting of permanent magnets and coils, converts reciprocal motions (kinetic energy) of the MR damper into electrical energy (electromotive force or emf). The EMI system was previously studied as an alternative power source for the MR damper control system, eliminating the need of external power sources, such as a battery. The primary goal of the current study, however, is to study a sensing capability of the EMI with an aim to eliminate a conventional velocity sensor being used to implement control policies for MR damper based vibration control systems. According to the Faraday’s law of electromagnetic induction, the emf signal, produced from the EMI, is an alternating voltage signal, and it is proportional to the velocity of the motion. As such, the induced voltage (emf) signal of the EMI can sufficiently provide necessary measurement information (i.e., relative velocity across the damper) to some of the well-known control methods designed for MR damper systems (such as skyhook and maximum energy dissipation algorithm). This is because such control methods only require the sign change of the velocity signal (or phase of the velocity), rather than the exact magnitude and phase of the velocity signal. In order to evaluate the proposed concept of the EMI sensor, an EMI system was constructed. The EMI was designed to be augmented to a large-scale MR damper system (MR-EMI). The MR-EMI system was then mounted on a hydraulic servo controlled shaking table. Both harmonic and scaled historic earthquake inputs were used in a series of shaking table tests. The emf signals generated by the EMI were compared with the velocity signals (derivative of the reference input displacements). The results show that the induced emf voltage signal coincided with the phase of the velocity signal, indicating that the EMI can act as a relative velocity sensor for common control methods for MR damper systems.
Cancer Symptom Clusters: Old Concept But New Data
Authors: Kirkova Jordanka , Walsh Declan , Aktas Aynur , Davis Mellar P.
Published: March 2010

Individuals with cancer have multiple symptoms, which frequently co-occur. A nonrandom distribution of symptoms suggests a common mechanism. Symptom clusters (SCs) were considered part of various syndromes in the early years of medicine. The SC concept in clinical medicine is old. Symptom clusters were commonly described in the psychology/psychiatry and neurology literature. Symptom cluster may be defined either clinically or statistically. Statistically derived clusters can differ from clinically defined clusters. The clinical importance of statistically derived clusters is unclear. Pain-insomnia-fatigue and pain-depression-fatigue are commonly recognized clinical clusters. Nausea-vomiting and anxiety-depression are also statistically observed clusters. The longitudinal stability of clusters is unknown. Certain SCs, appear to have a greater adverse influence on outcomes (such as performance status and survival) than others. Comorbidities probably influence symptoms at different levels, but their effect on cancer clusters is unknown. Comprehensive symptom assessment is crucial to cluster identification. The potential use of the cluster concept to abbreviate symptom assessment tools needs validation. Symptom cluster can be disease and/or treatment related and may change as individuals undergo antitumor therapies. Polypharmacy in symptom management is frequent but could be minimized if 1 drug could be used to treat cluster symptoms. Symptom cluster appears to vary with the assessment tool, disease stage, symptom domain used to cluster, cluster methodology, and number of symptoms assessed. The validity and reliability of SCs need universally accepted statistical methods, assessment tools, and symptom domains. For now, nausea-vomiting is recognized as a consistent cluster across multiple studies. Pain-depression-fatigue and pain-insomnia-fatigue are also well recognized. Symptom clusters may help in cancer diagnosis, symptom management, and prognostication. However, the cluster method, reliability, and validity need to be established before assessment or treatment guidelines are established. Symptom clusters require further research before becoming part of routine medical symptom assessment and management.
High-dose immunoablation with autologous haematopoietic stem cell transplantation in aggressive multiple sclerosis: a single centre 10-year experience
Authors: Krasulová Eva , Trněný Marek , Kozák Tomáš , Vacková Blanka , Pohlreich David , Kemlink David , Kobylka Petr , Kovářová Ivana , Lhotáková Petra , Havrdová Eva
Published: March 2010

There are multiple sclerosis patients who suffer from an aggressive course of the disease with severe relapses and rapid accumulation of disability despite adequate treatment. In such cases high-dose immunoablation with autologous haematopoietic stem cell transplantation (ASCT) may be considered. Our objective was to report our experience with 26 multiple sclerosis patients treated with ASCT within the years 1998—2008. Twenty-six patients (Expanded Disability Status Scale 2.5—7.5 (median 6.0), multiple sclerosis duration 2—19 years (median 7)) with aggressive multiple sclerosis underwent autologous haematopoietic stem cell transplantation. Stem cells were mobilized by high-dose cyclophosphamide and granulocyte colony-stimulating factor, BEAM (carmustine, etoposide, cytarabine, melphalan) was used for immunoablation. Patients were evaluated at baseline and every six months post ASCT for adverse events and clinical outcome. Follow-up period was 11—132 months (median 66). Progression-free survival was calculated using the Kaplan— Meier method. At 3 and 6 years of follow-up 70.8% and 29.2% of patients respectively were free of progression. Patients with relapsing multiple sclerosis course, disease duration <5 years and age <35 years had a more favourable outcome. There was no death within 100 days after ASCT. We conclude that ASCT represents a viable and effective treatment option for aggressive multiple sclerosis.
Lesional magnetization transfer ratio: a feasible outcome for remyelinating treatment trials in multiple sclerosis
Authors: van den Elskamp IJ , Knol DL , Vrenken H. , Karas G. , Meijerman A. , Filippi M. , Kappos L. , Fazekas F. , Wagner K. , Pohl C. , Sandbrink R. , Polman CH , Uitdehaag BMJ , Barkhof F.
Published: March 2010

Magnetization transfer ratio (MTR) is a sensitive parameter to quantify the integrity of myelinated white matter in patients with multiple sclerosis. Lesional MTR decreases in the acute phase due to demyelination, and subsequently shows recovery depending on the degree of remyelination in the absence of axonal loss. Recovery of average lesion MTR therefore might prove a viable outcome measure to assess the effect of remyelinating agents. Our objective was to determine the required sample size for phase II multicentre clinical trials using the recovery of average lesion MTR as primary outcome measure. With 7-monthly MRI scans, the MTR evolution of 349 new enhancing lesions before and after enhancement was assessed in 32 MS patients from 5 centres. Multilevel models were fitted to the data yielding estimates for the variance components, which were applied in power calculations. Sample sizes were determined for placebo-controlled, multicentre trials using lesional MTR recovery post-enhancement as primary outcome measure. Average lesion MTR decreased slightly in the build-up to enhancement, decreased dramatically during enhancement and showed recovery in the period after cessation. The power calculations showed that for a power of 80%, approximately 136 patients per trial (mean number of 6 lesions per patient) are required to detect a 30% increase in lesional MTR post-enhancement compared with placebo, whereas 48 subjects are required to detect a 50% increase in lesional MTR compared with placebo. Recovery of lesion MTR is a feasible outcome measure for future multicentre clinical trials measuring the effect of remyelinating agents.
Outcome of psychiatric symptoms presenting at onset of multiple sclerosis: a retrospective study
Authors: Lo Fermo Salvatore , Barone Rita , Patti Francesco , Laisa Patrizia , Cavallaro Tiziana L , Nicoletti Alessandra , Zappia Mario
Published: March 2010

Psychiatric disturbances may occur at the onset of multiple sclerosis. However, information on their outcome is lacking. Our objective was to document the characteristics of psychiatric symptoms at presentation of multiple sclerosis and to define the long-term evolution of psychiatric disturbances in these patients.

Based on a clinical record analysis of patients with defined multiple sclerosis diagnosis and coming under the care of a university multiple sclerosis centre within the period 1997—2007, patients with both psychiatric and neurological symptoms at presentation were identified. Clinical data at onset and at last follow-up were considered.

Among 682 evaluated patients, psychiatric disturbances were associated with multiple sclerosis onset in 16 cases (2.3%). Most patients (56%) presented with a mood disorder with clinical characteristics of a major depressive-like episode, five (32%) had psychotic symptoms. Initial psychiatric disturbances improved later than neurological symptoms, or never fully recovered, regardless of the concomitant use of psychotropic medications. In most of the subjects psychiatric disturbances tended to remain over the follow-up period and at last visit, after a mean follow-up of 7.6 years (±2.3), 14 subjects (87%) had a supplementary diagnosis of psychiatric illness.

Psychiatric symptoms at onset of multiple sclerosis may be indicators of possible maintenance of psychiatric morbidity in a sizeable proportion of patients.
Cognitive “Category-Based Induction” Research and Social “Persuasion” Research Are Each About What Makes Arguments Believable
Authors: Ranganath Kate A. , Spellman Barbara A. , Joy-Gaba Jennifer A.
Published: March 2010

Social and cognitive psychologists each study factors that influence the believability of arguments, but they have worked mostly in parallel. We briefly examine and compare the dominant theories explaining argument believability in the social persuasion literature and the cognitive category-based induction literature. Although the two areas ask similar questions, they use different paradigms to study different aspects of the issues. We describe each area’s major paradigms and questions and then examine the conclusions that each area draws regarding the role of five variables important to argument believability: (a) the number of sources/premises, (b) the similarity between sources/premises, (c) individual differences in characteristics of the reasoner, (d) the available resources, and (e) the reasoner’s background knowledge and beliefs. Comparing the two literatures provides a more complete picture of the factors influencing argument believability and provides fruitful new avenues for integration and exploration.
Episodic Future Thought
Authors: Szpunar Karl K.
Published: March 2010

The ability to mentally simulate hypothetical scenarios is a rapidly growing area of research in both psychology and neuroscience. Episodic future thought, or the ability to simulate specific personal episodes that may potentially occur in the future, represents one facet of this general capacity that continues to garner a considerable amount of interest. The purpose of this article is to elucidate current knowledge and identify a number of unresolved issues regarding this specific mental ability. In particular, this article focuses on recent research findings from neuroimaging, neuropsychology, and clinical psychology that have demonstrated a close relation between episodic future thought and the ability to remember personal episodes from one’s past. On the other hand, considerations of the role of abstracted (semantic) representations in episodic future thought have been noticeably absent in the literature. The final section of this article proposes that both episodic and semantic memory play an important role in the construction of episodic future thoughts and that their interaction in this process may be determined by the relative accessibility of information in memory.
Moral Complexity
Authors: Narvaez Darcia
Published: March 2010

Recently, intuitionist theories have been effective in capturing the academic discourse about morality. Intuitionist theories, like rationalist theories, offer important but only partial understanding of moral functioning. Both can be fallacious and succumb to truthiness: the attachment to one’s opinions because they “feel right,” potentially leading to harmful action or inaction. Both intuition and reasoning are involved in deliberation and expertise. Both are malleable from environmental and educational influence, making questions of normativity—which intuitions and reasoning skills to foster—of utmost importance. Good intuition and reasoning inform mature moral functioning, which needs to include capacities that promote sustainable human well-being. Individual capacities for habituated empathic concern and moral metacognition—moral locus of control, moral self-regulation, and moral self-reflection—comprise mature moral functioning, which also requires collective capacities for moral dialogue and moral institutions. These capacities underlie moral innovation and are necessary for solving the complex challenges humanity faces.
The Limits of Cost-Benefit Calculation: Commentary on Bennis, Medin, & Bartels (2010)
Authors: Schwartz Barry
Published: March 2010

Bennis, Medin, and Bartels (2010, this issue) correctly identify real limits to the efficacy of cost-benefit analysis in comparison to moral rules. In this commentary, I suggest that those very same limits apply to decision making in general. Cost-benefit analysis may be the best way to arrive at decisions under a set of “closed-world assumptions” like those described by Bennis et al. But those assumptions virtually never hold, and in the absence of those assumptions, cost-benefit analysis often substitutes counting for thinking.
Situated Social Identities Constrain Morally Defensible Choices: Commentary on Bennis, Medin, & Bartels (2010)
Authors: Tetlock Philip E. , Mitchell Gregory
Published: March 2010

Conceptual distinctions that loom large to philosophers—such as the distinction between utilitarian and deontic decision norms—may be far less salient to most other mortals. Building on an intuitive-politician model of judgment and choice and on the empirical work reported by Bennis, Medin, and Bartels (2010, this issue), we argue that the overriding goal of most decision makers in the paradigms under scrutiny is to offer judgments that are readily defensible and that reinforce their social identities as both cognitively flexible (responsive to evidence and cost-benefit considerations) and morally principled (prepared to defend sacred values and censure those who do not). People are best classified neither as utilitarians nor Kantians but rather as pragmatic social beings embedded in complex cultural-political systems.