Miracle-dz/UniFAR-FTUs huggingface dataset:
Pediatric Off-label Use of Recombinant Factor VIIa

OBJECTIVE. Our goal was to report our institutional experience with recombinant factor VIIa for the treatment and/or prevention of bleeding in nonhemophiliac children. METHODS. This was a retrospective case series in a tertiary pediatric referral hospital. RESULTS. During 1999–2006, 135 patients received recombinant factor VIIa for off-label use. The median number of doses was 2; the median dose was 88 μg/kg. The most common diagnoses among patients receiving recombinant factor VIIa were disseminated intravascular coagulation/sepsis (28), surgical bleeding (19), procedural prophylaxis (16), and trauma (15). The median volume of blood products administered 24 hours before recombinant factor VIIa treatment was 29.7 vs 11.7 mL/kg 24 hours after treatment. Only 1 high-risk patient had significant bleeding after receiving prophylactic recombinant factor VIIa before an invasive procedure. Nonsurvivors had significantly increased incidence of multiple organ dysfunction syndrome (75%) compared with survivors (23%). The largest group of patients (n = 28) received recombinant factor VIIa for bleeding and/or coagulopathy because of disseminated intravascular coagulation; the mortality in this group was 26 (93%) of 28. Eleven patients received multiple doses of recombinant factor VIIa to treat bleeding complications after hematopoietic stem cell transplant, without improvement in blood use. Mortality in medical patients was 58% vs 16% in surgical patients. Three patients had significant thrombotic adverse events after receiving recombinant factor VIIa, resulting in 2 deaths and 1 leg amputation. CONCLUSIONS. Off-label use of recombinant factor VIIa significantly decreases blood-product administration; surgical patients had control of life-threatening bleeding with low associated mortality. Prophylactic recombinant factor VIIa may be effective in preventing bleeding if given before invasive procedures in children at high risk. Prolonged use of recombinant factor VIIa for bleeding complications after hematopoietic stem cell transplant is not effective in preventing packed red blood cell transfusion. Presence of disseminated intravascular coagulation and mulitorgan dysfunction syndrome may help predict futility of recombinant factor VIIa treatment. Off-label use of recombinant factor VIIa is associated with thromboembolic events in children.
The effect of waveguide parameters on gan based S-bend Y-junction optical power divider

GaN-based structures have attracted many researchers in developing photonic devices. These semiconductor structures can operate at high temperatures and high-power levels due to their mechanical hardness. So far, optical splitters design based on Y-junction splitters are widely used on the various material structure. The problem of these structures is radiation loss at the junction area. In this paper, we study the effect of various waveguide parameters on GaN-based S-bend Y-junction optical power divider. The design consists of three sections: linear rectangular rib waveguide, parabolic taper and two S-bend sine branches with the total length of 1000μm. We use optical beam propagation methods (BPM) to obtain the characteristic of the guided wave to calculate the field propagation through the structure as a function of waveguide parameters, such as branching angle and input wavelength. All simulations are carried out using the OptiBPM software. From the simulation results, it shows that to maintain 90% transmitted power, the branching angle for the design should be at the range of 0.5–1.5°. It is also demonstrated that the transmitted power almost stable through the wavelength range from 1.5 up to 1.6 μm with an average of power loss at about 0.35 dB. The simulation results presented can be applied for future GaN Y-junction based waveguide photonic devices design.
Optimization of scan parameters in pulmonary partial pressure oxygen measurement by hyperpolarized 3He MRI

The dependence of hyperpolarized (HP) 3He T1 on local oxygen concentration provides the basis for measuring the partial pressure of oxygen (pO2) and oxygen depletion rate (R) in the lungs. Precise measurements of this type are difficult because the oxygen effect manifests itself through a decay of signal, leading to noisy images at the end of the series. The depolarization caused by RF excitation pulses further complicates the problem. It is therefore important to optimize scan parameters, such as measurement timing and flip angle, to obtain accurate and reproducible measurements. This work presents a new single‐acquisition technique in conjunction with the multiple regression fitting method for data evaluation. Analytical expressions for the measurement uncertainties are derived. A total of four types of single‐acquisition timing schemes are investigated; simulation shows a large uncertainty variation between these schemes (pO2: 7.5–30.2%; R: 47.4–173.7%). A basic procedure for optimizing scan parameters is then described. A phantom experiment was conducted to verify the simulation results. Repeated in vivo measurements with the optimal scheme in a rabbit experiment showed that average variation of global mean is 6.2% for pO2 and 12.0% for R, and that the average variation of percentiles (10th, 25th, 50th, 75th, and 90th) is 8.7% for pO2 and 19.0% for R. Magn Reson Med, 2007. © 2007 Wiley‐Liss, Inc.
Electrical Stimulation and Swallowing: How Much Do We Know?

Abstract Consequences of dysphagia substantially reduce quality of life, increase the risk of medical complications and mortality, and pose a substantial cost to healthcare systems. As a result, it is of no wonder that the clinical and scientific communities are showing interest in new avenues for dysphagia rehabilitation. Electrical stimulation (e-stim) for the treatment of swallowing impairments is among the most studied swallowing interventions in the published literature, yet many unanswered questions about its efficacy remain. In the meantime, many speech-language pathologists who treat dysphagia are attending educational and training sessions to obtain certifications to use this technique. Here, we review the values and limitations of the published literature on the topic of e-stim for swallowing to assist clinicians in decision making in their clinical practice. The discussion provides a review of swallowing anatomy and physiology, the fundamentals of e-stim, and information essential for the readers' independent critique of these studies—all of which are crucial for evaluating the possible effects of e-stim.
Designing an Appropriate Information Systems Development Methodology for Different Situations

The number of information systems development methodologies has proliferated and practitioners and researchers alike have struggled to select a ‘one best’ approach for all applications. But there is no single methodology that will work for all development situations. The question then arises: ‘when to use which methodology? ’ To address this question we used the design research approach to develop a radar diagram consisting of eight dimensions. Using three action research cycles, we attempt to validate our design in three projects that took place in a large administrative organization and elsewhere with groups of IT project managers. Our artefact can be used to suggest a particular one-off approach for a particular situation.
Purification and identification of positive regulators binding to a Novel element in the c‐jun promoter

A putative response element, GAGCCTC, was investigated to regulate c‐jun expression in this study. Electrophoretic mobility shift assays demonstrate that sequence‐specific binding proteins form a specific complex with this element in HEK293 cells. Additionally, unlabeled consensus AP‐1 element DNA, but not a similar NF‐jun element DNA, competes with complex formation. Mutations of this element decrease c‐jun promoter reporter activity by nearly 5‐fold in HEK293 cells. A new, two‐step oligonucleotide trapping technique was developed to purify the element binding proteins. LC‐Nanospray‐ESI‐MS/MS identification and western blotting analysis show that the purified complex contains Ku80, Ku70 and c‐jun, which was further confirmed by antibody supershift and immunoprecipitation analysis, and by southwestern blot and UV crosslinking analysis in vitro as well as chromatin immunoprecipitation in vivo. c‐Jun promoter activity decreases after Ku80 was significantly decreased by its siRNA, and c‐jun expression decreased at both the mRNA and protein levels. A mutant Ku80 with normal amino acid sequence but immune to the siRNA recovers c‐jun promoter activity from siRNA inhibition. Similarly, Ku70 wild type transfection can also up‐regulate c‐jun promoter activity. Thus, we speculate that Ku80‐Ku70‐c‐jun trimer activates c‐jun expression by binding to this GAGCCTC element in the c‐jun promoter.
Effects of Administration of Exogenous Growth Factors on Biomechanical Properties of the Elongation-type Anterior Cruciate Ligament Injury with Partial Laceration

Background No studies have been conducted to clarify the in vivo effect of growth factor application on healing in the injured anterior cruciate ligament. Hypothesis Administration of exogenous growth factors significantly increases the structural properties of the injured anterior cruciate ligament. Study Design Controlled laboratory study. Methods Thirty-six rabbits were randomly divided into 4 groups of 9 animals each after an overstretched injury was made in the right anterior cruciate ligament. In group 1, no treatment was applied around the injured anterior cruciate ligament. In group 2, 0.2 mL fibrin sealant was applied around it. In group 3, 4 ng transforming growth factor–β1 mixed with 0.2 mL fibrin sealant was applied. In group 4, 20 μg platelet-derived growth factor–BB mixed with 0.2 mL fibrin sealant was applied. Each rabbit was sacrificed at 12 weeks after the surgery. In addition, 9 knees randomly harvested from all the left knees were used to obtain normal control data. The femur–anterior cruciate ligament–tibia complex specimens were biomechanically and histologically evaluated. Results Concerning the maximum load and the stiffness, group 3 was significantly greater than groups 1 and 2, whereas there were no significant differences among groups 1, 2, and 4. Groups 1, 2, 3, and 4 were significantly lower than the control group. Conclusions The application of 4 ng transforming growth factor–β1 significantly enhances healing in the injured anterior cruciate ligament. Clinical Relevance Administration of certain growth factors is of value to be studied as one of the future therapeutic options for the overstretched anterior cruciate ligament injury.
The effect of acetylsalicylic acid on platelet adhesion in the injured abdominal aorta.

The effect of a single oral dose of acetylsalicylic acid (ASA) on platelet adhesion in the rabbit abdominal aorta following a standard mechanical removal of the endothelium has been observed with both the scanning and transmission electron microscopes, in conjunction with studies on the agglutination properties of the platelets in vitro. It was found that the ASA did not prevent adhesion of platelets to the subendothelial surface although they did not appear to be adhering to the exposed collagen fibres but rather to endothelial basement membrane and microfibrils of the internal elastic lamina, often in small clumps. A large number of leucocytes were also observed adhering to the surface denuded to endothelium. The platelets obtained from ASA treated animals were morphologically normal, but unlike platelets obtained before treatment, did not adhere to collagen fibres in vitro; even when ADP was added the platelets adhered to one another but not to the collagen.
Clinical Validation of a Type-Specific Real-Time Quantitative Human Papillomavirus PCR against the Performance of Hybrid Capture 2 for the Purpose of Cervical Cancer Screening

ABSTRACT To be acceptable for use in cervical cancer screening, a new assay that detects DNA of high-risk human papillomavirus (hrHPV) types must demonstrate high reproducibility and performance not inferior to that of a clinically validated HPV test. In the present study, a real-time quantitative PCR (qPCR) assay targeting the E6 and E7 genes of hrHPV was compared with Hybrid Capture 2 (hc2) in a Belgian cervical cancer screening setting. In women >30 years old, the sensitivity and specificity for intraepithelial neoplasias of grade 2 or worse (93 cases of cervical intraepithelial neoplasias of grade 2 or worse (CIN2+) and 1,207 cases of no CIN or CIN1) were 93.6% and 95.6%, respectively, and those of hc2 were 83.9% and 94.5%, respectively {relative sensitivity of qPCR/hc2 = 1.12 [95% confidence interval (CI), 1.01 to 1.23]; relative specificity = 1.01 [95% CI, 0.99 to 1.03]}. A score test showed that the sensitivity (P < 0.0001) and specificity (P < 0.0001) of the qPCR assay were not inferior to those of hc2 at the required thresholds of 90% and 98%, respectively. The overall agreement of hrHPV positivity between the two runs of the qPCR tests was 98.7% (95% CI, 97.5 to 99.4%), with a kappa value of 0.96 (95% CI, 0.83 to 1.00). The qPCR assay used in this study can be considered a reliable HPV assay that fulfills the clinical validation criteria defined for use in cervical cancer screening.
Discussion Paper No . 573 Contract Enforcement and Firms ’ Financing

This paper studies how the degree of contract enforcement in a country influences firms’ financing decisions. We first document empirical facts on debt financing for two new firm-level datasets in the United Kingdom and Ecuador. In the United Kingdom, small firms borrow more relative to their assets than large firms, whereas in Ecuador small firms borrow less. We build a dynamic model of firms’ debt financing where debt is constrained by the likelihood of default, which varies across firms and economies with different degrees of enforcement. Because of their low firm values, small firms are mostly affected by abundance or scarcity of economy-wide loans generated by weak or strong contract enforcement. We calibrate our model to the datasets in the two countries and find that our mechanism can quantitatively account for the patterns observed in the data. ∗Arellano: arellano@econ.umn. edu; Bai: yan.bai@asu.edu; Zhang: jzhang@umich.edu. We thank Katya Kartashova for excellent research assistance and Francisco Arellano for help with the dataset of Ecuador.
Role of Preoperative Screening for Adult Patients for Obstructive Sleep Apnea

Abstract Obstructive sleep apnea (OSA) is a chronic disease with increasing prevalence. Underdiagnosed in the surgical population, OSA can reach a prevalence of up to 70% in bariatric surgery, and be associated with difficult airways and postoperative cardiopulmonary adverse events. Despite its association with escalation of care, increased health care resource utilization, and length of hospital stay, < 25% of health care institutions in the United States have OSA perioperative protocols to improve patient safety. This is explained in part by a lack of studies that support a widely accepted systematic approach to preoperative screening and risk stratification. This review evaluates the role of preoperative screening tools for adult patients with suspected OSA.
Chemical Amplification (or Dampening) of the Twomey Effect: Conditions Derived from Droplet Activation Theory

Cloud droplet number concentrations are controlled by both meteorological and microphysical factors. Microphysical factors include aerosol number concentration and composition. This paper examines the importance of microphysical phenomena compared to the sensitivity with respect to parcel updraft velocity in the activation of aerosols to become cloud droplets. Of the compositional (chemical) factors that can influence droplet number concentration, the effect of organics is examined through their ability to alter droplet surface tension and to contribute solute. A recent parameterization of aerosol activation (by Abdul-Razzak et al.) is extended to obtain analytical expressions for the sensitivity of activation to microphysical factors relative to updraft velocity. It is demonstrated that, under some conditions, the droplet number concentration can be as much as 1.5 times more sensitive to changes in aerosol composition than to updraft velocity. Chemical effects seem to be most influential for size distributions typical of marine conditions and decrease in importance for strongly anthropogenically perturbed conditions. The analysis indicates that the presence of surface-active species can lead to as much uncertainty as results from variations in updraft velocity. The presence of surfactant species also drastically changes the response of the cloud condensation nuclei to changes in the updraft velocity spectrum. Conditions are found under which an increase in dissolved organic compounds can actually lead to a decrease in cloud droplet number, a “contra-Twomey effect. ” Results presented have more general implications than just for organic compounds and can apply, in principle, for any chemically induced activation effect.
Design considerations of a high frequency and low voltage clock generator

A low voltage, 1.2 V, 4 GHz CMOS phase lock loop for clock generation is reported. This low voltage clock generator consists of a ring oscillator as the VCO that works from 100 MHz to 4 GHz with a maximum power consumption of 11 mW. Employing a charge pump circuit with suitable loop filter, a ripple free control voltage is provided for VCO. The total power consumption of this PLL, simulated in a 0.13 /spl mu/m CMOS technology, is about 54 mW.
Total Knee Replacement for Patellofemoral Disease

This study evaluates the technical results and outcomes of total knee replacement (TKR) in a group of patients with isolated patellofemoral disease based on the amount of bone loss and patella subluxation seen at the time of surgery. Thirty-three TKRs in 25 patients comprised the study group. All patients had radiographic evidence of isolated end-stage disease in the patellofemoral joint and had cemented tri-compartmental knee replacements. All patellae could be resurfaced. Average follow-up was 5.2 years (range: 3.8-8.4 years). Average Knee Society Scores was 62 preoperatively and 96 at final follow-up. There was no correlation in outcomes related to either the amount of patellar wear, size of the patella, or amount of subluxation of the patella. Total knee replacement is an effective means of managing end-stage arthritis of the patellofemoral joint.
Rhodococcus equi foal pneumonia: protective effects of immune plasma in experimentally infected foals.

The immunoprophylactic capacity of specific immune plasma was evaluated in pony foals infected experimentally with Rhodococcus equi. Immune plasma, produced by repeated parenteral administration of viable R. equi to adult horses, was harvested and frozen. Group I (six control foals) and Group II (six principal foals) received lactated Ringers solution and immune plasma respectively at three and five days of age. R. equi were aerosolised into a caudal lung lobe of all foals at seven days of age. Clinical signs, haematological alterations, immune responses, thoracic radiographs and technetium99m pulmonary perfusion scans were monitored. All foals were destroyed and complete post mortem examinations performed. All foals developed pneumonia as evidenced by clinical, radiographic and perfusion alterations, but the survival rate of principal foals was significantly (P less than 0.01) greater than that of control foals. Five control foals developed terminal disease, whereas all principal foals recovered. There was no significant (P greater than 0.05) difference in temperature response, or peripheral blood leucocyte, neutrophil or fibrinogen concentrations between groups. ELISA values for R. equi antibody were significantly (P less than 0.001) greater in principal foals following treatment, but there was no significant (P greater than 0.05) difference in IgG or IgM concentrations between groups. Results of the haemolysis inhibition assay indicated that equi factor neutralising antibodies were transferred by immune plasma to the principal foals. Post mortem examinations of five control foals destroyed at approximately three weeks post infection because of terminal disease, revealed severe pyogranulomatous pneumonia. One control and all principal foals were either free of lesions or had resolving lesions and/or minimal scar formation at three months post infection. (ABSTRACT TRUNCATED AT 250 WORDS)
The transcription cofactor c-JUN mediates phenotype switching and BRAF inhibitor resistance in melanoma

The transcriptional regulator c-JUN is a key mediator of the metastatic potential and drug resistance in melanoma. Inhibiting two MAPKs is better than one Mitogen-activated protein kinase (MAPK) pathways, such as the ERK and JNK pathways, mediate critical cellular processes, such as survival, stress responses, and proliferation. These pathways can be hijacked by cancer cells, leading to uncontrolled cell division and metastasis. Many melanoma patients have activating mutations in an upstream kinase, BRAF, in the ERK pathway, but inhibitors of BRAF only produce short-term improvement. Using panels of melanoma cell lines and BRAF inhibitor–treated patient samples, Ramsdale et al. found that increased abundance of the transcription cofactor c-JUN, which is activated by the JNK pathway, mediated both inherent and adaptive resistance to BRAF inhibitors and contributed to metastatic potential. Blocking c-JUN abundance or its activation by the kinase JNK enhanced the efficacy of BRAF inhibitors against melanoma cells. Thus, targeting both MAPK pathways may overcome resistance to treatment with only inhibitors of the ERK pathway. Most patients with BRAF-mutant metastatic melanoma display remarkable but incomplete and short-lived responses to inhibitors of the BRAF kinase or the mitogen-activated protein kinase kinase (MEK), collectively BRAF/MEK inhibitors. We found that inherent resistance to these agents in BRAFV600-mutant melanoma cell lines was associated with high abundance of c-JUN and characteristics of a mesenchymal-like phenotype. Early drug adaptation in drug-sensitive cell lines grown in culture or as xenografts, and in patient samples during therapy, was consistently characterized by down-regulation of SPROUTY4 (a negative feedback regulator of receptor tyrosine kinases and the BRAF-MEK signaling pathway), increased expression of JUN and reduced expression of LEF1. This coincided with a switch in phenotype that resembled an epithelial-mesenchymal transition (EMT). In cultured cells, these BRAF inhibitor-induced changes were reversed upon removal of the drug. Knockdown of SPROUTY4 was sufficient to increase the abundance of c-JUN in the absence of drug treatment. Overexpressing c-JUN in drug-naïve melanoma cells induced similar EMT-like phenotypic changes to BRAF inhibitor treatment, whereas knocking down JUN abrogated the BRAF inhibitor-induced early adaptive changes associated with resistance and enhanced cell death. Combining the BRAF inhibitor with an inhibitor of c-JUN amino-terminal kinase (JNK) reduced c-JUN phosphorylation, decreased cell migration, and increased cell death in melanoma cells. Gene expression data from a panel of melanoma cell lines and a patient cohort showed that JUN expression correlated with a mesenchymal gene signature, implicating c-JUN as a key mediator of the mesenchymal-like phenotype associated with drug resistance.