Development of an AI based automated analysis of pediatric Apple Watch iECGs.

Introduction: The Apple Watch valuably records event-based electrocardiograms (iECG) in children, as shown in recent studies by Paech et al. In contrast to adults, though, the automatic heart rhythm classification of the Apple Watch did not provide satisfactory results in children. Therefore, ECG analysis is limited to interpretation by a pediatric cardiologist. To surmount this difficulty, an artificial intelligence (AI) based algorithm for the automatic interpretation of pediatric Apple Watch iECGs was developed in this study. Methods: A first AI-based algorithm was designed and trained based on prerecorded and manually classified i.e., labeled iECGs. Afterward the algorithm was evaluated in a prospectively recruited cohort of children at the Leipzig Heart Center. iECG evaluation by the algorithm was compared to the 12-lead-ECG evaluation by a pediatric cardiologist (gold standard). The outcomes were then used to calculate the sensitivity and specificity of the Apple Software and the self-developed AI. Results: The main features of the newly developed AI algorithm and the rapid development cycle are presented. Forty-eight pediatric patients were enrolled in this study. The AI reached a specificity of 96.7% and a sensitivity of 66.7% for classifying a normal sinus rhythm. Conclusion: The current study presents a first AI-based algorithm for the automatic heart rhythm classification of pediatric iECGs, and therefore provides the basis for further development of the AI-based iECG analysis in children as soon as more training data are available. More training in the AI algorithm is inevitable to enable the AI-based iECG analysis to work as a medical tool in complex patients.

Fast two-qubit logic with holes in germanium.

Universal quantum information processing requires the execution of single-qubit and two-qubit logic. Across all qubit realizations1, spin qubits in quantum dots have great promise to become the central building block for quantum computation2. Excellent quantum dot control can be achieved in gallium arsenide3-5, and high-fidelity qubit rotations and two-qubit logic have been demonstrated in silicon6-9, but universal quantum logic implemented with local control has yet to be demonstrated. Here we make this step by combining all of these desirable aspects using hole quantum dots in germanium. Good control over tunnel coupling and detuning is obtained by exploiting quantum wells with very low disorder, enabling operation at the charge symmetry point for increased qubit performance. Spin-orbit coupling obviates the need for microscopic elements close to each qubit and enables rapid qubit control with driving frequencies exceeding 100 MHz. We demonstrate a fast universal quantum gate set composed of single-qubit gates with a fidelity of 99.3 per cent and a gate time of 20 nanoseconds, and two-qubit logic operations executed within 75 nanoseconds. Planar germanium has thus matured within a year from a material that can host quantum dots to a platform enabling two-qubit logic, positioning itself as an excellent material for use in quantum information applications.

Spin Lifetime and Charge Noise in Hot Silicon Quantum Dot Qubits.

We investigate the magnetic field and temperature dependence of the single-electron spin lifetime in silicon quantum dots and find a lifetime of 2.8 ms at a temperature of 1.1 K. We develop a model based on spin-valley mixing and find that Johnson noise and two-phonon processes limit relaxation at low and high temperature, respectively. We also investigate the effect of temperature on charge noise and find a linear dependence up to 4 K. These results contribute to the understanding of relaxation in silicon quantum dots and are promising for qubit operation at elevated temperatures.

Gate-controlled quantum dots and superconductivity in planar germanium.

Superconductors and semiconductors are crucial platforms in the field of quantum computing. They can be combined to hybrids, bringing together physical properties that enable the discovery of new emergent phenomena and provide novel strategies for quantum control. The involved semiconductor materials, however, suffer from disorder, hyperfine interactions or lack of planar technology. Here we realise an approach that overcomes these issues altogether and integrate gate-defined quantum dots and superconductivity into germanium heterostructures. In our system, heavy holes with mobilities exceeding 500,000 cm2 (Vs)-1 are confined in shallow quantum wells that are directly contacted by annealed aluminium leads. We observe proximity-induced superconductivity in the quantum well and demonstrate electric gate-control of the supercurrent. Germanium therefore has great promise for fast and coherent quantum hardware and, being compatible with standard manufacturing, could become a leading material for quantum information processing.

Blood group O: A novel risk factor for increased postpartum blood loss?

INTRODUCTION: Blood group O is known to be associated with lower levels of von Willebrand factor (VWF) and with increased bleeding complications. The influence of blood group O on postpartum blood loss was assessed by a few studies, however, without adjustment for important obstetric risk factors for postpartum blood loss. AIM: Aim of this study was to investigate whether women with blood group O exhibit increased blood loss after delivery in consideration of established risk factors for postpartum bleeding. METHODS: A total of 1487 patients were prospectively included into this cohort study. Blood loss was assessed by estimated blood loss (in mL), and drop of haemoglobin (Δ haemoglobin) was calculated. Association of blood loss with risk factors (such as blood group O, cervical tears, morbidly adherent placenta, placenta praevia and uterine atony amongst others) was assessed with appropriate tests. Significant variables were entered into a stepwise multivariate regression analysis. RESULTS: Women with blood group O showed a significantly higher blood loss when compared to women with blood group non-O (529.2 mL ± 380.4 mL and 490.5 mL ± 276.4 mL, respectively, P = .024)). The increased blood loss in women with blood group O remained significant after multivariate regression analysis (difference 47 mL, P = .019). CONCLUSION: This is the first study reporting significantly increased blood loss following delivery in women with blood group O after adjustment for major risk factors for postpartum blood loss. Albeit having a statistically significant, but clinically minor effect on absolute blood loss, blood group O carriers may suffer from aggravated bleeding in the presence of additional obstetric bleeding pathologies.

ATSAS 2.8: a comprehensive data analysis suite for small-angle scattering from macromolecular solutions.

ATSAS is a comprehensive software suite for the analysis of small-angle scattering data from dilute solutions of biological macromolecules or nanoparticles. It contains applications for primary data processing and assessment, ab initio bead modelling, and model validation, as well as methods for the analysis of flexibility and mixtures. In addition, approaches are supported that utilize information from X-ray crystallography, nuclear magnetic resonance spectroscopy or atomistic homology modelling to construct hybrid models based on the scattering data. This article summarizes the progress made during the 2.5-2.8 ATSAS release series and highlights the latest developments. These include AMBIMETER, an assessment of the reconstruction ambiguity of experimental data; DATCLASS, a multiclass shape classification based on experimental data; SASRES, for estimating the resolution of ab initio model reconstructions; CHROMIXS, a convenient interface to analyse in-line size exclusion chromatography data; SHANUM, to evaluate the useful angular range in measured data; SREFLEX, to refine available high-resolution models using normal mode analysis; SUPALM for a rapid superposition of low- and high-resolution models; and SASPy, the ATSAS plugin for interactive modelling in PyMOL. All these features and other improvements are included in the ATSAS release 2.8, freely available for academic users from https://www.embl-hamburg.de/biosaxs/software.html.

Quadrupole shift of nuclear magnetic resonance of donors in silicon at low magnetic field.

Shifts from the expected nuclear magnetic resonance frequencies of antimony and bismuth donors in silicon of greater than a megahertz are observed in electrically detected magnetic resonance spectra. Defects created by ion implantation of the donors are discussed as the source of effective electric field gradients generating these shifts via quadrupole interaction with the nuclear spins. The experimental results are modeled quantitatively by molecular orbital theory for a coupled pair consisting of a donor and a spin-dependent recombination readout center.

[Primary liver tumours in childhood]. / Primäre Lebertumoren im Kindesalter.

The reported prevalence of focal liver lesions in adult patients and children is different. The article discusses pediatric liver tumors under the criteria of histopathology and contrast enhanced ultrasound (CEUS) features. Aim of this article is also to support the already established Pediatric Registry of the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) to collect data on safety and applications of ultrasound contrast agents in children (www.efsumb.org).

von Willebrand factor, clotting factors, and clotting inhibitors in apheresis platelet concentrates.

BACKGROUND: Apheresis platelet concentrates (APCs) are usually stored in citrated plasma at 22°C. The stability of coagulation proteins-von Willebrand factor (vWF), clotting factors (CFs), and their inhibitors-has often been described in association with the storage of thawed plasma. However, fewer data are available regarding changes in APCs. STUDY DESIGN AND METHODS: We measured CF activities and inhibitors in APCs on the day of manufacture (Day 0) and on Days 4, 5, and 7. vWF was determined by measuring vWF antigen (vWF:Ag) and vWF ristocetin cofactor (vWF:RCo) and by multimer analysis. RESULTS: Twenty-one PCs obtained by plateletpheresis were studied. Major changes were observed for Factor (F)VIII (37% loss of activity within 4 days), FV (20% within 4 days), and protein S (76% within 4 days). All other CF activities remained higher than 80% over the 7 days. Fibrinogen and the inhibitors antithrombin and protein C remained quite stable. FXI, FXII, and FXIII actually increased during storage (8, 11, and 12% within 4 days). vWF:Ag increased during storage of APCs by 2% per day, with a relative loss of vWF:RCo and high-molecular-weight multimers. CONCLUSION: Even after 7 days of storage at 22°C, the hemostatic potential of the plasma content in APCs was roughly preserved. The increase in FXII antigen indicates that this CF may also be stored in platelets; however, this has not yet been described.

Nonlinear pulse propagation in a quantum dot laser.

We investigate the nonlinear propagation of an ultra-short, 150 fs, optical pulse along the waveguide of a quantum dot (QD) laser operating above threshold. We demonstrate that among the various nonlinear processes experienced by the propagating pulse, four-wave mixing (FWM) between the pulse and the two oscillating counter-propagating cw fields of the laser is the dominant one. FWM has two important consequences. One is the creation of a spectral hole located in the vicinity of the cw oscillating frequency. The width of the spectral hole is determined by an effective carrier and gain relaxation time. The second is a modification of the shape of the trailing edge of the pulse. The wave mixing involves first and second order processes which result in a complicated interaction among several fields inside the cavity, some of which are cw while the others are time varying, all propagating in both directions. The nonlinear pulse propagation is analyzed using two complementary theoretical approaches. One is a semi-analytical model which considers only the wave mixing interaction between six field components, three of which propagate in each direction (two cw fields and four time-varying signals). This model predicts the deformation of the tail of the output signal by a secondary idler wave, produced in a cascaded FWM process, which co-propagates with the original injected pulse. The second approach is a finite-difference time-domain simulation, which considers also additional nonlinear effects, such as gain saturation and self-phase modulation. The theoretical results are confirmed by a series of experiments in which the time dependent amplitude and phase of the pulse after propagation are measured using the cross-frequency-resolved optical gating technique.

Desmopressin testing in haemophilia A patients and carriers: results of a multi centre survey.

INTRODUCTION: Desmopressin (DDAVP) testing (DT) in patients (pts) with haemophilia A (HA) and carriers (CHA) is up to now not standardized. This prompted us to evaluate results of DT carried out between 1996 and 2011 in centres of the Competence Network Haemorrhagic Diatheses East. PATIENTS AND METHOD: An increase of the factor VIII activity (FVIII) above 50% or at least the two fold of initial values within 120 min after DDAVP was defined as complete response (CR). Data from 80 patients (31 children, 49 adults) of whom 64 suffered from HA (sub-HA: n=48; mild: n=14; moderate: n=2) and 16 patients CHA were evaluated. RESULTS: In 34 patients DDAVP was given i.v. (dose range: 0.26-0.6 µg/kg body weight, mean: 0.33), in 31 intranasally (i.n. 300-600 µg) and in 15 s.c. (15-40 µg). The maximal FVIII increase was reached 60 min after DDAVP. For i.v. application the mean FVIII increase was 3.1-fold, for i.n. 2.1-fold and for s.c. 2.4-fold. A CR was detected in 71 patients, a non-response in 9. Mild side effects such as flush, headaches or nausea were observed in 11 patients (14%). CONCLUSION: For desmopressin testing in patients with haemophilia A and carriers i.v. application at 0.3 µg/kg body weight and the determination of FVIII before and 60 min after desmopressin infusion is recommended.

An extensive comparison of quantitative trait Loci mapping methods.

BACKGROUND: The choices of study design and statistical approach for mapping a quantitative trait (QT) are of great importance. Larger sibships and a study design based upon phenotypically extreme siblings can be expected to have a greater statistical power. On the other hand, selected samples and/or deviation from normality can influence the robustness and power. Unfortunately, the effects of violation of multivariate normality assumptions and/or selected samples are only known for a limited number of methods. Some recommendations are available in the literature, but an extensive comparison of robustness and power under several different conditions is lacking. METHODS: We compared eight freely available and commonly applied QT mapping methods in a Monte-Carlo simulation study under 36 different models and study designs (three genetic models, three selection schemes, two family structures and the possible effect of deviation from normality). RESULTS: Empirical type I error fractions and empirical power are presented and explained as a whole and for each method separately, followed by a thorough discussion. CONCLUSIONS: The results from this extensive comparison could serve as a valuable source for the choice of the study design and the statistical approach for mapping a QT.

[Desmopressin testing in children with von Willebrand syndrome in haemostaseologic centers of Saxonia, Saxonia-Anhalt and Thuringia]. / Desmopressin-Tests bei Kindern mit von-Willebrand-Syndrom in den Gerinnungszentren Sachsens, Sachsen-Anhalts und Thüringens.

The influence of desmopressin on hemostasis is mediated by the release of von Willebrand factor and of coagulation factor VIII from vascular endothelium. The necessity of testing desmopressin effectiveness on hemostasis is a matter of controversy and the performance of the test is not yet standardized. For this reason the desmopressin tests in 114 children with von Willebrand syndrome (type 1, n=98; type 2A, n=12; type 2M, n=2; type 2N, n=2) carried out in 7 paediatric haemostaseologic centers were retrospectively analyzed. The effectiveness of desmopressin was assessed using defined response criteria. As expected, the test performance showed a wide variation among the centers. In 99 children desmopressin was given intravenously as a short infusion at a dosage ranging from 0.25 to 0.41 microg/kg and in 15 intranasally at an absolute dose of 40 to 300 microg. The points of time for blood taking after desmopressin application ranged from 0.5 to 12 h. The absent desmopressin response in 7 patients (6%) and the partial response in 15 indicate the necessity of testing desmopressin effectiveness before the first therapeutic use. The application of desmopressin was well tolerated by the patients.

Single nucleotide polymorphisms in Brahman steers and their association with carcass and tenderness traits.

Data from purebred Brahman steers (N = 467) were used to study the association of single nucleotide polymorphisms (SNP) with carcass traits and measures of tenderness. Fall weaned calves were grazed and fed in a subtropical environment and then harvested for processing in a commercial facility. Carcass data were recorded 24 h postmortem. Muscle samples and primal ribs were obtained to measure calpastatin activity and shear force. DNA was used to determine genotypes of thyroglobulin (TG5), calpastatin (CAST) and mu-calpain (CAPN 316 and CAPN 4751) SNP. Minor allele frequencies for CAST, CAPN 316 and CAPN 4751 were 0.342, 0.031, and 0.051, respectively. CAST genotypes were associated with calpastatin enzyme activity (P < 0.01) and shear force of steaks aged for 14-day postmortem (P < 0.05). CAPN 316 genotypes were also associated with variation in shear force of steaks aged for 14 days (P < 0.05). CAPN 4751 genotypes approached significance for association with shear force of steaks after 7 and 14 days (P < 0.08). Genotypes for TG5 were non-polymorphic (i.e., minor allele frequency = 0.004) and omitted from further analyses. Neither CAST nor CAPN SNP was associated with variation in other carcass traits.

Intracranial germinoma as a very rare cause of panhypopituitarism in a 23-year old man.

A 23 year-old patient was referred to the endocrine outpatient clinic with the suspicion of diabetes insipidus as he complained of nycturia and polydipsia since 2-3 months. Further he presented with nausea, vomiting, loss of appetite, rapid weight loss, diffuse body pain and fatigue. No headache, blurred vision, or fever were reported. The clinical examination showed sexual infantilism (poor beard, pubic and axillary hair growth, small testis). The patient's skin was strikingly pale as well as dry and scaly. Lymph node palpation was unremarkable. Endocrine evaluation revealed diabetes insipidus as well as complete anterior pituitary insufficiency. MR imaging demonstrated contrast-enhancing mass lesions at the pineal gland, hypothalamus, and anterior horn of lateral ventricles bilaterally. The localization pattern deemed to be highly suspicious for intracranial germinoma. As beta-HCG and AFP were negative in serum and cerebrospinal fluid the diagnosis of germinoma was confirmed histologically. After radiotherapy with cranio-spinal radiation therapy with 24 Gy followed by two weeks of local tumor boost with 16 Gy, the posttherapy MRI scan indicated complete tumor removal. This case demonstrates a very rare and potentially curable tumor as the cause of panhypopituitarism in adults.

Influence of Angus and Belgian Blue bulls mated to Hereford x Brahman cows on growth, carcass traits, and longissimus steak shear force.

Steers and heifers were generated from Angus (A) and Belgian Blue (BB) sires mated to Brahman x Hereford (B x H) F(1) cows to characterize their growth, carcass traits, and LM shear force. A total of 120 B x H cows purchased from 2 herds and 35 bulls (14 A and 21 BB) produced calves during the 5-yr project. After the stocker phase, a representative sample of A- and BB-sired heifers and steers were transported to the Iberia Research Station to be fed a high-concentrate diet. The remaining cattle were transported to a commercial feedlot facility. Each pen of cattle from the commercial feedlot was slaughtered when it was estimated that heifers and steers had 10 mm of fat or greater. The BB-sired calves were heavier at birth (P < 0.01) than the A-sired calves. During the feedlot phase, the A-sired calves gained more BW (P < 0.05) than the BB-sired calves. The BB-sired calves had heavier (P < 0.01) carcass weights than the A-sired calves. This was due to a combination of a heavier final BW and greater dressing percent. Because of their greater muscling and reduced (P < 0.01) fat, carcasses from BB-sired calves had greater yield (P < 0.01) compared with carcasses from A-sired calves. Carcasses from A-sired calves had a greater (P < 0.01) marbling score and greater (P < 0.01) USDA quality grade than carcasses from BB-sired calves. Tenderness, as measured by shear force of the steaks aged for 7 d, was similar for A- and BB-sired calves. However, steaks aged for 14 d from the A-sired calves had a reduced shear force (P < 0.01) compared with steaks from the BB-sired calves. Steer calves were heavier (P < 0.01) at birth and weaning, and had more total BW gain in the feedlot, which resulted in a heavier final BW and HCW compared with the heifers. Steer carcasses also had greater marbling scores and quality grades, whereas the heifer carcasses had larger LM area per 100 kg of carcass weight. In conclusion, the BB-sired calves had heavier carcass weights and greater cutability, whereas the A-sired calves had a greater degree of marbling and greater quality grade, and steaks from carcasses of A-sired calves were more tender as measured by shear force at 14 d.

Automated sample-changing robot for solution scattering experiments at the EMBL Hamburg SAXS station X33.

There is a rapidly increasing interest in the use of synchrotron small-angle X-ray scattering (SAXS) for large-scale studies of biological macromolecules in solution, and this requires an adequate means of automating the experiment. A prototype has been developed of an automated sample changer for solution SAXS, where the solutions are kept in thermostatically controlled well plates allowing for operation with up to 192 samples. The measuring protocol involves controlled loading of protein solutions and matching buffers, followed by cleaning and drying of the cell between measurements. The system was installed and tested at the X33 beamline of the EMBL, at the storage ring DORIS-III (DESY, Hamburg), where it was used by over 50 external groups during 2007. At X33, a throughput of approximately 12 samples per hour, with a failure rate of sample loading of less than 0.5%, was observed. The feedback from users indicates that the ease of use and reliability of the user operation at the beamline were greatly improved compared with the manual filling mode. The changer is controlled by a client-server-based network protocol, locally and remotely. During the testing phase, the changer was operated in an attended mode to assess its reliability and convenience. Full integration with the beamline control software, allowing for automated data collection of all samples loaded into the machine with remote control from the user, is presently being implemented. The approach reported is not limited to synchrotron-based SAXS but can also be used on laboratory and neutron sources.

Genetic parameters for growth and carcass traits of Brahman steers.

Spring-born purebred Brahman bull calves (n = 467) with known pedigrees, sired by 68 bulls in 17 private herds in Louisiana, were purchased at weaning from 1996 through 2000 to study variation in growth, carcass, and tenderness traits. After purchase, calves were processed for stocker grazing on ryegrass, fed in a south Texas feedlot, and processed in a commercial facility. Carcass data were recorded 24 h postmortem. Muscle samples and primal ribs were taken to measure calpastatin activity and shear force. An animal model was used to estimate heritability, genetic correlations, and sire EPD. Relatively high heritability estimates were found for BW at slaughter (0.59 +/- 0.16), HCW (0.57 +/- 0.15), LM area (0.50 +/- 0.16), yield grade (0.46 +/- 0.17), calpastatin enzyme activity (0.45 +/- 0.17), and carcass quality grade (0.42 +/- 0.16); moderate heritability estimates were found for hump height (0.38 +/- 0.16), marbling score (0.37 +/- 0.16), backfat thickness (0.36 +/- 0.17), feedlot ADG (0.33 +/- 0.14), 7-d shear force (0.29 +/- 0.14), and 14-d shear force (0.20 +/- 0.11); relatively low heritability estimates were found for skeletal maturity (0.10 +/- 0.10), lean maturity (0.00 +/- 0.07), and percent KPH (0.00 +/- 0.07). Most genetic correlations were between -0.50 and +0.50. Other genetic correlations were 0.74 +/- 0.27 between calpastatin activity and 7-d shear force, 0.72 +/- 0.25 between calpastatin activity and 14-d shear force, (0.90 +/- 0.30 between yield grade and 7-d shear force, and -0.82 +/- 0.27 between backfat thickness and 7-d shear force. Heritability estimates and genetic correlations for most traits were similar to estimates reported in the literature. Sire EPD ranges for carcass traits approached those reported for sires in other breeds. The magnitude of heritability estimates suggests that improvement in carcass yield, carcass quality, and consumer acceptance traits can be made within the Brahman population.

Validation of commercial DNA tests for quantitative beef quality traits.

Associations between 3 commercially available genetic marker panels (GeneSTAR Quality Grade, GeneSTAR Tenderness, and Igenity Tender-GENE) and quantitative beef traits were validated by the US National Beef Cattle Evaluation Consortium. Validation was interpreted to be the independent confirmation of the associations between genetic tests and phenotypes, as claimed by the commercial genotyping companies. Validation of the quality grade test (GeneSTAR Quality Grade) was carried out on 400 Charolais x Angus crossbred cattle, and validation of the tenderness tests (GeneSTAR Tenderness and Igenity Tender-GENE) was carried out on over 1,000 Bos taurus and Bos indicus cattle. The GeneSTAR Quality Grade marker panel is composed of 2 markers (TG5, a SNP upstream from the start of the first exon of thyroglobulin, and QG2, an anonymous SNP) and is being marketed as a test associated with marbling and quality grade. In this validation study, the genotype results from this test were not associated with marbling score; however, the association of substituting favorable alleles of the marker panel with increased quality grade (percentage of cattle grading Choice or Prime) approached significance (P < or = 0.06), mainly due to the effect of 1 of the 2 markers. The GeneSTAR Tenderness and Igenity TenderGENE marker panels are being marketed as tests associated with meat tenderness, as assessed by Warner-Bratzler shear force. These marker panels share 2 common mu-calpain SNP, but each has a different calpastatin SNP. In both panels, there were highly significant (P < 0.001) associations of the calpastatin marker and the mu-calpain haplotype with tenderness. The genotypic effects of the 2 tenderness panels were similar to each other, with a 1 kg difference in Warner-Bratzler shear force being observed between the most and least tender genotypes. Unbiased and independent validation studies are important to help build confidence in marker technology and also as a potential source of data required to enable the integration of marker data into genetic evaluations. As DNA tests associated with more beef production traits enter the marketplace, it will become increasingly important, and likely more difficult, to find independent populations with suitable phenotypes for validation studies.