Miracle-dz/UniFAR-FTUs huggingface dataset:
Wild-Type MIC Distributions and Epidemiological Cutoff Values for Posaconazole and Voriconazole and Candida spp. as Determined by 24-Hour CLSI Broth Microdilution

ABSTRACT We tested 16,191 strains of Candida against posaconazole and voriconazole, using the CLSI M27-A3 broth microdilution (BMD) method (24-h incubation), in order to define wild-type (WT) populations and epidemiological cutoff values (ECVs). From 2001 to 2009, 8,619 isolates of Candida albicans, 2,415 isolates of C. glabrata, 2,278 isolates of C. parapsilosis, 1,895 isolates of C. tropicalis, 508 isolates of C. krusei, 205 isolates of C. lusitaniae, 177 isolates of C. guilliermondii, and 93 isolates of C. kefyr were obtained from over 100 centers worldwide. The modal MICs (μg/ml) for posaconazole and voriconazole, respectively, were as follows: for C. albicans, 0.016 and 0.007; for C. glabrata, 0.5 and 0.06; for C. parapsilosis, 0.06 and 0.007; for C. tropicalis, 0.03 and 0.015; for C. krusei, 0.25 and 0.12; for C. lusitaniae, 0.03 and 0.007; for C. guilliermondii, 0.12 and 0.03; and for C. kefyr, 0.06 and 0.007. The ECVs (μg/ml [% of isolates that had MICs equal to or less than the ECV]) for posaconazole and voriconazole, respectively, were as follows: 0.06 (98.5) and 0.03 (98.9) for C. albicans, 2 (96.2) and 0.5 (90.4%) for C. glabrata, 0.25 (99.3) and 0.12 (97.9) for C. parapsilosis, 0.12 (97.6) and 0.06 (97.2) for C. tropicalis, 0.5 (99.8) and 0.5 (99.4) for C. krusei, 0.12 (95.6) and 0.03 (96.6) for C. lusitaniae, 0.5 (98.9) and 0.25 (98.3) for C. guilliermondii, and 0.25 (100.0) and 0.015 (100.0) for C. kefyr. In the absence of clinical breakpoints (CBPs) for posaconazole, these WT distributions and ECVs will be useful in surveillance for emergence of reduced susceptibility to posaconazole among Candida spp. Whereas a CBP for susceptibility of ≤1 μg/ml has been established for voriconazole and all species of Candida, it is notable that ECVs for this agent range from 10- to >100-fold lower than the CBP, depending on the species of Candida. The CBP is inadequate in detecting the emergence of voriconazole resistance among most Candida species encountered clinically. The CBPs for voriconazole should be reassessed, with consideration for development of species-specific CBPs.
Reference intervals for thyrotropin and thyroid hormones and ultrasonographic thyroid volume during the neonatal period

Objective. To determine thyrotropin (TSH) and thyroid hormones reference ranges in healthy term newborns during the neonatal period and to assess the ranges of thyroid volume in newborns using ultrasound scanning. Methods. Blood samples were collected from 296 healthy newborns at birth (cord; n: 47) and before feeding on the 1st, 3rd, 5th, 7th, 10th, 14th, and 28th days of life. The levels of TSH and thyroid hormones of the newborns were then compared with results from 50 healthy adults. Thyroid ultrasonography (USG) was performed by the same radiologist on 38 newborns aged 10 days. Results. TSH and thyroid hormone levels in newborns were statistically higher than those in adults for each day (p < 0.001). Serum TSH concentration on the 1st day of life was higher than at other times (p < 0.001). Mean TSH concentration reverted to the cord level at the 5th or 7th day of life (p > 0.05). TSH levels were no higher than 10 mIU/ml after 2 weeks postnatal age. There was no correlation between hormone levels and Ponderal index (PI), birth weight, gender, or delivery type. Mean thyroid volume was 0.72 ± 0.24 ml (0.36–1.62 ml). Conclusions. We conclude that our results are important for CH screening regarding time-dependent changes of TSH and thyroid hormones besides diagnosis of thyroid hypoplasia or hyperplasia.
Reduced dose OKT3 prophylaxis in sensitised kidney recipients

Prophylactic use of the monoclonal antibody OKT3 has been studied for the prevention of rejection in sensitised renal transplant recipients. Patients receiving a full dose (FD) regimen were compared to a subsequent consecutive group of patients receiving a reduced dose (RD) regimen. The characteristics of the two groups were not significantly different with regard to age, HLA mismatch and panel-reactive antibody (PRA) status. The number of days that OKT3 was given was 12.9±1.8 for the FD regimen and 11.3±2.8 for the RD regimen. The total dose of OKT3 given was 64.4±9 mg (FD) and 38.3±8.5 mg (RD). Patient survival at 12 months was 8/8 for FD and 17/17 for RD. Graft survival at 12 months was 7/8 for FD and 17/17 for RD. Creatinine at 24 months was 185±68 and 201±81 μmol/l for FD and RD, respectively. A reduced dose regimen of OKT3 produced excellent and comparable results to the standard recommended fulldose regimen. The cost per patient was reduced 40% from £5676 for FD to £3344 for RD.
Interim Third-Party Selection in Bargaining

Third-party intervention can reduce the risk of conflict in situations where the bargaining failure is due to asymmetric information. In this paper, I consider the selection of a third party in a two-person bargaining problem where each disputant has private information about its relative strength or weakness. I find that the disputants choose the third party that is best for the strong type but worst for the weak type due to the incentive of each disputant to avoid seeming weak to their adversary. The selected third party's intervention entails a higher ex ante chance of conflict than intervention by any other alternative. This paper shows how the process of interim third-party selection can have important consequences for the outcome of a third-party intervention in bargaining.
Laparoscopic donor nephrectomy increases the supply of living donor kidneys: a center-specific microeconomic analysis.

BACKGROUND A tenet of microeconomics is that new technology will shift the supply curve to the right. Laparoscopic donor nephrectomy (LDN) is a new technique for removal of living donor kidneys. Centers performing this procedure have noted an increased number of patients presenting for donor evaluation. This has not been previously studied. METHODS The records of all LDN performed from May 1998 to February 1999 were reviewed. The following variables were examined: sex, age, related vs. unrelated donation, estimated blood loss, i.v. analgesia, length of stay, and time out of work. Donors undergoing traditional open donor nephrectomy during January 1997 to May 1998 served as the control group. A composite cost index was constructed. RESULTS LDN significantly decreased length of stay, pain, and time out of work; the supply function shifted to the right. Telephone interviews revealed that 47% donated solely because of the LDN procedure. CONCLUSIONS LDN increases the supply of living donor kidneys.
From strategic planning to meaningful learning: diverse perspectives on the development of web-based teaching and learning in higher education

This paper reports the results of a study on strategic planning and implementation of information and communication technology (ICT) in teaching and describes the level of quality awareness in web-based teaching at the University of Helsinki. Questionnaire survey data obtained from deans and institutional leaders, ICT support staff, teachers and students (n = 333) at the University indicate that strategic planning has proceeded well, and all the faculties of the University have developed virtual university strategies in order to continue existing ICT initiatives, to further increase the use of ICT in teaching and to assure student information literacy. The data indicate that all the faculties and institutions have monitored and reported the use of ICT in teaching, but quality assurance or enhancement as tools for monitoring were mentioned less frequently. The available ICT training was found satisfactory to meet the actual training needs of the teachers, but their lack of time was judged to be the main obstacle to their participation in it. The teachers identified two basic functions of ICT in teaching: (1) distribution of course material via the web, and (2) the creation of interactive and collaborative learning opportunities. The male teachers and students consistently estimated that their ICT skills were stronger when compared with the judgements made by female teachers and students. The teachers generally felt that the greatest problems arose from students’ lack of time management skills and from deficiencies in the usability of the technology. The students did not perceive lack of time management as a problem. Rather, they experienced isolation, loneliness and the lack of practical ICT usability to be the main obstacles to learning. The teachers had a higher assessment of students’ learning than the students did. The greatest difference between teachers and students concerned the contextual nature of learning in a virtual environment. The fact that the teachers’ views were markedly more positive signals a distinct challenge for pedagogy.
Lumbar Intervertebral Foramens: An in Vitro Study of Their Shape in Relation to Intervertebral Disc Pathology

The lumbar intervertebral foramens of 20 isolated cadaveric spines were investigated by the use of a molding technique to assess their dimensions accurately and how intervertebral disc pathology altered their configuration. Oval foramens predominated over auricularly shaped foramens when the disc was normal, but when the disc was abnormal, the converse was true. Foraminal size varied from 40 to 160 mm2 but showed great variation even at individual levels; these were not accurately reflected by simple radiologic measurements.
Binaural interaction in low-frequency neurons in inferior colliculus of the cat. I. Effects of long interaural delays, intensity, and repetition rate on interaural delay function.

Detailed, quantitative studies were made of the interaural phase sensitivity of 197 neurons with low best frequency in the inferior colliculus (IC) of the barbiturate-anesthetized cat. We analyzed the responses of single cells to interaural delays in which tone bursts were delivered to the two ears via sealed earphones and the onset of the tone to one ear with respect to the other was varied. For most (80%) cells the discharge rate is a cyclic function of interaural delay at a period corresponding to that of the stimulating frequency. The cyclic nature of the interaural delay curve indicates that these cells are sensitive to the interaural phase difference. These cells are distributed throughout the low-frequency zone of the IC, but they are less numerous in the medial and caudal zones. Cells with a wide variety of response patterns will exhibit interaural phase sensitivities at stimulating frequencies up to 3,100 Hz, although above 2,500 Hz the number of such cells decrease markedly. Using dichotic stimuli we could study the cell's sensitivity to the onset delay and interaural phase independently. The large majority of IC cells respond only to changes in interaural phase, with no sensitivity to the onset delay. However, a small number (7%) of cells exhibit a sensitivity to the onset delay as well as to the interaural phase disparity, and most of these cells show an onset response. The effects of changing the stimulus intensity equally to both ears or of changing the interaural intensity difference on the mean interaural phase were studied. While some neurons are not affected by level changes, others exhibit systematic phase shifts for both average and interaural intensity variations, and there is a continuous distribution of sensitivities between these extremes. A few cells also showed systematic changes in the shape of the interaural delay curves as a function of interaural intensity difference, especially at very long delays. These shifts can be interpreted as a form of time-intensity trading. A few cells demonstrated orderly changes in the interaural delay curve as the repetition rate of the stimulus was varied. Some of these changes are consonant with an inhibitory effect that occurs at stimulus offset. The responses of the neurons show a strong bias for stimuli that would originate from he contralateral sound field; 77% of the responses display mean interaural phase angles that are less than 0.5 of a cycle, which are delays to the ipsilateral tone. (ABSTRACT TRUNCATED AT 400 WORDS)
Loss of Emi1-Dependent Anaphase-Promoting Complex/Cyclosome Inhibition Deregulates E2F Target Expression and Elicits DNA Damage-Induced Senescence

ABSTRACT Expression of the anaphase-promoting complex/cyclosome (APC/C) inhibitor Emi1 is required for the accumulation of APC/C substrates crucial for DNA synthesis and mitotic entry. We show that in vivo Emi1 expression correlates with the proliferative status of the cellular compartment and that cells lacking Emi1 undergo cellular senescence. Emi1 depletion leads to strong decreases in E2F target mRNA and APC/C substrate protein abundances. However, cyclin E mRNA and cyclin E protein levels and associated kinase activities are increased. Cells lacking Emi1 undergo DNA damage, likely explained by replication stress upon deregulated cyclin E- and A-associated kinase activities. Inhibition of ATM kinase prevents induction of senescence, implying that senescence is a consequence of DNA damage. Surprisingly, no senescence or no extensive amount of senescence is evident upon depletion of the Emi1-stabilizing factor Evi5 or Pin1, respectively. Our data suggest that maintenance of a protein stabilization/mRNA expression positive-feedback circuit fueled by Emi1 is required for accurate cell cycle progression, maintenance of DNA integrity, and prevention of cellular senescence.
Long-term live cell microscopy studies of lipid droplet fusion dynamics in adipocytes[S]

During the adipogenic differentiation process of mesenchymal stem cells, lipid droplets (LDs) grow slowly by transferring lipids between each other. Recent findings hint at the possibility that a fusion pore is involved. In this study, we analyze lipid transfer data obtained in long-term label-free microscopy studies in the framework of a Hagen-Poiseuille model. The data obtained show a LD fusion process in which the lipid transfer directionality depends on the size difference between LDs, whereas the respective rates depend on the size difference and additionally on the diameter of the smaller LDs. For the data analysis, the viscosity of the transferred material has to be known. We demonstrate that a viscosity-dependent molecular rotor dye can be used to measure LD viscosities in live cells. On this basis, we calculate the diameter of a putative lipid transfer channel which appears to have a direct dependence on the diameter of the smaller of the two participating LDs.
Intravenous Iloprost: A New Therapeutic Option for Patients with Post‐Transplant Distal Limb Syndrome (PTDLS)

The purpose of this study was to investigate the application of intravenous iloprost as a novel therapy for the treatment of post‐transplant distal limb syndrome (PTDLS). PTDLS is a benign but disabling complication in the first year after renal transplantation. It is characterized by bilateral, often incapacitating pain in the feet and or knees on motion and a significant rise in alkaline phosphatase levels on laboratory evaluation. On MRI, bone marrow edema of the affected bone regions can be demonstrated. PTDLS differs from steroid induced osteonecrosis of the hip in terms of localization, an average cumulative steroid dosage within expected limits, and a benign outcome, as PTDLS does not progress to overt cell necrosis. From August 2003 to April 2005 we treated 10 patients with MRI‐proven diagnosis of PTDLS following a standardized regimen of intravenous iloprost over 5 days. Iloprost led to prompt pain relief measured on a visual analogous scale (VAS) ranging from 1 to 10 (5.6 ± 1.5 before vs. 2.1 ± 1.3 after treatment, p = 0.0004). PTDLS represents a benign but disabling complication following renal transplantation. Intravenous iloprost might be a promising therapeutic concept leading to a quick relief of symptoms without relevant side effects.
"I would have never allowed it": User Perception of Third-party Tracking and Implications for Display Advertising

This study examines the perception on third-party tracking of German Internet users. For that purpose, 20 users without a technical background were interviewed. Results indicate that users are not aware of online tracking. They are often surprised by the magnitude of tracking programs they are exposed to during everyday life online activities like travel planning, job or product research. While the interviewees were willing to concede the theoretical advantages of such data collection, e.g. for behavioral targeting, they considered the price as too high to compensate for the loss of privacy control. The participants showed concerns that tracking could possibly lead to disadvantages in real life. In addition, behavioral targeting is assessed fairly redundant. Asked about concepts for enhanced transparency and control, the interviewed people still emphasized their distrust toward tracking. Thus, third-party tracking is a doubled edged sword for online advertising. On the one hand, it is a central means to improve the relevancy of the often unwanted display ads. At the same time, there is a great danger of increasing ad aversion for privacy reasons.
Crystallographic and Optical Properties of Z-Cut High Index Soft Proton Exchange (HISoPE) LiNbO3 Waveguides

Highly confining nonlinear optical waveguides are extremely interesting for highly efficient and ultracompact nonlinear and/or electro-optical devices. In this paper, we concentrate on correlations between structural and optical properties of channel waveguides on z-cut lithium niobate fabricated using a new waveguide fabrication method, we call HISoPE for high index soft proton exchange, which allows obtaining a guiding layer presenting an index increase as high as 0.1 and a nonlinear coefficient equal to its value in the bulk.
High frequency of CYP2C19*2 carriers in PCI-treated patients switched over from clopidogrel to prasugrel based on platelet function monitoring

To the editor Among patients undergoing percutaneous coronary intervention (PCI), subjects with high on-clopidogrel treatment platelet reactivity (HCPR) exhibit a high risk for postprocedural thrombotic events including stent thrombosis [1]. Numerous non-genetic and genetic variables were discovered as major factors causing HCPR. Among the genetic variables, the common loss-of-function CYP2C19*2 polymorphism was found to be associated with an attenuated response to clopidogrel [2] and a higher risk for stent thrombosis [3]. However, prior studies suggested that – based on statistical models – this genetic marker may only account for about 5–12% of the observed variability in clopidogrel response [4, 5]. This suggests that a single genetic variant such as CYP2C19*2 may only have little impact on the overall response to clopidogrel treatment and genotyping of this variant may be of limited value in routine clinical practice. The prevalence of CYP2C19*2 as a causative factor for high levels of on-clopidogrel treatment platelet reactivity was never investigated in a clinical scenario where patients are switched over from clopidogrel to prasugrel treatment due to clopidogrel treatment failure. To close this gap of knowledge, the aim of this study was to determine CYP2C19*2 allele carriage in PCI-treated patients initially treated with clopidogrel and switched over to prasugrel therapy due to high levels of platelet reactivity on clopidogrel treatment in a setting of routine platelet function testing. The prevalence of the CYP2C19*2 allele was compared between two consecutively recruited PCI cohorts: The first consecutive (¼control) cohort of patients (n ¼1524) stems from a study that enrolled clopidogrel-treated patients undergoing PCI and that aimed to determine the prognostic value of HCPR [6] and genetic markers [7]. As a consecutive cohort, this study included patients with and without HCPR but without any switch of antiplatelet treatment based on obtained platelet function testing results. The second consecutive cohort of PCI-treated patients (n ¼143) was recruited between 2009 and 2011 [8] and within this cohort all patients were switched over from clopidogrel to prasugrel treatment based on detected high levels of platelet reactivity on clopidogrel treatment. Blood for genotyping was available in 124 (87%) of the 143 patients who constitute the study group (¼cases) for this specific analysis. Genotypes in both cohorts were determined by a TaqMan assay as previously described [7] and were compared between groups by chi-square test. In both cohorts, the adenosine diphosphate (ADP)-induced platelet aggregation
Associations of Memory and Executive Functioning With Academic and Adaptive Functioning Among Youth With Perinatal HIV Exposure and/or Infection.

BACKGROUND Perinatally acquired HIV (PHIV) confers risk for neurocognitive impairment, which potentially affects school performance and functional independence of infected children. In this study, we examined the associations of 2 key neurocognitive domains, memory and executive function (EF), with academic and adaptive skills among youth with PHIV and perinatally HIV-exposed but uninfected (PHEU) youth. METHODS Participants ages 9 to <19 years enrolled in the Pediatric HIV/AIDS Cohort Study's Memory and Executive Functioning Study completed standardized measures of reading and math. The primary caregivers completed a standardized measure of their child's adaptive behavior. Participants with PHIV, those with (PHIV/C) and without (PHIV/non-C) a Centers for Disease Control and Prevention class C diagnosis, and PHEU participants were compared. Retrospective memory (RM), prospective memory (PM), and EF were evaluated relative to outcomes using general linear regression models adjusted for sociodemographic characteristics. RESULTS Of the participants (N = 258; mean age, 14.1 years), 46% were male, 75% were black, and 18% were Hispanic. Adjusted mean scores in math and adaptive behavior did not differ among the youth with PHIV/C (n = 45), those with PHIV/non-C (n = 128), and PHEU youth (n = 85). Youth with PHIV/C had lower adjusted mean reading scores than PHIV/non-C and PHEU youth (86.9 vs 93.8 [P = .02] and 93.2 [P = .04], respectively). There were positive associations of RM, PM, EF, and some sociodemographic characteristics with higher reading and math scores. Immediate and delayed verbal memory, delayed visual memory, PM, and some EF measures were positively associated with adaptive behavior. CONCLUSIONS Higher-order cognitive abilities such as memory and EF seem to play a key role in academic and adaptive capacities, regardless of a child's HIV status, and might serve as intervention targets for improving functional outcomes.