Measurement sensitivity improvement in tapping-mode atomic force microscopy through bi-harmonic drive signal

This article presents a novel method to improve the measurement sensitivity and reduce impact forces in tapping-mode atomic force microscopy by reshaping the tip trajectory. A tapping drive signal composed of two harmonics is used to generate an oscillating trajectory with a broader valley compared to the typical sinusoidal trajectory. The wide broad valley reduces the velocity of the tip in the vicinity of the sample and allots a greater portion of each period in the vicinity of the sample. Numerical simulations show that this results in decreased impact force and increased sensitivity of the cantilever oscillation to changes in tip-sample offset. Experimental results demonstrate an increase in image sharpness and decrease in tip wear using the bi-harmonic driving signal.     

Suppression of afterpulsing in photomultipliers by gating the photocathode

A number of gating schemes to minimize the long-term afterpulse signal in photomultipliers have been evaluated. Blocking the excitation pulse by gating the photocathode was found to reduce the gate-on afterpulse background by a factor of 230 over that for nongated operation. This afterpulse or signal-induced background (SIB), which is particularly troublesome in stratospheric lidar measurements, appears as a weak exponentially decaying signal extending into the millisecond region after the photomultiplier tube (PMT) is exposed to an intense submicrosecond optical pulse. Photocathode gating is not feasible in PMTs with semitransparent bialkali photocathodes because of their slow gate response time, but is easily implemented in PMTs with opaque bialkali or semitransparent multialkali (S-20) photocathodes that can be gated with nanosecond response. In those PMTs with semitransparent bialkali photocathodes, a gated (adjacent) focus grid (if available) also produces a significant reduction in the SIB.     

Variation of nitric oxide concentration during inspiration

OBJECTIVE: To evaluate the pattern of inspiratory nitric oxide concentration in a simple, constant flow delivery system during the use of two phasic-flow ventilatory modes. DESIGN: Laboratory study in a lung model. SETTING: University experimental laboratory. SUBJECT: Nitric oxide (800 ppm in nitrogen) was administered continuously into the inspiratory circuit to deliver a nitric oxide concentration of 10 and 40 ppm to a test lung during volume-controlled (constant flow) and pressure-controlled (decelerating flow) ventilation, with an FIO2 of 1.0. INTERVENTIONS: In each mode, minute ventilation of 7, 14, and 21 L/min and installation of mixing chambers (none, 1-L, 2-L, and 3.2-L turbulence boxes) were studied, respectively. Nitric oxide and nitric dioxide were monitored by chemiluminescence. Since the nitric oxide/nitrogen gas is the only nitrogen source in the system during ventilation with an FIO2 of 1.0, we evaluated the fluctuation in the inspiratory nitric oxide (NOx) concentration by measuring nitrogen with a fast-response analyzer. To test the effect of the measurement site, we measured nitric oxide concentrations using chemiluminescence at different positions in the inspiratory and expiratory limbs, with and without the mixing chambers, with a minute ventilation of 14 L/min and a nitric oxide concentration of 40 ppm. MEASUREMENTS AND MAIN RESULTS: Nitrogen dioxide production was not influenced by the flow pattern. During a nitric oxide concentration of 10 ppm, nitrogen dioxide was always < 0.6 ppm. During a nitric oxide concentration of 40 ppm, the highest nitrogen dioxide (4.47 ppm) concentration was found at the lowest minute ventilation and the largest inspiratory circuit volume. Nitric oxide values displayed by chemiluminescence indicated stable concentrations at all settings. However, without mixing chambers, NOx concentration calculated from nitrogen measurements demonstrated marked inspiratory fluctuations and was highest with a minute ventilation of 21 L/min and higher during pressure-controlled ventilation compared with volume-controlled ventilation (nitric oxide concentration of 40 ppm, pressure-controlled ventilation: 14.5 to 130.5 ppm; volume-controlled ventilation: 21.6 to 104.7 ppm; nitric oxide concentration of 10 ppm, pressure-controlled ventilation: 3.2 to 30.9 ppm; volume-controlled ventilation: 4.5 to 27.1 ppm). NOx concentration fluctuation decreased with an increasing mixing chamber, and was negligible at all settings with the 3.2-L turbulence box. Nitric oxide concentration fluctuation influenced chemiluminescence measurements. The displayed nitric oxide values varied, depending on the sampling site, and did not accurately reflect mean inspiratory nitric oxide concentration. Incorporation of a mixing chamber eradicated this sampling site influence. CONCLUSIONS: Continuous flow delivery of nitric oxide into the circuit of a phasic-flow ventilator results in marked inspiratory nitric oxide concentration fluctuation that is not detected by a slow-response chemiluminescence analyzer. Moreover, nitric oxide concentration fluctuation can influence the accuracy of the chemiluminescence measurements. These effects can be diminished by using additional mixing chambers to facilitate a stable gas concentration. As these mixing volumes increase the contact time of nitric oxide with oxygen, an increase of nitrogen dioxide has to be taken into account.     

Combined oral positive inotropic and beta-blocker therapy for treatment of refractory class IV heart failure

OBJECTIVES: We sought to assess the effects of combined oral positive inotropic and beta-blocker therapy in patients with severe heart failure. BACKGROUND: Patients with severe, class IV heart failure who receive standard medical therapy exhibit a 1-year mortality rate >50%. Moreover, such patients generally do not tolerate beta-blockade, a promising new therapy for chronic heart failure. Positive inotropes, including phosphodiesterase inhibitors, are associated with increased mortality when administered over the long term in these patients. The addition of a beta-blocker to positive inotropic therapy might attenuate this adverse effect, although long-term oral inotropic therapy might serve as a bridge to beta-blockade. METHODS: Thirty patients with severe heart failure (left ventricular ejection fraction [LVEF] 17.2+/-1.2%, cardiac index 1.6+/-0.1 liter/min per m2) were treated with the combination of oral enoximone (a phosphodiesterase inhibitor) and oral metoprolol at two institutions. Enoximone was given at a dose of < or = 1 mg/kg body weight three times a day. After clinical stabilization, metoprolol was initiated at 6.25 mg twice a day and slowly titrated up to a target dose of 100 to 200 mg/day. RESULTS: Ninety-six percent of the patients tolerated enoximone, whereas 80% tolerated the addition of metoprolol. The mean duration of combination therapy was 9.4+/-1.8 months. The mean length of follow-up was 20.9+/-3.9 months. Of the 23 patients receiving the combination therapy, 48% were weaned off enoximone over the long term. The LVEF increased significantly, from 17.7+/-1.6% to 27.6+/-3.4% (p=0.01), whereas the New York Heart Association functional class improved from 4+/-0 to 2.8+/-0.1 (p=0.0001). The number of hospital admissions tended to decrease during therapy (p=0.06). The estimated probability of survival at 1 year was 81+/-9%. Heart transplantation was performed successfully in nine patients (30%). CONCLUSIONS: Combination therapy with a positive inotrope and a beta-blocker appears to be useful in the treatment of severe, class IV heart failure. It may be used as a palliative measure when transplantation is not an option or as a bridge to heart transplantation. Further study of this form of combined therapy is warranted.     

Eucapnic hypoxia lowers human cold thermoregulatory response thresholds and accelerates core cooling

Hypoxia lowers the basic thermoregulatory responses of animals and humans. In cold-exposed animals, hypoxia increases core temperature (Tco) cooling rate and suppresses shivering thermogenesis. In humans, the experimental effects of hypoxia on thermoregulation are equivocal. Also, the effect of hypoxia has not been separated from that of hypocapnia consequent to hypoxic hyperventilation. To determine the isolated effects of hypoxia on warm and cold thermoregulatory responses and core cooling during mild cold stress, we examined the Tco thresholds for sweating, vasoconstriction, and shivering as well as the core cooling rates of eight subjects immersed in 28 degrees C water under eucapnic conditions. On 2 separate days, subjects exercised on an underwater cycle ergometer to elevate Tco above the sweating threshold. They then rested and cooled until they shivered vigorously. Subjects inspired humidified room air during the control trial. For the eucapnic hypoxia trial, they inspired 12% O2-balance N2 with CO2 added to maintain eucapnia. Eucapnic hypoxia lowered the Tco thresholds for vasoconstriction and shivering by 0.14 and 0.19 degrees C, respectively, and increased core cooling rate by 33% (1.83 vs. 1.38 degrees C/h). These results demonstrate that eucapnic hypoxia enhances the core cooling rate in humans during mild cold stress. This may be attributed in part to a delay in the onset of vasoconstriction and shivering as well as increased respiratory heat loss during hypoxic hyperventilation.     

Use of instructions and apparatus-enhanced suggestion in treating a case of headaches, nightmares and nocturnal enuresis.

Verbal suggestions combined with an elaborate placebo ritual and apparatus (polygraph, relay rack, and oscilloscope) eliminated headaches, nightmares, and nocturnal enuresis in a 10-yr-old girl. S had no prior history of abnormal or maladaptive behavior and had begun exhibiting the problem behaviors after a serious accident. Treatment consisted of 4 placebo sessions. Target behaviors decreased rapidly and in a sequence consistent with a psychophysiologic analysis of their components but somewhat inconsistent with apparent sources of reinforcement. Treatment effects are attributed to cognitive process variables such as expectancy and attribution. Treatment gains were maintained at a 24-mo follow-up. (14 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The design of the SensVest

The SensVest is an item of wearable technology that measures, records and transmits aspects of human physical performance such as heart rate, temperature and movement. The SensVest has been designed for use by science teachers and students to meet their requirements. This paper reports the stages undertaken to design the SensVest, from determining appropriate methods of assessing human performance, to considerations of mounting the technology on the body. Trials have shown that concessions need to be made with ease of use and cost to ensure that the data collected is reliable and usable, with an awareness of the sensors limitations. By designing the SensVest with the wearer in mind a system has been developed that is comfortable, does not inhibit normal performance and is wearable. User trials have shown that meaningful, reliable and useful data can be collected using the SensVest.

Increased protein kinase C activity and expression of Ca2+-sensitive isoforms in the failing human heart

BACKGROUND: Increased expression of Ca2+-sensitive protein kinase C (PKC) isoforms may be important markers of heart failure. Our aim was to determine the relative expression of PKC-beta1, -beta2, and -alpha in failed and nonfailed myocardium. METHODS AND RESULTS: Explanted hearts of patients in whom dilated cardiomyopathy or ischemic cardiomyopathy was diagnosed were examined for PKC isoform content by Western blot, immunohistochemistry, enzymatic activity, and in situ hybridization and compared with nonfailed left ventricle. Quantitative immunoblotting revealed significant increases of >40% in PKC-beta1 (P<0.05) and -beta2 (P<0.04) membrane expression in failed hearts compared with nonfailed; PKC-alpha expression was significantly elevated by 70% in membrane fractions (P<0.03). PKC-epsilon expression was not significantly changed. In failed left ventricle, PKC-beta1 and -beta2 immunostaining was intense throughout myocytes, compared with slight, scattered staining in nonfailed myocytes. PKC-alpha immunostaining was also more evident in cardiomyocytes from failed hearts with staining primarily localized to intercalated disks. In situ hybridization revealed increased PKC-beta1 and -beta2 mRNA expression in cardiomyocytes of failed heart tissue. PKC activity was significantly increased in membrane fractions from failed hearts compared with nonfailed (1021+/-189 versus 261+/-89 pmol. mg-1. min-1, P<0.01). LY333531, a selective PKC-beta inhibitor, significantly decreased PKC activity in membrane fractions from failed hearts by 209 pmol. min-1. mg-1 (versus 42.5 pmol. min-1. mg-1 in nonfailed, P<0.04), indicating a greater contribution of PKC-beta to total PKC activity in failed hearts. CONCLUSIONS: In failed human heart, PKC-beta1 and -beta2 expression and contribution to total PKC activity are significantly increased. This may signal a role for Ca2+-sensitive PKC isoforms in cardiac mechanisms involved in heart failure.