Miracle-dz/UniFAR-FTUs huggingface dataset:
Pharmacokinetic Analysis of Mycophenolate Mofetil and Enteric-Coated Mycophenolate Sodium in Calcineurin Inhibitor–Free Renal Transplant Recipients

Background: Considerable interest exists in identifying calcineurin inhibitor (CNI)-free and thus, less-toxic immunosuppressive regimens, with mycophenolic acid (MPA)–based treatments being a suitable approach. Because pharmacokinetic analyses of MPA treatments in stable CNI-free renal transplant recipients are lacking, the authors aimed at comparing the steady-state pharmacokinetic characteristics of MPA in patients on stable treatment with mycophenolate mofetil (MMF) or enteric-coated mycophenolate sodium (EC-MPS) plus prednisone (⩽5 mg/d). Methods: In the prospective, nonrandomized, open-label study, patients with stable transplant function since ≥6 months received their routine single dose of either MMF (n = 12) or EC-MPS (n = 11). The MPA plasma concentration was recorded over 12 hours. Parameters assessed were predose MPA concentration (C0), postdose minimum and maximum concentration (Cmin and Cmax), time to maximum concentration (Tmax), and area under the concentration–time curve (AUC) for the 12-hours of exposure (AUC0-12). Results: Baseline characteristics were comparable between both the groups. Consistent with enteric coating, the mean Tmax was significantly longer after the intake of EC-MPS compared with MMF (2.2 versus 0.8 hours; P = 0.0002). The exposure measures Cmin, Cmax, and AUC0-12 were not significantly different despite the higher mean MPA equivalent dose in patients receiving MMF compared with those receiving EC-MPS (85% versus 64% of the recommended single dose, respectively). Exposures as reflected by the median AUC0-12 values were 50.7 and 58.7 mg·h−1·L−1 with MMF and EC-MPS, respectively (P = 0.340). All patients achieved a target AUC of >30 mg·h−1·L−1, and 61% had an AUC of >50 mg·h−1·L−1. Conclusions: The study provides first results on the steady-state pharmacokinetics of the 2 MPA drugs in CNI-free immunosuppressant regimens. Pharmacokinetic parameters measured in this study under real-life conditions were comparable in patients receiving MMF or EC-MPS.
Energetics of Lizard Embryos Are Not Canalized by Thermal Acclimation

In some species of ectotherms, temperature has little or no effect on the amount of energy expended during embryonic development. This phenomenon can result from either of two mechanisms: (1) a shorter incubation period at higher temperatures, which offsets the expected increase in metabolic rate, or (2) a compensatory decrease in the rate at which embryos expend energy for maintenance. To distinguish the relative importance of these two mechanisms, we quantified the acute and chronic effects of temperature on embryonic metabolism in the eastern fence lizard (Sceloporus undulatus). First, we measured metabolic rates of individual embryos at 27°, 31°, and 34°C. Second, we examined the capacity for thermal acclimation by measuring the metabolic rates of embryos at 30°C, after a period of incubation at either 28° or 32°C. As with adult reptiles, the metabolic rates of embryos increased with an acute increase in temperature; the Q10 of metabolic rate from 27° to 34°C was 2.1 (±0.2). No evidence of thermal acclimation was observed either early or late in development. In S. undulatus, a shorter incubation period at higher temperatures appears to play the primary role in canalizing the energy budget of an embryo, but a reduction in the cost of growth could play a secondary role.
The Area Postrema in Deoxycorticosterone‐Salt Hypertension in Rats

Ablation of the area postrema in rats prevents sustained hypertension during angiotensin II infusion and after unilateral renal artery constriction (two-kidney, one clip hypertension). The current experiment was performed to determine whether an intact area postrema is required for hypertension development in a low renin model of experimental hypertension in rats. In 11 rats, the area postrema was destroyed using electrical current; the extent and specificity of each lesion was confirmed later by blind histological analysis. In 12 rats, sham operations were performed. All rats were uninephrectomized and drank saline. During once-weekly injections of deoxycorticosterone pivalate (5 mg/wk) for 4 weeks, sham-operated rats (n = 10) showed a significant increase in mean arterial pressure (Days 6–28) and saline intake (Days 12–28), but no significant increase in sodium or water retention. Deoxycorticosterone-treated rats with area postrema ablation (n = 9) exhibited no change in arterial pressure, sodium retention, or water retention, but a significant increase in saline intake (Days 17–28). Plasma renin activity was equally suppressed in both groups of rats. The depressor response to ganglion blockade with hexamethonium (20 mg/kg i.v.) was significantly increased during the 2nd, 3rd, and 4th weeks of steroid treatment in sham-operated, but not area postrema-ablated, rats. Four rats (2 sham-operated; 2 ablated) showed no change in any variable over 28 days in the absence of steroid treatment. It is concluded that the area postrema may be important in some non-angiotensin-dependent forms of experimental hypertension, possibly by affecting neurogenic control mechanisms.
Arbeidsvoorwaarden en arbeidsverhoudingen op ondernemingsniveau : AVON monitor 2007

In 2007 is de " Arbeidsvoorwaarden en Arbeidsverhoudingen Monitor" voor de derde keer afgenomen. De eerste meting vond plaats in 2002 in de tweede in 2004. Onderzocht arbeidsvoorwaarden zijn: resultaatgerichte beloning; aanpassing werktijden; opleiding, inclusief POP, POB en ECV; keuzemogelijkheden. Werknemers zijn redelijk tevreden met hun primaire en secundaire arbeidsvoorwaarden. Steeds meer werknemers (29 %) werken in een bedrijf met resultaatgerichte beloning, met name binnen de financiele dienstverlening. De helft van de medewerkers geeft aan een opleiding te hebben gevolgd die betaald wordt door de werkgever. Daarvan geeft de 23 procent aan dat met hen een persoonlijk ontwikkelingsplan- en opleidingsplan (POP) is overeengekomen. De arbeidsverhoudingen die zijn onderzocht betreffen:1. Overleg:-functioneringsgesprekken;-werkoverleg; 2. Instituties:-ondernemingsraad,-vakbond,-werkgeversorganisatie; 3. Regelingen: -cao;-individueel arbeidscontract;-klachtenregeling; 4. regelruimte en maatwerkafspraken. Werknemers en leidinggevenden beoordelen het belang van functioneringsgesprekken met een ruime voldoende en de tevredenheid ermee iets minder. Leidinggevenden vinden het werkoverleg belangrijk. 67 % van de werknemers en 57 % van leidinggevenden geeft aan dat er in hun bedrijf een OR of PVT is. Werknemers geven voor het belang van de vakbonden een hoger rapportcijfer dan leidinggevenden. Werknemers en vinden de cao belangrijker dan leidinggevenden. Zes op de tien leidinggevenden wier bedrijf valt onder een cao wijkt wel eens af van de cao als ze afspraken maken met werknemers.
What Can We Learn from the Implementation of Monetary and Macroprudential Policies: A Systematic Literature Review

The emergence of macroprudential policies, implemented by central banks as a means of promoting financial stability, has raised many questions regarding the interaction between monetary and macroprudential policies. Given the limited number of studies available, this paper sheds light on this issue by providing a critical and systematic review of the literature. To this end, we divide the theoretical and empirical studies into two broad channels of borrowers – consisting of the cost of funds and the collateral constraint – and financial intermediaries – consisting of risk‐taking and payment systems. In spite of the existing ambiguity surrounding coordination issues between monetary and macroprudential policies, it is argued that monetary policy alone is not sufficient to maintain macroeconomic and financial stability. Hence, macroprudential policies are needed to supplement monetary. In addition, we find that the role of the exchange rate is critical in the implementation of monetary and macroprudential policies in emerging markets, while volatile capital flows pose another challenge. In so far as how the arrangement of monetary and macroprudential policies varies across countries, key theoretical and policy implications have been identified.
Effect of galanin on plasma levels of oxytocin and cholecystokinin.

Galanin, oxytocin and cholecystokinin (CCK) are peptides that influence feeding behaviour. Galanin has been found to stimulate food intake and oxytocin and CCK have been suggested to be satiety agents. The present study was performed in order to investigate if galanin influences the secretion of oxytocin and CCK as a possible indication of a functional relationship between these peptides with respect to their influence on feeding behaviour. Galanin (0.1 and 1 micrograms) was administered intracerebroventricularly (i.c.v.) and intraperitoneally (i.p.) to anaesthetized rats and blood samples were collected 20 and 60 min after administration. Plasma levels of oxytocin and CCK were measured with radioimmunoassay. Galanin, 0.1 and 1 microgram, caused a significant decrease in oxytocin levels after 60 min, both when administered i.c. v. and i.p. In contrast, CCK levels increased following i.c. v. and also i.p. galanin. The possible mechanisms by which galanin causes a decrease in oxytocin and an increase in CCK levels are discussed.
Essential Role of the 90-Kilodalton Heat Shock Protein in Mediating Nongenomic Estrogen Signaling in Coronary Artery Smooth Muscle

Under normal physiological conditions, estrogen is a coronary vasodilator, and this response involves production of NO from endothelial cells. In addition, estrogen also stimulates NO production in coronary artery smooth muscle (CASM); however, the molecular basis for this nongenomic effect of estrogen is unclear. The purpose of this study was to investigate a potential role for the 90-kDa heat shock protein (Hsp90) in estrogen-stimulated neuronal nitric-oxide synthase (nNOS) activity in coronary artery smooth muscle. 17β-Estradiol produced a concentration-dependent relaxation of endothelium-denuded porcine coronary arteries in vitro, and this response was attenuated by inhibiting Hsp90 function with 1 μM geldanamycin (GA) or 100 μg/ml radicicol (RAD). These inhibitors also prevented estrogen-stimulated NO production in human CASM cells and reversed the stimulatory effect of estrogen on calcium-activated potassium (BKCa) channels. These functional studies indicated a role for Hsp90 in coupling estrogen receptor activation to NOS stimulation in CASM. Furthermore, coimmunoprecipitation studies demonstrated that estrogen stimulates bimolecular interaction of immunoprecipitated nNOS with Hsp90 and that either GA or RAD could inhibit this association. Blocking estrogen receptors with ICI182780 (fulvestrant) also prevented this association. These findings indicate an essential role for Hsp90 in nongenomic estrogen signaling in CASM and further suggest that Hsp90 might represent a prospective therapeutic target to enhance estrogen-stimulated cardiovascular protection.
Results of a 4-week head-down tilt with and without LBNP countermeasure: II. Cardiac and peripheral hemodynamics--comparison with a 25-day spaceflight.

Cardiovascular hemodynamics were assessed by ultrasound echography and Doppler during a 28-d head-down tilt "CNES HDT: 87-88," and during the 25-d French-Soviet spaceflight "Aragatz 88. " For both studies we used the same ultrasound methodology. The main hemodynamic parameters of the left heart function and of the peripheral arterial system (cerebral, renal, femoral arteries) were measured four times during the HDT (day 7, 14, 21, 28) and twice post-HDT. The same measurements were performed six times during the flight (day 4, 5, 15, 18, 20, 24) and five times postflight. During the HDT, two groups were studied: six subjects no countermeasures and six subjects with repeated lower body negative pressure (LBNP). In the first group the cardiac volumes and the cardiac output were significantly decreased, whereas in the group with LBNP these parameters were superior to the basal value. In the group without LBNP the cerebral flow was maintained because of a decrease of the brain vascular resistance. In this group the renal vascular resistance was decreased as inflight. In the lower limbs we observed a loss of the vasomotor control. The vascular resistance was decreased after the end of the HDT and the subjects suffered orthostatic intolerance. In the population with LBNP, we did not observe the same decrease of vascular resistance during the HDT, and after the HDT no sign of orthostatic intolerance was observed. During the flight, the left ventricular volume was significantly decreased. The carotid flow was maintained owing to a decrease of the cerebral vascular resistance. (ABSTRACT TRUNCATED AT 250 WORDS)
Atypical Genetic Locus Associated with Constitutive Production of Enterocin B by Enterococcus faecium BFE 900

ABSTRACT A purified bacteriocin produced by Enterococcus faeciumBFE 900 isolated from black olives was shown by Edman degradation and mass spectrometric analyses to be identical to enterocin B produced byE. faecium T136 from meat (P. Casaus, T. Nilsen, L. M. Cintas, I. F. Nes, P. E. Hernández, and H. Holo, Microbiology 143:2287–2294, 1997). The structural gene was located on a 2.2-kb HindIII fragment and a 12.0-kb EcoRI chromosomal fragment. The genetic characteristics and production of EntB by E. faecium BFE 900 differed from that described so far by the presence of a conserved sequence like a regulatory box upstream of the EntB gene, and its production was constitutive and not regulated. The 2.2-kb chromosomal fragment contained the hitherto undetected immunity gene for EntB in an atypical orientation that is the reverse of that of the structural gene. Typical transport and other genes associated with bacteriocin production were not detected on the 12.0-kb chromosomal fragment containing the EntB structural gene. This makes the EntB genetic system different from most other bacteriocin systems, where transport and possible regulatory genes are clustered. EntB was subcloned and expressed by the dedicated secretion machinery of Carnobacterium piscicola LV17A. The structural gene was amplified by PCR, fused to the divergicin A signal peptide, and expressed by the general secretory pathway in Enterococcus faecalis ATCC 19433.
Matchable-Observable Linear Models and Direct Filter Tuning: An Approach to Multivariable Identification

Identification of linear time-invariant multivariable systems can best be understood as comprising three separate problems: selection of system model structure, filter design, and parameter estimation itself. Approaching the first using matchable-observable models originally developed in the adaptive control literature and the second via direct or derivative-free optimization, effective least-squares algorithms can be used for parameter estimation. The accuracy, robustness and moderate computational demands of the methods proposed are demonstrated via simulations with randomly generated models and applied to identification using real process data. The results obtained are comparable or superior to the best results obtained using standard implementations of the algorithms described in the literature.
Why Military Personnel Fail to Keep Medical Appointments

Objectives Failure to keep medical appointments, commonly referred to as ‘Did Not Attend’ (DNA), is a frequent problem in both primary and secondary health care and leads to a waste of valuable resources. Although the reasons for DNA within the general population are well documented, little is known about this behaviour amongst people serving in the armed forces. In this paper we report the findings of a questionnaire-based study investigating the reasons why military personnel fail to keep hospital appointments. Method A postal questionnaire asking questions about the reasons for not attending the appointment and how they perceived the condition for which treatment had been sought, were sent to 167 military patients known to have missed appointments in either a hospital outpatient department or regional rehabilitation unit. 162 controls, who attended appointments, were also sent a questionnaire asking them about factors leading to their appointment and how they perceived the condition that they attended the appointment for. Illness perception was measured using a previously validated Illness perception Questionnaire (IPQ-R). The controls were matched by rank, gender and corps. Results The overall response rate was 51.5%, with 46% response in the DNA group and 55% in the controls. A previous history of hospital DNA (though not DNA in primary care) and attempting to change the appointment date were associated with DNA (p=0.01). Those who received a reminder about the appointment were less likely to DNA (p=<0.001). Although patients who perceived their condition to be less important were more likely to fail to attend their appointment (p=0.01), illness perception as measured on the IPQ-R, was not associated with appointment attendance. The most frequent reasons cited for missed appointments were due to administrative problems, with many (38%) respondents being simply unaware that they had an appointment at all or believing that they had cancelled it (14%). Forgetting the appointment (8%) or mixing up the date (21%) were also cited by respondents as reasons for not attending. Only 11% of respondents gave reasons that were specific to a military population, most frequently being on exercise at the time of their appointment. Demographic differences such as age and gender, and practical factors such as appointment day, distance travelled, method of appointment notification, or type of hospital were not found to be associated with attendance. Conclusion The most common reasons for not attending appointments were due to administrative error and an inability amongst patients to recall the correct date of the appointment. Whilst efforts to improve attendance through various reminder systems have been found to be effective in the short term at least, improvements in the efficiency of appointment administration is likely to generate a reduction in DNA and in turn will reduce the wastage of resources.
Differential effects of early postinjury treatment with neuroprotective drugs in a mouse model using diffuse reflectance spectroscopy

Abstract. The time required for the arrival of an ambulance crew and administration of first aid is critical to clinical outcome, particularly in the case of head injury victims requiring neuroprotective drugs following a car accident, falls, and assaults. Short response times of the medical team, together with proper treatment, can limit injury severity and even save a life before transportation to the nearest medical center. We present a comparative evaluation of five different neuroprotective drugs frequently used in intensive care and operating units in the early phase following traumatic brain injury (TBI): hypertonic saline (HTS), mannitol, morphine, melatonin, and minocycline. The effectiveness of these drugs in terms of changes in brain tissue morphology (cell organelle size, density, distribution, etc.) and biochemical tissue properties (chromophores’ content) was experimentally evaluated through analysis of the spectral reduced scattering and optical absorption coefficient parameters in the near-infrared (NIR) optical range (650 to 1000 nm). Experiments were conducted on anesthetized male mice subjected to a noninvasive closed head weight-drop model of focal TBI (n=50 and n=10 control) and monitored using an NIR diffuse reflectance spectroscopy system utilizing independent source–detector separation and location. After 10 min of baseline measurement, focal TBI was induced and measurements were conducted for 20 min. Subsequently, a neuroprotective drug was administrated and measurements were recorded for another 30 min. This work’s major findings are threefold: first, minocycline was found to improve hemodynamic outcome at the earliest time postinjury. Second, HTS decreased brain water content and inhibited the increase in intracranial pressure. Third, the efficacy of neuroprotective drugs can be monitored noninvasively with diffuse reflectance spectroscopy. The demonstrated ability to noninvasively detect cerebral physiological properties following early administration of neuroprotective drugs underlines the need for more extensive investigation of the combined use of clinical drugs in larger-scale preclinical experiments to find the most beneficial drug treatment for brain injury patients.
Electrophysiological Responses of the Naupactus bipes Beetle to Essential Oils from Piperaceae Species

Electrophysiological responses based on electroantennographic detection (GC-EAD) and electroantennography (EAG) analysis of Naupactus bipes beetles (Germar, 1824) (Coleoptera: Curculionidae: Brachycerinae) were used to test volatile oils of Piper gaudichaudianum, P. regnellii and P. hispidum. In the EAG experiments, female and male beetles showed significant EAG response to the three volatile oils of Piper species, with the females’ responses slightly higher than the males’. The experiments with GC-EAD revealed that some terpenoids (namely, α-pinene, β-pinene, myrcene, α-copaene and germacrene) present in the leaf essential oils of the Piper species are perceptible to female and male beetles.
The Effect of altering ADL thresholds on active life expectancy estimates for older persons.

OBJECTIVES Research on disability and active life expectancy (ALE) has often criticized the measurement of disability but has rarely empirically investigated the effect of changing measurement. The purpose of this study was to determine whether altering the number of activities of daily living (ADLs) required to consider an individual "disabled" affects population-based ALE estimates after considering parametric uncertainty and sampling error. METHODS The authors develop a Bayesian approach to estimating multistate life tables for a three-dimensional state space, using data on community-dwelling older adults from the 1989 and 1994 National Long Term Care Survey analytic files. Empirical confidence intervals for ALE are compared across 6 models using successively higher ADL cutoffs for defining individuals as being disabled. RESULTS After considering sampling and other errors in the estimation of transition probabilities, the authors found that altering the threshold for measuring disability has relatively little effect on ALE estimates, especially with higher ADL-level thresholds and at older ages. DISCUSSION The implications of the results include that disability measurement, including altering the definition of being disabled and possibly expanding the state space of a model, may not affect population-based estimates of ALE.