We introduce a solid-state qubit in which exchange interactions among confined electrons provide both the static longitudinal field and the oscillatory transverse field, allowing rapid and full qubit ...control via rf gate-voltage pulses. We demonstrate two-axis control at a detuning sweet spot, where leakage due to hyperfine coupling is suppressed by the large exchange gap. A π/2-gate time of 2.5 ns and a coherence time of 19 μs, using multipulse echo, are also demonstrated. Model calculations that include effects of hyperfine noise are in excellent quantitative agreement with experiment.
The Dominantly Inherited Alzheimer's Network Trials Unit (DIAN-TU) was formed to direct the design and management of interventional therapeutic trials of international DIAN and autosomal dominant ...Alzheimer's disease (ADAD) participants. The goal of the DIAN-TU is to implement safe trials that have the highest likelihood of success while advancing scientific understanding of these diseases and clinical effects of proposed therapies. The DIAN-TU has launched a trial design that leverages the existing infrastructure of the ongoing DIAN observational study, takes advantage of a variety of drug targets, incorporates the latest results of biomarker and cognitive data collected during the observational study, and implements biomarkers measuring Alzheimer's disease (AD) biological processes to improve the efficiency of trial design. The DIAN-TU trial design is unique due to the sophisticated design of multiple drugs, multiple pharmaceutical partners, academics servings as sponsor, geographic distribution of a rare population and intensive safety and biomarker assessments. The implementation of the operational aspects such as home health research delivery, safety magnetic resonance imagings (MRIs) at remote locations, monitoring clinical and cognitive measures, and regulatory management involving multiple pharmaceutical sponsors of the complex DIAN-TU trial are described.
Le Dominantly Inherited Alzheimer's Network Trials Unit (DIAN-TU) a été créé afin de structurer les essais thérapeutiques interventionnels internationaux destinés aux membres de DIAN concernés par la maladie d’Alzheimer autosomique dominante. L’objectif de DIAN-TU est de mettre en place des essais sécurisés ayant la plus grande probabilité de succès en fonction des avancées scientifiques concernant à la fois la compréhension de ces maladies et les effets cliniques des thérapeutiques proposées. Le DIAN-TU a lancé un essai thérapeutique qui s’appuie sur les infrastructures actuelles de l’étude observationnelle DIAN, considère les bénéfices de plusieurs cibles pharmacologiques, prend en compte les résultats les plus récents des biomarqueurs et des données cognitives collectés pendant l’étude observationnelle et intègre les biomarqueurs physiopathologiques de la maladie d’Alzheimer afin d’améliorer l’efficience du protocole. Le DIAN-TU est original par son protocole sophistiqué concernant plusieurs molécules, par le nombre de partenaires de l’industrie pharmaceutique et des promoteurs académiques, par la dispersion géographique d’une population rare et par les procédures multiples d’évaluation en termes de sécurité et de biomarqueurs. Cet article présente la mise en place des aspects opérationnels, tels que la délivrance des thérapeutiques à domicile, la réalisation des IRM de surveillance à distance des sites d’évaluation, le monitoring des données cliniques et cognitives et les aspects réglementaires impliquant plusieurs partenaires industriels de cet essai DIAN-TU.
Ballistic semiconductor structures have allowed the realization of optics-like phenomena in electronic systems, including the magnetic focusing and electrostatic lensing of electrons. An extension ...that appears unique to graphene is to use both n and p carrier types to create electronic analogues of optical devices with both positive and negative indices of refraction. Here, we use the gate-controlled density of both p and n carrier types in graphene to demonstrate the electronic analogue of fibre-optic guiding. Two basic effects are investigated: bipolar p-n junction guiding, based on the principle of angle-selective transmission through the interface between the graphene and the p-n junction; and unipolar fibre-optic guiding, using total internal reflection controlled by carrier density. We also demonstrate modulation of the guiding efficiency through gating, and comparison of these data with numerical simulations indicates that guiding performance is limited by the roughness of the interface. The development of p-n and fibre-optic guiding in graphene may lead to electrically reconfigurable wiring in high-mobility devices.
The rising prevalence of smokers in the community, specifically psychiatric patients, necessitates smoking cessation as an important strategy for reducing the harmful effects of tobacco. This study ...aims to compare the profiles of depressed and non-depressed smokers and evaluate how psychiatric symptoms influence respiratory symptoms. A cross-sectional survey was administered to 276 non-depressed adult smokers in the community and 69 adult smokers who had been formally diagnosed with depression in the outpatient clinic of a University Hospital in Singapore. Participants were administered questionnaires on smoking attitudes and perceptions, psychiatric symptoms, and respiratory symptoms. Correlations and multiple regression analyses were conducted. The mean age of smokers in the study was 35.32 ± 13.05 years. Smokers in the community and psychiatric samples were largely similar on all of the sociodemographic factors, except that fewer depressed people were employed (χ² = 8.35,
< 0.01). Smokers with depression also reported more attempts to quit smoking (χ² = 7.14,
< 0.05), higher mean depressive, anxiety, and stress symptom (DASS) scores (t = -10.04,
< 0.01), and endorsed more respiratory symptoms than smokers in the community (t = -2.40,
< 0.05). The DASS scores, number of cigarettes smoked daily, years of smoking, general perception of smokers getting heart disease, and presence of lung disease were positively and significantly correlated with respiratory symptoms. On multiple regression, only anxiety symptoms (β = 0.26, p < 0.05) and the presence of lung disease (β = 0.22, p < 0.001) were significantly correlated with respiratory symptoms. Depressed smokers reported greater difficulty in quitting tobacco use, and they perceived more severe respiratory symptoms compared to non-depressed counterparts. Anxiety symptoms were positively associated with the severity of respiratory symptoms. Smoking cessation campaigns need to specifically target psychological symptoms in smokers and focus more psychoeducation on the risk of cardiovascular disease in the middle-aged population.
We report repeated single-shot measurements of the two-electron spin state in a GaAs double quantum dot. The readout allows measurement with a fidelity above 90% with a approximately 7 micros cycle ...time. Hyperfine-induced precession between singlet and triplet states of the two-electron system are directly observed, as nuclear Overhauser fields are quasistatic on the time scale of the measurement cycle. Repeated measurements on millisecond to second time scales reveal the evolution of the nuclear environment.
Cutaneous lesions in patients with mastocytosis are highly heterogeneous and encompass localized and disseminated forms. Although a classification and criteria for cutaneous mastocytosis (CM) have ...been proposed, there remains a need to better define subforms of cutaneous manifestations in patients with mastocytosis. To address this unmet need, an international task force involving experts from different organizations (including the European Competence Network on Mastocytosis; the American Academy of Allergy, Asthma & Immunology; and the European Academy of Allergology and Clinical Immunology) met several times between 2010 and 2014 to discuss the classification and criteria for diagnosis of cutaneous manifestations in patients with mastocytosis. This article provides the major outcomes of these meetings and a proposal for a revised definition and criteria. In particular, we recommend that the typical maculopapular cutaneous lesions (urticaria pigmentosa) should be subdivided into 2 variants, namely a monomorphic variant with small maculopapular lesions, which is typically seen in adult patients, and a polymorphic variant with larger lesions of variable size and shape, which is typically seen in pediatric patients. Clinical observations suggest that the monomorphic variant, if it develops in children, often persists into adulthood, whereas the polymorphic variant may resolve around puberty. This delineation might have important prognostic implications, and its implementation in diagnostic algorithms and future mastocytosis classifications is recommended. Refinements are also suggested for the diagnostic criteria of CM, removal of telangiectasia macularis eruptiva perstans from the current classification of CM, and removal of the adjunct solitary from the term solitary mastocytoma.
Patients subjected to haemodilution during surgery are at increased risk of bleeding. We hypothesised that, in the acquired dilutional coagulopathy, insufficient haemostasis is due to either ...insufficient thrombin generation or insufficient fibrin clot formation. In tissue factor-activated plasmas from patients with coagulation deficiency, we measured time curves of thrombin generation and fibrin clot formation (thromboelastography). Investigated were in study A: 10 patients treated with vitamin K antagonist and five healthy subjects; in study B: 30 patients undergoing cardiopulmonary bypass (CPB) surgery and infused with on average 2,000 ml crystalloids and colloids (no major bleeding); in study C: 58 patients undergoing major general surgery, and transfused with >5,000 ml crystalloids, colloids and red cell concentrates, who experienced major bleeding and were post-transfused with fresh frozen plasma. The treatment with vitamin K antagonist led to a progressive reduction in thrombin generation but not fibrin clot formation. In CPB patients, plasma factor levels post-surgery were 53-60% of normal. This was accompanied by moderate reduction in both haemostatic processes. In plasmas from patients undergoing major surgery, factor levels were 38-41% of normal, and these levels increased after plasma transfusion. Taking preset thresholds for normal thrombin generation and fibrin clot formation, at least one of these processes was low in 88-93% of the patients with (persistent) bleeding, but only in 40-53% of the patients without bleeding. In conclusion, the ability of thrombin generation and fibrin clot formation is independently reduced in acquired dilutional coagulopathy, while minimal levels of both are required for adequate haemostasis.
We demonstrate strong suppression of charge dispersion in a semiconductor-based transmon qubit across Josephson resonances associated with a quantum dot in the junction. On resonance, dispersion is ...drastically reduced compared to conventional transmons with corresponding Josephson and charging energies. We develop a model of qubit dispersion for a single-channel resonance, which is in quantitative agreement with experimental data.
In this work, the effect of lithium hydroxide (LiOH) amalgamation on the properties of polyvinyl alcohol thermoplastic membranes, obtained by the solvent casting method, is presented. FTIR and Raman ...spectroscopy show the effect of
Li
+
on vibrations of C=O, C–O and O–H functional groups. Moreover, DRX analysis confirmed the semi-crystalline nature of the samples. The density functional theory indicates an insulator–metal transition due to the lithium incorporation in the polymer. Moreover, the formation energy and structural properties have also been calculated to understand the PVA–Li interaction. The complex impedance study at room temperature indicates an improvement in the resistance values of the membranes, with the increase of the lithium content, up to 7% of
LiOH
(7 * 10
2
Ω). The results reveal the importance of this type of material as candidates in solid-state electrolytes.
Preclinical studies have suggested that platelets influence the host response during sepsis. We sought to assess the association of admission thrombocytopenia with the presentation, outcome, and host ...response in patients with sepsis. Nine hundred thirty-one consecutive sepsis patients were stratified according to platelet counts (very low <50 × 109/L, intermediate-low 50 × 109 to 99 × 109/L, low 100 × 109 to 149 × 109/L, or normal 150 × 109 to 399 × 109/L) on admission to the intensive care unit. Sepsis patients with platelet counts <50 × 109/L and 50 × 109 to 99 × 109/L presented with higher Acute Physiology and Chronic Health Evaluation scores and more shock. Both levels of thrombocytopenia were independently associated with increased 30-day mortality (hazard ratios with 95% confidence intervals 2.00 1.32-3.05 and 1.72 1.22-2.44, respectively). To account for baseline differences besides platelet counts, propensity matching was performed, after which the association between thrombocytopenia and the host response was tested, as evaluated by measuring 17 plasma biomarkers indicative of activation and/or dysregulation of pathways implicated in sepsis pathogenesis and by whole genome blood leukocyte expression profiling. In the propensity matched cohort, platelet counts < 50 × 109/L were associated with increased cytokine levels and enhanced endothelial cell activation. All thrombocytopenic groups showed evidence of impaired vascular integrity, whereas coagulation activation was similar between groups. Blood microarray analysis revealed a distinct gene expression pattern in sepsis patients with <50 × 109/L platelets, showing reduced signaling in leukocyte adhesion and diapedesis and increased complement signaling. These data show that admission thrombocytopenia is associated with enhanced mortality and a more disturbed host response during sepsis independent of disease severity, thereby providing clinical validity to animal studies on the role of platelets in severe infection.
•Thrombocytopenia on intensive care unit admission is independently associated with increased mortality in patients with sepsis.•Thrombocytopenia is associated with a more disturbed host response in critically ill patients with sepsis independent of disease severity.
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