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Silicon-based microelectronics technology is extremely mature, yet this profoundly important material is now also poised to become a foundation for quantum information processing technologies. In this article, we review the properties of silicon that have made it the material of choice for semiconductor-based qubits with an emphasis on the role that modeling and simulation have played in understanding and quantifying these properties. We also address some of the challenges that remain for silicon qubits for which modeling can play an important role and we offer our perspective on the future of this technology.

Singlet-triplet spin states of a quantum dot support promising semiconductor-based qubits, yet often suffer from poor state preparation and measurement, due to low-lying excited states. Engineering a large energy splitting is impeded by the inability to accurately measure both large and small energy splittings with the device biased to nominal operation. The authors present a measurement and fitting approach that accurately extracts both large and small splittings in this regime. They also find evidence that both orbital and valley degrees of freedom may set this energy separation, significantly affecting which paths to pursue in device design.

Treatment of congenital adrenal hyperplasia (CAH) in childhood focuses on growth and development and adult final height (FH) is a measure of effective treatment. We hypothesized that shorter adults will have more severe underlying disease and worse health outcomes.This was a cross-sectional analysis of 199 adults with CAH. FH and quality of life were expressed as z-scores adjusted for midparental target height or UK population height.FH correlated inversely with age (men, r = -0.38; women, r = -0.26, P.01). Men and women had z-scores adjusted for midparental target height of -2 and -1, respectively, and both groups had UK population height z-scores of -1 below the UK population (P.01). In women, FH was shorter in non-salt-wasting than salt-wasting classic CAH (P.05) and in moderately affected genotype group B women than either more severely affected groups null and A (P.01) or the mildest group C (P.001). Short stature and a higher prevalence of hypertension were observed in classic CAH patients diagnosed late (after 1 y) compared with those diagnosed early and in women treated with glucocorticoid only compared with those treated with both glucocorticoids and mineralocorticoids (P.05). FH did not associate with insulin sensitivity, lipid profile, adiposity, or quality of life.Adult CAH patients remain short, although height prognosis has improved over time. The shortest adults are those diagnosed late with moderate severity CAH and are at increased risk of adult hypertension; we hypothesize that these patients are exposed in childhood to high androgens and/or excessive glucocorticoids with potential programming of hypertension. Another possibility is inadequate mineralocorticoid treatment early in life in the late-diagnosed patient group. Prospective studies are now required to examine these hypotheses.

We report on a quantum dot device design that combines the low disorder properties of undoped SiGe heterostructure materials with an overlapping gate stack in which each electrostatic gate has a dominant and unique function -- control of individual quantum dot occupancies and of lateral tunneling into and between dots. Control of the tunneling rate between a dot and an electron bath is demonstrated over more than nine orders of magnitude and independently confirmed by direct measurement within the bandwidth of our amplifiers. The inter-dot tunnel coupling at the (0,2)(1,1) charge configuration anti-crossing is directly measured to quantify the control of a single inter-dot tunnel barrier gate. A simple exponential dependence is sufficient to describe each of these tunneling processes as a function of the controlling gate voltage., Comment: 4 pages, 5 figures

We report the first experimental demonstration of a lateral graphene heterostructure field-effect transistor (HFET) at wafer scale, where the graphene heterostructure channel consists of epitaxial graphene (Gr)/fluorographene (GrF)/graphene (Gr). GrF is a widebandgap material, providing a potential barrier to lateral carrier transport. Gate bias modulation of the Gr/GrF/Gr barrier via an electric field effect results in normally-off enhancement-mode graphene HFETs with an ON-OFF switching ratio of 105 at room temperature. These devices also demonstrate excellent current-voltage saturation, providing a potential path for active RF applications.

Three coupled quantum dots in isotopically purified silicon enable all-electrical qubit control with long coherence time., Like modern microprocessors today, future processors of quantum information may be implemented using all-electrical control of silicon-based devices. A semiconductor spin qubit may be controlled without the use of magnetic fields by using three electrons in three tunnel-coupled quantum dots. Triple dots have previously been implemented in GaAs, but this material suffers from intrinsic nuclear magnetic noise. Reduction of this noise is possible by fabricating devices using isotopically purified silicon. We demonstrate universal coherent control of a triple-quantum-dot qubit implemented in an isotopically enhanced Si/SiGe heterostructure. Composite pulses are used to implement spin-echo type sequences, and differential charge sensing enables single-shot state readout. These experiments demonstrate sufficient control with sufficiently low noise to enable the long pulse sequences required for exchange-only two-qubit logic and randomized benchmarking.

Current treatment in Europe for adrenal insufficiency in neonates and infants is unsatisfactory as unlicensed adult dosage formulations are used. These are difficult to administer and may give rise to inconsistencies in dose as the content uniformity of the dosage form cannot be verified. As there is no licensed hydrocortisone formulation for children < 6 years hydrocortisone is often compounded by pharmacies using adult hydrocortisone tablets. In a recent study of compounded hydrocortisone up to 20% of the batches did not meet European Pharmacopeial accuracy and precision criteria (ECE 2014 Abstract #1278). This medication safety study investigated hydrocortisone individually and extemporaneously compounded for paediatric use in adrenally insufficient patients, meaning the current therapy is inadequate in up to every 5th child treated. Thus, there is a need for specifically designed and licensed hydrocortisone formulations for this vulnerable paediatric patient group especially neonates and infants.

We report on the fabrication and characterization of a few-electron quantum dot controlled by a single gate electrode. Our device has a double-quantum-well design, in which the doping controls the occupancy of the lower well while the upper well remains empty under the free surface. A small air-bridged gate contacts the surface, and is positively biased to draw laterally confined electrons into the upper well. Electrons tunneling between this accumulation-mode dot and the lower well are detected using a quantum point contact (QPC), located slightly offset from the dot gate. The charge state of the dot is measured by monitoring the differential transconductance of the QPC near pinch-off. Addition spectra starting with N=0 were observed as a function of gate voltage. DC sensitivity to single electrons was determined to be as high as 8.6%, resulting in a signal-to-noise ratio of ~9:1 with an equivalent noise bandwidth of 12.1 kHz. Analysis of random telegraph signals associated with the zero to one electron transition allowed a measurement of the lifetimes for the filled and empty states of the one-electron dot: 0.38 ms and 0.22 ms, respectively, for a device with a 10 nm AlInAs tunnel barrier between the two wells., 3 pages, 3 figures

We report on an experimental demonstration of graphene-metal ohmic contacts with contact resistance below 100 Ω µm. These have been fabricated on graphene wafers, both with and without hydrogen intercalation, and measured using the transmission line method. Specific contact resistivities of 3 × 10−7 to 1.2 × 10−8 Ω cm2 have been obtained. The ultra-low contact resistance yielded short-channel (source-drain distance of 0.45 µm) HfO2/graphene field effect transistors (FETs) with a low on-resistance (Ron) of 550 Ω µm and a high current density of 1.7 A/mm at a source-drain voltage of 1 V. These values represent state-of-the-art (SOA) performance in graphene-metal contacts and graphene FETs. This ohmic contact resistance is comparable to that of SOA high-speed III–V high electron mobility transistors.

Two patients underwent resection and replacement of the ascending aorta using a low-porosity Teflon graft anastomosed with silk suture. In both patients false aneurysms developed that required operation 13 and 23 years postoperatively. The clinical courses of these patients, along with data from the literature, suggest that the combination of a low-porosity Teflon graft and a silk suture anastomosis presents a major potential hazard for the development of anastomotic false aneurysm.

A preliminary report is presented of a prospective randomized trial conducted by eight cooperative institutions under the auspices of the National Heart and Lung Institute to compare the effectiveness of medical and surgical therapy in the management of the acute stages of unstable angina pectoris. To date 150 patients have been included in the randomized trial, 80 assigned to medical and 70 to surgical therapy; the clinical presentation, coronary arterial anatomy and left ventricular function in the two groups are similar. Some physicians have been reluctant to prescribe medical or surgical therapy by a random process, and the ethical basis of the trial has been questioned. Since there are no hard data regarding the natural history and outcome of therapy for unstable angina pectoris, randomization appears to provide a rational way of selecting therapy. Furthermore, subsets of patients at high risk may emerge during the process of randomization. The design of this randomized trial is compared with that of another reported trial. Thus far, the study has shown that it is possible to conduct a randomized trial in patients with unstable angina pectoris, and that the medical and surgical groups have been similar in relation to the variables examined. The group as a whole presented with severe angina pectoris, either as a crescendo pattern or as new onset of angina at rest, and 84 percent had recurrence of pain while in the coronary care unit and receiving vigorous medical therapy. It is anticipated that sufficient patients will have been entered into the trial within the next 12 months to determine whether medical or surgical therapy is superior in the acute stages of unstable angina pectoris.

Attention is called to the development of total obstruction to right ventricular outflow in patients with cyanotic congenital cardiac disease after systemic to pulmonary arterial anastomoses. The clinical and necropsy features are described in 4 patients in whom right ventricular outflow obstruction developed (in 3 at valve level-“acquired pulmonic atresia”-and in 1 at infundibulum) from 13 to 19 years after pulmonary to systemic shunt operations. The mechanism of development of right ventricular outflow obstruction in these patients is discussed.

Ventricular function was evaluated in 18 patients prior to left ventriculography and selective coronary arteriography. Simultaneous left ventricular pressure (catheter-tip manometer) and dP/dt were recorded at resting heart rates and during tachycardia induced by right atrial pacing. Pressure-velocity curves were constructed from which V max and maximum measured contractile element velocity (max V CE ) were obtained. V max and max V CE initially increased with pacing-induced tachycardia in 17 of the 18 patients. Eight patients developed evidence of myocardial ischemia during atrial pacing. During the period of myocardial ischemia there was a decrease in V max and max V CE in all eight patients despite constant or increasing heart rate. In the 10 patients who did not develop evidence of myocardial ischemia with pacing-induced tachycardia, V max and max V CE continued to increase or remained constant with increasing rate. Peak left ventricular dP/dt increased coincident with the onset of myocardial ischemia in six of eight patients despite a fall in V max and max V CE in all eight patients during the ischemic period. A highly significant difference was demonstrated between V max values of patients with normal ejection fractions and patients with low ejection fractions, both at rest and during pacing-induced tachycardia.

Infarct site, extent, and the degree of associated asynergy are major determinants of the hemodynamic consequences of myocardial infarction. Although conventional electrocardiography and vectorcardiography are routinely employed in assessing the location and size of infarction, they are relatively nonspecific. The newer techniques of high-frequency electrocardiography and isopotential mapping offer promise but have yet to undergo systematic evaluation. A rough measure of the extent of infarction is obtained from serum enzyme measurements. However, they furnish no information with regard to localization. The region of infarction may be detected by precordial scanning following the intravenous or intracoronary injection of a radioisotope. The infarct may be revealed as an area of decreased perfusion (cold spot) or as an area to which a specific radioactive label is bound (hot spot). With the availability of newer radionuclides such as 43 potassium and the use of computer techniques, a more precise means of localizing and quantifying myocardial infarction may become available. Optimal definition of asynergy is obtained with contrast angiography. However, the risk of this procedure has limited its use, to date, in acute myocardial infarction. Apex- and kinetocardiography, chest X-ray, and fluoroscopy often suggest regional ventricular dysfunction, but these techniques are not sufficiently specific. Newer noninvasive methods for objectively evaluating regional ventricular dysfunction are ECG-gated cardiac scintiphotography and radarkymography. With ECG-gated scintiphotography, end-diastolic and end-systolic cardiac isotope images are obtained following intravenous injection of 99m technetium-albumin. From these images, assessment of asynergy and extent and location of infarct can be made. With radarkymography, heart-wall motion is assessed and quantitated by tracking segments of the cardiac silhouette visualized on a cinefluorogram. These techniques are ideally suited to the acutely ill patient. Echocardiography is another noninvasive technique with potential application to the study of asynergy. However, at present, only posterior-wall motion can be measured. At the time of surgery regions of infarction may be localized by means of chemical indicators (fluoroscein), isotope techniques, or epicardial electrocardiographic mapping. Recently much has been learned about the hemodynamics of myocardial infarction. Through the use of the techniques described, further insight into regional ventricular abnormality and extent and localization of myocardial infarction could be obtained. With this information better approaches to therapy and prognosis could be developed. Many students of the coronary circulation must have noted that the ventricular zone affected by ligating a large coronary branch not only appears cyanotic and dilated, but that it seems to alter in its mode of contraction. The detailed and sequential changes in contraction are not easily followed by the unaided eye and so far have not been recorded myographically. The reasons for this were the lack of an adequate and suitable myograph and a technique for the application of one to a limited ventricular surface so that records obtained represent, at least reasonably well, changes in muscle length and not predominantly artifacts due to position changes, thrusts and vibrations of the vigorously beating ventricle. 1

Indicators can be used to measure myocardial blood flow if the myocardial circulation can be isolated from other segments of the systemic circulation. Methods of measuring myocardial blood flow can be divided into groups according to the technic employed to provide "isolation" of the myocardium. There is no practical method of proved accuracy whereby coronary blood flow can be measured in man in absolute terms of ml./min. All the so-called clearance methods measure myocardial blood flow in flow/volume units or ml./min./100 Gm. Myocardial blood flow measurements in these flow/volume units have not proved useful in separation of normal individuals from those with ischemic heart disease at rest, but have been useful in the study of acute intervention such as exercise or the administration of drugs.

In 11 patients with hypertension associated with acute myocardial infarction intravenous phentolamine decreased the elevated left ventricular filling pressure. Cardiac index increased with a small decrease in arterial pressure, and therefore the same or increased stroke work was achieved at a lower filling pressure. In patients with acute hypertension myocardial oxygen demand was decreased and this may tend to increase infarct size. The potentially beneficial effects were less great in patients with chronic hypertension antedating the myocardial infarction.

In three patients with the tetralogy of Fallot cardiac catheterization has revealed increased pulmonary vascular resistance four to ten years following construction of systemic to pulmonary anastomoses. The continuous murmur disappeared in two patients and became barely audible in another. The initial clinical improvement was reversed in all three. As the pulmonary artery pressure rose, the pressure gradient between the right ventricle and pulmonary artery diminished in four patients and disappeared in one. In one patient cyanosis had not yet developed and the continuous murmur was audible, although pulmonary hypertension was present. In another patient massive pulmonary artery dilatation was present and the pulmonary artery pressure rose, but pulmonary vascular resistance was not strikingly increased.

The pharmacodynamics of nitroglycerin have been studied in dogs and man. In dogs, intravenous nitroglycerin (TNG) caused a decrease in left ventricular work, myocardial blood flow (MFB), and myocardial oxygen consumption, and no significant change in coronary vascular resistance. Intracoronary artery TNG in dogs caused an immediate increase in MBF and a decrease in coronary vascular resistance that persisted until arterial pressure fell. In man, sublingual TNG (0.4 mg.) caused a decrease in left ventricular work, MBF, and myocardial oxygen consumption, and no significant decrease in coronary vascular resistance in patients with and without arteriographically proven coronary artery disease. The injection of doses of 0.1 to 0.2 mg. of TNG directly into the coronary artery in man caused an immediate increase in MBF and a decrease in coronary vascular resistance in patients with and without arteriographically proven coronary artery disease. The hypothesis proposed for the mechanism of action of TNG in the relief of angina pectoris is first, a decrease in coronary vascular resistance due to its effect on the coronary circulation, and, secondly, a decrease in cardiac work due to its effect on the systemic circulation.

Five cases of postoperative aneurysm of the ductus arteriosus are presented and discussed, together with 12 from the literature. The ductus had become recanalized in all 17 patients. Infection was present in 11, having existed preoperatively in only two of these cases. The evidence suggests that contamination at the time of surgery was responsible for the infection in at least seven cases.

decade ago cardiac surgical teams were organized in many hospitals throughout the United States. Some of these failed to function satisA factorily because of poor planning, inadequate staff and material resources, or insufficient case loads. Others remained in existence but with resources and case loads so marginal as to raise serious questions about their effectiveness, safety, and economic soundness. With the introduction of new techniques for coronary artery surgery, hospitals are again being stimulated to expand their surgical programs, and there is evidence that we may again

Summary It is difficult to predict what the ultimate role of vein bypass surgery may be in the management of patients with ischemic heart disease. There is reason for optimism and it seems likely that this operation or its derivatives will find a permanent place in the therapeutic armamentarium. It is equally clear that there is need for a more precise definition of indications. The population to which the procedure should be offered may be much smaller or possibly much larger than that in which it is currently used. The best summary would appear to be the following listing of the facts that are known and not known at the time of this writing.

1. 1. Left ventricular cineangiograms of 9 patients with “idiopathic hypertrophic subaortic stenosis” were studied with reference to rate and pattern of left ventricular contraction, and compared with similar studies of 11 normal subjects and 8 patients with valvular aortic stenosis. 2. 2. The ventricle in “idiopathic hypertrophic subaortic stenosis” emptied more completely and in less time than did the unobstructed normal ventricle. The left ventricle in valvular aortic stenosis emptied more completely than did the normal, but required a significantly longer time interval. 3. 3. Increased pressure gradients in the same IHSS patient after premature beats or after isoproterenol were associated with more rapid and complete ventricular emptying, rather than evidence of increased obstruction. 4. 4. In no case was significant narrowing of the left ventricular outflow tract seen in the RAO projection. Additional LAO views were obtained in 4 patients, and no narrowing was seen. There was no distinguishable difference in the pattern of subvalvular versus apical contraction between the three groups to suggest outflow tract obstruction in the “idiopathic hypertrophic subaortic stenosis” group—i.e., neither early subvalvular contraction nor delayed apical emptying were seen. 5. 5. These data provide evidence that the pressure gradient in “idiopathic hypertrophic subaortic stenosis” is not due to obstruction in those patients in whom obstruction is not clearly demonstrated by other means.

An early systolic click and a normal or accentuated aortic second sound have been found in cases of aortic valve stenosis characterized cineradiographically by a mobile, dome-shaped valve. Impaired valve mobility was usually associated with a systolic click of low intensity, and in the presence of an immobile aortic valve there was no systolic click. The aortic second sound was correspondingly diminished or absent. Early systolic clicks and loud aortic closure sounds were also present in patients in whom a diseased aortic valve had been replaced by three Teflon prosthetic leaflets. In most of these patients there was no systolic click before insertion of the prosthesis. In the patients studied, the systolic click occurred at the end of the opening movement of the aortic valve at the onset of left ventricular ejection. It followed the crossover point of the left ventricular and aortic pressure pulses by a time interval ranging from 15 to 45 msec. (average 33 msec.). The opening movement of the valve was thought to produce the systolic click by causing sudden tension of the valve membrane or sudden alteration in the velocity of blood flow. By analogy with the opening snap in mitral stenosis, the early systolic click may be regarded as the "opening snap" of the aortic valve. A systolic click is clinical evidence of a mobile aortic valve in patients with aortic valve disease.

1. 1. Fourteen patients with pulmonary hypertension received 20 mg. of sublingual isoproterenol, and the hemodynamic effects were measured. 2. 2. Isoproterenol increased pulmonary blood flow and decreased pulmonary vascular resistance, whereas pulmonary arterial and pulmonary arterial wedge pressures remained unchanged. 3. 3. Isoproterenol caused active vasodilatation of the hypertensive pulmonary vascular bed.

Summary Angiocardiography has been demonstrated to be a useful supplement to left heart catheterization in the study of mitral valve disease. Angiocardiography appears to be a sensitive method of detecting mitral regurgitation. The characteristic cineangiocardiographic features of mitral regurgitation have been described.

Seventeen patients with late hemodynamic complications of anastomotic surgery for the tetralogy of Fallot have been studied. Two syndromes have been noted and both seem related to shunts of greater than ideal size. The clinical characteristics of these syndromes are delineated.

Ten hospitalized patients performed two exercise tests per day on five consecutive days to determine the efficacy and duration of action of three sublingual long-acting nitrate preparations: isosorbide dinitrate, pentaerythritol trinitrate, and erythrityl tetranitrate. The duration of exercise to the point of ischemia, manifest as typical anginal pain and/or 1.0 mm ST-segment depression, was determined 45 min and 100 min after each long-acting nitrate was administered. These results were compared with the duration of exercise after placebo and two minutes after nitroglycerin administration. The mean durations of exercise in two tests after placebo were 62.5 sec and 58.4 sec (not significant) and the mean durations of exercise after nitroglycerin administration were 90.5 sec and 88.4 sec, both different from placebo ( P < .001). There was no difference from placebo found 55 min after taking nitroglycerin. The mean durations of exercise 45 min after erythrityl tetranitrate, isosorbide dinitrate and pentaerythritol trinitrate were 89.1, 87.5, and 87.5 sec respectively and all were different from placebo ( P < .01). Mean durations of exercise 100 min after erythrityl tetranitrate, isosorbide dinitrate, and pentaerythritol trinitrate were 76.4, 75.5, and 69.7 sec and none were significantly different from placebo. This study indicates that each long-acting nitrate is effective for at least 45 min and suggests that they should not be given on a fixed dosage schedule but rather should be taken prophylactically whenever an angina-provoking situation is anticipated.

The safety and value of the transseptal technique of left heart catheterization previously reported from the National Heart Institute has been confirmed in 55 patients studied at the Johns Hopkins Hospital.

A system of multiple-lead exercise electrocardiography has been applied to the study of 107 normal subjects and 67 patients with angina pectoris. The results of this test are compared to those of coronary cinearteriography in 84 patients. In-exercise ECGs gave useful additional information in 59% of the angina patients but were essential for interpretation in 9%. It added considerably to the safety of the test. The value of each individual lead and of the multiple lead system was assessed. Lead V 6 was the most often positive, but each made a contribution in some cases. Test-retest reproducibility survey indicated that five of 65 tests on 25 subjects failed to conform. Evidence has been presented that 1.0 mm of ischemic S-T segment shift was the best criterion for a positive test in the subjects studied. The test was positive in 84% of 67 patients with angina pectoris and 3.7% of 107 normal subjects (excluding vasoregulatory hyperreactors). The double two-step test given to the first 41 of the same angina patients for comparison was found to give 61% positive reactions despite the use of multiple leads and in-exercise recording. The test was administered to 84 subjects who were studied concurrently by selective coronary cinearteriograms and these two parameters were compared with the clinical diagnosis of angina in each patient. Since each of these parameters represents a different facet of coronary arterial disease, the agreement among them is very instructive.

Thirty years ago most patients with a myocardial infarction were required to remain at rest in bed in a hospital for six weeks. Ten years ago the period of bed rest was three weeks, but six weeks o...

The results of phase II of the National Institutes of Health–sponsored Thrombolysis in Myocardial Infarction trial (TIMI II), which appear in this issue of the Journal,1 constitute a giant step for...