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.

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.

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.

Characteristics of microcontact printing with polyelectrolyte ink for the precise preparation of patches on silica particles.

This publication demonstrates the abilities of a precise and straightforward microcontact printing approach for the preparation of patchy silica particles. In a broad particle size range, it is possible to finely tune the number and parameters of three-dimensional patches like diameter and thickness using only polyethyleneimine ink, poly(dimethoxysilane) as stamp material and a suitable release solvent.

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.

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.

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.

Noninvasive pacing study via pacemakers and implantable cardioverter-defibrillators for differentiating right from left atrial flutter.

BACKGROUND: Patients with atrial flutter who are implanted with a pacemaker (PM) or implantable cardioverter-defibrillator (ICD) present with the opportunity to perform a noninvasive pacing study (NIPS) using the right atrial pacing lead to differentiate right from left atrial flutter. OBJECTIVES: The purpose of this study was to study the feasibility and accuracy of NIPS to distinguish right from left atrial flutter. METHODS: We enrolled consecutive patients scheduled for an electrophysiological study or ablation procedure who were in atrial flutter and who were implanted with a PM or ICD with a functional atrial lead in the right atrial appendage. Flutter tachycardia cycle lengths (TCLs) and postpacing intervals (PPIs) were measured noninvasively via the device during the procedure. RESULTS: A total of 48 (67%) patients were studied. Right atrial flutter was present in 32 patients (of whom 29 had typical cavotricuspid isthmus-dependent flutter) and 16 (33%) patients had left atrial flutter. A PPI-TCL interval of >100 ms was 100% specific and 81% sensitive to identify left atrial flutter, with an overall accuracy of 94% and a c statistic of 0.94 (95% confidence interval 0.87-1.00). A PPI-TCL interval of ≤100 ms had a positive predictive value of 86% for diagnosing typical flutter. CONCLUSION: NIPS via PMs and ICDs with a PPI-TCL interval of >100 ms can reliably identify left atrial flutter (although we have only validated this cutoff for leads implanted in the right atrial appendage). This simple maneuver may allow planning for left-sided access and may avoid an unnecessary invasive electrophysiological study if left atrial flutter ablation is not to be considered.

When inappropriate becomes beneficial.

We report the case of a young man who accidentally received a prolonged electric discharge from electrical wires and released the electric source with the help of an inappropriate shock from his implantable cardioverter-defibrillator (ICD), after misinterpretation of the electrical signal by the device as a ventricular tachycardia. This case illustrates the "electrical noise" phenomenon, and underscores the need for precautions for patients with an ICD and their physicians.

Annotated chemical patent corpus: a gold standard for text mining.

Exploring the chemical and biological space covered by patent applications is crucial in early-stage medicinal chemistry activities. Patent analysis can provide understanding of compound prior art, novelty checking, validation of biological assays, and identification of new starting points for chemical exploration. Extracting chemical and biological entities from patents through manual extraction by expert curators can take substantial amount of time and resources. Text mining methods can help to ease this process. To validate the performance of such methods, a manually annotated patent corpus is essential. In this study we have produced a large gold standard chemical patent corpus. We developed annotation guidelines and selected 200 full patents from the World Intellectual Property Organization, United States Patent and Trademark Office, and European Patent Office. The patents were pre-annotated automatically and made available to four independent annotator groups each consisting of two to ten annotators. The annotators marked chemicals in different subclasses, diseases, targets, and modes of action. Spelling mistakes and spurious line break due to optical character recognition errors were also annotated. A subset of 47 patents was annotated by at least three annotator groups, from which harmonized annotations and inter-annotator agreement scores were derived. One group annotated the full set. The patent corpus includes 400,125 annotations for the full set and 36,537 annotations for the harmonized set. All patents and annotated entities are publicly available at www.biosemantics.org.

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.

Slower heart rate and altered rate dependence of ventricular repolarization in patients with lone atrial fibrillation.

BACKGROUND: Electrophysiological alterations in atrial fibrillation (AF) may be genetically based and may lead to changes in ventricular repolarization. Short QT syndrome is a rare channelopathy with abbreviated ventricular repolarization and a propensity for AF. AIMS: To determine if minor unrecognized forms of short QT syndrome can explain some cases of lone AF. METHODS: We prospectively compared QT intervals in 66 patients with idiopathic lone AF and 132 age- and sex-matched controls. QT intervals were measured during sinus rhythm in each of the 12 surface electrocardiogram leads and corrected using Bazett's formula (QTc). QT intervals were also corrected using other formulae. Uncorrected QT and heart rate regression lines were compared between AF patients and controls. RESULTS: AF patients presented with a slower resting heart rate (64 ± 10 beats per minute [bpm] vs 69 ± 9 bpm; P=0.0006). QTc intervals were shorter in AF patients in 11/12 electrocardiogram leads (significant in 7/12, borderline in 2/12; mean QTc 381 ± 21 ms vs 388 ± 22 ms; P=0.02). QTc intervals were also shorter in AF patients, significantly or not, using other correction formulae. For similar heart rates, uncorrected QT intervals were shorter in patients when heart rates were greater than 70 bpm and longer when heart rates were less than 60 bpm. AF patients displayed steeper QT/heart rate regression line slopes than controls (P=0.009). CONCLUSION: Heart rate is significantly slower and the rate dependence of ventricular repolarization is significantly altered in patients with lone AF compared with controls. Further study is warranted to determine if AF induces subsequent ventricular repolarization changes or if these modifications are caused by an underlying primary electrical disease.

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.

Mucormycosis of the head and neck.

INTRODUCTION: Mucormycosis of the head and neck is a rare disease increasingly occurring in immunocompromised patients. We report on two cases with different outcomes. CASE REPORTS: A 63-year-old female presented with a recently developed deformation of her right cheek and nose combined with a loosening of the teeth. Further examination revealed mucormycosis of the maxilla. Hemimaxillectomy and secondary bony reconstruction with oral rehabilitation were performed. The second patient was a 54-year-old male who suffered from multiple myeloma. After receiving an allogeneic haematopoietic stem cell transplant, he developed a necrotizing infection of the right midface. Histopathological investigation confirmed the diagnosis of mucormycosis. The patient died one day after radical surgical resection. DISCUSSION: These two cases demonstrate the variability of mucormycosis. Although slow progression of the disease is possible, a high level of attentiveness and expedient treatment are necessary due to the high risk of a devastating course.