Probing single electrons across 300-mm spin qubit wafers.

Building a fault-tolerant quantum computer will require vast numbers of physical qubits. For qubit technologies based on solid-state electronic devices1-3, integrating millions of qubits in a single processor will require device fabrication to reach a scale comparable to that of the modern complementary metal-oxide-semiconductor (CMOS) industry. Equally important, the scale of cryogenic device testing must keep pace to enable efficient device screening and to improve statistical metrics such as qubit yield and voltage variation. Spin qubits1,4,5 based on electrons in Si have shown impressive control fidelities6-9 but have historically been challenged by yield and process variation10-12. Here we present a testing process using a cryogenic 300-mm wafer prober13 to collect high-volume data on the performance of hundreds of industry-manufactured spin qubit devices at 1.6 K. This testing method provides fast feedback to enable optimization of the CMOS-compatible fabrication process, leading to high yield and low process variation. Using this system, we automate measurements of the operating point of spin qubits and investigate the transitions of single electrons across full wafers. We analyse the random variation in single-electron operating voltages and find that the optimized fabrication process leads to low levels of disorder at the 300-mm scale. Together, these results demonstrate the advances that can be achieved through the application of CMOS-industry techniques to the fabrication and measurement of spin qubit devices.

How Valley-Orbit States in Silicon Quantum Dots Probe Quantum Well Interfaces.

The energies of valley-orbit states in silicon quantum dots are determined by an as yet poorly understood interplay between interface roughness, orbital confinement, and electron interactions. Here, we report measurements of one- and two-electron valley-orbit state energies as the dot potential is modified by changing gate voltages, and we calculate these same energies using full configuration interaction calculations. The results enable an understanding of the interplay between the physical contributions and enable a new probe of the quantum well interface.

Evaluating a brief online compassion-focused intervention for intensive care nurses.

BACKGROUND: High levels of stress have been found within health care staff, particularly in the nursing population, which is somewhat attributed to the Covid-19 pandemic. The development of self-compassion, a protective psychological construct, may promote well-being in the health care staff population. As part of a service development project, the authors delivered and evaluated a brief online compassion-focused intervention with nurses working within Intensive Care Units (ICUs). AIMS: Aims were to explore feasibility within the ICU nursing population and consider potential benefits to psychological well-being. METHODS: ICU nurses registered for an online, 4 week, compassion-focused intervention as part of a service development project. Measures of compassion, burnout, trauma, and the emotional climate of their work environment were analysed in two groups; those who completed the intervention and those who did not. Baseline and post-intervention measures were analysed to infer the potential benefits of the intervention. RESULTS: Compared with their baseline scores, those who completed the intervention showed improvements on measures of compassion, soothing in emotional climate, and reductions in burnout, trauma and threat in emotional climate. At baseline, those who did not complete the intervention scored lower on measures of compassion and soothing within their emotional climate, as well as higher levels of trauma and threat within the emotional climate, compared with those who engaged with the intervention. CONCLUSIONS: Brief online compassion-focused interventions may be a useful platform to promote well-being in ICU nurses, but possibly only for those who have a pre-established level of self-compassion.

Coherent Control and Spectroscopy of a Semiconductor Quantum Dot Wigner Molecule.

Semiconductor quantum dots containing more than one electron have found wide application in qubits, where they enable readout and enhance polarizability. However, coherent control in such dots has typically been restricted to only the lowest two levels, and such control in the strongly interacting regime has not been realized. Here we report quantum control of eight different transitions in a silicon-based quantum dot. We use qubit readout to perform spectroscopy, revealing a dense set of energy levels with characteristic spacing far smaller than the single-particle energy. By comparing with full configuration interaction calculations, we argue that the dense set of levels arises from Wigner-molecule physics.

Substance abuse and criminal activities following traumatic brain injury in childhood, adolescence, and early adulthood.

OBJECTIVE: Use a longitudinal birth cohort to evaluate the association of traumatic brain injury at ages 0 to 5, 6 to 15, and 16 to 21 years with drug and alcohol abuse and engagement in criminal activities. MAIN MEASURES: Follow-up over 21 to 25 years using self-report of drug and alcohol use, arrests, and violent and property offenses. Outcomes were assessed for 2 levels of severity (inpatient, hospitalized; outpatient, seen by general practitioner or at emergency department). PARTICIPANTS: Members of the Christchurch Health and Development Study, a longitudinal birth cohort. SETTING: Christchurch, New Zealand. RESULTS: Adjusted for child and family factors, compared with noninjured individuals, inpatients injured at 0 to 5 years or 16 to 21 years were more likely to have symptoms consistent with drug dependence. All inpatient groups had increased risk of arrest, with the age groups of 0 to 5 and 6 to 15 years more likely to be involved in violent offenses and the age group of 0 to 5 years more likely to engage in property offenses. Outpatient group had an increased risk of violent offenses for first injury 0 to 5 years, arrests and property offenses for injury 6 to 15 years, and increased risk of arrests and violent offenses for injury 16 to 21 years of age. However, when alcohol dependence and drug dependence were added as an additional covariate, traumatic brain injury was no longer associated with criminal behavior for the age group of 0 to 5 years. CONCLUSIONS: Traumatic brain injury is associated with increased criminal behavior and may represent a risk factor for offending. However, early substance use is a mediating factor for those injured early in life.

Neuropsychiatric Lupus with Antibody-Mediated Striatal Encephalitis.

Systemic lupus erythematosus is a chronic autoimmune disease characterized by the production of autoantibodies resulting in tissue injury across multiple organs; up to 50% of patients develop neurologic involvement, collectively referred to as neuropsychiatric systemic lupus erythematosus. The cases in this clinical report will highlight a subtype of neuropsychiatric systemic lupus erythematosus demonstrating imaging findings of striatal inflammation responsive to plasmapheresis similar to those in the subset of N-methyl-D-aspartate receptor autoimmune encephalitis that involves the striatum. Although the cause for this striking imaging appearance is not definitely known, literature will be presented supporting the hypothesis that it is due to peripheral anti-double-stranded DNA antibodies entering the central nervous system to cross-react with N-methyl-D-aspartate receptor antigens.

TRPV1 antagonists that cause hypothermia, instead of hyperthermia, in rodents: Compounds' pharmacological profiles, in vivo targets, thermoeffectors recruited and implications for drug development.

AIM: Thermoregulatory side effects hinder the development of transient receptor potential vanilloid-1 (TRPV1) antagonists as new painkillers. While many antagonists cause hyperthermia, a well-studied effect, some cause hypothermia. The mechanisms of this hypothermia are unknown and were studied herein. METHODS: Two hypothermia-inducing TRPV1 antagonists, the newly synthesized A-1165901 and the known AMG7905, were used in physiological experiments in rats and mice. Their pharmacological profiles against rat TRPV1 were studied in vitro. RESULTS: Administered peripherally, A-1165901 caused hypothermia in rats by either triggering tail-skin vasodilation (at thermoneutrality) or inhibiting thermogenesis (in the cold). A-1165901-induced hypothermia did not occur in rats with desensitized (by an intraperitoneal dose of the TRPV1 agonist resiniferatoxin) sensory abdominal nerves. The hypothermic responses to A-1165901 and AMG7905 (administered intragastrically or intraperitoneally) were absent in Trpv1-/- mice, even though both compounds evoked pronounced hypothermia in Trpv1+/+ mice. In vitro, both A-1165901 and AMG7905 potently potentiated TRPV1 activation by protons, while potently blocking channel activation by capsaicin. CONCLUSION: TRPV1 antagonists cause hypothermia by an on-target action: on TRPV1 channels on abdominal sensory nerves. These channels are tonically activated by protons and drive the reflectory inhibition of thermogenesis and tail-skin vasoconstriction. Those TRPV1 antagonists that cause hypothermia further inhibit these cold defences, thus decreasing body temperature. SIGNIFICANCE: TRPV1 antagonists (of capsaicin activation) are highly unusual in that they can cause both hyper- and hypothermia by modulating the same mechanism. For drug development, this means that both side effects can be dealt with simultaneously, by minimizing these compounds' interference with TRPV1 activation by protons.

Health care quality in the 21st century.

The concepts of healthcare quality have evolved over the years. Many stakeholders have become quite engaged in the movement towards improvement in healthcare quality and safety. The standardization and national endorsement of performance measures, the assessment of outcomes, and the reporting for accountability are now being coupled with more transparency, and technological innovation. As the quality landscape changes to evaluation of episodes of care and performance at the individual clinician level measures (primary and specialty care), collaboration is critical among consumers, purchasers, measure developers, implementers of measures to identify and adopt national standards to tell a clear story of healthcare quality.

Autoimmune Encephalitis: Pathophysiology and Imaging Review of an Overlooked Diagnosis.

Autoimmune encephalitis is a relatively new category of immune-mediated disease involving the central nervous system that demonstrates a widely variable spectrum of clinical presentations, ranging from the relatively mild or insidious onset of cognitive impairment to more complex forms of encephalopathy with refractory seizure. Due to its diverse clinical features, which can mimic a variety of other pathologic processes, autoimmune encephalitis presents a diagnostic challenge to clinicians. Imaging findings in patients with these disorders can also be quite variable, but recognizing characteristic findings within limbic structures suggestive of autoimmune encephalitis can be a key step in alerting clinicians to the potential diagnosis and ensuring a prompt and appropriate clinical work-up. In this article, we review antibody-mediated encephalitis and its various subtypes with a specific emphasis on the role of neuroimaging in the diagnostic work-up.

Coinage metal coordination chemistry of stable primary, secondary and tertiary ferrocenylethyl-based phosphines.

Ferrocene-based phosphines constitute an important auxiliary ligand in inorganic chemistry. Utilizing the (ferrocenylethyl)phosphines (FcCH2CH2)3-nHnP (Fc = ferrocenyl; n = 2, 1; n = 1, 2; n = 0, 3) the synthesis of a series of coordination complexes [(FcCH2CH2)3-nHnPCuCl]4 (n = 2, 1-CuCl; n = 0, 3-CuCl), [(FcCH2CH2)2HPCuCl] (2-CuCl), {[(FcCH2CH2)H2P]2AgCl}2 (1-AgCl), [(FcCH2CH2)2HPAgCl] (2-AgCl), [(FcCH2CH2)3PAgCl]4 (3-AgCl), [(FcCH2CH2)3PM(OAc)]4 (M = Cu, 3-CuOAc M = Ag, 3-AgOAc), [(FcCH2CH2)3-nHnPAuCl] (n = 1, 2-AuCl; n = 0, 3-AuCl), via the reaction between the free phosphine and MX (M = Cu, Ag and Au; X = Cl, OAc), is described. The reaction between the respective phosphine with a suspension of metal-chloride or -acetate in a 1 : 1 ratio in THF at ambient temperature affords coordinated phosphine-coinage metal complexes. Varying structural motifs are observed in the solid state, as determined via single crystal X-ray analysis of 1-CuCl, 3-CuCl, 1-AgCl, 3-AgCl, 3-CuOAc, 3-AgOAc, 2-AuCl and 3-AuCl. Complexes 1-CuCl and 3-CuCl are tetrameric Cu(i) cubane-like structures with a Cu4Cl4 core, whereas silver complexes with primary and tertiary phosphine reveal two different structural types. The structure of 1-AgCl, unlike the rest, displays the coordination of two phosphines to each silver atom and shows a quadrangle defined by two Ag and two Cl atoms. In contrast, 3-AgCl is distorted from a cubane structure via elongation of one of the ClAg distances. 3-CuOAc and 3-AgOAc are isostructural with step-like cores, while complexes 2-AuCl and 3-AuCl reveal a linear geometry of a phosphine gold(i) chloride devoid of any aurophilic interactions. All of the complexes were characterized in solution by multinuclear (1)H, (13)C{(1)H} and (31)P NMR spectroscopic techniques; the redox chemistry of the series of complexes was examined using cyclic voltammetry. This class of complexes has been found to exhibit one reversible Fe(ii)/Fe(iii) oxidation couple, suggesting the absence of electronic communication between the ferrocenyl units on individual phosphine ligands as well as between different phosphines on the polymetallic cores.

Effect of vitamin E on prothrombin levels in warfarin-induced vitamin K deficiency.

Rats rendered lightly vitamin K deficient with warfarin (0.01 mg/100 g, IP) and given the equivalent of 1000 units of vitamin E/kg IM for 7 days, showed a marked reduction in functional factor II activity, but normal factor II levels using Echis venom on coagulation analysis. In 12 humans receiving warfarin, vitamin E was administered in doses of 100 or 400 units/day orally for 4 wk. The results in these patients showed no significant change in the prothrombin time, factor II coagulant activity, or factor II antigen (by electroimmunoassay). However, by using a ratio of factor II coagulant activity to immunoreactive protein, significant reduction was observed when compared to pretreatment ratios. These data suggest that vitamin E acts at the step mediated by vitamin K and not in the synthesis of the factor II precursor. Although the administration of high doses of vitamin E in animals, and possibly humans, with vitamin K deficiency potentiates the vitamin K deficiency, this effect is not clinically obvious with 400 IU/day or less.

Basophilic meningitis secondary to lymphoma.

In this case report of basophilic meningitis, the patient was a 5-year-old girl under treatment for a diffuse lymphocytic lymphoma. She presented with headache and bilateral papilledema. Cerebrospinal fluid examination showed 60 percent basophils. Subsequent specimens showed a rare blast. It is postulated that after the lymphoma cells had spread to the meninges, a cell-mediated immune reaction was initiated with the appearance of basophils in the exudate.

The in vivo development of plasma cells: a morphologic study of human cerebrospinal fluid.

This is a case study of a patient with the clinical diagnosis of meningoencephalitis. It demonstrates the in vivo development of plasma cells in the central nervous system. All the stages of in vitro mitogen-induced lymphocyte transformation previously described by light and electron microscopy are recapitulated in this analysis of cerebrospinal fluid. It is postulated that this represents a local humoral immune reaction in the central nervous system and provides morphologic support for the concept that the gamma globulin in cerebrospinal fluid is produced locally in part, in addition to its origin from the plasma proteins.

Tissue-type plasminogen activator, plasminogen activator inhibitor, and histidine-rich glycoproteins in stressed human newborns.

Normal newborns have reduced levels of tissue-type plasminogen activator (tPA). Stressed newborns have an increased prevalence of thrombotic diseases. An impaired release of tPA and/or increased plasminogen activator inhibitor (PAI) is associated with thrombotic risk in the adult patient. The purpose of this study was to assay the plasma levels of tPA, PAI, histidine-rich glycoprotein (HRG), and other fibrinolytic proteins in 15 severely stressed newborns. The stressed babies showed significantly higher (p less than .001) levels of tPA antigen compared with normal newborns. Also, PAI activity and PAI-1 antigen levels were increased. Levels of both HRG and plasminogen were higher in the stressed group but the ratio of HRG to plasminogen was the same as that in the normal control newborns (1:3), suggesting an insignificant effect of HRG. D-dimers were significantly elevated in the stressed newborns. However, 8 patients died and 4 of these were found to have massive thrombotic disease on autopsy. These results show that the newborn when stressed will increase tPA levels and activate the lytic system. However, the activity is suboptimal inasmuch as PAI activity did not decrease and thrombotic disease was observed.

Fibrin metabolism in patients with acute myocardial infarction during and after treatment with tissue-type plasminogen activator.

In order to define some of the determinants of successful thrombolysis and reocclusion during fibrinolytic therapy for acute myocardial infarction (AMI), specific molecular markers of fibrin metabolism were serially measured in 15 patients with AMI treated with tissue-type plasminogen activator (t-PA). Fibrin formation was assessed by measurement of fibrinopeptide A (FpA) and fibrinolysis by assay of B-beta peptides 1-42 and 15-42 and crosslinked fibrin degradation products (XDP). At baseline, FpA levels were high while markers of fibrinolysis were near normal. Following a 90-minute infusion of t-PA (0.5-1.1 mg kg-1 hr-1), all markers of fibrinolysis increased. Levels of FpA remained elevated despite heparin at the initiation of cardiac catheterization. None of these markers discriminated between patients with successful reperfusion from those without. At 4 hours, B-beta 15-42 peptide and XDP levels remained elevated suggesting persistence of fibrinolysis beyond the short circulatory half-life of t-PA. FpA levels at 4 hours were lower in patients who underwent acute coronary angioplasty compared to those who received additional low dose t-PA (12.3 +/- 4.5 vs. 30.4 +/- 5.5 ng/ml, p less than 0.05). By 48 hours, markers of fibrinolysis had returned toward normal except in 2 patients with persistently elevated B-beta 15-42 peptide levels who suffered reocclusion on days 5 and 6 (75 and 44 vs. 29 +/- 3 nM, p less than 0.005). In conclusion, molecular markers of fibrin metabolism during fibrinolytic therapy may provide clinically relevant data.

The effect of vitamin E on warfarin-induced vitamin K deficiency.

Vitamin K-deficient animals and humans developed a more severe coagulopathy when treated with vitamin E, which was due to further reduction in the vitamin K-dependent coagulation factors (II, VII, IX, and X). This phenomenon was not seen in normal vitamin K-sufficient animals or human subjects. The mechanism by which vitamin E causes this effect is not known. These coagulation factors are produced by the liver in precursor forms and are converted to functional proteins by a vitamin K-dependent reaction. Analysis of one of these coagulation factors, prothrombin (factor II), in plasma of vitamin K-deficient animals and humans treated with vitamin E was done in this study. The precursor of factor II is antigenically similar to biologically active factor II and can be activated to form thrombin by Echis carinatus venom. The data showed that functional factor II coagulant activity was reduced below base in warfarin-treated humans and animals given vitamin E. Factor II antigen as determined by electroimmunoassay in humans and factor II coagulant activity as measured using Echis venom in animals were unchanged and no different from untreated controls. The data suggest that vitamin E acts at the vitamin K-carboxylase step of carboxylation of precursor prothrombin and not in the synthesis of the precursor protein.

Splenic artery ligation in experimental hypersplenism.

The effects of splenic artery ligation (SAL) were examined in Sprague-Dawley rats with methyl-cellulose-induced hypersplenism. When performed close to the splenic hilium, SAL effectively reduced functioning splenic mass and raised peripheral counts of leukocytes and platelets, a response similar to that following total splenectomy. In hypersplenism, therefore, a satisfactory hematologic response may not necessary require total ablation of the spleen but merely substantial reduction of functioning splenic tissue.

Alterations in the prothrombin coagulation pathway due to preeclampsia.

Circulating plasma levels of human prothrombin antigen and activity were determined in normal pregnancy and in pregnancies complicated by hypertension, eclampsia, or preeclampsia. The ratio of prothrombin antigen to activity (Ag/Act) was within normal limits for all hypertensive patients. However, every untreated preeclamptic patient, as well as 2 eclamptic patients, had abnormal prothrombin antigen to activity ratios.