The Boltzmann project.

The International Committee for Weights and Measures (CIPM), at its meeting in October 2017, followed the recommendation of the Consultative Committee for Units (CCU) on the redefinition of the kilogram, ampere, kelvin and mole. For the redefinition of the kelvin, the Boltzmann constant will be fixed with the numerical value 1.380 649 × 10-23 J K-1. The relative standard uncertainty to be transferred to the thermodynamic temperature value of the triple point of water will be 3.7 × 10-7, corresponding to an uncertainty in temperature of 0.10 mK, sufficiently low for all practical purposes. With the redefinition of the kelvin, the broad research activities of the temperature community on the determination of the Boltzmann constant have been very successfully completed. In the following, a review of the determinations of the Boltzmann constant k, important for the new definition of the kelvin and performed in the last decade, is given.

Appraisals of psychotic experiences: an experimental investigation of symptomatic, remitted and non-need-for-care individuals.

BACKGROUND: Appraisals are suggested to play a determining role in the clinical outcome of psychotic experiences (PEs). We used experimental tasks that mimic PEs to investigate appraisals in individuals with PEs with and without a 'need-for-clinical-care', and psychosis patients whose symptoms have remitted. We predicted that patients would appraise the tasks as threatening regardless of current symptom level, while non-clinical and control groups would appraise them as non-threatening. METHOD: Appraisals following three anomalous experiences-inducing tasks [Telepath, Cards task, Virtual acoustic space paradigm (VASP)] were examined in 71 individuals: symptomatic (n = 18) and remitted (n = 16) psychosis patients; non-clinical group with PEs (n = 16); controls without PEs (n = 21). RESULTS: As predicted, symptomatic patients endorsed more threatening appraisals for all tasks than non-clinical and control groups, who did not differ from each other. However, remitted patients were less likely to endorse threatening appraisals of the Cards and Telepath than their symptomatic counterparts, although they did not differ in global ratings of how striking, threatening and distressing they found the tasks. Moreover, remitted participants endorsed more threatening appraisals of the Telepath and VASP than non-clinical participants, and of the VASP than controls. Remitted participants also rated all three tasks as globally more threatening than the non-clinical group and controls. CONCLUSIONS: Clinical outcome may not necessarily be driven by the presence of symptoms, with threatening appraisals of PEs representing a key factor. The remitted group's intermediate appraisal scores imply that the relationship between appraisal and clinical outcome is not straightforward, and potential mediating factors need to be determined.

The paradoxical psychological effects of lysergic acid diethylamide (LSD).

BACKGROUND: Lysergic acid diethylamide (LSD) is a potent serotonergic hallucinogen or psychedelic that modulates consciousness in a marked and novel way. This study sought to examine the acute and mid-term psychological effects of LSD in a controlled study. METHOD: A total of 20 healthy volunteers participated in this within-subjects study. Participants received LSD (75 µg, intravenously) on one occasion and placebo (saline, intravenously) on another, in a balanced order, with at least 2 weeks separating sessions. Acute subjective effects were measured using the Altered States of Consciousness questionnaire and the Psychotomimetic States Inventory (PSI). A measure of optimism (the Revised Life Orientation Test), the Revised NEO Personality Inventory, and the Peter's Delusions Inventory were issued at baseline and 2 weeks after each session. RESULTS: LSD produced robust psychological effects; including heightened mood but also high scores on the PSI, an index of psychosis-like symptoms. Increased optimism and trait openness were observed 2 weeks after LSD (and not placebo) and there were no changes in delusional thinking. CONCLUSIONS: The present findings reinforce the view that psychedelics elicit psychosis-like symptoms acutely yet improve psychological wellbeing in the mid to long term. It is proposed that acute alterations in mood are secondary to a more fundamental modulation in the quality of cognition, and that increased cognitive flexibility subsequent to serotonin 2A receptor (5-HT2AR) stimulation promotes emotional lability during intoxication and leaves a residue of 'loosened cognition' in the mid to long term that is conducive to improved psychological wellbeing.

Estimates of the difference between thermodynamic temperature and the International Temperature Scale of 1990 in the range 118 K to 303 K.

Using exceptionally accurate measurements of the speed of sound in argon, we have made estimates of the difference between thermodynamic temperature, T, and the temperature estimated using the International Temperature Scale of 1990, T90, in the range 118 K to 303 K. Thermodynamic temperature was estimated using the technique of relative primary acoustic thermometry in the NPL-Cranfield combined microwave and acoustic resonator. Our values of (T-T90) agree well with most recent estimates, but because we have taken data at closely spaced temperature intervals, the data reveal previously unseen detail. Most strikingly, we see undulations in (T-T90) below 273.16 K, and the discontinuity in the slope of (T-T90) at 273.16 K appears to have the opposite sign to that previously reported.

Cardiac sarcoidosis: diagnosis and management.

Cardiac sarcoidosis is one of the most serious and unpredictable aspects of this disease state. Heart involvement frequently presents with arrhythmias or conduction disease, although myocardial infiltration resulting in congestive heart failure may also occur. The prognosis in cardiac sarcoidosis is highly variable, which relates to the heterogeneous nature of heart involvement and marked differences between racial groups. Electrocardiography and echocardiography often provide the first clue to the diagnosis, but advanced imaging studies using positron emission tomography and MRI, in combination with nuclear isotope perfusion scanning are now essential to the diagnosis and management of this condition. The identification of clinically occult cardiac sarcoidosis and the management of isolated and/or asymptomatic heart involvement remain both challenging and contentious. Corticosteroids remain the first treatment choice with the later substitution of immunosuppressive and steroid-sparing therapies. Heart transplantation is an unusual outcome, but when performed, the results are comparable or better than heart transplantation for other disease states. We review the epidemiology, developments in diagnostic techniques and the management of cardiac sarcoidosis.

Neutron emission spectrometer to measure ion temperature on the Fusion Demonstration Plant.

General Fusion is building the Fusion Demonstration Plant to demonstrate a magnetized target fusion scheme in which a deuterium plasma is heated from 200 eV to 10 keV by piston-driven compression of a liquid-lithium liner. The multilayer coaxial time-of-flight neutron emission spectrometer is designed to measure the ion temperature near peak compression at which time the neutron yield will approach 1018 neutrons/s. The neutron energy distribution is expected to be Gaussian since the machine uses no neutral beam or radio-frequency heating. In this case, analysis shows that as few as 500 coincidence events should be sufficient to accurately measure the ion temperature. This enables a fast time resolution of 10 µs, which is required to track the rapid change in temperature approaching peak compression. We overcome the challenges of neutron pile-up and event ambiguity with a compact design having two layers of segmented scintillators. The error in the ion temperature measurement is computed as a function of the neutron spectrometer's geometric parameters and used to optimize the design for the case of reaching 10 keV at peak compression.

Inlet protein aggregation: a new mechanism for lubricating film formation with model synovial fluids.

This paper reports a fundamental study of lubricant film formation with model synovial fluid components (proteins) and bovine serum (BS). The objective was to investigate the role of proteins in the lubrication process. Film thickness was measured by optical interferometry in a ball-on-disc device (mean speed range of 2-60 mm/s). A commercial cobalt-chromium (CoCrMo) metal femoral head was used as the stationary component. The results for BS showed complex time-dependent behaviour, which was not representative of a simple fluid. After a few minutes sliding BS formed a thin adherent film of 10-20 nm, which was attributed to protein absorbance at the surface. This layer was augmented by a hydrodynamic film, which often increased at slow speeds. At the end of the test deposited surface layers of 20-50 nm were measured. Imaging of the contact showed that at slow speeds an apparent 'phase boundary' formed in the inlet just in front of the Hertzian zone. This was associated with the formation of a reservoir of high-viscosity material that periodically moved through the contact forming a much thicker film. The study shows that proteins play an important role in the film-forming process and current lubrication models do not capture these mechanisms.

Comparing oxalic acid and sucrocide treatments for Varroa destructor (Acari: Varroidae) control under desert conditions.

The effectiveness of oxalic acid (OA) and Sucrocide (S) (AVA Chemical Ventures, L.L.C., Portsmouth, NH) in reducing populations of the varroa mite Varroa destructor Anderson & Trueman (Acari: Varroidae) in honey bee, Apis mellifera L. (Hymenoptera: Apidae) colonies was measured under the desert conditions of Arizona, USA. OA and S were applied three times 7 d apart. A 3.2% solution of OA was applied in sugar syrup via a large volume syringe, trickling 5 ml per space between frames in the colony. S was applied at a concentration of 0.625% (mixed with water), according to the label directions, using a compressed air Chapin sprayer at 20 psi to apply 59 ml per frame space. Varroa mites, collected on a sticky board before, during, and after the treatments, were counted to assess the effectiveness of the treatments. This study showed that a desert climate zone did not confer any positive or negative results on the acaricidal properties of OA. Even with brood present in colonies, significant varroa mite mortality occurred in the OA colonies. In contrast, we found that Sucrocide was not effective as a mite control technique. Despite its ability to increase mite mortality in the short-term, varroa mite populations measured posttreatment were not affected any more by Sucrocide than by no treatment at all.

Reflex influence of selective coronary artery occlusion on the total capacitance vasculature in the dog.

While the reflex influence of selective coronary arterial occlusion on the resistance vasculature has been well delineated, the reflex influence of coronary occlusion on the total capacitance vasculature has not been examined. Thus, selective coronary occlusions were performed in 65 anesthetized dogs. Blood was drained from the vena cavae and returned to the right atrium at a constant rate so that changes in total intravascular volume could be recorded as reciprocal changes in extracorporeal reservoir volume. In 10 animals, 2.5 min of left anterior descending occlusion was associated with only an insignificant total volume increase of 6 +/- 4 ml (SEM), whereas 2.5 min of left circumflex occlusion was associated with a 27 +/- 4 ml (P less than 0.001) increase in volume, which was significantly attenuated (P less than 0.001) to only a 7 +/- 3 ml increase after cervical vagectomy. Epicardial lidocaine in four animals reduced the volume increment associated with circumflex occlusion from 30 +/- 3 to 11 +/- 4 ml (P less than 0.025). The volume increase was attenuated from 45 +/- 6 to 24 +/- 5 ml with propranolol administration (P less than 0.001) (seven animals) and from 26 +/- 5 to 17 +/- 6 ml with atropine (P less than 0.025) (eight animals), but was not attenuated with phenoxybenzamine (28 +/- 7 ml before and 25 +/- 2 ml after phenoxybenzamine) (five animals). Double blockade with propranolol and atropine reduced the volume increase to 3 +/- 2 ml (NS) in four of these animals. In order to compare the influences of selective beta-1 adrenergic blockade and combined beta-1 and beta-2 blockade, volume responses were assessed before and after administration of metoprolol or propranolol in doses that produced the same amount of beta-1 blockade (15 animals). The volume increase associated with circumflex occlusion was not attenuated after beta-1 blockade (20 +/- 4 ml before and 18 +/- 5 ml after metoprolol) (eight animals) but was attenuated from 30 +/- 5 to 14 +/- 5 ml after propranolol (P less than 0.05) (seven animals). To examine further the efferent limb of the observed reflex, circumflex occlusions were performed before and after either vagectomy at the level of the diaphragm or section of the sympathetic splanchnic nerves in 12 animals. The volume increment was significantly attenuated after either procedure. In four animals undergoing prior arterial baroreceptor denervation, volume still increased 30 +/- 6 ml (P less than 0.001) with circumflex occlusion. Thus, inferior myocardial ischemia is associated with an autonomic reflex that acts to increase total intravascular volume. The afferent limb is mediated through the vagi, and the efferent limb, throug

The regulation of plasma 18-hydroxy 11-deoxycorticosterone in man.

18-hydroxy 11-deoxycorticosterone (18-OH DOC), a weak mineralocorticoid, was estimated by a radioimmunoassay procedure after purification in 49 patients with hypertension and 38 normal control subjects. The sensitivity of the method was 2-4 pg; there was no detectable blank, and the precision was 9-10%. In normal subjects the absolute plasma levels were similar to those of aldosterone. ACTH administration produced a 23-fold increase, and sodium restriction resulted in a 4-fold increase (5.4+/-0.7-20.5+/-3.0 ng/dl). On the other hand, the plasma levels of 18-OH DOC declined by nearly 50% with upright posture or angiotensin II infusion. During both of these procedures, plasma aldosterone levels significantly increased. Patients with normal and low renin hypertension had similar changes in plasma 18-OH DOC levels with sodium restriction. However, the mean high sodium level in the normal renin essential hypertension group (11.6+/-1.6 ng/dl) was significantly greater (P is less than 0.001) than in the control group (5.4+/-0.7 ng/dl). In addition, at least 22% and perhaps as high as 37% of the hypertensive subjects had levels greater than the upper limits of normal on a high sodium intake. Differences between the groups were less impressive in the sodium-restricted studies. There were no significant differences in age, duration of hypertension, sodium balance, serum sodium, potassium, or blood urea nitrogen in those patients who had elevated levels of plasma 18-OH DOC. Patients with primary aldosteronism had levels within the normal range on both dietary intake. However, in contrast to the other groups there were no significant changes in the plasma levels with sodium restriction. Thus, a significant number of patients with essential hypertension presumably have an alteration in 18-OH DOC secretion.

Studies of the control of plasma aldosterone concentration in normal man. II. Effect of dietary potassium and acute potassium infusion.

The responses of plasma aldosterone, cortisol, and corticosterone to an infusion of 75 mEq of potassium chloride over 120 min were studied in 10 normal subjects. Five subjects were fed a 10 mEq and five a 200 mEq sodium diet, while all subjects ingested 40 mEq and 200 mEq potassium sequentially. Two potassium infusions were performed in each subject when in balance on a fixed sodium intake and low and then high potassium diets. Regardless of dietary intake, increases of serum potassium of 0.5-1.5 mEq/liter above preinfusion levels were usually associated with significant increments in plasma aldosterone concentration. Our data agree with previous evidence that the potassium ion stimulates the adrenal cortex directly to secrete aldosterone. Peripheral renin activity did not increase after the potassium infusion. Plasma cortisol and corticosterone levels generally followed the expected diurnal decline during the infusion, implying that ACTH secretion did not increase. The plasma aldosterone response to incremental changes in serum potassium was linear on each of the four diets. The slopes of these linear relationships increased significantly when the potassium intake was increased from 40 to 200 mEq. No increase in slope occurred on either potassium intake when dietary sodium was restricted from 200 to 10 mEq. Thus, identical increases in serum potassium were associated with greater increments in plasma aldosterone above preinfusion levels on either sodium intake when the 200 mEq potassium diet was compared with the 40 mEq potassium intake.

Studies of the control of plasma aldosterone concentration in normal man. I. Response to posture, acute and chronic volume depletion, and sodium loading.

The peripheral plasma levels of aldosterone, renin activity (PRA), potassium, corticosterone, cortisol, and in some cases angiotensin II, were measured in normal subjects undergoing postural changes, acute diuretic-induced volume depletion, and alterations in dietary sodium. On a 10 mEq sodium/100 mEq potassium intake, subjects supine for 3 consecutive days had identical diurnal patterns of PRA, angiotensin II, aldosterone, cortisol, and corticosterone, with peaks at 8 a.m. and nadirs at 11 p.m. With an increase in sodium intake to 200 mEq, plasma levels of aldosterone and PRA fell to one-third their previous levels but the diurnal pattern in supine subjects was unchanged and again parallel to that of cortisol and corticosterone. There was no diurnal variation of plasma potassium on either sodium intake in the supine subjects. On a 10 mEq sodium/100 mEq potassium intake, supine 8 a.m. plasma aldosterone (55+/-7 ng/100 ml) and PRA (886+/-121 ng/100 ml per 3 hr) increased by 150-200% after subjects were upright for 3 hr. However, even though the patients maintained an upright activity pattern, there was a significant fall in plasma aldosterone to 33+/-5 ng/100 ml at 11 p.m. Potassium levels varied in a fashion parallel to aldosterone and PRA. Plasma cortisol and corticosterone had a diurnal pattern similar to that found in supine subjects. In response to acute diuretic-induced volume depletion, the nocturnal fall in aldosterone levels did not occur. The 11 p.m. value (102+/-20 ng/100 ml) and the 8 a.m. value postdiuresis (86+/-15 ng/100 ml) were both significantly greater than the prediuresis levels. PRA showed a similar altered pattern while potassium levels fell throughout the day. In some but not all studies, changes in plasma aldosterone coincided with changes in plasma cortisol, corticosterone, and/or potassium. However, in all studies, changes in plasma aldosterone were invariably associated with parallel changes in plasma renin activity and/or angiotensin II levels. These findings support the concept that PRA is the dominant factor in the control of aldosterone when volume and/or dietary sodium is altered in normal man.

Potentiation of the immune response in HIV-1+ individuals.

T cells from HIV-1+ individuals have a defect in mounting an antigen specific response. HIV-1 Tat has been implicated as the causative agent of this immunosuppression. We have previously shown that HIV-1 Tat inhibits antigen specific proliferation of normal T cells in vitro by binding to the accessory molecule CD26, a dipeptidase expressed on the surface of activated T cells. We now demonstrate that the defective in vitro recall antigen response in HIV-1 infected individuals can be restored by the addition of soluble CD26, probably by serving as a decoy receptor for HIV-1 Tat. The restored response is comparable to that of an HIV-1- individual, suggesting that early in HIV infection there is a block in the memory cell response, rather than deletion of these cells.

Distinct patterns of expression of fibroblast growth factors and their receptors in human atheroma and nonatherosclerotic arteries. Association of acidic FGF with plaque microvessels and macrophages.

Because fibroblast growth factors (FGFs) modulate important functions of endothelial cells (EC) and smooth muscle cells (SMC), we studied FGF expression in human vascular cells and control or atherosclerotic arteries. All cells and arteries contained acidic (a) FGF and basic (b) FGF mRNA. Northern analysis detected aFGF mRNA only in one of five control arteries but in all five atheroma tested, while levels of bFGF mRNA did not differ among control (n = 3) vs. plaque specimens (n = 6). Immunolocalization revealed abundant bFGF protein in control vessels (n = 10), but little in plaques (n = 14). In contrast, atheroma (n = 14), but not control arteries (n = 10), consistently exhibited immunoreactive aFGF, notably in neovascularized and macrophage-rich regions of plaque. Because macrophages colocalized with aFGF, we tested human monocytoid THP-1 cells and demonstrated accumulation of aFGF mRNA during PMA-induced differentiation. We also examined the expression of mRNA encoding FGF receptors (FGFRs). All cells and arteries contained FGFR-1 mRNA. Only SMC and control vessels had FGFR-2 mRNA, while EC and some arteries contained FGFR-4 mRNA. The relative lack of bFGF in plaques vs. normal arteries suggests that this growth factor may not contribute to cell proliferation in advanced atherosclerosis. However, aFGF produced by plaque macrophages may stimulate the growth of microvessels during human atherogenesis.

Studies of the control of plasma aldosterone concentration in normal man. 3. Response to sodium chloride infusion.

The peripheral plasma levels of aldosterone, renin activity, potassium, sodium, corticosterone, and cortisol were measured in six normal subjects four times daily-10 a.m., 2 p.m., 5 p.m., 11 p.m.-on 3 consecutive days. A constant daytime activity program was maintained throughout the study. After 5 days on a 10 mEq sodium/100 mEq potassium isocaloric intake, the mean upright 10 a.m. plasma renin activity was 1773+/-186 ng/100 ml per 3 hr and the mean plasma aldosterone, 81+/-14 ng/100 ml. These two parameters fell continuously throughout the day parallel to the fall in plasma cortisol and corticosterone. In response to 2 liters of normal saline infused from 10 a.m. to 2 p.m. on 2 consecutive days, plasma aldosterone levels fell significantly to 13+/-5 ng/100 ml at 2 p.m. after the 1st day's infusion and to 6+/-1 ng/100 ml at 2 p.m. after the 2nd. Plasma renin activity demonstrated a parallel fall to 368+/-63 ng/100 ml per 3 hr and 189+/-27 ng/100 ml per 3 hr at 2 p.m. on the 1st and 2nd days, respectively. There was no significant alteration in plasma levels of cortisol, corticosterone, potassium, or sodium on the 2 days of sodium loading in comparison with the control day. In an additional study, five normal supine subjects received 500 ml saline/hr for 6 hr. As in the 2 day study, plasma aldosterone and renin activity had parallel decrements at 1, 2, 4, and 6 hr after the start of the saline infusion. From these studies, it is concluded that plasma renin activity is the dominant factor controlling plasma aldosterone when sodium-depleted normal subjects are acutely repleted.

A mouse model to evaluate the interface between skin and a percutaneous device.

Percutaneous medical devices are integral in the management and treatment of disease. The space created between the skin and the device becomes a haven for bacterial invasion and biofilm formation and results in infection. We hypothesize that sealing this space via integration of the skin into the device will create a barrier against bacterial invasion. The purpose of this study was to develop an animal model in which the interaction between skin and biomaterials can be evaluated. Porous poly(2-hydroxyethyl methacrylate) [poly(HEMA)] rods were implanted for 7 days in the dorsal skin of C57 BL/6 mice. The porous poly(HEMA) rods were surface-modified with carbonyldiimidazole (CDI) or CDI plus laminin 5; unmodified rods served as control. Implant sites were sealed with 2-octyl cyanoacrylate; corn pads and adhesive dressings were tested for stabilization of implants. All rods remained intact for the duration of the study. There was histological evidence of both epidermal and dermal integration into all poly(HEMA) rods regardless of treatment. This in vivo model permits examination of the implant/skin interface and will be useful for future studies designed to facilitate skin cell attachment where percutaneous devices penetrate the skin.

Body surface mapping using an ECG belt to characterize electrical heterogeneity for different left ventricular pacing sites during cardiac resynchronization: Relationship with acute hemodynamic improvement.

BACKGROUND: Electrical heterogeneity (EH) during cardiac resynchronization therapy may vary with different left ventricular (LV) pacing sites. OBJECTIVE: The purpose of this study was to evaluate the relationship between such changes and acute hemodynamic response (AHR). METHODS: Two EH metrics-standard deviation of activation times and mean left thorax activation times-were computed from isochronal maps based on 53-electrode body surface mapping during baseline AAI pacing and biventricular (BiV) pacing from different pacing sites in coronary veins in 40 cardiac resynchronization therapy-indicated patients. AHR at different sites was evaluated by invasive measurement of LV-dp/dtmax at baseline and BiV pacing, along with right ventricular (RV)-LV sensing delays and QRS duration. RESULTS: The site with the greatest combined reduction in standard deviation of activation times and left thorax activation times from baseline to BiV pacing was hemodynamically optimal (defined by AHR equal to, or within 5% of, the largest dp/dt response) in 35 of 40 patients (88%). Sites with the longest RV-LV and narrowest paced QRS were hemodynamically optimal in 26 of 40 patients (65%) and 28 of 40 patients (70%), respectively. EH metrics from isochronal maps had much better accuracy (sensitivity 90%, specificity 80%) for identifying hemodynamically responsive sites (∆LV dp/dtmax ≥10%) compared with RV-LV delay (69%, 85%) or paced QRS reduction (52%, 76%). Multivariate prediction model based on EH metrics showed significant correlation (R2 = 0.53, P <.001) between predicted and measured AHR. CONCLUSION: Changes in EH from baseline to BiV pacing more accurately identified hemodynamically optimal sites than RV-LV delays or paced QRS shortening. Optimization of LV lead location by minimizing EH during BiV pacing, based on body surface mapping, may improve CRT response.

The regulatory background of nuclear cardiology in Europe: a survey by the European Council of Nuclear Cardiology.

PURPOSE: Nuclear cardiology is a well-validated, non-invasive imaging modality that is highly cost-effective as a diagnostic and prognostic tool in the evaluation of patients with known or suspected coronary artery disease. However, the number of procedures in Europe is very far from that which would be expected on the basis of epidemiological data, particularly when comparison is made with the USA. As a preliminary step for future action aimed at improving and increasing nuclear cardiology practice in Europe, the European Council of Nuclear Cardiology performed a survey to identify the regulatory issues and the training components pertaining to the practice of nuclear cardiology. METHODS: a questionnaire was sent to 31 national nuclear medicine societies and to 40 national cardiology societies. The main areas covered by the survey were: (1) the license requirements, (2) the theoretical and practical aspects of training and (3) supervision of the stress test during a nuclear cardiology study. RESULTS: The results show that, in a setting of wide heterogeneity of national regulations, education and professional practice, nuclear medicine is a restricted and closely regulated specialty. This situation guarantees the quality and safe use of radionuclides; at the same time, however, it limits integration of nuclear medicine into the clinical arena. CONCLUSION: Cardiologists should become more involved in nuclear cardiology, to further stimulate the use of this powerful diagnostic and prognostic imaging modality.