RESUMEN
We provide the most accurate results for the QCD transition line so far. We optimize the definition of the crossover temperature T_{c}, allowing for its very precise determination, and extrapolate from imaginary chemical potential up to real µ_{B}≈300 MeV. The definition of T_{c} adopted in this work is based on the observation that the chiral susceptibility as a function of the condensate is an almost universal curve at zero and imaginary µ_{B}. We obtain the parameters κ_{2}=0.0153(18) and κ_{4}=0.00032(67) as a continuum extrapolation based on N_{t}=10, 12, 16 lattices with physical quark masses. We also extrapolate the peak value of the chiral susceptibility and the width of the chiral transition along the crossover line. In fact, both of these are consistent with a constant function of µ_{B}. We see no sign of criticality in the explored range.
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To understand the importance of host' habitat choice in determining parasite burden, we studied the distribution of two helminth parasites of the red fox (Vulpes vulpes) in south-eastern Europe (Romania): Crenosoma vulpis and Eucoleus aerophilus, both widely distributed respiratory nematodes parasitic in various carnivores. Even though the life cycle and biology of the two nematodes follow a different pattern, both parasites appear to be co-distributed and often co-infect foxes with variable prevalences across their range. Between July 2016 and August 2018, 550 red foxes, V. vulpes were collected by hunters in different localities from 22 counties of Romania and examined by necropsy. All parasites found in the trachea and bronchial system were collected and preserved in 70% ethanol. We characterised red fox/parasite habitats using seven predictors (fragmentation, altitude, presence/absence of water surface, per cent cover of arable land/grassland/urbanized areas/forest cover/wetlands). Prevalence, abundance, intensity, and sex ratio were calculated and statistically analysed using the R software. Out of the 550 examined foxes, 76.2% were infected with lungworms. The overall prevalence was 32.0% for C. vulpis and 72.5% for E. aerophilus. The mean intensity of infection was 13.70 for C. vulpis 6.15 for E. aerophilus. For both nematodes, the prevalence was significantly higher in males than in females, and there was no influence of hosts' age. No statistical differences were found for intensity and mean intensity in the case of infection with C. vulpis and E. aerophilus between age and sex categories. The abundance of C. vulpis showed a strong positive relationship with the presence of wetlands and habitat fragmentation. We found a significant correlation between the abundance of E. aerophilus and altitude, with foxes from higher elevations showing higher prevalences.
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Metacercariae of various species within the genus Holostephanus Szidat, 1936 (Trematoda: Digenea: Cyathocotylidae) occur in muscles of both farmed and wild fish, including common carp (Cyprinus carpio Linnaeus, 1758). The life cycle includes a snail as first intermediate host, fish as second intermediate host and birds or mammals as final hosts. We studied the zoonotic potential and the viability of Holostephanus metacercariae from common carp following exposure to various physical and chemical treatments. Muscle tissue samples of common carp specimens from a fish farm in the north-eastern part of Hungary were examined and metacercariae recovered. The zoonotic potential was evaluated experimentally by using small mammals as models (albino mice, n = 2; and Syrian hamsters, n = 4) infected per os with Holostephanus cysts. Parallelly, Metagonimus metacercariae were used as positive controls. We could not confirm the zoonotic potential of Holostephanus metacercariae as they did not survive in the mammalian intestine whereas Metagonimus metacercariae developed to the adult stage. We assessed the viability of metacercariae isolated from common carp specimens during exposure to different physical treatments (temperatures of -18°C, +20°C, +40°C and +60°C) and chemical agents (5% and 10% acetic acid and 10% sodium chloride (NaCl)). Metacercariae lost viability by freezing at -18°C (2 h), heating at 60°C (20 min), incubation in 5% and 10% acetic acid (5 min) and 10% NaCl (2 h). These methods served as models to investigate the effectiveness of food preparation techniques (such as cold and hot smoking, freezing, salting and pickling) on the survival of metacercariae.
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Carpas/parasitología , Productos Pesqueros/parasitología , Metacercarias/aislamiento & purificación , Trematodos , Infecciones por Trematodos/veterinaria , Ácido Acético/farmacología , Animales , Bioensayo/métodos , Inocuidad de los Alimentos/métodos , Congelación , Estadios del Ciclo de Vida , Mesocricetus/parasitología , Metacercarias/patogenicidad , Ratones , Músculos/parasitología , Cloruro de Sodio/farmacología , Temperatura , Trematodos/aislamiento & purificación , Infecciones por Trematodos/tratamiento farmacológico , Infecciones por Trematodos/transmisión , Zoonosis/parasitologíaRESUMEN
In parasite surveys of fishes from Lake Balaton and its tributaries in Hungary, infections with metacercariae of a species of the digenean genus Echinochasmus (Trematoda: Echinostomatidae) were found in seven species of fish. In ruffe, Gymnocephalus cernuus, malformations of the gill filaments apparently caused by these infections were observed. These malformations were in the form of bifurcations of the filaments at about their mid-length. At the point where the filaments bifurcate, an Echinochasmus metacercaria was always embedded in the cartilaginous ray of the gill filament. All specimens of the ruffe were found to be infected by these metacercariae, and each ruffe specimen was infected by 30-300 metacercariae. Such a bifurcation was found in all of the ruffe specimens, but, apart from these gill malformations, the metacercariae produced only local changes in the cartilage. In the other six infected fish species, only local signs were observed in the cartilage. Experimental infections of chicks with metacercariae resulted in the finding of the sexual adult (marita) of an unidentified species of Echinochasmus. ITS sequences of the adult and metacercaria corresponded with each other, and also with a cercaria isolated from a gravel snail (Lithoglyphus naticoides), with a 99.5-100% similarity.
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Echinostomatidae/fisiología , Percas , Infecciones por Trematodos/veterinaria , Animales , Echinostomatidae/genética , Echinostomatidae/crecimiento & desarrollo , Enfermedades de los Peces/parasitología , Enfermedades de los Peces/patología , Branquias/anomalías , Branquias/parasitología , Metacercarias/genética , Metacercarias/crecimiento & desarrollo , Metacercarias/fisiología , Filogenia , ARN de Helminto/genética , Análisis de Secuencia de ADN/veterinaria , Infecciones por Trematodos/parasitología , Infecciones por Trematodos/patologíaRESUMEN
About 70% of patients with primary membranous nephropathy (MN) have circulating anti-phospholipase A2 receptor (PLA2R) antibodies that correlate with disease activity, but their predictive value in post-transplant (Tx) recurrent MN is uncertain. We evaluated 26 patients, 18 with recurrent MN and 8 without recurrence, with serial post-Tx serum samples and renal biopsies to determine if patients with pre-Tx anti-PLA2R are at increased risk of recurrence as compared to seronegative patients and to determine if post-Tx changes in anti-PLA2R correspond to the clinical course. In the recurrent group, 10/17 patients had anti-PLA2R at the time of Tx versus 2/7 patients in the nonrecurrent group. The positive predictive value of pre-Tx anti-PLA2R for recurrence was 83%, while the negative predictive value was 42%. Persistence or reappearance of post-Tx anti-PLA2R was associated with increasing proteinuria and resistant disease in 6/18 cases; little or no proteinuria occurred in cases with pre-Tx anti-PLA2R and biopsy evidence of recurrence in which the antibodies resolved with standard immunosuppression. Some cases with positive pre-Tx anti-PLA2R were seronegative at the time of recurrence. In conclusion, patients with positive pre-Tx anti-PLA2R should be monitored closely for recurrent MN. Persistence or reappearance of antibody post-Tx may indicate a more resistant disease.
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Glomerulonefritis Membranosa/inmunología , Fallo Renal Crónico/cirugía , Receptores de Fosfolipasa A2/química , Receptores de Fosfolipasa A2/inmunología , Adulto , Anciano , Biopsia , Femenino , Supervivencia de Injerto , Humanos , Terapia de Inmunosupresión/métodos , Inmunosupresores/uso terapéutico , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Proteinuria/inmunología , Recurrencia , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
We present possible indications for flavor separation during the QCD crossover transition based on continuum extrapolated lattice QCD calculations of higher order susceptibilities. We base our findings on flavor-specific quantities in the light and strange quark sector. We propose a possible experimental verification of our prediction, based on the measurement of higher order moments of identified particle multiplicities. Since all our calculations are performed at zero baryochemical potential, these results are of particular relevance for the heavy-ion program at the LHC.
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The Quantitative Selected Ion Monitoring Processing System (QSIMPS) is a collection of software and hardware which was designed with the capacity to analyze 30,600 samples per year in support of pharmacokinetic studies. On a per sample basis, QSIMPS was designed to inject a sample into the GC, control the GC divert valve, collect selected ion monitoring data, identify the peaks for the drug and one metabolite and each compound's reference standard, fit the peaks to a relevant chromatographic model, calculate chromatographic features of merit, calculate the peak heights and ratio of the drug and its reference standard and the metabolite and its reference standard, and, using calibration data, convert the ratio to an amount of drug. On a per tray (batch) basis, QSIMPS was designed to fit all the peak height ratios from the calibration standards to either a linear equation, or a generalized nonlinear isotope dilution equation, report a statistical analysis of the fit, and, using aliquot factors, convert the measured amount of drug into concentrations. On a per project basis, QSIMPS prints reports summarizing statistical data on the calibration standards and the quality assurance samples, and prints reports presenting the concentration data as a function of, for examples, subject, drug treatment, time postdose, etc., along with other ancillary data such as subject sex, weight, species, etc. In addition, QSIMPS can fit the concentration data to a number of common pharmacokinetic model-derived equations, and report the resulting pharmacokinetic parameters along with a statistical comparison of the parameters.
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Farmacocinética , Cromatografía de Gases/instrumentación , Computadores , Humanos , Preparaciones Farmacéuticas/sangre , Programas InformáticosRESUMEN
Twenty-five healthy, adult male volunteers entered two open-label parallel studies, each designed to define the pharmacokinetics of single and multiple oral doses of cibenzoline. Each volunteer received a single 160-mg oral dose of cibenzoline followed two or three days later by 160 mg of cibenzoline q12h for seven days. Plasma concentration-time profiles and urinary excretion rate data were used to determine pharmacokinetic parameters for unchanged drug. The apparent half-life following administration of the last dose (9.7 hours) was slightly longer than that observed after the first dose (8.4 hours). Total body clearance and nonrenal clearance were decreased after the last dose compared with the first dose, whereas renal clearance was not significantly altered. After both the first and last dose, the renal clearance greatly exceeded the glomerular filtration rate, suggesting that tubular secretion participates in the renal excretion of cibenzoline. Plasma concentrations from samples collected during the multiple-dose regimen suggest that a slight but statistically significant diurnal variation in the absorption and/or clearance of drug occurred during the course of the study. Overall, the pharmacokinetics of cibenzoline are characterized by a slightly longer half-life during multiple dosing than that observed following a single dose, due to a decrease in the nonrenal clearance. The multiple-dose pharmacokinetics reported herein are consistent with bid dosing for the maintenance of therapeutic plasma concentrations in patients taking chronic therapy.
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Imidazoles/metabolismo , Adulto , Factores de Edad , Humanos , Imidazoles/administración & dosificación , Cinética , MasculinoRESUMEN
The disposition and metabolic fate of cibenzoline (CBZ) following single oral 153-mg doses of 14C-CBZ succinate were studied in five healthy adult males. The mean maximum plasma radioactivity of 386 ng eq/ml occurred at 2.4 hr after administration. The mean half-life, determined from the 14C plasma concentration and urinary excretion rate data, was 13.1 and 14.8 hr, respectively. The mean maximum CBZ concentration was 196 ng/ml at 1.2 hr post-dose. The mean half-life, determined from the plasma concentration and urinary excretion rate data, was 7.2 and 7.3 hr, respectively. The mean total clearance of radioactivity and CBZ was 300 ml/min and 1224 ml/min, respectively, due to elimination via both renal and nonrenal pathways. The only unconjugated metabolite in the plasma was 4,5-dehydrocibenzoline which, together with other unidentified metabolites, is presumed responsible for the longer observed half-life for total radioactivity. Approximately 75% of the dose was recovered in the urine in the first 24 hr after dosing, 80% of which was present at CBZ and known metabolites. After 6 days, a mean of 85.7% of the dose was excreted in urine and 13.2% in feces. The predominant excreted compound was CBZ (55.7% of the dose) in the 0-72 hr urine. Although several metabolites were identified in urine samples, none were found in substantial amounts relative to the parent drug. Two of these substances showed slight antiarrhythmic activity, whereas the 4,5-dehydro metabolite, representing approximately 4% of radioactivity in urine, was inactive.
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Antiarrítmicos/metabolismo , Imidazoles/metabolismo , Adulto , Biotransformación , Radioisótopos de Carbono , Semivida , Humanos , Cinética , Espectroscopía de Resonancia Magnética , Masculino , Tasa de Depuración MetabólicaRESUMEN
The pharmacokinetics of intravenous (IV) cibenzoline were studied in six healthy male volunteers ranging in age from 51 to 78 years. The subjects received intravenous (IV) cibenzoline 100 mg over 20 minutes, and plasma and urine specimens were collected for 48 hours. Cibenzoline plasma concentrations at the end of the infusion ranged from 730 to 1,420 ng/mL and exhibited triexponential decline thereafter. The following mean model independent pharmacokinetic parameters were calculated from the plasma and urine concentration data: terminal half-life, 9.8 hours (range, 8.5-11.9); plasma clearance, 523 mL/min (range, 387-687); volume of distribution, 445 L (range, 328-506); and renal clearance, 289 mL/min (range, 202-334). Approximately 31% to 59% of the dose was recovered unchanged in the urine in 48 hours. A triexponential pharmacokinetic equation with zero order input was used to curve fit the plasma and urine data, and the model-dependent parameters agreed well with the model-independent estimates. A hysteresis loop was observed in the relationship between cibenzoline plasma concentration and QRS prolongation, indicating an initial lag between plasma concentration and effect after IV administration. Based on these results, the following preliminary dosing regimen was proposed to rapidly achieve and maintain therapeutic plasma concentrations equal to or slightly greater than 200-400 ng/mL: 0.25 mg/kg/min IV bolus over one minute followed by 1-1.5 mg/kg/hr for one hour and 0.2-0.4 mg/kg/hr for long-term infusion.
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Antiarrítmicos/farmacología , Hemodinámica/efectos de los fármacos , Imidazoles/farmacología , Anciano , Antiarrítmicos/metabolismo , Presión Sanguínea/efectos de los fármacos , Frecuencia Cardíaca/efectos de los fármacos , Humanos , Imidazoles/metabolismo , Inyecciones Intravenosas , Cinética , Masculino , Persona de Mediana Edad , Modelos BiológicosRESUMEN
Oral cibenzoline kinetics were followed in 36 healthy subjects aged from 22 to 78 yr divided into groups of six subjects per decade between 20 and 80 yr. Each received a single, oral, 160-mg dose of cibenzoline. Blood and urine samples were collected for 72 hr. Cibenzoline plasma and urine concentrations were measured by HPLC. Maximum plasma cibenzoline concentrations (Cmax) ranged from 283 to 1100 ng/ml and occurred 1 to 2.5 hr after dosing. Apparent oral clearance (ClT) ranged from 401 to 1677 ml/min and the t 1/2 ranged from 5.9 to 13.4 hr. Nonrenal clearance (ClNR) ranged from 65 to 1113 ml/min, renal clearance (ClR) ranged from 165 to 645 ml/min, and 31% to 86% of the dose was recovered unchanged in urine (Xu). The volume of distribution (Vd) was large, ranging from 236 to 948 l. There was a significant relationship between age and the following kinetic parameters: Cmax, Xu, t 1/2 (all of which increased with age), ClT, ClR, ClNR, the terminal elimination rate constant beta, and Vd (which decreased with age). Mean ClT was 999 +/- 371 ml/min in the 20- to 30-yr age group and was 465 +/- 78 ml/min in the 70- to 80-yr age group. The change in ClT with age resulted from a decreased in both ClR and ClNR. Mean t 1/2 varied from 7 hr in the youngest group to 10.5 hr in the oldest group. The age-related changes in cibenzoline kinetics occurred over the entire age range studied and the relationship between age and these kinetic parameters appeared to be linear.(ABSTRACT TRUNCATED AT 250 WORDS)