Miracle-dz/UniFAR-FTUs huggingface dataset:
Prevalence of Platelet Nonresponsiveness to Aspirin in Patients Treated for Secondary Stroke Prophylaxis and in Patients With Recurrent Ischemic Events

To determine the prevalence of platelet nonresponsiveness to aspirin treatment for secondary stroke prophylaxis, the authors studied consecutive patients during a 29–month period. Information regarding their ischemic events, risk factors, and medications was collected. Platelet aggregation in response to collagen and arachidonic acid was used to determine platelet responsiveness to aspirin. A total of 653 patients were evaluated. Of these, 129 patients (20%) were determined to be nonresponsive to aspirin based on continued platelet aggregation in response to collagen, arachidonic acid, or both. A total of 87 (13%) of the 653 patients were clinical aspirin failures (ie, presented with new focal cerebral ischemic symptoms while taking aspirin). Of the patients with new cerebral ischemic symptoms, 57 (66%) were determined to be platelet nonresponsive to aspirin. The odds ratio for platelet nonresponsiveness to aspirin in patients who suffered a recurrent ischemic event while taking aspirin was 14.25 (95% confidence interval: 8.5–23.7; P < .5). Continued platelet aggregation despite aspirin treatment occurred in 20% of ambulatory patients treated for secondary stroke prophylaxis. The prevalence of nonresponsiveness to aspirin was statistically higher in those patients who suffered recurrent cerebral ischemia while taking aspirin (P < .5) compared with patients who remained without new ischemic symptoms.
Population Pharmacokinetics of Lamotrigine in Elderly Patients

Lamotrigine is being used more frequently in elderly patients. Dosing of lamotrigine in elderly patients is based largely on studies from younger adults and not evidence‐based data from elderly patients. The goal of this study is to determine the pharmacokinetic parameters, such as clearance, and the factors that have a significant effect on these parameters to provide evidence‐based information that can be used to dose elderly patients taking lamotrigine. Lamotrigine plasma concentrations from 148 elderly patients (aged 59–92 years) were used to develop a population pharmacokinetic model. Data were analyzed using NONMEM. Model evaluation was performed using the bootstrap approach and predictive check. The results showed that the blood urea nitrogen/serum creatinine ratio, weight, and phenytoin use significantly affect apparent clearance of lamotrigine. These results show that clinicians may need to take into account these covariates when dosing lamotrigine in this population.
Tissue Expanders in Total Knee Arthroplasty

Delays in wound healing after total knee replacement can be potentially devastating with increased risks of infection and prosthesis removal. Because of the limited vascularity of the skin overlying the knee, which comes predominantly from the medial side, patients with multiple prior incisions and systemic conditions that can also reduce the vascularity of the skin are at risk for wound complications after total knee replacement. Historically, in this group of patients, prophylactic muscle flap procedures were used, but these procedures are associated with significant cosmetic and functional limitations. The process of soft tissue expansion has been used extensively in various regions of the body and recently applied to patients undergoing knee reconstruction and joint replacement procedures. In this article, patient selection for tissue expander use before total knee arthroplasty, as well as the technique, results, and complications of this procedure are described.
Effect of Food on the Pharmacokinetics and Pharmacodynamics of an Oral Ghrelin Agonist (ARD‐07) in Healthy Subjects

ARD‐07 (also known as EP01572) is a peptidomimetic growth hormone secretagogue that can be administered orally. The primary objective of this study is to determine the effects of a meal on the oral bioavailability of ARD‐07 after a single oral dose (0.5 mg/kg). In addition, the pharmacodynamic effects (growth hormone release, insulin‐like growth factor‐1 concentrations) and the tolerability of ARD‐07 are investigated in this open‐label, randomized, crossover study. Sixteen healthy subjects (8 males, 8 females) receive ARD‐07 on 2 different days; the treatment consists of a single oral dose of ARD‐07 (0.5 mg/kg body weight), once with and the second day without a test meal. Plasma kinetics of ARD‐07 and pharmacodynamic effects are quantified by specific assays. Results are given as mean ± SEM: The area under the curve for 0 to 24 hours is approximately twice as high without food (27.8 ± 4.1) than with food (13.7 ± 1.2; P = .002). The maximum observed ARD‐07 concentration relative to dose administration (Cmax) is more than twice as high without food (10.6 ± 1.6 ng/mL) than with food (4.4 ± 0.5 ng/mL; P = .001). Cmax of growth hormone occurs at a significantly (P = .001) later stage with food (Cmax = 13.0 ± 3.5 ng/mL) than without food (37.1 ± 5.3 ng/mL). Food has a marked effect on the absorption of ARD‐07: there is a significant difference in bioavailability between administration of oral ARD‐07 with and without food.
Melbourne dietitians’ experience of Medicare policy on allied health services (strengthening Medicare; Enhanced Primary Care) in the first 12 months

Objective: To describe Victorian private practitioner dietitians’ experience of the Enhanced Primary Care (EPC) program funded under national heath insurance. Design: Dietitians’ experience of the EPC program was investigated between August 2004 and July 2005. A purposive sample of 10% (n = 15) of Victorian dietitians in private practice was interviewed via semi-structured interviews or focus groups. Focus group/interview data were audio-taped, transcribed verbatim and thematically analysed using NVIVO software to manage data. Subjects: Victorian dietitians. Setting: Dietetic private practice. Main outcome measures: Issues identified from narrative themes. Results: Thirteen (86%) participants were registered with the Medicare Australia and managed EPC-referred patients. Two chose not to. All those using the program supported it but voiced frustrations experienced in the first year. Five themes emerged from narrative analysis involving difficulties with implementation in the following areas: referral issues, client preparedness, annual number of consultations limit, impact of financial cost on client and non-reimbursed administration costs. Conclusion: For clients with chronic illness, access to dietitians in private practice under Medicare EPC is an important service. As increasing numbers of dietitians nationally work with EPC patients with chronic illness or complex care needs, there is a need for information sharing between professional groups about billing procedures and chronic care management. More dietitians need to structure practice to initiate bulk-billing. Rigorous evaluation is needed to understand which diagnosis types can benefit from the program and to implement an evidence-based model of chronic care improvement for dietetics consultations.
Impact of Autocorrelation on Principal Components and Their Use in Statistical Process Control

A basic assumption when using principal component analysis (PCA) for inferential purposes, such as in statistical process control (SPC), is that the data are independent in time. In many industrial processes, frequent sampling and process dynamics make this assumption unrealistic rendering sampled data autocorrelated (serially dependent). PCA can be used to reduce data dimensionality and to simplify multivariate SPC. Although there have been some attempts in the literature to deal with autocorrelated data in PCA, we argue that the impact of autocorrelation on PCA and PCA‐based SPC is neither well understood nor properly documented.
THE ELECTROCARDIOGRAM IN INSULIN SHOCK

The use of extreme states of insulin shock in the treatment of psychiatric patients, particularly of those with schizophrenia, has in the last few years afforded an opportunity to study electrocardiographic changes in presumably normal hearts under the influence of large doses of insulin. Insulin shock therapy was introduced by Sake 1 in 1933 for patients with hitherto relatively hopeless schizophrenia. After a preliminary period of suspicious aloofness, psychiatrists and physicians interested in mental disease have adopted the method on a large scale because of the brilliant results at times achieved. The method and technic are given in detail in Sakel's monograph and elsewhere. The usual technic requires patients to be in coma from hypoglycemia for an hour or more. This means that from the time the insulin is injected to the termination of the coma three to five hours elapses, during which severe hypoglycemia is present, with minimum blood sugar
Improved direct torque and flux vector control of PWM inverter-fed induction motor drives

In this paper, a direct torque and stator flux vector control system is presented. The principle of this method was proposed by Takahashi and Noguchi in 1985. In contrast to the field oriented control, no coordinate transformation and current control loop is required. In practical application, however, problems occur with starting and operation in the zero speed region. This paper shows how, by introducing an additional carrier signal to the torque controller input, a robust start and improved operation in the low speed region can be achieved. The simulation and experimental results which illustrate the performances of the proposed system are presented. Also, nomograms for controller design are given. >
Role of sarcolemmal KATP channels in cardioprotection against ischemia/reperfusion injury in mice

Recently it has been postulated that mitochondrial ATP-sensitive K+ (mitoKATP) channels rather than sarcolemmal KATP (sarcKATP) channels are important as end effectors and/or triggers of ischemic preconditioning (IPC). To define the pathophysiological significance of sarcKATP channels, we conducted functional experiments using Kir6.2-deficient (KO) mice. Metabolic inhibition with glucose-free, dinitrophenol-containing solution activated sarcKATP current and shortened the action potential duration in ventricular cells isolated from wild-type (WT) but not KO mice. MitoKATP channel function was preserved in KO ventricular cells. In anesthetized mice, IPC reduced the infarct size in WT but not KO mice. Following global ischemia/reperfusion, the increase of left ventricular end-diastolic pressure during ischemia was more marked, and the recovery of contractile function was worse, in KO hearts than in WT hearts. Treatment with HMR1098, a sarcKATP channel blocker, but not 5-hydroxydecanoate, a mitoKATP channel blocker, produced a deterioration of contractile function in WT hearts comparable to that of KO hearts. These findings suggest that sarcKATP channels figures prominently in modulating ischemia/reperfusion injury in the mouse. The rapid heart rate of the mouse (>600 beats per minute) may magnify the relative importance of sarcKATP channels during ischemia, prompting caution in the extrapolation of the conclusions to larger mammals.
The Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single Oral Doses of RO5068760, an MEK Inhibitor, in Healthy Volunteers: Assessment of Target Suppression

RO5068760, a substituted hydantoin, represents a new class of potent, highly selective, non‐adenosine triphosphate (ATP)–competitive MEK1/2 inhibitors. The study aimed to determine the safety/tolerability, pharmacokinetics, and pharmacodynamics of single ascending doses of RO5068760 in human healthy volunteers. All participants received a single dose followed by 48 hours of pharmacokinetics, pharmacodynamics, and safety/tolerability assessments. The pharmacodynamics were measured by changes in ERK phosphorylation (pERK) in peripheral blood mononuclear cells, ex vivo stimulated by phorbol 12‐myristate 13‐acetate (PMA). Forty‐eight participants received 6 doses (50, 100, 200, 400, 600, 800 mg). RO5068760 was well tolerated up to 800 mg. There were no clinically significant safety findings, including laboratory, electrocardiogram, ophthalmological assessment, and fecal occult blood tests. Of the total 13 adverse events (n = 12), 11 were mild, 2 were moderate, and none were severe, and only 5 were considered by the investigator as possibly related to treatment. RO5068760 was absorbed with a tmax of 2 hours. Disposition appeared to be biphasic with a terminal elimination t1/2 of 5 to 9 hours. The variability was moderate to high, ranging from 38% to 62% for Cmax and 41% to 69% AUC. Within the dose range tested, pERK inhibition was relatively modest with a mean maximal pERK suppression of 55%.
Ultrasound as a secondary screening tool in mammographically dense breasts

It is well known that breast screening is a part of our society and is designed to reduce the mortality and morbidity from breast cancer. Mammography is the imaging modality of choice in a breast screening environment. Both the detection rate of mammography in a screening environment and the sensitivity of mammography in symptomatic women are known to be greater than that of ultrasound. However, after a review of literature both of these are said to increase when the two imaging modalities are combined. This paper will present that mammography has limitations in breast imaging, especially in women with dense breasts and that ultrasound can have a benefit as a secondary screening tool in these women. It will be shown that although ultrasound also has its limitations, these can be minimised with the implementation of effective education and imaging protocols. The paper will conclude that although further research into ultrasound as screening tool is required, its use as a complement to mammography can only be of benefit to the general population. (author abstract)
A Metastasis Caught in the Act

Figure 1. A 52-year-old man with no history of serious illness presented with abdominal pain, dark-colored urine, light-colored stools, and jaundice. Abdominal ultrasonography revealed dilatation of the intrahepatic and extrahepatic bile ducts. Surgical exploration and a pancreatoduodenectomy (Whipple's resection) were performed, revealing an infiltrating, poorly differentiated adenocarcinoma of the distal common bile duct. The carcinoma measured 2.0 cm in its greatest dimension. All margins of resection were negative for tumor. Fifteen lymph nodes were examined histologically for evidence of metastasis, and a single micrometastasis was identified (arrow). The carcinoma is present in sinusoids within the node and in a dilated .
Leukemia Inhibitory Factor Determines the Growth Status of Injured Adult Sensory Neurons

Conditioning injury to adult mammalian sensory neurons enhances their regeneration potential. Here we show that leukemia inhibitory factor (LIF) is a fundamental component of the conditioning response. Conditioning injury in vivo significantly increases the intrinsic growth capacity of sensory neurons in vitro from LIF+/+ mice. This conditioning effect is significantly blunted in sensory neurons from LIF−/− mice. Enhanced growth is rescued in vitro in LIF−/− mice by the addition of exogenous LIF, and the effect blocked by human LIF-05, an LIF receptor antagonist. Furthermore, we demonstrate that LIF promotes elongating but not arborizing neurite outgrowthin vitro and is required for normal regeneration of injured adult sensory neurons in vivo. LIF is also functionally protective to peptidergic sensory neurons after nerve damage in vivo. Our results indicate that the alteration in intrinsic growth status of injured sensory neurons depends, at least in part, on LIF.
Pharmacokinetics and Pharmacodynamics of AR9281, an Inhibitor of Soluble Epoxide Hydrolase, in Single‐ and Multiple‐Dose Studies in Healthy Human Subjects

AR9281, a potent and selective inhibitor of soluble epoxide hydrolase (s‐EH), is in clinical development targeting hypertension and type 2 diabetes. The safety, pharmacokinetics, and pharmacodynamics of AR9281 were evaluated in double‐blind, randomized, placebo‐controlled, ascending, single oral dose (10–1000 mg) and multiple dose (100–400 mg every 8 hours for 7 days) studies in healthy subjects. AR9281 was well tolerated, and no dose‐related adverse events were observed during either study. The drug was rapidly absorbed with a mean terminal half‐life ranging from 3 to 5 hours. The area under the plasma concentration—time curve increased in an approximately dose‐proportional manner up to the 500‐mg dose and exhibited a greater than dose linearity at higher doses. AR9281 directly and dose‐dependently inhibited blood s‐EH activity with 90% inhibition or greater over an 8‐hour period at the 250‐mg dose and over a 12‐hour period at the 500‐mg dose. Multiple doses of AR9281 ranging from 100 to 400 mg every 8 hours resulted in a sustained inhibition of s‐EH activity at 90% or greater during the trough. The current studies provide proof of safety and target inhibition of AR9281 in healthy subjects. AR9281 pharmacokinetic and pharmacodynamic characteristics support a twice‐daily or thrice‐daily dosing regimen in patients.
Light path-length distributions within the retina

Abstract. A Monte Carlo simulation of light propagation through the retina has been developed to understand the path-length distributions within the retinal vessel. For full-field illumination, the path-length distribution within the vessel comprises directly backscattered light and light that has passed once or twice through the vessel. The origins of these light path-length distributions can be better understood by investigating different combinations of single-point illumination and detection positions. Perhaps the most significant observation is that illumination at the edges of the vessel, rather than over the whole field of view, and detection directly above the vessel capture only the light that has taken a single pass through the vessel. This path-length distribution is tightly constrained around the diameter of the vessel and can potentially provide enhancements for oxygen saturation imaging. The method could be practically implemented using an offset-pinhole confocal imaging system or structured light illumination.
Pharmacokinetics and Relative Bioavailability of a Fixed‐Dose Combination of Enteric‐Coated Naproxen and Non‐Enteric‐Coated Esomeprazole Magnesium

This randomized, 4‐way crossover study assessed the single‐dose pharmacokinetics and relative bioavailability of naproxen and esomeprazole after administration of a fixed‐dose combination tablet of enteric‐coated (EC) naproxen 500 mg and non‐EC esomeprazole magnesium 20 mg (NAP/ESO tablet). Equivalent doses of an EC naproxen tablet plus an EC esomeprazole magnesium capsule taken concomitantly, an EC naproxen tablet alone, or an EC esomeprazole magnesium capsule alone were used as comparators. Forty healthy adults were randomized to receive 4 study treatments with a washout interval ≥12 days. Naproxen plasma profiles were similar between the NAP/ESO tablet and EC naproxen, although median tmax was longest for the NAP/ESO tablet (5.3 vs 3.5–4.0 hours). Naproxen Cmax, AUC0‐∞, and AUC0‐t showed bioequivalence between naproxen formulations. The NAP/ESO tablet produced much shorter esomeprazole tmax than the EC esomeprazole formulation (0.45 vs 2.5 hours). Esomeprazole Cmax and AUCs were comparable between the EC esomeprazole formulation administered with or without EC naproxen but were lower with the NAP/ESO tablet. In conclusion, there are no pharmacokinetic drug interactions between naproxen and esomeprazole. The NAP/ESO tablet is bioequivalent to EC naproxen, and as expected, the bioavailability of non‐EC esomeprazole from the NAP/ESO tablet is lower than the EC esomeprazole formulation.
Diffuser-aided time-domain diffuse optical imaging: a phantom study

Abstract. We present the first experimental results of time-resolved diffuser-aided diffuse optical imaging (DADOI) method in this paper. A self-manufactured diffuser plate was inserted between the optode and the surface of a scattering medium. The diffuser was utilized to enhance the multiple scattering that destroys the image information for baseline measurement of turbid medium. Therefore, the abnormality can be detected with the modified optical density calculation. The time-domain DADOI method can provide better imaging contrast and simpler imaging than the conventional diffuse optical tomography measurement. Besides, it also reveals rich depth information with temporal responses. Therefore, the DADOI offers a great potential to detect the breast tumor and chemotherapy monitoring in clinical diagnosis.
Monitoring the blood coagulation process under various flow conditions with optical coherence tomography

Abstract. Our previous work demonstrated that an optical coherence tomography (OCT) technique was able to characterize the whole blood coagulation process. The 1/e light penetration depth (d1/e) derived from the profiles of reflectance versus depth was developed for detecting the whole blood coagulation process in static state. To consider the effect of blood flow, in the present study, d1/e versus time from the coagulating porcine blood circulated in a mock flow loop with various steady laminar flows at mean flow speed in the range from 5 to 25 mm/s. The variation of d1/e was used to represent the change of blood properties during coagulation in different hematocrits (HCT) ranging from 25% to 55%, velocities from 5 to 25 mm/s, and tubing sizes from 0.9 to 2 mm. The results showed that there were positive correlations between coagulation time (tc) and HCT, velocity, and tubing size, respectively. In addition, the coagulation rate (Sr) was decreased with the increase of HCT, velocity, and tubing size. This study testified that HCT, flow velocity, and tubing size were substantial factors affecting the backscattering properties during flowing blood coagulation. Furthermore, OCT has the potential to represent the process of flowing blood coagulation with proper parameters.
Towards Best Practice for Multiword Expressions in Computational Lexicons

The importance a nd role of multi-word expressions (MWE) in the description and p rocessing o f natural l anguage has been long recognized. However, multi-word information has often been relegated to the marginal role of idiosyncratic lexical information. The need for MWE lexicons grows even more acute for multi-lingual applications, for which (sometimes complex) correspondences must be identified, classified, and recorded. Within the XMELLT and ISLE projects we have started to investigate the potential to develop multi-lingual, multi-word expression lexicons incorporating both syntactic and semantic information. We aim at specifying means to acquire and represent multi-word lexical entries for multiple languages, and establishing uniform (or inter-translatable) standards for describing multi-word lexical entries. We explored theoretical approaches used in large lexicon-building projects, in p articular FrameNet and SIMPLE. They constitute interesting frameworks for the explicit syntactic and semantic representation of MWEs, due mainly to their ability to capture semantic multidimensionality, through frame e lements and qualia relations respectively. We a lso developed an abstract data model for lexical information together with a representation in XML for it. Our goal is to define a set of minimal lexicon “objects”, which can serve not only as a model for MWEs but also for lexical data in general.