BRCA Challenge: BRCA Exchange as a global resource for variants in BRCA1 and BRCA2.

The BRCA Challenge is a long-term data-sharing project initiated within the Global Alliance for Genomics and Health (GA4GH) to aggregate BRCA1 and BRCA2 data to support highly collaborative research activities. Its goal is to generate an informed and current understanding of the impact of genetic variation on cancer risk across the iconic cancer predisposition genes, BRCA1 and BRCA2. Initially, reported variants in BRCA1 and BRCA2 available from public databases were integrated into a single, newly created site, www.brcaexchange.org. The purpose of the BRCA Exchange is to provide the community with a reliable and easily accessible record of variants interpreted for a high-penetrance phenotype. More than 20,000 variants have been aggregated, three times the number found in the next-largest public database at the project's outset, of which approximately 7,250 have expert classifications. The data set is based on shared information from existing clinical databases-Breast Cancer Information Core (BIC), ClinVar, and the Leiden Open Variation Database (LOVD)-as well as population databases, all linked to a single point of access. The BRCA Challenge has brought together the existing international Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) consortium expert panel, along with expert clinicians, diagnosticians, researchers, and database providers, all with a common goal of advancing our understanding of BRCA1 and BRCA2 variation. Ongoing work includes direct contact with national centers with access to BRCA1 and BRCA2 diagnostic data to encourage data sharing, development of methods suitable for extraction of genetic variation at the level of individual laboratory reports, and engagement with participant communities to enable a more comprehensive understanding of the clinical significance of genetic variation in BRCA1 and BRCA2.

From 2D to 3D patches on multifunctional particles: how microcontact printing creates a new dimension of functionality.

A straightforward approach for the precise multifunctional surface modification of particles with three-dimensional patches using microcontact printing is presented. By comparison to previous works it was possible to not only control the diameter, but also to finely tune the thickness of the deposited layer, opening up the way for three-dimensional structures and orthogonal multifunctionality. The use of PEI as polymeric ink, PDMS stamps for microcontact printing on silica particles and the influence of different solvents during particle release on the creation of functional particles with three-dimensional patches are described. Finally, by introducing fluorescent properties by incorporation of quantum dots into patches and by particle self-assembly via avidin-biotin coupling, the versatility of this novel modification method is demonstrated.

Physical Polyurethane Hydrogels via Charge Shielding through Acids or Salts.

Physical hydrogels with tunable stress-relaxation and excellent stress recovery are formed from anionic polyurethanes via addition of acids, monovalent salts, or divalent salts. Gel properties can be widely adjusted through pH, salt valence, salt concentration, and monomer composition. We propose and investigate a novel gelation mechanism based on a colloidal system interacting through charge repulsion and chrage shielding, allowing a broad use of the material, from acidic (pH 4-5.5) to pH-neutral hydrogels with Young's moduli ranging from 10 to 140 kPa.

Pulmonary Vein Isolation for Paroxysmal Atrial Fibrillation Using a Circular Multipolar Ablation Catheter: Safety and Efficacy Using Low-Power Settings.

INTRODUCTION: The circular irrigated decapolar nMARQ ablation catheter designed for treating atrial fibrillation (AF) has recently been recalled following two deaths due to esoatrial fistula. Injury to the esophagus has been previously reported in up to 50% of patients using 20-25 W unipolar radiofrequency (RF) energy. Low power of 15 W has been proposed to prevent this complication, but the efficacy of this strategy to avoid AF recurrence is unknown. METHODS AND RESULTS: Consecutive patients with drug-refractory, symptomatic AF were included. Under electroanatomical navigation, the nMARQ catheter was used to isolate all PVs by applying 15 W of unipolar RF simultaneously from up to 10 poles during 40 seconds. Multiple applications were used for each vein, until isolation was achieved. Follow-up was performed after a 2-month blanking period. A total of 50 patients (37 males, age 58 ± 10 years) were included. All PVs were acutely isolated without requiring touch-up by conventional ablation catheters. Pericardial effusion occurred in two patients, of whom one required periocardiocentesis. Right phrenic nerve palsy occurred in another patient, which partially resolved. There were no cases of esophageal fistula or stroke. After a follow-up of 15 ± 4 months, AF recurred in 27/50 (54%) patients. CONCLUSION: The recurrence rate of AF with 15 W unipolar applications is high. Despite use of low power, complications such as pericardial effusion and phrenic nerve palsy may occur.

Reorientation mechanisms of block copolymer/CdSe quantum dot composites under application of an electric field.

Time- and temperature-resolved in situ birefringence measurements were applied to analyze the effect of nanoparticles on the electric field-induced alignment of a microphase separated solution of poly(styrene)-block-poly(isoprene) in toluene. Through the incorporation of isoprene-confined CdSe quantum dots the reorientation behavior is altered. Particle loading lowers the order-disorder transition temperature, and increases the defect density, favoring nucleation and growth as an alignment mechanism over rotation of grains. The temperature dependent alteration in the reorientation mechanism is analyzed via a combination of birefringence and synchrotron SAXS. The detailed understanding of the effect of nanoparticles on the reorientation mechanism is an important prerequisite for optimization of electric-field-induced alignment of block copolymer/nanoparticle composites where the block copolymer guides the nanoparticle self-assembly into anisotropic structures.

Electrophysiological abnormalities in patients with paroxysmal atrial fibrillation in the absence of overt structural heart disease.

PURPOSE: The aim of the present study was to define the atrial electrical substrate in patients with paroxysmal atrial fibrillation (AF) occurring in the absence of overt structural heart disease and to assess if electrophysiological parameters could predict AF recurrence after radiofrequency ablation in this population. METHODS AND RESULTS: 45 consecutive patients (39 male, age 59 ± 10 years) with paroxysmal AF and without overt structural heart disease, referred for radiofrequency catheter ablation, were prospectively enrolled. A cohort of 12 age-matched patients without a history of AF, served as a control group. Atrial electrical substrate was assessed by P-wave signal-averaging, intracardiac conduction delays and refractory periods. Total P wave duration during signal-averaging was longer in patients with paroxysmal AF than in controls (140 ± 19 ms vs 123 ± 13 ms, p = 0.004). Patients with paroxysmal AF showed an increase in right intra-atrial (40.2 ± 11.3 ms vs 31.7 ± 11.8 ms, p = 0.02) and inter-atrial conduction delays (87.93 ± 22.0 ms vs 65.3 ± 15.6 ms, p = 0.001) in sinus rhythm. Refractory periods in the right atrium were longer in patients with paroxysmal AF (265 ± 44 ms vs 222 ± 32 ms, p = 0.002). After ablation, 22 patients had AF recurrence but showed no differences in electrophysiological parameters compared to patients without recurrence. CONCLUSION: Electrophysiological abnormalities are present in patients with paroxysmal AF without overt structural heart disease. Neither signal-averaged P-wave duration nor intracardiac atrial electrophysiology could predict arrhythmia recurrence after pulmonary vein isolation.

Usefulness of P-wave signal averaging to predict atrial fibrillation recurrences after electrical cardioversion.

BACKGROUND: Accurate markers of atrial fibrillation (AF) recurrences after electrical cardioversion (ECV) are lacking. This study was conducted to assess the value of P-wave signal averaging (SAPW) for predicting AF recurrences in a nonselected patients population submitted to ECV. METHODS: A total of 133 patients (107 males, 26 females, mean age 66 ± 9 years) were included after successful ECV for persistent AF (mean duration of AF 3.6 ± 2.2 months). The mean ejection fraction (EF) was 60 ± 9%, and left atrial (LA) diameter was 44 ± 6 mm. SAPW ECG was obtained immediately after ECV and patients were prospectively followed. RESULTS: During a mean follow-up of 8.9 ± 5.2 months, AF recurrences occurred in 40.6% (54/133). No SAPW parameters was statistically different between the group of patients with and the group without recurrences. Recurrences were less often observed in patients with a total P-wave duration <150 ms (16/52 or 31% vs 38/81 or 47% in patients with total P-wave duration ≥150 ms) but the difference was not statistically different (P = 0.07). P-wave duration was correlated with age (r = 0.32; P < 0.001) and left atrial diameter (r = 0.19; P = 0.02). Age, sex, structural heart disease, amiodarone therapy, or hypertension were not associated with AF recurrences but patients without recurrences had a shorter AF duration (P = 0.001) and more often had a history of previous ablation (P = 0.027). CONCLUSION: In this unselected "real-life" group of patients submitted to ECV for persistent AF, none of the SAPW parameters, including total filtered P-wave duration, was able to predict AF recurrences.

Value of P-wave signal averaging to predict atrial fibrillation recurrences after pulmonary vein isolation.

AIMS: Recurrences of atrial fibrillation (AF) after radiofrequency catheter ablation (RFCA) are usually caused by pulmonary vein (PV) re-conduction, by foci outside the PV or by previous electrical remodelling. Substrate alterations with conduction delays may be detected by signal-averaged P-wave analysis (SAPW). This study was conducted to assess the value of the SAPW to predict recurrences after RFCA in patients with paroxysmal or persistent AF. METHODS AND RESULTS: One hundred and two patients (59 ± 10 years, 83 males) underwent a first RFCA procedure for paroxysmal (n = 61) or persistent/long-standing persistent (n = 41) AF. A SAPW recording with measurement of total filtered P-wave duration (FPD), P-wave integral, and terminal root mean squared voltage was obtained immediately after the ablation procedure and the patients were prospectively followed. During a mean follow-up of 12 ± 7 months, recurrences occurred in 36 of 102 (35.3%) patients, 17 of 61 with paroxysmal AF, and 19 of 41 with persistent AF (P = 0.06). The FPD was significantly longer in patients with recurrences compared to those without (158 ± 22 vs. 140 ± 18 ms, P = 0.0008). The FPD was shorter in patients with paroxysmal AF compared with patients with persistent AF (142 ± 28 vs. 153 ± 20 ms, P = 0.03). A FPD of 140 ms was found to discriminate patients prone to recurrences (log-rank test, P = 0.008) with a sensitivity of 69%, a specificity of 53%, a positive predictive value of 45%, and a negative predictive value of 76%. CONCLUSION: A FPD >140 ms is a marker of AF recurrences after RFCA and probably reflects the extent of atrial remodelling.

Bone marrow transplantation improves hepatic fibrosis in Abcb4-/- mice via Th1 response and matrix metalloproteinase activity.

OBJECTIVE: Reports on the effects of bone marrow-derived cells on hepatic fibrosis are contradictory. Impaired fibrosis but increased inflammation has recently been demonstrated 10 weeks after bone marrow transplantation (BM-Tx) in Abcb4-/- mice. It is hypothesised that BM-Tx might have long-term therapeutic potential by altering the immunological and matrix remodelling processes leading to hepatic regeneration. METHODS: After lethal irradiation of recipient mice, BM cells from GFP+ donor mice (allogeneic Tx) or Abcb4-/- mice (syngeneic Tx) were transplanted via tail vein injection. Readouts were performed 2, 10 and 20 weeks after Tx. Liver integrity was assessed serologically and histologically. Surrogate markers for fibrogenesis, T helper (Th) response, inflammation, graft-versus-host disease and fibrolysis were analysed by quantitative real-time PCR, zymography and immunohistology. RESULTS: 20 weeks after syngeneic and allogeneic BM-Tx, hepatic grading and staging were significantly improved. In contrast, 2 weeks after BM-Tx inflammatory grading, expression of inflammatory cell markers and associated chemokines and their receptors were increased and subsequently declined. In parallel, CD8+/GFP+ donor-derived T cells infiltrated the liver 2 weeks after BM-Tx. The Th1 cyokine interferon γ was increased 2 and 10 weeks after BM-Tx whereas the Th2 associated interleukin 13 was not altered. The gene expression of matrix metalloproteinases MMP-2, MMP-7, MMP-9 and MMP-13 was transiently upregulated and MMP-9 protein remained elevated 20 weeks after BM-Tx with enhanced gelatinase activity located within the fibrotic areas. Neutrophils were identified as major sources of MMP-9. CONCLUSION: These results show that BM-Tx causes an antifibrotic Th1 response combined with transient inflammatory effects and subsequently upregulated MMP activity. Antifibrotic Th polarisation and prolonged proteolytic activity, especially of MMP-9, might be responsible for long-term amelioration of hepatic fibrosis.

Catheter ablation of arrhythmias in ebstein's anomaly: a multicenter study.

INTRODUCTION: In patients with Ebstein's anomaly (EA) arrhythmias are frequently encountered. Although most arrhythmias can be targeted with catheter ablation, specific issues render the procedure more challenging in EA. This study examines the mechanisms of the different arrhythmias related to EA and the outcome after catheter ablation. METHODS AND RESULTS: Clinical and procedural data of catheter ablation in patients with EA in 4 European centers were analyzed. In 32 patients (mean age 24 ± 15 years), 34 accessory pathways (APs), 8 intra-atrial reentry tachycardias (IART), 5 cavotricuspid isthmus-dependent atrial flutter (CTI-AFL), 2 focal atrial tachycardias, and 1 atrioventricular nodal reentry tachycardia were ablated. In 11 patients (34%), multiple ablation targets were present. Eighteen patients (56%) required multiple procedures either for repeat ablation of the same arrhythmia (n = 12), ablation of a different arrhythmia (n = 4), or both re-ablation of the same and of a different arrhythmia (n = 2). Procedural success rate after first ablation was 80% for APs and CTI-AFL ablation, and 100% for IART ablation. Redo procedures were necessary in 40% of the patients after ablation of an APs, and in 60% after CTI-AFL ablation, but in none of the patient with IART ablation. CONCLUSION: Most arrhythmias related to EA are amenable to catheter ablation. However, ablation procedures are challenging and the need for repeat procedure is particularly high, because some patients have multiple ablation targets and because of technical issues in relation with the dysplastic tricuspid annulus. In addition, several patients develop other arrhythmia mechanisms following ablation.

Utility of the surface electrocardiogram for confirming right ventricular septal pacing: validation using electroanatomical mapping.

AIMS: When targeting the interventricular septum during pacemaker implantation, the lead may inadvertently be positioned on the anterior wall due to imprecise fluoroscopic landmarks. Surface electrocardiogram (ECG) criteria of the paced QRS complex (e.g. negativity in lead I) have been proposed to confirm a septal position, but these criteria have not been properly validated. Our aim was to investigate whether the paced QRS complex may be used to confirm septal lead position. METHODS: Anatomical reconstruction of the right ventricle was performed using a NavX® system in 31 patients (70 ± 11 years, 26 males) to validate pacing sites. Surface 12-lead ECGs were analysed by digital callipers and compared while pacing from a para-Hissian position, from the mid-septum, and from the anterior free wall. RESULTS: Duration of the QRS complex was not significantly shorter when pacing from the mid-septum compared with the other sites. QRS axis was significantly less vertical during mid-septal pacing (18 ± 51°) compared with para-Hissian (38 ± 37°, P = 0.028) and anterior (53 ± 55°, P = 0.003) pacing, and QRS transition was intermediate (4.8 ± 1.3 vs. 3.8 ± 1.3, P < 0.001, and vs. 5.4 ± 0.9, P = 0.045, respectively), although no cut-offs could reliably distinguish sites. A negative QRS or the presence of a q-wave in lead I tended to be more frequent with anterior than with mid-septal pacing (9/31 vs. 3/31, P = 0.2 and 8/31 vs. 1/31, P = 1.0, respectively). CONCLUSION: No single ECG criterion could reliably distinguish pacing the mid-septum from the anterior wall. In particular, a negative QRS complex in lead I is an inaccurate criterion for validating septal pacing.

Low prevalence of atrial fibrillation in asymptomatic adults in Geneva, Switzerland.

AIMS: To determine the prevalence of atrial fibrillation (AF) in a population-based sample of adults. METHODS AND RESULTS: Between January 2005 and December 2007 individuals aged > or =50 years, residents of the city of Geneva, who had participated in a previous random survey were invited for follow-up examination. AF was assessed on a single resting 6-lead ECG. Reported prevalences were standardized for the age distribution of Canton Geneva. Overall participation was 72.8%. Twenty-nine cases of AF (22 men) were diagnosed among 3285 subjects (1696 men). The crude prevalence of AF (95% CI) was 0.88% (0.86, 0.90) overall, but higher in men [1.30% (1.26, 1.34)] than in women [0.44% (0.41, 0.47)]. The age-standardized AF prevalence was slightly higher [overall: 0.94% (0.91, 0.97), men: 1.23% (1.19, 1.27), women: 0.54% (0.47, 0.61)]. AF prevalence increased with age in both sexes. A 'history of suspected arterial embolism' (brain or legs) was higher in the AF cases (10.3 vs. 3.3%; P = 0.03). CONCLUSION: This population-based survey of a general Swiss population indicates that the prevalence of AF remains below 1%. These results are less alarming than those from previous studies based on patients seeking medical care.

Atrial fibrillation in Africa: clinical characteristics, prognosis, and adherence to guidelines in Cameroon.

AIMS: The purpose of this prospective study was to characterize the clinical profile of patients with atrial fibrillation (AF) in the urban population of a sub-Saharan African country and to assess how successfully current guidelines are applied in that context. METHODS AND RESULTS: This prospective study involved 10 cardiologists in Cameroon. Enrolment started on 1 June 2006 and ended on 30 June 2007. Consecutive patients were included if they were >18 years and AF was documented on an ECG during the index office visit. In this survey, 172 patients were enrolled (75 males and 97 females; mean age 65.8 +/- 13 years). The prevalence of paroxysmal, persistent, and permanent AF was 22.7, 21.5, and 55.8%, respectively. Underlying cardiac disorders, present in 156/172 patients (90.7%), included hypertensive heart disease (47.7%), valvular heart disease (25.6%), dilated cardiomyopathy (15.7%), and coronary artery disease (6%). A rate-control strategy was chosen in 83.7% of patients (144 of 172) and drugs most commonly used were digoxin and amiodarone. The mean CHADS(2) score was 1.9 +/- 1.1 and 158 of 172 patients (91.9%) had a CHADS(2) score > or =1. Among patients with an indication for oral anticoagulation (OAC), only 34.2% (54 of 158) actually received it. During a follow-up of 318 +/- 124 days, 26 of 88 patients died (29.5%), essentially from a cardiovascular cause (15 of 26). Ten patients (16.1%) had a non-lethal embolic stroke and 23 (26.1%) had symptoms of severe congestive heart failure. CONCLUSION: Clinical presentation of AF in Cameroon is much more severe than in developed countries. A rate-control strategy is predominant in Cameroon and OAC is prescribed in only 34.2% of eligible patients, despite a high CHADS(2) score at inclusion. Death and stroke rate at 1 year are very high in Cameroon possibly because of a lower use of OAC, and a higher prevalence of rheumatic mitral disease and of more severe co-morbidities.

Early prediction of circulatory failure in the intensive care unit using machine learning.

Intensive-care clinicians are presented with large quantities of measurements from multiple monitoring systems. The limited ability of humans to process complex information hinders early recognition of patient deterioration, and high numbers of monitoring alarms lead to alarm fatigue. We used machine learning to develop an early-warning system that integrates measurements from multiple organ systems using a high-resolution database with 240 patient-years of data. It predicts 90% of circulatory-failure events in the test set, with 82% identified more than 2 h in advance, resulting in an area under the receiver operating characteristic curve of 0.94 and an area under the precision-recall curve of 0.63. On average, the system raises 0.05 alarms per patient and hour. The model was externally validated in an independent patient cohort. Our model provides early identification of patients at risk for circulatory failure with a much lower false-alarm rate than conventional threshold-based systems.

Backup right ventricular pacing with a 0.035'' guidewire during implantation of left ventricular leads.

INTRODUCTION: During implantation of biventricular devices, manipulation of the guiding sheath during localization of the coronary sinus (CS) ostium may result in injury to the right bundle and complete heart block. A preventive measure is to implant the right ventricular (RV) lead first, though this may interfere with manipulation of the guiding sheath and dislodge the permanent lead. We tested the feasibility of backup pacing with a 0.035'' guidewire, advanced through the guiding sheath during CS localization. METHODS: One hundred six consecutive patients (mean age = 70 +/- 11 years, 81 men) undergoing biventricular device implantation were studied. A 0.035'' guidewire with an uncoated tip was advanced into the right ventricle through the guiding sheath, and unipolar capture threshold, R-wave sensing amplitude, and pacing impedance were measured. RESULTS: RV pacing was successful in all patients. The mean capture threshold was 3.8 +/- 2.1 V/0.5 ms, R-wave amplitude 5.4 +/- 4.3 mV, and pacing impedance 226 +/- 78 Omega. No arrhythmia was observed during the tests. Two patients developed complete heart block during the implant procedure and were successfully paced temporarily using the 0.035'' guidewire. CONCLUSION: Temporary RV pacing, using a 0.035'' guidewire within the guiding sheath, is a simple, reliable, and safe method that allows backup pacing in case of traumatic complete heart block, developing during the implantation of biventricular devices.

Effect of the lipoxygenase inhibitor baicalein on bone tissue and bone healing in ovariectomized rats.

BACKGROUND: Osteoporosis is one of the world's major medical burdens in the twenty-first century. Pharmaceutical intervention currently focusses on decelerating bone loss, but phytochemicals such as baicalein, which is a lipoxygenase inhibitor, may rescue bone loss. Studies evaluating the effect of baicalein in vivo are rare. METHODS: We administered baicalein to sixty-one three-month-old female Sprague-Dawley rats. They were divided into five groups, four of which were ovariectomized (OVX) and one non-ovariectomized (NON-OVX). Eight weeks after ovariectomy, bilateral tibial osteotomy with plate osteosynthesis was performed and bone formation quantified. Baicalein was administered subcutaneously using three doses (C1: 1 mg/kg BW; C2: 10 mg/kg BW; and C3: 100 mg/kg BW) eight weeks after ovariectomy for four weeks. Finally, femora and tibiae were collected. Biomechanical tests, micro-CT, ashing, histological and gene expression analyses were performed. RESULTS: Biomechanical properties were unchanged in tibiae and reduced in femora. In tibiae, C1 treatment enhanced callus density and cortical width and decreased callus area. In the C3 group, callus formation was reduced during the first 3 weeks after osteotomy, correlating to a higher mRNA expression of Osteocalcin, Tartrate-resistant acid phosphatase and Rankl. In femora, baicalein treatments did not alter bone parameters. CONCLUSIONS: Baicalein enhanced callus density and cortical width but impaired early callus formation in tibiae. In femora, it diminished the biomechanical properties and calcium-to-phosphate ratio. Thus, it is not advisable to apply baicalein to treat early bone fractures. To determine the exact effects on bone healing, further studies in which baicalein treatments are started at different stages of healing are needed.

Identification of new drug classification terms in textual resources.

UNLABELLED: Knowledge about biological effects of small molecules helps in the understanding of biological processes and supports the development of new therapeutic agents. DrugBank is a high quality database providing such information about drugs that contains annotation of drug effects and classification of therapeutic effects. However, to broaden the scope of such a database in classifying and annotating drugs, systems for automatic extraction of classification terms and the corresponding annotation of drugs are needed. We have developed an approach for the identification of new terms used in unstructured text that provide information about drug properties. It is based on the identification and extraction of phrases corresponding to lexico-syntactic patterns--so-called Hearst patterns that contain drug names and directly related drug annotation terms. Such phrases could be identified with a high performance in DrugBank text (0.89 F-score) and in Medline abstracts (0.83 F-score). In comparison to DrugBank annotation terminology, a huge amount of new drug annotation terms could be found. The evaluation of terms extracted from Medline showed that 29-53% of them are new valid drug property terms. They could be assigned to existing and new drug property classes not provided by the DrugBank drug annotation. We come to the conclusion that our system can support database content update by providing additionally drug descriptions of pharmacological effects not yet found in databases like DrugBank. Moreover, we propose that automatic normalization of terms improves the annotation and the retrieval of relevant database entries. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Atrial fibrillation management by practice cardiologists: a prospective survey on the adherence to guidelines in the real world.

AIMS: The purpose of this prospective study was to characterize the clinical profile of patients with atrial fibrillation (AF) in cardiology practice and to assess how successfully guidelines have been implemented in real-world practice. METHODS AND RESULTS: This prospective study involved 23 cardiologists established in office practice in Geneva. Enrollment started on 1 January 2005 and ended on 31 December 2005. Consecutive patients were included if they were >18 years and had AF documented on an ECG during the index office visit or during the preceding month. In this survey, 622 ambulatory patients were enrolled (390 males and 232 females; mean age 69.8 +/- 11.8 years). The prevalence of paroxysmal, persistent, and permanent AF was 35, 18, and 47%, respectively. Underlying cardiac disorders present in 513 patients (82%) included hypertensive heart disease (30%), valvular heart disease (27%), coronary artery disease (18%), and myocardial disease (11%). A rate-control strategy was chosen in 53% of the patients (331/622). The mean CHADS(2) score was 1.43 +/- 1.24, and 458/622 patients (73.6%) had a CHADS(2) score >or=1. Among patients with an indication to oral anticoagulant therapy (OAT), 88% (403/458) effectively received it. The rate of OAT was closely correlated with an increasing CHADS(2) score, particularly with patients age (72, 81, and 87% for patients <65, 65-75, and >75 years of age, respectively). True contraindication for OAT was present in 4% (18/458). In the low-risk group (CHADS(2) score = 0), 58% were prescribed OAT, but in 37% of them only for a short period of time (cardioversion/ablation). After a follow-up of 396 +/- 109 days, 72% of the study group (410/570) was still treated by OAT. During follow-up, 23/570 patients died (4%), essentially from a cardiovascular cause (15/23), 15 had a non-lethal embolic stroke (2.7%), and 8 had significant bleeding complications (1.5%). CONCLUSION: This study shows one of the highest OAT prescription rates for AF reported until now and demonstrates how successfully guidelines can be applied in the real world. A definite overinterpretation of current guidelines is observed in low-risk patients with AF. True contraindication for OAT (4%) and significant bleeding during OAT (1.5%) were rare.

Virtual high throughput screening (vHTS) on an optical high speed testbed.

Malaria remains a global health concern, which kills over a million people each year. In this paper we present work extending the approach of the WISDOM initiative by focusing on the problems noticed during the first WISDOM challenge against malaria and test the newly established, high bandwidth optical Grid environment VIOLA for advanced bioinformatics applications using the UNICORE middleware service. In addition we present an approach to reduce the size of the compound database to improve the efficiency of the screening.