Miracle-dz/UniFAR-FTUs huggingface dataset:
Population Pharmacokinetics of Piperacillin in Nonobese, Obese, and Morbidly Obese Critically Ill Patients

ABSTRACT The treatment of infections in critically ill obese and morbidly obese patients is challenging because of the combined physiological changes that result from obesity and critical illness. The aim of this study was to describe the population pharmacokinetics of piperacillin in a cohort of critically ill patients, including obese and morbidly obese patients. Critically ill patients who received piperacillin-tazobactam were classified according to their body mass index (BMI) as nonobese, obese, and morbidly obese. Plasma samples were collected, and piperacillin concentrations were determined by a validated chromatographic method. Population pharmacokinetic analysis and Monte Carlo dosing simulations were performed using Pmetrics software. Thirty-seven critically ill patients (including 12 obese patients and 12 morbidly obese patients) were enrolled. The patients' mean ± standard deviation age, weight, and BMI were 50 ± 15 years, 104 ± 35 kg, and 38.0 ± 15.0 kg/m2, respectively. The concentration-time data were best described by a two-compartment linear model. The mean ± SD parameter estimates for the final covariate model were a clearance of 14.0 ± 7.1 liters/h, a volume of distribution of the central compartment of 49.0 ± 19.0 liters, an intercompartmental clearance from the central compartment to the peripheral compartment of 0.9 ± 0.6 liters · h−1, and an intercompartmental clearance from the peripheral compartment to the central compartment of 2.3 ± 2.8 liters · h−1. A higher measured creatinine clearance and shorter-duration infusions were associated with a lower likelihood of achieving therapeutic piperacillin exposures in patients in all BMI categories. Piperacillin pharmacokinetics are altered in the presence of obesity and critical illness. As with nonobese patients, prolonged infusions increase the likelihood of achieving therapeutic concentrations.
Unethical Use of Information Technology: A Two-Country Study

This paper investigates the phenomenon of unethical use of information technology (IT) by developing and testing a model that postulates multiple influencing factors of unethical IT use. Results from two studies of young adult participants in USA and Finland show that unethical IT use is primarily influenced by social (e.g., subjective norms), situational (e.g., moral intensity), and technological (e.g., technological facilitation) considerations. Differences between the two countries regarding this phenomenon also surface. The results suggest that multiple interventions at various levels may be required to combat the growth of unethical IT use, showcasing the practical significance of these research results.
Verification and Protection of Confidentiality in an Advanced Smart Grid

Information flow typically refers to the explicit as well as implicit information resulting from the interaction of cyber processes constituting a system. Information flow also occurs in cyber-physical systems (CPSs). Information flow is difficult to detect in CPSs, due to their physical nature and complex interactions among various computational and physical components. In this work, formal methods of security specification and verification are extended to describe confidentiality in CPSs. This paper presents a general approach to specify and verify information flow properties, such as non-deducibility, in a CPS using bisimulation techniques. An advanced smart grid power management system's confidentiality is verified.
Activity of Ceftazidime-Avibactam against Clinical and Isogenic Laboratory Pseudomonas aeruginosa Isolates Expressing Combinations of Most Relevant β-Lactam Resistance Mechanisms

ABSTRACT The activity of ceftazidime-avibactam was compared with that of ceftazidime alone and meropenem against a collection of 190 Pseudomonas aeruginosa clinical isolates recovered from a multicenter study of bloodstream infections. The addition of avibactam increased ceftazidime susceptibility in the complete collection of strains (64.7% to 91.1%) and particularly among subsets of isolates showing AmpC hyperproduction (10.9% to 76.1%) or multidrug resistance (MDR) profiles (27% to 77.8%). The MICs of ceftazidime-avibactam, in contrast with those of ceftazidime or meropenem, remained at ≤4 μg/ml for a panel of 16 P. aeruginosa PAO1 isogenic mutants expressing multiple combinations of the most relevant β-lactam resistance mechanisms.
Amikacin Pharmacokinetics To Optimize Dosing in Neonates with Perinatal Asphyxia Treated with Hypothermia

ABSTRACT Aminoglycoside pharmacokinetics (PK) is expected to change in neonates with perinatal asphyxia treated with therapeutic hypothermia (PATH). Several amikacin dosing guidelines have been proposed for treating neonates with (suspected) septicemia; however, none provide adjustments for cases of PATH. Therefore, we aimed to quantify the differences in amikacin PK between neonates with and without PATH to propose suitable dosing recommendations. Based on amikacin therapeutic drug monitoring data collected retrospectively from neonates with PATH, combined with a published data set, we assessed the impact of PATH on amikacin PK by using population modeling. Monte Carlo and stochastic simulations were performed to establish amikacin exposures in neonates with PATH after dosing according to the current guidelines and according to proposed model-derived dosing guidelines. Amikacin clearance was decreased 40.6% in neonates with PATH, with no changes in volume of distribution. Simulations showed that increasing the dosing interval by 12 h results in a decrease in the percentage of neonates reaching toxic trough levels (>5 mg/liter), from 40 to 76% to 14 to 25%, while still reaching efficacy targets compared to the results of current dosing regimens. Based on this study, a 12-h increase in the amikacin dosing interval in neonates with PATH is proposed to correct for the reduced clearance, yielding safe and effective exposures. As amikacin is renally excreted, further studies into other renally excreted drugs may be required, as their clearance may also be impaired.
Ambliopia por estrabismo: estudo retrospectivo de pacientes em hospital universitário

OBJETIVO: Avaliar a influencia da adesao ao tratamento, da gravidade da ambliopia e da idade de inicio do tratamento em pacientes com ambliopia por estrabismo submetidos a terapia oclusiva. METODOS: Analisaram-se 569 prontuarios de pacientes com ambliopia por estrabismo atendidos no Hospital das Clinicas da Faculdade de Medicina da USP no periodo de 1983 a 2000. Os criterios de exclusao foram: perda de seguimento, idade maior que 12 anos, presenca de nistagmo e outras doencas oculares. Todos foram submetidos a exame oftalmologico completo com avaliacao da motilidade ocular, divididos por faixas etarias e classificados quanto ao tipo de estrabismo, gravidade da ambliopia e adesao ao tratamento. Os dados foram analisados estatisticamente pelo metodo de Fisher. RESULTADOS: Foram incluidos 198 pacientes (34,8%). Nao houve diferenca de adesao nos diversos grupos etarios. A taxa de sucesso foi maior nos pacientes com boa adesao independente da gravidade da ambliopia. Porem a adesao ao tratamento foi menor no grupo com ambliopia grave, que foi o mais frequente e obteve menor taxa de sucesso em nossa amostra. Nao houve relacao entre idade e sucesso terapeutico. CONCLUSOES: O estudo demonstrou que a adesao ao tratamento oclusivo desempenha papel fundamental na eficacia terapeutica. Com isto, idade de inicio do tratamento isoladamente nao teve influencia no sucesso terapeutico, uma vez que foi possivel obter boa adesao a despeito da idade. Alem disto, os resultados foram piores nos casos de ambliopia grave, nos quais a adesao foi menor.
Sinusoidal Versus Square-Wave Current Supply of PM Brushless DC Drives: A Convenience Analysis

Permanent-magnet (PM) brushless direct current (BLDC) drives are utilized in a variety of applications because of their inherent features and would be even more utilized if their torque performance could be improved. Indeed, when supplied with square-wave currents, the torque-speed characteristic undergoes a drop at high speeds, and a significant torque ripple arises at both low and high speeds due to the commutation phenomena. In this paper, the sinusoidal current supply of the PM BLDC motors is investigated in depth, and an analytical formulation of the torque-speed characteristic, the torque ripple, and the base speed for such a supply are found. Based on the resulting equations, a thorough convenience analysis of the sinusoidal current supply is carried out with respect to the square-wave current in the presence of the commutation phenomena, which is hereafter termed as the real square-wave current supply. Simulation and experimental tests for a study case are given to corroborate the theoretical results. Generation of the sinusoidal current references using Hall sensors is also discussed.
Quantifying Diffusion in a Biofilm of Streptococcus mutans

ABSTRACT In biofilms, diffusion may limit the chemical activity of nutrients, toxic compounds, and medicines. This study provides direct, noninvasive insight into the factors that will most effectively limit the transport of antibiotics and biocides in biofilms. Self-diffusion coefficients have been determined for a number of fluorescent probes in biofilms of Streptococcus mutans using fluorescence correlation spectroscopy. The effects of probe size and charge and the roles of biofilm pH, ionic strength, and heterogeneity were studied systematically. The relative diffusion coefficients (D in the biofilm divided by that in water) decreased with increasing probe size (3,000-molecular-weight [3K], 10K, 40K, 70K, and 2,000K dextrans). Studies using variably charged substrates (tetramethylrhodamine, Oregon Green, rhodamine B, and rhodamine 6G) showed that the self-diffusion coefficients decreased with an increasing negative charge of the fluorescent probes. No significant effect was observed for changes to the ionic strength (10−4 to 10−1 M) or pH (4 to 9) of the biofilm. Biofilm heterogeneity was responsible for variations of ca. one order of magnitude in the diffusion coefficients.
Evaluation of the In Vitro Activity of Voriconazole As Predictive of In Vivo Outcome in a Murine Aspergillus fumigatus Infection Model

ABSTRACT We have evaluated the in vitro activity of voriconazole against 61 strains of Aspergillus fumigatus by using broth microdilution, disk diffusion, and minimal fungicidal concentration procedures. We observed an excellent correlation between the results obtained with the three methods. Five percent of the strains showed MICs greater than or equal to the epidemiological cutoff value (ECV; 1 μg/ml). To assess whether MICs were predictive of in vivo outcome, we tested the efficacy of voriconazole at 25 mg/kg of body weight daily in an immunosuppressed murine model of disseminated infection using 10 strains representing various patterns of susceptibility to the drug as determined by the in vitro study. Voriconazole prolonged survival and reduced fungal load in the kidneys and brain in those mice infected with strains with MICs of ≤0.25 μg/ml, while in mice infected with strains with MICs of 0.5 to 2 μg/ml, the efficacy was varied and strain dependent and in mice infected with the strain with a MIC of 4 μg/ml, the antifungal did not show efficacy. Voriconazole reduced galactomannan antigenemia against practically all strains with a MIC of <4 μg/ml. Our results demonstrate that some relationship exists between voriconazole MICs and in vivo efficacy; however, further studies testing additional strains are needed to better ascertain which MIC values can predict clinical outcome.
Fluoroquinolone Impact on Nasal Methicillin-Resistant and Methicillin-Sensitive Staphylococcus aureus Colonization Durations in Neurologic Long-Term-Care Facilities

ABSTRACT Staphylococcus aureus nasal carriage is a risk factor for subsequent infection. Estimates of colonization duration vary widely among studies, and factors influencing the time to loss of colonization, especially the impact of antibiotics, remain unclear. We conducted a prospective study on patients naive for S. aureus colonization in 4 French long-term-care facilities. Data on nasal colonization status and potential factors for loss of colonization were collected weekly. We estimated methicillin-resistant S. aureus (MRSA) and methicillin-sensitive S. aureus (MSSA) colonization durations using the Kaplan-Meier method and investigated factors for loss of colonization using shared-frailty Cox proportional hazards models. A total of 285 S. aureus colonization episodes were identified in 149 patients. The median time to loss of MRSA or MSSA colonization was 3 weeks (95% confidence interval, 2 to 8 weeks) or 2 weeks (95% confidence interval, 2 to 3 weeks), respectively. In multivariable analyses, the methicillin resistance phenotype was not associated with S. aureus colonization duration (P = 0.21); the use of fluoroquinolones (hazard ratio, 3.37; 95% confidence interval, 1.31 to 8.71) and having a wound positive for a nonnasal strain (hazard ratio, 2.17; 95% confidence interval, 1.15 to 4.07) were associated with earlier loss of MSSA colonization, while no factor was associated with loss of MRSA colonization. These results suggest that the methicillin resistance phenotype does not influence the S. aureus colonization duration and that fluoroquinolones are associated with loss of MSSA colonization but not with loss of MRSA colonization.
Pubertal Development in Japanese Boys

Testicular enlargement is regarded as the earliest physical sign of the pubertal process in boys. In order to establish the maturational changes of testicular volume in Japanese boys, we measured testicular size of 425 males from birth to adolescence using a transparent plastic ruler. Maturational changes in testicular volume were noted in two periods, during early infancy and adolescence. The testicular volumes during the first three months of life were slightly greater than later in infancy. Thereafter, there was very little increase in testicular volume from the age of 1 to 10 years. After 11 years, there was a sudden increase in size. The mean combined volumes increased from 6.5cm3 at 11 years to 36.7cm3 at 14 years. The largest increment was observed between 13 and 14 years of age and between pubic hair stages I and II. These findings indicate that reaching a testicular volume of 6.5cm3 is a landmark of the earliest stage of puberty in contemporary Japanese boys. In order to correlate changes in testicular volume with those in gonadotropin and testosterone secretion during puberty, we examined also basal and 24-hr secretion of gonadotropin and testosterone in other cross-sectional studies. Basal gonadotropin was found to increase significantly from 10 years of age, and this increment preceded the increase of testicular volume and testosterone secretion. Analysis of 24-hr secretory dynamics of gonadotropin and testosterone concentration suggests that nighttime increase of gonadotropin concentration with initiation of pulsatile secretion, which is believed to be an endocrinological marker for pubertal onset, exists even in the prepubertal stage well before the development of secondary sexual characteristics. Furthermore, the day-night difference with a higher nocturnal level of testosterone indicates the importance of nocturnal testosterone measurement for assessing pubertal development.
Is Smartphone Usage Truly Smart? A Qualitative Investigation of IT Addictive Behaviors

Defined as the dependency to a technology that results in its excessive and compulsive use, IT addiction is seen as increasingly prevalent in today's societies. Recent research has revealed that IT addictive behaviors are creating serious problems for individuals and organizations alike. In this paper, we report the results of a qualitative study that aimed at investigating smart phone addictive usage. Building on 11 in-depth interviews and answers to 183 exploratory written questionnaires, we used a grounded theory approach to investigate this phenomenon. Our results reveal four smarphone user profiles. In two of these profiles, users are exhibiting addictive behaviors. In the first group, the users' profile corresponds to that of other types of additions. In the second group, known definitions of addiction do not apply and the characteristics of these users are very different. Our results thus suggest that adopting traditional conceptualizations of addiction will not be sufficient to define, understand and manage IT addictive behaviors.
Improved Detection of Candida sp. fks Hot Spot Mutants by Using the Method of the CLSI M27-A3 Document with the Addition of Bovine Serum Albumin

ABSTRACT Echinocandins are highly bound to serum proteins, altering their antifungal properties. The addition of 50% human serum to the MIC assay improves the identification of echinocandin-resistant Candida spp. harboring fks hot spot mutations. However, this modification cannot readily be applied to the method of the CLSI M27-A3 document due to safety and standardization difficulties. The aim of this study was to evaluate commercial bovine serum albumin (BSA) as a safe and standardized alternative to human serum. A collection of 28 echinocandin-susceptible strains, 10 Candida parapsilosis sensu lato strains (with naturally reduced echinocandin susceptibility), and 40 FKS hot spot mutants was used in this work. When RPMI 1640 was used for susceptibility testing, wild-type strains and fks mutants showed MIC range overlaps (−2, −1, and −3 2-fold-dilution steps separated these populations for anidulafungin, caspofungin, and micafungin, respectively). On the other hand, the addition of BSA to RPMI 1640 differentially increased echinocandin MIC values for these groups of strains, allowing better separation between populations, with no MIC range overlaps for any of the echinocandin drugs tested. Moreover, the use of RPMI-BSA reduced the number of fks hot spot mutant isolates for which MIC values were less than or equal to the upper limit for the wild type (very major errors) from 9, 2, and 7 with RPMI alone to 3, 0, and 3 for anidulafungin, caspofungin, and micafungin, respectively. When RPMI-BSA was used to study the susceptibility of C. parapsilosis sensu lato species to echinocandins, the strains behaved as anidulafungin- and micafungin-resistant isolates (MIC, ≥8 μg/ml). These data support the need for a revision of the CLSI protocol for in vitro testing of echinocandin susceptibility in order to identify all or most of the fks hot spot mutants. Also, caspofungin could be used as a surrogate marker of reduced susceptibility to echinocandins.
Antifungal Lock Therapy

ABSTRACT The widespread use of intravascular devices, such as central venous and hemodialysis catheters, in the past 2 decades has paralleled the increasing incidence of catheter-related bloodstream infections (CR-BSIs). Candida albicans is the fourth leading cause of hospital-associated BSIs. The propensity of C. albicans to form biofilms on these catheters has made these infections difficult to treat due to multiple factors, including increased resistance to antifungal agents. Thus, curing CR-BSIs caused by Candida species usually requires catheter removal in addition to systemic antifungal therapy. Alternatively, antimicrobial lock therapy has received significant interest and shown promise as a strategy to treat CR-BSIs due to Candida species. The existing in vitro, animal, and patient data for treatment of Candida-related CR-BSIs are reviewed. The most promising antifungal lock therapy (AfLT) strategies include use of amphotericin, ethanol, or echinocandins. Clinical trials are needed to further define the safety and efficacy of AfLT.
Vitamin D status, functional decline, and mortality in peripheral artery disease

Associations of vitamin D levels with prospectively measured functional decline and mortality in people with lower extremity peripheral artery disease (PAD) are unknown. We determined whether lower baseline vitamin D levels are associated with a faster decline in functional performance and higher mortality among people with and without PAD. A total of 658 participants (395 with PAD) underwent baseline measurement of 25-hydroxyvitamin D (DiaSorin radioimmunoassay), a 6-minute walk test, 4-meter walking velocity and the Short Physical Performance Battery (SPPB), and were followed annually for up to 4 years. Analyses were adjusted for age, sex, race, body mass index, comorbidities, the ankle–brachial index, and other confounders. Among participants with PAD, lower baseline vitamin D levels were associated with a faster decline in the 6-minute walk (vitamin D < 30 nmol/L: –70.0 feet/year; vitamin D 30 to < 50 nmol/L: –72.3 feet/year; vitamin D 50 to < 75 nmol/L: –35.5 feet/year; vitamin D 75 to < 120 nmol/L: –35.9 feet/year; p trend=0.012). PAD participants with vitamin D < 30 nmol/L had a faster decline in the SPPB and 6-minute walk compared to those with levels of 50 to < 75 (p=0.034 and p=0.04, respectively). Among participants without PAD, lower vitamin D was associated with a faster decline in the fast 4-meter walking velocity (p trend=0.003). There were no significant associations of baseline vitamin D levels with all-cause or cardiovascular disease mortality in PAD or non-PAD participants. In conclusion, among individuals with and without PAD, low vitamin D status was associated with a faster decline in some measures of functional performance but was not related to mortality.
Online Search and Buying Behaviour in Consumer Markets

Online search behaviour is analysed using a novel methodology based on an international panel of two million users. Consumer search is measured by the size and distribution of online consideration sets and the use of price comparison engines in a range of US and UK consumer markets. It is shown that most online researchers who are considering competing suppliers only view two or three competitor websites, which results in an average online consideration set of between 2.1 and 2.8, regardless of the use of price comparison websites. Consumer perceived risk is negatively correlated with the size of online consideration sets and online price competition intensity. Using international data from fifteen countries it is shown that online research and online purchasing are negatively correlated with shop density. The implications for managers are outlined, in particular the importance of branding and advertising to improve the likelihood of inclusion in online consideration sets.
Comparative Efficacies of Candidate Antibiotics against Yersinia pestis in an In Vitro Pharmacodynamic Model

ABSTRACT Yersinia pestis, the bacterium that causes plague, is a potential agent of bioterrorism. Streptomycin is the “gold standard” for the treatment of plague infections in humans, but the drug is not available in many countries, and resistance to this antibiotic occurs naturally and has been generated in the laboratory. Other antibiotics have been shown to be active against Y. pestis in vitro and in vivo. However, the relative efficacies of clinically prescribed regimens of these antibiotics with streptomycin and with each other for the killing of Yersinia pestis are unknown. The efficacies of simulated pharmacokinetic profiles for human 10-day clinical regimens of ampicillin, meropenem, moxifloxacin, ciprofloxacin, and gentamicin were compared with the gold standard, streptomycin, for killing of Yersinia pestis in an in vitro pharmacodynamic model. Resistance amplification with therapy was also assessed. Streptomycin killed the microbe in one trial but failed due to resistance amplification in the second trial. In two trials, the other antibiotics consistently reduced the bacterial densities within the pharmacodynamic systems from 108 CFU/ml to undetectable levels (<102 CFU/ml) between 1 and 3 days of treatment. None of the comparator agents selected for resistance. The comparator antibiotics were superior to streptomycin against Y. pestis and deserve further evaluation.