Intrinsic Low-Temperature Magnetism in SmB_{6}.

By means of new muon spin relaxation experiments, we disentangle extrinsic and intrinsic sources of low-temperature bulk magnetism in the candidate topological Kondo insulator (TKI) SmB_{6}. Results on Al-flux-grown SmB_{6} single crystals are compared to those on a large floating-zone-grown ^{154}Sm ^{11}B_{6} single crystal in which a 14 meV bulk spin exciton has been detected by inelastic neutron scattering. Below ∼10 K, we detect the gradual development of quasistatic magnetism due to rare-earth impurities and Sm vacancies. Our measurements also reveal two additional forms of intrinsic magnetism: (1) underlying low-energy (∼100 meV) weak magnetic moment (∼10^{-2} µ_{B}) fluctuations similar to those detected in the related candidate TKI YbB_{12} that persist down to millikelvin temperatures, and (2) magnetic fluctuations consistent with a 2.6 meV bulk magnetic excitation at zero magnetic field that appears to hinder surface conductivity above ∼4.5 K. We discuss potential origins of the magnetism.

Maternal Support of Children's Early Numerical Concept Learning Predicts Preschool and First-Grade Math Achievement.

The primary goal in this study was to examine maternal support of numerical concepts at 36 months as predictors of math achievement at 4½ and 6-7 years. Observational measures of mother-child interactions (n = 140) were used to examine type of support for numerical concepts. Maternal support that involved labeling the quantities of sets of objects was predictive of later child math achievement. This association was significant for preschool (d = .45) and first-grade math (d = .49), controlling for other forms of numerical support (identifying numerals, one-to-one counting) as well as potential confounding factors. The importance of maternal support of labeling set sizes at 36 months is discussed as a precursor to children's eventual understanding of the cardinal principle.

Interaction between the Val158Met catechol-O-methyltransferase gene variant and second-generation antipsychotic treatment on blood pressure in children.

Second-generation antipsychotic (SGA) medications are associated with cardiometabolic risk factors such as obesity and elevated blood pressure (BP) in some individuals. The goal of this study is to determine whether the Val158Met variant (rs4680) in the catechol-O-methyltransferase (COMT) gene, associated with BP in adults, is associated with elevated BP in SGA-treated children. A cross-sectional population of SGA-treated (n=134) and SGA-naive (n=168) children, ⩽18 years of age, were genotyped and assessed for markers of cardiometabolic health. An interaction was found between SGA treatment and COMT genotype for BP. After adjusting for covariates, SGA-treated children with the Met allele had higher systolic and diastolic BP (P=0.014 and P=0.034, respectively), and higher fasting glucose concentrations (P=0.030) compared with children with the Val/Val genotype. This was not observed in SGA-naive children. The Met allele of the COMT Val158Met variant may identify SGA-treated children at risk for elevated BP and fasting blood glucose concentrations.

Deformation twinning and the role of amino acids and magnesium in calcite hardness from molecular simulation.

We employ classical molecular dynamics to calculate elastic properties and to model the nucleation and propagation of deformation twins in calcite, both as a pure crystal and with magnesium and aspartate inclusions. The twinning is induced by applying uniaxial strain to the crystal and relaxing all stress components except the uniaxial component. A detailed analysis of the atomistic processes reveal that the twinning mechanism involves small displacements of the Ca ions and cooperative rotations of the CO3 ions. The volume of the twinned region expands under increased uniaxial strain via the propagation of steps along the twin boundaries. The energy cost of the twin boundaries is compensated by the reduced hydrostatic stress and strain energy. The presence of biogenic impurities is shown to decrease the strain required to induce twin formation in calcite and, thus, the yield stress. This increased propensity for twinning provides a possible explanation for the increased hardness and penetration resistance observed experimentally in biominerals.

Comparing the Finapres and Caretaker systems for measuring pulse transit time before and after exercise.

We aimed to compare the Finapres system, which is designed for accurate intra-arterial amplitude measurement, to the Caretaker system, which is designed for temporal accuracy of intra-arterial measurement, in regard to measurement of pulse transit time (PTT) at baseline and following an endurance exercise session. Pulse transit time was evaluated between the R-wave of the ECG and the foot of the arterial waveform using either the Finapres (fpPTT) or Caretaker (ctPTT). 23 participants were measured before and after completion of endurance exercise. When comparing PTT values before and after an exercise intervention within devices, ctPTT was significantly different following exercise (P=0.03); however, the Finapres obtained values did not differ significantly. Before exercise, there was no significant relationship between devices, however, after exercise a significant moderate correlation was observed (r=0.45, P=0.02). Significant differences existed between ctPTT and fpPTT (P< 0.001). The Caretaker system appears to be more accurate at detecting changes in PTT occurring as a result of a single aerobic exercise session. This may be due to the servo-controller feedback loop in the waveform contour predicting algorithm within the Finapres system, which is not present in the Caretaker unit. The Finapres system also appears to have an inherent delay in pulse contour reporting.

Systemic arterial compliance following ultra-marathon.

There is a growing interest in training for and competing in race distances that exceed the marathon; however, little is known regarding the vascular effects of participation in such prolonged events, which last multiple consecutive hours. There exists some evidence that cardiovascular function may be impaired following extreme prolonged exercise, but at present, only cardiac function has been specifically examined following exposure to this nature of exercise. The primary purpose of this study was to characterize the acute effects of participation in an ultra-marathon on resting systemic arterial compliance. Arterial compliance and various resting cardiovascular indices were collected at rest from 26 healthy ultra-marathon competitors using applanation tonometry (HDI CR-2000) before and after participation in a mountain trail running foot race ranging from 120-195 km which required between 20-40 continuous hours (31.2±6.8 h) to complete. There was no significant change in small artery compliance from baseline to post race follow-up (8.5±3.4-7.7±8.2 mL/mmHgx100, p=0.65), but large artery compliance decreased from 16.1±4.4 to 13.5±3.8 mL/mmHgx10 (p=0.003). Participation in extreme endurance exercise of prolonged duration was associated with acute reductions in large artery compliance, but the time course of this effect remains to be elucidated.

PIERS proteinuria: relationship with adverse maternal and perinatal outcome.

OBJECTIVE: To examine the ability of three different proteinuria assessment methods (urinary dipstick, spot urine protein:creatinine ratio [Pr/Cr], and 24-hour urine collection) to predict adverse pregnancy outcomes. METHODS: We performed a prospective multicentre cohort study, PIERS (Preeclampsia Integrated Estimate of RiSk), in seven academic tertiary maternity centres practising expectant management of preeclampsia remote from term in Canada, New Zealand, and Australia. Eligible women were those admitted with preeclampsia who had at least one antenatal proteinuria assessment by urinary dipstick, spot urine Pr/Cr ratio, and/or 24-hour urine collection. Proteinuria assessment was done either visually at the bedside (by dipstick) or by hospital clinical laboratories for spot urine Pr/Cr and 24-hour urine collection. We calculated receiver operating characteristic area under the curve (95% CI) for each proteinuria method and each of the combined adverse maternal outcomes (within 48 hours) or adverse perinatal outcomes (at any time). Models with AUC ≥ 0.70 were considered of interest. Analyses were run for all women who had each type of proteinuria assessment and for a cohort of women ("ALL measures") who had all three proteinuria assessments. RESULTS: More women were proteinuric by urinary dipstick (≥ 2+, 61.4%) than by spot urine Pr/Cr (≥ 30 g/mol, 50.4%) or 24-hour urine collection (≥ 0.3g/d, 34.7%). Each proteinuria measure evaluated had some discriminative power, and dipstick proteinuria (categorical) performed as well as other methods. No single method was predictive of adverse perinatal outcome. CONCLUSION: The measured amount of proteinuria should not be used in isolation for decision-making in women with preeclampsia. Dipstick proteinuria performs as well as other methods of assessing proteinuria for prediction of adverse events.

A systematic review of exercise as a therapeutic intervention to improve arterial function in persons living with spinal cord injury.

STUDY DESIGN: All randomized controlled trials, prospective cohort, case-controlled, pre-post studies and case reports that assessed exercise interventions, which influence arterial structure and function after spinal cord injury (SCI), were included. OBJECTIVE: To review systematically the evidence for exercise as a therapy to alter arterial function in persons with SCI. SETTING: Literature searches were conducted for appropriate articles using several electronic databases (e.g. MEDLINE, EMBASE). METHODS: Three independent reviewers evaluated each investigation's quality, using the Physiotherapy Evidence Database Scale for randomized controlled trials and Downs and Black Scale for all other studies. Results were tabulated and levels of evidence assigned. RESULTS: A total of 283 studies were found through the systematic literature search. Upon review of the articles, 27 were included. The articles were separated into those investigating arterial benefits, resulting from either acute bouts of exercise or long-term exercise interventions. The ability of both acute and long-term exercise interventions to improve arterial structure and function in those with SCI was supported by limited to moderate methodological quality. Upper body wheeling is the most commonly examined exercise therapy for improving arterial function. It appears from the evidence that a variety of exercise interventions, including passive exercise, upper body wheeling, functional electrical stimulation and electrically stimulated resistance exercise, can improve arterial function in those living with SCI. CONCLUSIONS: Although the quality and volume of evidence is low, the literature supports exercise as a useful intervention technique for improving arterial function in those with SCI.

[Coumarin-induced necrosis--a rare complication of oral anticoagulant therapy]. / Necroza cumarinica--complicatie rara a terapiei anticoagulante orale.

Coumarin-induced skin necrosis represents a clinical entity that occurs very rarely, with an approximate incidence of 0.01-0.1% at patients following oral anticoagulant therapy. Most of the cases become clinical manifest between the 3rd and 6th of anticoagulant treatment (there were reports of late onset of skin necrosis after 15 years of anticoagulant therapy) and the most involved areas include breast, buttocks and thighs microcirculation-rich areas. Early symptoms include paresthesia and sensation of tension associated with an erythematous flush in the affected area. Lesions are well demarcated, painful, initially erythematous or hemorrhagic, with the onset of skin necrosis in the end stage. Early lesions can be reversible with the discontinuation of anticoagulant therapy, but skin necrosis can reoccur even without any other coumarin based treatment. We report the case of a 55-year-old female who presented with coumarin-induced skin necrosis affecting the right breast and the right deltoid area.

[Beyond benefit evaluation: Considering the unintended consequences of telehealth]. / Au-delà de l'évaluation des bénéfices : réflexion sur les conséquences inattendues de la télésanté.

Telehealth is seen as a key lever in health policy choices. However, many challenges remain in terms of its successful integration into clinical practices. To date, many telehealth initiatives are struggling to move beyond the pilot project stage. This is partly due to a culture of innovation that is mainly focused on the expected benefits of the technology and less on the changes and transformations it can generate. Telehealth is used in health care organizations with complex social dynamics, to say the least. Its introduction has unintended consequences that can affect patients, communities, professionals, organizations, health systems and society as a whole. The aim of this article is to discuss some of the unintended consequences of using telehealth in health care organizations and systems.

[Left laparoscopic lobectomy]. / Lobectomie stânga pe cale laparoscopica pentru hepatocarcinom dezvoltat pe ficat non-cirotic--prezentare de caz.

The authors present a case of a 61-year-old patient diagnosed with a hepatic tumor located in the second segment with expression on the anterior (diaphragmatic) side. The diagnosis and treatment applied in this case are presented. The specific feature was the surgical intervention because it was performed a left laparoscopic lobectomy using the LigaSure Atlas sealer. The short hospitalization period and quick recovery make this method an efficient one, with a wide application. Laparoscopic surgery started with a cholecystectomy which was performed by Mouret in 1987. Since then it knew a continuous development with progressive extension of this type of approach to almost all of the digestive tract organs, cavitary as well as parenchymal organs like liver or spleen. Second and third bisegmentectomy was made for the first time in 1996 by Azagra. The segments II, III, IVb, V and VI are the most frequently resected in hepatic laparoscopic surgery. Surgeons are more interested in left hepatic lobe diseases because of the anatomy which makes the approach of the biliary and blood vessels easier. Lately we assist to an increase of hepatic cancer incidence, primary or secondary; therefore we consider necessary the development of hepatic laparoscopic surgical techniques.

Coexistence of ferromagnetic fluctuations and superconductivity in the actinide superconductor UTe2.

We report low-temperature muon spin relaxation/rotation (µSR) measurements on single crystals of the actinide superconductor UTe2. Below 5 K we observe a continuous slowing down of magnetic fluctuations that persists through the superconducting transition temperature (T c = 1.6 K), but we find no evidence of long-range or local magnetic order down to 0.025 K. The temperature dependence of the dynamic relaxation rate down to 0.4 K agrees with the self-consistent renormalization theory of spin fluctuations for a three-dimensional weak itinerant ferromagnetic metal. Our µSR measurements also indicate that the superconductivity coexists with the magnetic fluctuations.

DNA methylation reprogramming, TE derepression, and postzygotic isolation of nascent animal species.

The genomic shock hypothesis stipulates that the stress associated with divergent genome admixture can cause transposable element (TE) derepression, which could act as a postzygotic isolation mechanism. TEs affect gene structure, expression patterns, and chromosome organization and may have deleterious consequences when released. For these reasons, they are silenced by heterochromatin formation, which includes DNA methylation. Here, we show that a significant proportion of TEs are differentially methylated between the "dwarf" (limnetic) and the "normal" (benthic) whitefish, two nascent species that diverged some 15,000 generations ago within the Coregonus clupeaformis species complex. Moreover, TEs are overrepresented among loci that were demethylated in hybrids, indicative of their transcriptional derepression. These results are consistent with earlier studies in this system that revealed TE transcriptional derepression causes abnormal embryonic development and death of hybrids. Hence, this supports a role of DNA methylation reprogramming and TE derepression in postzygotic isolation of nascent animal species.

Neonatal intensive care unit discharge of infants with cardiorespiratory events: Tri-country comparison of academic centers.

OBJECTIVE: Compare how NICUs within academic centers in Canada, France, and the United States make discharge decisions regarding cardiorespiratory recordings and home use of apnea monitors, oximeters and caffeine. STUDY DESIGN: An anonymous survey was sent to neonatologists through the member listserv of the American Academy of Pediatrics Section on Perinatal Pediatrics, the Canadian Fellowship Program Directory, and to Level 3 NICUs in France. RESULTS: The response rates were 89% , 83% , and 79% for US, Canada and France respectively. In Canada, 45% perform pre-discharge recordings vs. 38% in France and 24% in the US. Apnea free days prior to discharge were required in 100% of centers in Canada, 96% in France, and 92% in the US. In Canada and France, 65% and 68% of units discharge patients on monitors vs. 99% in the US. 64% of the US centers sometimes use home caffeine compared to 40% in Canada and 34% in France. Over 60% of the centers in Canada and France wait until at least 40 weeks post menstrual age to discharge patients, whereas only about 33% of the US wait that late to discharge patients. CONCLUSIONS: Discharge practices from NICUs are not well standardized across institutions or countries. Canada and France keep infants in the hospital longer and are less likely than the US to use home monitoring and home caffeine.

Needle muscle biopsy with the automatic Biopty instrument.

Needle muscle biopsies are less traumatic and easier to do than open biopsies, but their main disadvantage is the small specimen size. One hundred and five patients underwent needle biopsies with a 14-gauge spring-loaded device that guillotines the muscle automatically (Bard Radiology). Fifty patients had more than one muscle biopsy. One hundred and forty-six of 155 specimens contained over 200 muscle fibers, some as many as 500 fibers. Having evaluated various needles, we found the Bard Biopty instrument more efficient than manual needles and open biopsy techniques, and it provides muscle specimens for pathologic interpretation that are comparable with open surgical procedures.

Phosphorylation and dephosphorylation of chromaffin cell proteins in response to stimulation.

Stimulation of bovine chromaffin cell in culture changed (increased or decreased) the phosphorylation state of several proteins as examined by 32P incorporation. Enhanced phosphorylation of 22 protein bands as well as increased dephosphorylation of a 20.4 kilodaltons protein band was observed when extracts of cultured chromaffin cells stimulated by either acetylcholine or high K+ were subjected to mono-dimensional gel electrophoresis. For several protein bands, the degree of phosphorylation was larger in cells stimulated by acetylcholine than in those challenged by a depolarizing concentration of K+. The most affected phosphoproteins have apparent molecular weights of 14,800, 29,000, 33,000, 57,000 (tubulin subunit), 63,000 (tyrosine hydroxylase subunit) and 94,000. The presence of a low extracellular calcium concentration (0.5 mM Ca2+ plus 15 mM Mg2+) in the incubation medium inhibited (38-100%) the acetylcholine-evoked increases in protein phosphorylation observed previously for 18 protein bands. Trifluoperazine at the concentration required for 50% inhibition of acetylcholine-induced catecholamine release decreases (33-100%) the stimulation-induced phosphorylation in all polypeptides, with the exception of the 14.8 kilodaltons and the dephosphorylated 20.4 kilodaltons components which were not affected. Two-dimensional gel electrophoresis analysis revealed that exposure of chromaffin cells to acetylcholine produced two types of effect on protein phosphorylation: activation of protein kinase activities affecting about 30 polypeptides; activation of protein phosphatase activities resulting in the dephosphorylation of about 40 polypeptides, most of them appearing as minor phosphoproteins, with the exception of the alpha-subunit of pyruvate dehydrogenase and the 20.4 kilodaltons polypeptide. On the basis of their molecular properties (molecular weight and pI) and their abundance in chromaffin cells, the 80 kilodaltons phosphoprotein which focused at pI 4.8 and the 117.5 kilodaltons phosphoprotein which focused at pI 5.0 were identified as chromogranins A and B, respectively. The relationship between acetylcholine-induced protein phosphorylation (or dephosphorylation) and catecholamine secretion was also investigated. The time course of protein phosphorylation (or dephosphorylation) paralleled or preceded [3H]noradrenaline release for 16 phosphoproteins.(ABSTRACT TRUNCATED AT 400 WORDS)

Trifluoperazine, a calmodulin inhibitor, blocks secretion in cultured chromaffin cells at a step distal from calcium entry.

Trifluoperazine, a calmodulin antagonist, inhibited the secretory response of cultured bovine adrenal medullary chromaffin cells to acetylcholine (10(-4) M) or a depolarizing concentration of [K+] (56 mM KCl) in a dose-related fashion. The ID50s of this effect were 2 x 10(-7) M and 2.2 x 10(-6) M for acetylcholine and high [K+], respectively. A decrease in external [Ca2+] concentration of the incubation medium from 4.4 to 0.275 mM resulted in an increase in the percentage of inhibition produced by trifluoperazine on the acetylcholine-evoked secretory response from 20.7 to 96.5%, respectively. However, trifluoperazine inhibited the acetylcholine-evoked catecholamine output by a similar absolute magnitude for all [Ca2+] concentrations tested with the exception of 4.4 mM [Ca2+]. Trifluoperazine, unlike the [Ca2+] channel blocker Ni2+, in concentrations (10(-6)-10(-5) M) that were found to inhibit significantly [K+]-induced amine output did not modify [K+]-induced 45Ca uptake or 45Ca efflux. However, trifluoperazine at a concentration of 2.5 x 10(-5) M was found to produce a small decrease in the 45Ca efflux curve and a decrease in the [K+]-evoked 45Ca uptake of 30 +/- 14% (n = 6). In addition, 2.5 x 10(-6) M trifluoperazine, a concentration which was found to suppress high [K+]-induced amine release by 64 +/- 5%, did not inhibit the 45Ca2+-Ca2+ exchange mechanism. These results demonstrate that trifluoperazine, an antipsychotic agent with anticalmodulin activity, blocks catecholamine release from cultured chromaffin cells at a step distal from calcium entry and, consequently, suggests a role for calmodulin in the secretory process of these cells.

Tyrosine hydroxylase phosphorylation in bovine adrenal chromaffin cells. Clonidine stimulates basal but inhibits nicotinic receptor evoked phosphorylation.

Clonidine inhibited the uptake of calcium and the overall phosphorylation of tyrosine hydroxylase induced by nicotinic receptor activation in bovine adrenal medullary chromaffin cells in culture. However, clonidine did not inhibit the increase in these parameters that accompanied K+ depolarisation of the cells. There was also no effect of clonidine on the overall phosphorylation of tyrosine hydroxylase when cells were stimulated by muscarine. Nicotinic receptor activation increased the phosphorylation of Ser-19, Ser-31, and Ser-40 on tyrosine hydroxylase, and this was inhibited by clonidine in a concentration-dependent manner. On the other hand, clonidine had no effect on calcium uptake, yet increased the phosphorylation of Ser-19 under basal conditions. Using calcium and calmodulin-stimulated protein kinase II obtained from rat brain clonidine increased the autophosphorylation of the alpha-subunit of the kinase by 37%, and also its activity against an exogenous peptide substrate by 29%. These data are consistent with the hypothesis that clonidine inhibits nicotinic receptor-induced tyrosine hydroxylase phosphorylation by decreasing calcium influx into chromaffin cells, perhaps by an action at the nicotinic receptor. Clonidine also increases the basal phosphorylation of tyrosine hydroxylase at Ser-19, perhaps by directly activating calcium and calmodulin-stimulated protein kinase II.

Autophosphorylation of calmodulin-stimulated protein kinase II in intact synaptosomes.

The major phosphoproteins observed after lysis of synaptosomes and incubation in the presence of [gamma-32P]ATP and calmodulin are the autophosphorylated 50-kDa and 60-kDa subunits of calmodulin-stimulated protein kinase II (CMK II). However, when intact synaptosomes are preincubated with 32Pi, these subunits are hardly labeled even after depolarization. The aim of this study was to determine the extent to which methodological factors contribute to this discrepancy. The distribution of CMK II between the outside and the inside of synaptosomes was determined by incubating intact and lysed synaptosomes with [gamma-32P]ATP. Some 38% of the 50-kDa subunit was found on the inside of synaptosomes, and at this location it would be accessible to ATP generated within synaptosomes during the preincubation with 32Pi and could be autophosphorylated. The rest (62%) was on the outside of the synaptosomes, presumably associated with postsynaptic densities, where it could not be autophosphorylated. The effect of preincubation at 37 degrees C on CMK II autophosphorylation was determined by incubating intact synaptosomes for 45 min. This reduced calmodulin-stimulated autophosphorylation of the 50-kDa subunit in lysed synaptosomes by 38% and in intact synaptosomes by 29%. Thus, 9% of the 50-kDa autophosphorylation activity within synaptosomes was lost by thermal inactivation during preincubation. The extent of this loss of activity depended on the synaptosomal protein concentration during preincubation. CMK II activity against its major endogenous substrate synapsin I and an exogenous peptide substrate was also decreased by preincubation. The effect of the ionic environment on CMK II autophosphorylation was determined by incubating lysed synaptosomes with [gamma-32P]ATP in the absence or presence of ions at concentrations that mimic the extra or intracellular environment.(ABSTRACT TRUNCATED AT 250 WORDS)

Hemorrhagic and vascular complications after percutaneous coronary intervention with adjunctive abciximab.

OBJECTIVES: To examine the frequency and nature of hemorrhagic and peripheral vascular complications associated with use of abciximab during percutaneous coronary intervention and to characterize high-risk patients. PATIENTS AND METHODS: We report the frequency and severity of bleeding and vascular complications recorded prospectively in 2,559 consecutive nonselected patients who underwent percutaneous coronary intervention at Mayo Clinic, Rochester, Minn, between July 1, 1996, and April 30, 1998, 831 of whom received abciximab and 1,728 did not. Abciximab and heparin were administered according to guidelines of the Evaluation of PTCA [percutaneous transluminal coronary angioplasty] to Improve Long-Term Outcome With Abciximab GP IIb/IIIa Blockade (EPILOG). RESULTS: Patients who received abciximab were more likely to be men, were more often treated within 12 hours of an acute myocardial infarction, and were more likely to have received heparin after the procedure (8.7 % vs 4.5%, P<.001). Major bleeding occurred in 18 patients (2.4%) who received abciximab and in 10 patients (0.6%) who did not receive abciximab (P<.001). Minor bleeding occurred in 108 patients (14.3%) and in 92 patients (5.9%), respectively (P<.001). Both major bleeding and minor bleeding were more frequent among patients within 12 hours of an acute myocardial infarction and were more frequent if abciximab had been used. Multivariate analysis revealed that use of abciximab was independently associated with major and minor bleeding. CONCLUSION: In this clinical setting, use of adjunctive abciximab during percutaneous coronary intervention was associated with a significantly increased risk of both major and minor bleeding.