Miracle-dz/UniFAR-FTUs huggingface dataset:
Effects of Obesity and Sex on Antimicrobial Pharmacokinetics and Acute Kidney Injury: Validation of a Preclinical Model

ABSTRACT Obese patients may be at a greater risk for acute kidney injury (AKI) with the use of certain antimicrobial agents that are dosed by weight. Current preclinical models of AKI utilize the male rat within a narrow weight range that limits extrapolation of the generated results. We evaluated the pharmacokinetics and AKI potential of gentamicin in 14-week-old diet-induced obesity-prone (n = 40) and obesity-resistant (n = 40) rats of both sexes. Single daily doses of gentamicin (12.5, 18.75, or 25 mg/kg of body weight) or saline (control) were administered intraperitoneally for 14 doses. Blood samples were collected after doses 1, 7, and 14, assayed by liquid chromatography-tandem mass spectrometry (LC-MS/MS), and analyzed using a nonparametric population pharmacokinetic approach for gentamicin. Urine was collected after doses 1, 3, and 5 and assayed for kidney injury molecule 1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) and normalized to creatinine (Cr) values. Histology was performed on all animals, and the degree of proximal tubular injury was graded. The mean (minimum, maximum) weight of the rats was 330 (136, 580) g. NGAL/Cr predicted AKI better than did KIM-1/Cr and was detectable in male rats after dose 1 and in obesity-prone female rats after dose 5. Proximal tubular injury by histology was significantly higher in male than in female rats. A significant relationship between the gentamicin area under the curve from zero to 24 hours (AUC0–24) estimates and the maximum NGAL/Cr ratio was observed. This preclinical model has the potential to aid with dose extrapolation for body size and improve assessment of the toxicology potential of antimicrobials in development.
Selection for the direct and maternal genetic effects for dystocia in Holsteins.

The effects of selection for the direct and maternal components of dystocia were estimated for first, second and later, and all parities. The effect of restricting maternal change to zero and the effect of selection for only the direct component were also examined. Gene flow procedure was used to compute economic weights as 1 and . 347 for the direct and maternal effects, respectively. Genetic gain in aggregate genotype was the largest for first parity. For all parities all the gain in the aggregate genotype was accounted for by the direct effects. At the same time, a slight decrease in the genetic maternal effects was observed. For all cases, selection for both traits had almost no loss in aggregate genotype or accuracy compared with when maternal changes were restricted to zero. Total genetic gain and genetic gain for the direct effect of dystocia were greater and accuracy of selection was lower when selection was for the genetic direct effect only versus the index that included both direct and maternal effects. Selection for only the direct effects is not likely to produce any significant change in dystocia as a maternal trait.
Isolation of the copper redox steps in the standard selective catalytic reduction on Cu-SSZ-13.

Operando X-ray absorption experiments and density functional theory (DFT) calculations are reported that elucidate the role of copper redox chemistry in the selective catalytic reduction (SCR) of NO over Cu-exchanged SSZ-13. Catalysts prepared to contain only isolated, exchanged Cu(II) ions evidence both Cu(II) and Cu(I) ions under standard SCR conditions at 473 K. Reactant cutoff experiments show that NO and NH3 together are necessary for Cu(II) reduction to Cu(I). DFT calculations show that NO-assisted NH3 dissociation is both energetically favorable and accounts for the observed Cu(II) reduction. The calculations predict in situ generation of Brønsted sites proximal to Cu(I) upon reduction, which we quantify in separate titration experiments. Both NO and O2 are necessary for oxidation of Cu(I) to Cu(II), which DFT suggests to occur by a NO2 intermediate. Reaction of Cu-bound NO2 with proximal NH4(+) completes the catalytic cycle. N2 is produced in both reduction and oxidation half-cycles.
Nebulized Gentamicin as an Alternative to Nebulized Tobramycin for Tracheitis in Pediatric Patients.

OBJECTIVES Tracheitis is an infection of the lower respiratory tract and is defined by the US Centers for Disease Control and Prevention (CDC) based on signs and symptoms with no radiographic evidence of pneumonia. One method of treatment involves the use of tobramycin given by nebulizer. The purpose of this study was to compare the safety and efficacy of nebulized gentamicin with nebulized tobramycin. METHODS This study was conducted in patients under 21 years of age who received greater than or equal to 1 day of gentamicin, 80 mg, or tobramycin, 300 mg, given twice a day by nebulization within the 14-month study period. The primary endpoint was amount of time until the patient no longer met the CDC definition of tracheitis. RESULTS There were 19 patients who presented with 60 separate encounters. The average age of the patients within the gentamicin group was 7.2 and 5 years old within the tobramycin group. The average duration of time for the gentamicin treatment encounters to be free of the CDC definition of tracheitis was 3.36 days compared to 3.17 days with tobramycin. No adverse effects were observed that were attributable to aminoglycoside nebulization. CONCLUSIONS No differences were detected between the safety and efficacy of intravenous gentamicin administered twice a day by nebulizer and that of tobramycin inhalation solution given twice daily in children without cystic fibrosis.
The Photovoltage of Macaque Cone Photoreceptors: Adaptation, Noise, and Kinetics

Whole-cell voltage and current recordings were obtained from red and green cone photoreceptors in isolated retina from macaque monkey. It was demonstrated previously that the cone photovoltage is generated from two sources, phototransduction current in the cone outer segment and photocurrent from neighboring rods. Rod signals are likely transmitted to cones across the gap junctions between rods and cones. In this study, the “pure” cone and rod components of the response were extracted with rod-adapting backgrounds or by subtracting the responses to flashes of different wavelength equated in their excitation of either rods or cones. For dim flashes, the pure cone component was similar in waveform to the cone outer segment current, and the rod component was similar to the photovoltage measured directly in rods. With bright flashes, the high frequencies of the rod signal were filtered out by the rod/cone network. The two components of the cone photovoltage adapted separately to background illumination. The amplitude of the rod component was halved by backgrounds eliciting ∼100 photoisomerizations sec−1 per rod; the cone component was halved by backgrounds of 8700 photoisomerizations sec−1 per cone. Coupling between rods and cones was not modulated by either dim backgrounds or dopamine. Voltage noise in dark-adapted cones was dominated by elementary events other than photopigment isomerizations. The dark noise was equivalent in magnitude to a steady light eliciting ∼3800 photoisomerizations sec−1 per cone, a value significantly higher than the psychophysical estimates of cone “dark light. ”
Biofilm Formation in a Hydrodynamic Environment by Novel FimH Variants and Ramifications for Virulence

ABSTRACT Type 1 fimbriae are surface-located adhesion organelles ofEscherichia coli that are directly associated with virulence of the urinary tract. They mediated-mannose-sensitive binding to different host surfaces by way of the minor fimbrial component FimH. Naturally occurring variants of FimH that bind strongly to terminally exposed monomannose residues have been associated with a pathogenicity-adaptive phenotype that enhances E. coli colonization of extraintestinal locations such as the urinary tract. The FimH adhesin also promotes biofilm formation in a mannose-inhibitable manner on abiotic surfaces under static growth conditions. In this study, we used random mutagenesis combined with a novel selection-enrichment technique to specifically identify mutations in the FimH adhesin that confer onE. coli the ability to form biofilms under hydrodynamic flow (HDF) conditions. We identified three FimH variants from our mutant library that could mediate an HDF biofilm formation phenotype to various degrees. This phenotype was induced by the cumulative effect of multiple changes throughout the receptor-binding region of the protein. Two of the HDF biofilm-forming FimH variants were insensitive to mannose inhibition and represent novel phenotypes not previously identified in naturally occurring isolates. Characterization of our enriched clones revealed some similarities to amino acid alterations that occur in urinary tract infection (UTI) strains. Subsequent screening of a selection of UTI FimH variants demonstrated that they too could promote biofilm formation on abiotic surfaces under HDF conditions. Interestingly, the same correlation was not observed for commensal FimH variants. FimH is a multifaceted protein prone to rapid microevolution. In addition to its previously documented roles in adherence and invasion, we have now demonstrated its function in biofilm formation on abiotic surfaces subjected to HDF conditions. The study indicates that UTI FimH variants possess adaptations that enhance biofilm formation and suggests a novel role for FimH in UTIs associated with medical implants such as catheters.
The Effects of Mastery, Competitive, and Cooperative Goals on the Performance of Simple and Complex Basketball Skills

This study investigated the effects of different goal and feedback conditions on performance of a basketball shooting task and a more complex one-on-one offensive basketball task. Subjects (N= 1(D) were matched, based on pretest performance, into one of five conditions: competitive goal, cooperative goal, mastery goal, "do your best" with feedback, and "do your best" without feedback. Subjects also responded to questionnaires to allow an assessment of the strength of mastery, competitive, and social goal orientations, which reflected personal achievement goals held before goal-setting instructions were offered. Results indicated that the competitive goal group performed significantly better than the do-your-best-without-feedback group in one-on-one posttest trials. No other between-group performance differences were significant. Subjects' goal orientations were not related to performance in the competitive and cooperative goal conditions, but significant relationships were found for mastery goal group sub.
A Bird’s Eye View of Unethical Behavior

Results from Trautmann and colleagues’ large, representative survey of Dutch people suggest a more nuanced relationship between class and ethics than previous research has demonstrated (Trautmann, Van de Kuilen, & Zeckhauser, 2013, this issue). Following their analysis, we suggest that it is unlikely that either upper- or lower-class people are unequivocally more moral. Rather, several psychological and external forces are at play in ethical decision making, which likely vary in strength depending on the conceptualization of class and the sociocultural context. Furthermore, people from different social classes may have different ethical standards or different degrees of willingness to breach these standards (or both), a distinction that should be explored in future research.
Business Intelligence Capability: The Effect of Top Management and the Mediating Roles of User Participation and Analytical Decision Making Orientation

: In this study, we draw on the structurational model of technology in an institutional setting to investigate how top management affects the development of a firm’s business intelligence (BI) capability. We propose a multiple mediator model in which organizational factors, such as user participation and analytical decision making orientation, act as mediating mechanisms that transmit the positive effects of top management championship to advance a firm’s BI capability. BI capability has two distinct aspects: information capability and BI system capability. Drawing on data collected from 486 firms from six different countries, we found support for the mediating effects of top management championship through user participation and analytical decision making orientation. These findings contribute to a nuanced understanding of how firms can develop BI capability. This study is one of the first to comprehensively investigate the antecedents of BI capability. on IT-related capabilities’ impact on firm performance. The results also provide instrumental insights for managers to foster user participation and fact-based decision making values when promoting the advancement of BI in organizations. We hope that this work inspires future attempts at a more elaborate and comprehensive understanding of such capability-building phenomena.
Sequential nitric oxide measurements during the emergency department treatment of acute vasoocclusive sickle cell crisis

This prospective study was designed to examine the relationship between serial serum nitric oxide (NO) levels and pain during the emergency department (ED) treatment of acute vasoocclusive sickle cell crisis (SCC). 102 patient visits, age ≥18 years of age, presenting to the ED with uncomplicated, typical SCC pain had serum NO levels obtained at 2‐hr intervals during treatment of pain and were measured using an NO‐specific chemiluminesence technique. Pain was measured prior to each NO measurement using a 10 cm visual analog scale (VAS), and subjects were divided into a persistent pain group and an improved pain group. Patients with persistent pain had significantly low initial NO levels (11.51 μM ± 2.8, P < 0.05) while those with pain improvement had higher initial NO levels (18.1 μM ± 3.08, P < 0.05). There was no significant correlation between changes in NO and changes in pain scores. These results suggest that the initial NO level may serve as a marker for the severity of tissue ischemia. Sequential NO levels do not appear useful in predicting the course of SCC. Am. J. Hematol. 64:15–19, 2000. © 2000 Wiley‐Liss, Inc.
WAIS-R Features of Preclinical Huntington’s Disease: Implications for Early Detection

Background/Aims: The main purpose of the study was to determine whether the predicted age of onset of Huntington’s disease (HD) affects cognitive function as measured by the Wechsler Adult Intelligence Scale-Revised (WAIS-R). The subscales and subtests, and their potential selectivity were examined in preclinical HD (30 mutation carriers and 34 noncarriers) with no motor or neuropsychiatric signs of HD. Methods: The predicted age of onset in mutation carriers was calculated by a regression equation allowing this group to be divided according to whether onset was predicted as within 12 years (HD+CLOSE) or longer than this (HD+DISTANT). Results: The HD+CLOSE group scored significantly lower on Verbal, Performance, and Full Scale IQ compared to noncarriers and performed significantly lower on 7 of the 11 WAIS-R subtests, with low average scores in language abilities, attention, abstract thinking, problem solving, visuospatial ability, and psychomotor speed. Conclusion: These low average scores affect general intelligence and functioning of HD+CLOSE carriers and are likely to reflect dysfunction of frontal cortex and frontostriatal circuits more than a decade before manifest symptoms. Our findings support a continuous linear model of slow cognitive decline in HD.
Projecting Future Health Care Expenditure at European Level: Drivers, Methodology and Main Results

Summary for non-specialistsTo correctly assess the demography-related risks facing public finances in the EU over the next couple of decades and establish adequate policy responses to the demographic, social and economic developments, it is essential to devise a reliable method to estimate future health care expenditure. To tackle this issue, the European Commission and the Economic Policy Committee projected future public health care expenditure in all EU Member States over the period 2007-2060. A unique internationally comparable database has been established and a model built allowing to project health care spending in a common, coherent framework of macroeconomic variables. The model incorporates the most recent developments in demography and epidemiology and draws on new insights from health economics, allowing the comparison of the challenges facing both individual countries' health care systems and European society in its entirety.
Cognitive-behavioral treatment for alcohol dependence: a review of evidence for its hypothesized mechanisms of action.

OBJECTIVE This review examined support for the hypothesis that cognitive-behavioral treatment (CBT) for alcohol dependence works through increasing cognitive and behavioral coping skills. METHOD Ten studies were identified that examined the hypothesized mechanisms of action of CBT. These studies involved random assignment (or its near equivalent) of participants to CBT and at least one comparison condition. RESULTS Although numerous analyses of the possible causal links have been conducted to evaluate whether CBT works through increasing coping, the results indicate little support for the hypothesized mechanisms of action of CBT. CONCLUSIONS Research has not yet established why CBT is an effective treatment for alcohol dependence. Negative findings may reflect methodological flaws of prior studies. Alternatively, findings may indicate one or more conceptual assumptions underlying CBT require revision.
Cutaneous complications in heart transplant recipients in Norway 1983-1993.

All Norweigian heart transplant recipients with more than one year's survival (n = 140) were investigated for dermatological disorders. Observation time after transplantation was 1-10 years (mean 5.0 years). Patients alive at the end of 1993 (n = 122) were examined clinically, and medical records for all patients were reviewed. The histopathological diagnoses of excised skin specimens were reevaluated. Malignant skin tumours (i.e. basal cell carcinoma, squamous cell carcinoma and malignant melanoma) and/or premalignant skin tumours (i.e. morbus Bowen (carcinoma in situ), solar keratosis and keratoacanthoma) were found in 34 patients (24.3%), of which 18 patients (12.9%) had malignant skin tumours. Seventeen lesions diagnosed as keratoacanthoma and two lesions diagnosed as morbus Bowen had primarily been diagnosed as squamous cell carcinoma. Five patients (3.6%) had multiple keratoacanthomas. Other frequent dermatological diagnoses included hypertrichosis (86.9%), steroid-induced skin features (59.8%), common warts (42.6%) and seborrheic skin disorders (20.5%). This study demonstrates the importance of dermatological surveillance in the follow-up of heart transplant recipients.
Adaptive generalized space shift keying and downlink multi-user transmission in MIMO fading channels

To achieve spatial diversity and improve the average bit error probability (ABEP) of Generalized Space Shift Keying (GSSK) in Multiple-Input and Multiple-Output (MIMO) channels with low feedback overhead and computational complexity, we propose a three-step adaptive precoding strategy for single-user GSSK (SU-GSSK) transmission by exploiting the channel state information at the transmitter (CSIT). First, a norm based reference receive antenna selection is conducted to maximize the selection gain. Second, active transmit antennas are coherently superposed to boost the signal to noise ratio (SNR) on the reference receive antenna. Third, phase-rotation processing is introduced to maximize the Euclid distance of the spatial constellation diagram. By applying the above steps, better ABEP performance can be obtained compared to the baseline schemes, with remarkably reduced feedback and complexity. Moreover, combining with the proposed adaptive precoding strategy, we design a resource-saving method for multi-user (MU) data conveying by preprocessing and stacking all users' spatial constellations on increased number of active antennas and then implement a downlink MU-GSSK transmission scheme to provide several times the sum rate compared to SU-GSSK with acceptable ABEP performance. Complexity analysis and simulations show the effectiveness and scalability of our proposed schemes.
In vitro fertilization (IVF) in Sweden: risk for congenital malformations after different IVF methods.

BACKGROUND The possible excess of congenital malformations in infants born after in vitro fertilization (IVF) has been much discussed in the literature, with controversial conclusions. This population based study is aimed at analyzing the presence of congenital malformations in a large group of infants born after IVF and to compare malformation risk both with that of all infants born and according to IVF method used. METHODS Infants born after IVF during the period 1982-2001 were ascertained from all IVF clinics in Sweden. The presence of congenital malformations was identified from three national health registers: the Swedish Medical Birth Register, the Swedish Registry of Congenital Malformations, and the Swedish Hospital Discharge Register. The IVF children were compared with all children born in Sweden during the same period and recorded in the Swedish Medical Birth Register. RESULTS Among 16,280 IVF children (30% conceived after intracytoplasmatic sperm injection [ICSI]) a 42% excess of any congenital malformation was found, explainable by parental characteristics and in some cases by the high rate of multiple births. Among these children, 8% had a congenital malformation, and 5% had a relatively severe condition. For neural tube defects, choanal atresia, and alimentary tract atresia, an additional risk increase was seen. There was no difference in malformation rate according to IVF method except for an excess of hypospadias after ICSI. CONCLUSIONS An increased risk for congenital malformations occurs after IVF, similar for the different IVF techniques used, and mainly a consequence of parental characteristics. A few specific conditions show an extra increase in risk.
Pain effects of glutamate injections into human jaw or neck muscles.

AIMS To document and compare the intensity, localization, and quality of pain evoked by glutamate injections into the human masseter or splenius muscles and to determine the effect of glutamate-evoked pain on the pressure pain thresholds (PPTs) in both jaw and neck muscles. METHODS Twenty-six healthy men were given painful injections of glutamate (1.0 mol/L) and control injections of isotonic saline (0.165 mol/L) into the masseter and splenius muscles. The subjects rated the perceived intensity of pain on a visual analog scale (VAS), drew the area of the pain on maps of the face and neck, and filled out a Danish version of the McGill Pain Questionnaire (MPQ). PPTs were used to assess the sensitivity of the masseter and splenius muscles to mechanical stimuli (n = 11). RESULTS Glutamate injection into the masseter or splenius evoked pain lasting almost 10 minutes. Peak pain intensity usually occurred within 2 minutes of the injection, and VAS scores of peak pain were significantly higher for the masseter muscle compared with the splenius muscle (paired t test, P = .003). The pain area from the masseter injections did not extend into the neck region, although in some subjects the pain from the neck region extended into the temporal region. There were no significant relationships between the area of perceived pain and the VAS pain scores (Pearson correlation, P > .297). Glutamate-evoked pain in either the masseter or splenius muscles was associated with significant decreases in masseter or splenius PPTs, respectively (2-wayANOVAs, P < .016). Isometric saline injections were almost pain-free and caused no PPT changes. CONCLUSION The data suggest that the masseter muscle is more sensitive to glutamate injections and mechanical stimuli than the splenius muscle. The relatively limited overlap between the sensory manifestations of pain from masseter and splenius muscles may have potential implications for diagnosis and management of myofascial pain complaints in the craniofacial and neck region.