Absolute energies and emission line shapes of the L x-ray transitions of lanthanide metals.

We use an array of transition-edge sensors, cryogenic microcalorimeters with 4 eV energy resolution, to measure L x-ray emission-line profiles of four elements of the lanthanide series: praseodymium, neodymium, terbium, and holmium. The spectrometer also surveys numerous x-ray standards in order to establish an absolute-energy calibration traceable to the international system of units for the energy range 4 keV to 10 keV. The new results include emission line profiles for 97 lines, each expressed as a sum of one or more Voigt functions; improved absolute energy uncertainty on 71 of these lines relative to existing reference data; a median uncertainty on the peak energy of 0.24 eV, four to ten times better than the median of prior work; and six lines that lack any measured values in existing reference tables. The 97 lines comprise nearly all of the most intense L lines from these elements under broad-band x-ray excitation. The work improves on previous measurements made with a similar cryogenic spectrometer by the use of sensors with better linearity in the absorbed energy and a gold x-ray absorbing layer that has a Gaussian energy-response function. It also employs a novel sample holder that enables rapid switching between science targets and calibration targets with excellent gain balancing. Most of the results for peak energy values shown here should be considered as replacements for the currently tabulated standard reference values, while the line shapes given here represent a significant expansion of the scope of available reference data.

Energy Calibration of Nonlinear Microcalorimeters with Uncertainty Estimates from Gaussian Process Regression.

The nonlinear energy response of cryogenic microcalorimeters is usually corrected through an empirical calibration. X-ray or gamma-ray emission lines of known shape and energy anchor a smooth function that generalizes the calibration data and converts detector measurements to energies. We argue that this function should be an approximating spline. The theory of Gaussian process regression makes a case for this functional form. It also provides an important benefit previously absent from our calibration method: a quantitative uncertainty estimate for the calibrated energies, with lower uncertainty near the best-constrained calibration points.

Role of the H-2 complex in induction of T helper cells in vivo. III. Contribution of the I-E subregion to restriction sites recognized by I-A/E-restricted T cells.

Previous studies on negative selection of T cells to sheep erythrocytes in irradiated mice showed that CBA (I-Ak,I-Ek) (kk) T cells comprise two subgroups of cells restricted by I-A (A alpha-A beta) and I-A/E (E alpha-E beta) molecules. Selection of the I-A/E-restricted by I-A (A alpha-A beta) and I-A/E (E alpha-E beta) molecules. Selection of the I-A/E-restricted subset requires that the donor T cells and the selection host share both I-A (E beta) and I-E (E alpha) gene products; only the I-A-restricted cells undergo selection in B10.A(4R) (kb) mice. This paper demonstrates that negative selection of the I-A/E-restricted subgroup of CBA T cells can occur in F1 hybrids between B10.A(4R) and various Ia.7+ (E alpha+) I-E-incompatible strains; selection does not occur in hybrids between B10.A(4R) and Ia.7- (E alpha-) strains. These data suggest that, despite the fact that E alpha chains display detectable structural allelic variations, these chains are functionally nonpolymorphic. This conclusion applies to E alpha k,d,p,r,j chains. With F1 hybrids between B10.A(4R) and another Ia.7+ strain, B10.PL (H-2u), in contrast, only intermediate selection is observed. This finding is consistent with recent evidence that cell surface expression of E alpha-u-E beta dimers displays strong cis preference. In contrast to E alpha+ CBA T cells, E alpha- B10.A(4R) (kb) T cells undergo complete negative selection in hosts matched only in the I-A (and H-2K) subregion, i.e., B10.BR (kk) mice; no selection occurs in B10 (bb) mice. These data imply that Ia-restricted T cells in E alpha- strains are probably restricted solely by I-A molecules.

Role of the H-2 complex in induction of T helper cells in vivo. II Negative selection of discrete subgroups of T cells restricted by I-A and I-A/E determinants.

Previous studies have shown that negative selection of T cells to sheep erythrocytes (SRC) after adoptive transfer to irradiated mice requires a sharing of H-2 determinants between the donor T cells and the selection hosts. This paper examines which part of the H-2 complex controls selection. The results show that, in the case of T cells of the H-2k haplotype, complete selection occurs with donor host matching limited to the I-A through I-E subregions of the H-2 complex. Selection to SRC was partial in I-A compatible, I-E incompatible hosts, minimal or not detectable in I-A incompatible, I-E compatible hosts, but near-complete in hosts matched at both the I-A and I-E subregions. Consecutive selection in hosts matched solely at (a) the I-A subregion and (b) the I-E subregion led to incomplete selection. From these and other findings it is argued that H-2k T cells comprise a mixture of T cells restricted by I-A and I-A/E hybrid molecules.

Are cuffless devices challenged enough? Design of a validation protocol for ambulatory blood pressure monitors at the wrist: the case of the Aktiia Bracelet.

The US and European guidelines for the diagnosis and management of hypertension recommend the introduction of systematic home and night Blood Pressure (BP) monitoring. Fully-automated wearable devices can address the needs of patients and clinicians by improving comfort while achieving measurement accuracy. Often located at the wrist and based on indirect BP measurements, these devices must address the challenges of ambulatory scenarios. New validation strategies are needed, but little guidance has been published so far.In this work, we propose an experimental protocol for the validation of cuffless wrist BP monitors that addresses ambulatory environment challenges in a controlled experimental setting. The protocol assesses the robustness of the measurement for different body postures, the ability of the device to track BP changes, and its ability to deal with hydrostatic pressure changes induced by different arm heights.Performance testing using Aktiia Bracelet is provided as an illustration. The results of this pilot study indicate that the Aktiia Bracelet can generate accurate BP estimates for sitting and lying positions and is not affected by hydrostatic pressure perturbations.Clinical Relevance- Automated cuffless BP monitoring is opening a new chapter in the way patients are being diagnosed and managed. This paper provides a guidance on how to assess the clinical utility of such devices when used in different body positions.

Porphyrin triplet state probing the diffusion of oxygen in hemoglobin.

Laser photolysis study of porphyrin-globin shows that the triplet state of the porphyrin is detectable by its light absorption and that it can be used to determine the rate of penetration of oxygen into the hemoglobin pocket in which the porphyrin is embedded. The oxygen penetration rate does not determine the binding rate of oxygen to iron in hemoglobin.

A Robust Principal Component Analysis for Outlier Identification in Messy Microcalorimeter Data.

A principal component analysis (PCA) of clean microcalorimeter pulse records can be a first step beyond statistically optimal linear filtering of pulses toward a fully nonlinear analysis. For PCA to be practical on spectrometers with hundreds of sensors, an automated identification of clean pulses is required. Robust forms of PCA are the subject of active research in machine learning. We examine a version known as coherence pursuit that is simple and fast and well matched to the automatic identification of outlier records, as needed for microcalorimeter pulse analysis.

A comprehensive classification of mandibular fractures: a preliminary agreement validation study.

This study evaluates a comprehensive classification system for mandibular fractures based on imaging analysis. The AO/ASIF scheme, defining three fracture types (A, B, C), three groups within each type (e.g. A1, A2, A3) and three subgroups within each group (e.g. A1.1, A1.2, A1.3) with increasing severity from A1.1 (lowest) to C3.3 (highest) was used. The mandible is divided into two vertical units (I and V), two lateral horizontal units (II and IV) and one central unit (III) comprising the symphyseal and parasymphyseal region. Type A fractures are non-displaced, type B are displaced and type C are multifragmentary/defect injuries. Groups and subgroups are further defined in the classification system. Two classification sessions using semi-automatic software with 7 and 9 surgeons were performed to evaluate 100 fracture cases in the first session and 50 in the second. Inter-observer reliability and individual rater's accuracy were evaluated by kappa coefficient and latent class analysis, respectively. The analysis of inter-observer agreement for the detailed coding showed kappa coefficients around 0.50 with higher agreement among raters in the vertical units. This system allows standardization of documentation of mandibular fractures, although improvement in the definition of categories and their application is required.

A practical superconducting-microcalorimeter X-ray spectrometer for beamline and laboratory science.

We describe a series of microcalorimeter X-ray spectrometers designed for a broad suite of measurement applications. The chief advantage of this type of spectrometer is that it can be orders of magnitude more efficient at collecting X-rays than more traditional high-resolution spectrometers that rely on wavelength-dispersive techniques. This advantage is most useful in applications that are traditionally photon-starved and/or involve radiation-sensitive samples. Each energy-dispersive spectrometer is built around an array of several hundred transition-edge sensors (TESs). TESs are superconducting thin films that are biased into their superconducting-to-normal-metal transitions. The spectrometers share a common readout architecture and many design elements, such as a compact, 65 mK detector package, 8-column time-division-multiplexed superconducting quantum-interference device readout, and a liquid-cryogen-free cryogenic system that is a two-stage adiabatic-demagnetization refrigerator backed by a pulse-tube cryocooler. We have adapted this flexible architecture to mate to a variety of sample chambers and measurement systems that encompass a range of observing geometries. There are two different types of TES pixels employed. The first, designed for X-ray energies below 10 keV, has a best demonstrated energy resolution of 2.1 eV (full-width-at-half-maximum or FWHM) at 5.9 keV. The second, designed for X-ray energies below 2 keV, has a best demonstrated resolution of 1.0 eV (FWHM) at 500 eV. Our team has now deployed seven of these X-ray spectrometers to a variety of light sources, accelerator facilities, and laboratory-scale experiments; these seven spectrometers have already performed measurements related to their applications. Another five of these spectrometers will come online in the near future. We have applied our TES spectrometers to the following measurement applications: synchrotron-based absorption and emission spectroscopy and energy-resolved scattering; accelerator-based spectroscopy of hadronic atoms and particle-induced-emission spectroscopy; laboratory-based time-resolved absorption and emission spectroscopy with a tabletop, broadband source; and laboratory-based metrology of X-ray-emission lines. Here, we discuss the design, construction, and operation of our TES spectrometers and show first-light measurements from the various systems. Finally, because X-ray-TES technology continues to mature, we discuss improvements to array size, energy resolution, and counting speed that we anticipate in our next generation of TES-X-ray spectrometers and beyond.

Phase I clinical trial of orally administered 4-demethoxydaunorubicin (idarubicin) with pharmacokinetic and in vitro drug sensitivity testing in children with refractory leukemia.

Fifteen children with acute leukemia in relapse, refractory to conventional therapy, were treated with idarubicin administered orally for 3 consecutive days in dosages ranging from 30 to 50 mg/m2 per day at 19- to 21-day intervals. Gastrointestinal complications, including nausea, vomiting, abdominal pain, diarrhea and stomatitis, were the major forms of dose-limiting toxicity, affecting the majority of patients at all levels of idarubicin dosage. Two patients who had received total-body irradiation for bone marrow transplantation developed life-threatening gastrointestinal toxicity suggestive of a radiation "recall" phenomenon. Echocardiographic evidence of depressed cardiac function, without clinical symptoms or signs, was noted in six of 11 patients, although the changes were judged to be significant in only one child. The maximal tolerated oral dose of idarubicin was 40 mg/m2 per day. The medium terminal plasma half-life of idarubicin was 9.2 h (range, 6.4-25.5 h). Both idarubicin and its metabolite, idarubicinol, accumulated during the 3 days of therapy. Among the five patients with acute nonlymphoblastic leukemia whose cells were tested for drug sensitivity in vitro, the idarubicin concentration resulting in 50% inhibition (IC50) of cluster and colony formation ranged from 1.6 x 10(-10) M to 5 x 10(-7) M. There was no obvious relationship between the IC50 for idarubicin and that for epirubicin or daunorubicin. Oral idarubicin produced definite antileukemic effects, clearing blast cells from the circulation in 13 of the 14 evaluable patients. Future studies should define an optimal dose schedule to circumvent the limiting gastrointestinal complications associated with this agent.

Parameters controlling the kinetics of ferric and ferrous hemeproteins reduction by hydrated electrons.

To clarify the processes of hemeproteins reduction, three classes of these proteins (ferric, ferrous and desFe) were reduced by hydrated electrons generated by pulse radiolysis. Spectral and kinetic investigations were made on alpha hemoglobin chain and myoglobin. Human alpha chain has been chosen to avoid all ferric contaminations and horse ferric myoglobin to eliminate all ferrous protein fractions. We have successively studied the influences of: the iron presence, its oxidation state (II and III), the protein charge and the iron-ligand nature (H2O, OH-, N3- and CN-). For alpha human hemoglobin chain without metallic ion or with ferrous iron, the reduction rates are the same: 1.1 +/- 0.2.10(10) M-1.s-1. In the case of horse ferric myoglobin, the reduction rates depend principally on the protein charge (from pH 6.3 to pH 9.5, the reduction rate of Mb(FeIII)N3- decreases from 2.5 +/- 0.5.10(10) M-1.s-1 to 1.2 +/- 0.2.10(10) M-1.s-1) and are also modulated by the equilibrium constant of the hemeprotein-ligand association (1.2 +/- 0.2.10(10) M-1.s-1 for Mb(FeIII)N3- and 0.8 +/- 0.2.10(10) M-1.s-1 for Mb(FeIII)CN-, at pH 9.8).

Racial differences in hemodynamic responses to environmental thermal stress among adolescents.

BACKGROUND: Previous studies by our laboratory and others have shown that blood pressure (BP) responses to many short-term laboratory stressors are greater in black than in white children. We sought to determine the cardiac and vascular contributions to these differences in BP reactivity and whether racial differences in vascular reactivity involve excessive vasoconstriction or deficient vasodilation. METHODS AND RESULTS: We evaluated BP, heart rate, and impedance cardiographic measures of preejection period (PEP) and total peripheral resistance (TPR) in healthy black (n=76) and white (n=60) adolescents (mean age, 14.8 years) during passive exposure to a vasoconstrictive cold chamber (8 degrees C to 10 degrees C) and a vasodilatory heat chamber (40 degrees C to 42 degrees C). Results indicated greater decreases in PEP and increases in TPR in blacks than whites during cold exposure (P<0.05) but no group differences during heat exposure. Covariance analyses indicated that the racial differences during cold exposure probably reflected greater beta-adrenergic cardiac reactivity and alpha-adrenergic vasoconstrictive reactivity in blacks than whites. CONCLUSIONS: Blacks and whites exhibited comparable myocardial and vasodilatory responses to heat stress, but blacks exhibited heightened myocardial and vasoconstrictive reactivity to cold stress. These results suggest that the locus of racial differences in vascular reactivity involves vasoconstrictive rather than vasodilatory function. The pattern of racial differences during cold stress raises the possibility that both myocardial and vasoconstrictive mechanisms may contribute to the increased risk of hypertension in blacks.

Pulmonary/systemic flow ratio in children after cavopulmonary anastomosis.

OBJECTIVES: This study attempted to provide a formula for calculation of the pulmonary/systemic flow ratio in children after bidirectional cavopulmonary anastomosis. BACKGROUND: With the bidirectional cavopulmonary anastomosis, only the superior vena cava blood is oxygenated by the lungs. The inferior vena cava flow recirculates into the systemic circulation. The ratio of these flows will determine systemic arterial saturation. METHODS: According to the Fick principle, 1) Systemic cardiac output (liters/min) = Pulmonary venous flow + Inferior vena cava flow; 2) Systemic blood oxygen transport (ml/min) = Pulmonary venous blood oxygen transport + Inferior vena cava blood oxygen transport. By substituting the first equation into the second, Pulmonary/systemic flow ratio = (Systemic saturation - Inferior vena cava saturation)/(Pulmonary venous saturation - Inferior vena cava saturation). RESULTS: We applied the third formula to data obtained from 34 catheterizations in 29 patients after bidirectional cavopulmonary anastomosis. Mean [+/- SD] age at operation was 1.70 +/- 1.43 years, and mean age at catheterization was 2.95 +/- 1.65 years. The pulmonary/systemic flow ratio calculated for all 29 patients was 0.58 +/- 0.09. Of 17 patients with aortography, 10 had systemic to pulmonary collateral vessels. Patients with collateral vessels had a significantly higher pulmonary/systemic flow ratio (0.61 +/- 0.07 vs. 0.53 +/- 0.07, respectively, p < 0.02) and systemic saturation (88 +/- 4% vs. 82 +/- 4%, respectively, p < 0.002) than those without collateral vessels. The pulmonary/systemic flow ratio in those patients with no collateral vessels was similar to the previously reported echocardiographically derived superior vena cava/systemic flow ratio in normal children. CONCLUSIONS: The pulmonary/systemic flow ratio after bidirectional cavopulmonary anastomosis can be calculated. Pulmonary blood flow in these patients determines systemic saturation and accounts for the majority of venous return in young children.

Long-term multicenter experience with a second-generation implantable pacemaker-defibrillator in patients with malignant ventricular tachyarrhythmias. The Guardian Multicenter Investigators Group.

A second-generation implantable pacemaker-cardioverter-defibrillator was evaluated in 200 patients with sustained ventricular tachycardia, ventricular fibrillation or prior cardiac arrest. The device permits demand ventricular pacing for bradyarrhythmias and for long QT interval or tachycardia suppression, uses programmable (3 to 30 J) energy shocks for conversion of ventricular tachycardia and ventricular fibrillation and is used with conventional pacing and defibrillation leads. Ventricular tachycardia/fibrillation recognition is based on the ventricular electrogram rate and requires reconfirmation before shock delivery. Two hundred patients (mean age 62 years, mean left ventricular ejection fraction 36%) were enrolled and followed up for 0 to 23 months (mean 12). Epicardial lead system implantation was performed with use of an anterolateral thoracotomy (38%), median sternotomy (26%) and subxiphoid (20%) or subcostal (16%) approach. Perioperative mortality rate was 5.5% (all nonarrhythmic deaths). Implant defibrillation threshold ranged from 3 to 30 J (mean 15), with initial programmed shock energy ranging from 3 to 30 J (mean 22). Ventricular tachycardia/fibrillation sensing threshold ranged from 0.7 to 1.8 mV (median 1) and the tachycardia detection interval from 288 to 416 ms (median 320). Reprogramming of implant variables was necessary for reliable electrographic sensing (54 patients), programmed shock therapy (61 patients) and tachycardia detection rate (63 patients). Device activation for potential shock delivery occurred in 111 patients (55.5%) with actual shock delivery after ventricular tachycardia/fibrillation reconfirmation in 66 patients (33%). During follow-up study, there was a 1% arrhythmia mortality rate, 6.5% cardiac mortality rate and 10.5% total mortality rate. This study demonstrates that the programmable implantable pacemaker-cardioverter-defibrillator is effective in preventing arrhythmic death, yet reduces patient exposure to repeated shock therapy. Reprogramming is usually necessary during follow-up for optimal function.

Clinical and chemical assessment of thyroid function during therapy with amiodarone.

Clinical and chemical variables of thyroid function were studied in 26 patients with symptomatic ventricular tachyarrhythmias before and during long-term oral treatment with amiodarone. The mean (+/-SEM) pretreatment thyroxine (T4) level in the 26 patients was 7.32 +/- 0.33 micrograms/dL, and increased notably to 10.15 +/- 0.47 micrograms/dL by 30 to 120 days after treatment. The free thyroxine index (FT4I) was also notably elevated. Clinical hyperthyroidism or goiter did not develop, but clinical hypothyroidism occurred in four patients during and in one patient after discontinuation of amiodarone treatment. Notable titers of antithyroid antibodies were found in the serum of two of the five and a family history of thyroid disease was present in three of the five hypothyroid patients. An elevation of both the T4 level and the FT4I above the normal range is an expected finding in patients receiving amiodarone and does not by itself indicate hyperthyroidism. Patients with positive antithyroid antibodies or a family history of thyroid disease prior to treatment with amiodarone may be at an increased risk of hypothyroidism developing when treated with this drug.

Algorithms for Identification of Nearly-Coincident Events in Calorimetric Sensors.

For experiments with high arrival rates, reliable identification of nearly-coincident events can be crucial. For calorimetric measurements to directly measure the neutrino mass such as HOLMES, unidentified pulse pile-ups are expected to be a leading source of experimental error. Although Wiener filtering can be used to recognize pile-up, it suffers errors due to pulse-shape variation from detector nonlinearity, readout dependence on sub-sample arrival times, and stability issues from the ill-posed deconvolution problem of recovering Dirac delta-functions from smooth data. Due to these factors, we have developed a processing method that exploits singular value decomposition to (1) separate single-pulse records from piled-up records in training data and (2) construct a model of single-pulse records that accounts for varying pulse shape with amplitude, arrival time, and baseline level, suitable for detecting nearly-coincident events. We show that the resulting processing advances can reduce the required performance specifications of the detectors and readout system or, equivalently, enable larger sensor arrays and better constraints on the neutrino mass.

The Practice of Pulse Processing.

The analysis of data from x-ray microcalorimeters requires great care; their excellent intrinsic energy resolution cannot usually be achieved in practice without a statistically near-optimal pulse analysis and corrections for important systematic errors. We describe the essential parts of a pulse-analysis pipeline for data from x-ray microcalorimeters, including steps taken to reduce systematic gain variation and the unwelcome dependence of filtered pulse heights on the exact pulse-arrival time. We find these steps collectively to be essential tools for getting the best results from a microcalorimeter-based x-ray spectrometer.

HOLMES: The electron capture decay of [Formula: see text]Ho to measure the electron neutrino mass with sub-eV sensitivity.

The European Research Council has recently funded HOLMES, a new experiment to directly measure the neutrino mass. HOLMES will perform a calorimetric measurement of the energy released in the decay of [Formula: see text]Ho. The calorimetric measurement eliminates systematic uncertainties arising from the use of external beta sources, as in experiments with beta spectrometers. This measurement was proposed in 1982 by A. De Rujula and M. Lusignoli, but only recently the detector technological progress allowed to design a sensitive experiment. HOLMES will deploy a large array of low temperature microcalorimeters with implanted [Formula: see text]Ho nuclei. The resulting mass sensitivity will be as low as 0.4 eV. HOLMES will be an important step forward in the direct neutrino mass measurement with a calorimetric approach as an alternative to spectrometry. It will also establish the potential of this approach to extend the sensitivity down to 0.1 eV. We outline here the project with its technical challenges and perspectives.

Ethnicity, pressor reactivity, and children's blood pressure. Five years of observations.

During the 5 years of this investigation, resting blood pressure and pressor reactivity were measured in 292 white children and 46 black children in 1987, 1988, 1989, and 1991. In 1987, all children were in the third grade; in 1991, the children were in the seventh grade. Reactivity was assessed with a standardized psychological stressor, a television video game. Children displayed significant stability of absolute blood pressure and heart rate reactivity between grades 3 and 7. At all examinations, black children demonstrated blood pressure reactivity that was significantly greater in magnitude (both absolute level and change from resting measurements) than that of white children. Black children exhibited significantly greater heart rate reactivity only when defined as change from the resting measurements; absolute levels of heart rate reactivity were comparable for blacks and whites. For black children, blood pressure reactivity in 1987 was the strongest predictor of resting blood pressure (both systolic and diastolic) in 1991. Among white children, resting blood pressure was the strongest predictor of future resting blood pressure. Further research is needed to determine if ethnic differences in children's pressor reactivity are associated with ethnic differences in the prevalence of hypertension.

Patterns of sodium excretion during sympathetic nervous system arousal.

The purpose of this study was to examine Na+ handling and regulation during 1 hour of behaviorally induced sympathetic nervous system (SNS) arousal followed by 2 hours of recovery. Two patterns of response were observed among experimental subjects, despite similar changes in blood pressure and heart rate. In one group (n = 19), Na+ excretion increased significantly during SNS arousal, which then decreased significantly during recovery (12.3 versus 16.0 versus 13.1 meq/hr, baseline, SNS arousal, recovery, respectively). Changes in Na+ excretion were correlated with changes in creatinine clearance from baseline to SNS arousal (r = 0.54) and SNS arousal to recovery (r = 0.58), and were accompanied by significant increases in plasma renin activity (1.5 versus 2.0 ng/ml/hr) and aldosterone (8.5 versus 10.3 ng/ml/hr) from baseline to SNS arousal. Na+ excretion decreased during SNS arousal in the other group of subjects (n = 17) and remained below baseline levels during recovery (16.2 versus 12.7 versus 11.9 meq/hr). These changes were associated with significant decreases in creatinine clearance from baseline to recovery (138 versus 121 ml/min/1.73 m2) and significant increases in plasma renin activity from baseline to SNS arousal (1.3 versus 2.2 ng/ml/hr) but not in aldosterone. Control subjects (n = 24) maintained baseline levels of each variable throughout the procedure. These results suggest that individuals differ in Na+ handling and regulation during behavioral arousal. Decreases in Na+ have been reported previously in humans and animals at risk for the development of hypertension.