Miracle-dz/UniFAR-FTUs huggingface dataset:
Randomized phase II study of erlotinib plus tivantinib versus erlotinib plus placebo in previously treated non-small-cell lung cancer.

PURPOSE c-MET (MET) receptor activation is associated with poor prognosis and epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) resistance in non-small-cell lung cancer (NSCLC). This global, randomized phase II trial examined erlotinib plus tivantinib (ARQ 197; ArQule, Woburn, MA), a novel MET inhibitor. METHODS Previously treated patients with EGFR TKI-naive advanced NSCLC were randomly assigned to receive oral erlotinib (150 mg daily) plus oral tivantinib (360 mg twice daily) or erlotinib plus placebo (EP). The primary end point was progression-free survival (PFS). At the time of progression, cross-over from EP to erlotinib plus tivantinib (ET) was permitted. Archival tumor tissue specimens were required. RESULTS One hundred sixty-seven patients were randomly assigned to ET (n = 84) and to EP (n = 83). Median PFS was 3.8 months for ET and 2.3 months for EP (hazard ratio [HR], 0.81; 95% CI, 0.57 to 1.16; P = .24). Exploratory analysis revealed that the small cohort with KRAS mutations achieved a PFS HR of 0.18 (95% CI, 0.05 to 0.70; interaction P = .006). Objective responses were seen in 10% of patients on ET, 7% of patients on EP, and in two patients who crossed over from EP to ET, including one with EGFR mutation and MET gene copy number greater than 5. There were no significant differences in adverse events between study arms. CONCLUSION The combination of the MET inhibitor tivantinib and erlotinib is well-tolerated. Although the study did not meet its primary end point, evidence of activity was demonstrated, especially among patients with KRAS mutations. Additional study of tivantinib and erlotinib in patients with NSCLC is planned.
Occupational Medicine and the State: The Lessons from Hungary

I N THIS ARTICLE, WE WILL DESCRIBE THE Hungarian experience of organizing occupational health services within the context of a national health care system. Specifically, we will examine the contributions made by health professionals' sense of mission and also self-interest, and the demand articulated by labor to shaping the form and quality of services provided by occupational health clinics. Health professionals and labor are, of course, some of the same actors who will shape occupational health services within a reorganized American health insurance system, and thus the Hungarian example is a useful one for us to contemplate. Occupational health constitutes an important part of the Hungarian health care system. In 1989, occupational health services operating at approximately 2,900 firms covered between 2 million and 2.5 million employees, bearing in mind that the total number of employees in the country was approximately 4.5 million. This means that complete primary care is delivered to about half of the Hungarian workers in the employment setting. Among company doctors, 940 were full-time employees; 1,426 were part-timers; and 500 worked both in companies and in community settings as ger.eral practitioners. Thus about 8 percent of Hungary's medical practitioners are involved in delivering occupational health services. The number of patient visits was 10.5million in the same year. These data reflect the important role occupational health servicesplay in the overall Hungarian health care system. (1) This system has a number of problems. Perhaps the most glaring of them is the inadequate funding of workplace health care, reflected in the statistics cited above, which reveal that less than 10 percent of practitioners deliver about 50 percent of the primary medical care received by Hungarian workers. The problems that follow from starving the occupational health system (for example, driving occupational health providers into the arms of management), are further
Behavioral Responses of Catnip (Nepeta cataria) by Two Species of Mosquitoes, Aedes aegypti and Anopheles harrisoni, in Thailand

ABSTRACT An investigation of the biological effect of catnip oil (Nepeta cataria L.) on the behavioral response of field collected Aedes aegypti and Anopheles harrisoni was conducted using an automated excito-repellency test system. Aedes aegypti showed significantly higher escape rates from the contact chamber at 5% catnip oil compared to other concentrations (P < 0.05). With Anopheles harrisoni, a high escape response was seen at 2.5% catnip oil from the contact chamber, while in the noncontact chamber a higher escape response was observed at a concentration of 5%. Results showed that this compound exhibits both irritant and repellent actions.
Accurate prediction of basicity in aqueous solution with COSMO‐RS

The COSMO‐RS method, a combination of the quantum chemical dielectric continuum solvation model COSMO with a statistical thermodynamics treatment for realistic solvation simulations, has been used for the prediction of base pKa constants. For a variety of 43 organic bases the directly calculated values of the free energies of dissociation in water showed a very good correlation with experimental base pKa values (r2 = 0.98), corresponding to a standard deviation of 0.56 pKa units. Thus, we have an a priori prediction method for base pKa with the regression constant and the slope as only adjusted parameters. In accord with recent findings for pKa acidity predictions, the slope of pKa vs. ΔGdiss was significantly smaller than the theoretically expected value of 1/RTln(10). The predictivity of the presented method is general and not restricted to certain compound classes, but systematic corrections of 1 and 2 pKa units for secondary and tertiary aliphatic amines are required, respectively. The pKa prediction method was validated on a set of 58 complex multifunctional drug‐like compounds, yielding an RMS accuracy of 0.66 pKa units. © 2005 Wiley Periodicals, Inc. J Comput Chem 27: 11–19, 2006
Animal models of inflammatory bowel disease.

The human inflammatory bowel diseases, ulcerative colitis and Crohn's disease, remain enigmas in respect of their causes, whether or not they are separate entities or part of a spectrum, and the optimum means of treatment. As with other obscure diseases, investigators turn to animal models for a number of reasons, and three recent articles in the International Journal of Experimental Pathology have explored aspects of these models (Anthony A. et a/. 1995; Anthony D. et a/. 1995; Smith et a/. 1995). Similar naturally occurring diseases in animals may already have been explained aetiologically. Similar inflammatory states in animal gut, whether naturally occurring or experimentally induced, may be more readily investigated to identify key steps in the development and expression of gut disease than is possible in man. Finally, a very wide variety of therapeutic strategies can be piloted in animal models. The ideal model for exploitation for these aims should be effectively identical to one or other form of human inflammatory bowel disease, in respect of pathology, pathophysiology and symptomatology. It should occur in an animal species that is accessible, easy to maintain, immunologically similar to man, and manipulable in respect of exposure of the gut to infectious agents and other toxic factors. In the model it should be possible to alter gut commensal flora, dietary intake and aspects of immune status. In addition, the species should be acceptable, in terms of ethical aspects of animal experimentation, to the generality of the public. Clearly, we do not have such an animal model, but the assessment and exploitation of less perfect alternatives remains a growth industry. Consideration of any animal model involves the recognition that there are potentially two stages of any inflammatory response in the gut. After an initial episode of inflammation has been induced, there is a strong likelihood that the mucosal integrity of the gut will be, at least temporarily, altered (Hobson et a/. 1988,
Regulation of Vegetative Phase Change in Arabidopsis thaliana by Cyclophilin 40

During its development, a plant shoot progresses from a juvenile to an adult phase of vegetative growth and from a reproductively incompetent to a reproductively competent state. InArabidopsis, loss-of-function mutations in SQUINT(SQN) reduced the number of juvenile leaves and had subtle effects on inflorescence morphology but had no effect on flowering time or on reproductive competence. SQN encodes theArabidopsis homolog of cyclophilin 40 (CyP40), a protein found in association with the Hsp90 chaperone complex in yeast, mammals, and plants. Thus, in Arabidopsis, CyP40 is specifically required for the vegetative but not the reproductive maturation of the shoot.
Effects of reserpine on calcium levels in cardiac tissue of mice.

In four stocks (TS, DBA, RF, and C) of mice the calcium contents of atrium and ventricle were measured. After seven daily injections of 0·1 mg/kg reserpine the amounts of calcium were reduced in both heart chambers of all four stocks. Reserpine exerted its most depleting action on the stocks (DBA and TS) which had the highest control levels of calcium.
Phospholipase A2 Modification of Low Density Lipoproteins Forms Small High Density Particles with Increased Affinity for Proteoglycans and Glycosaminoglycans*

The presence of a lipoprotein profile with abundance of small, dense low density lipoproteins (LDL), low levels of high density lipoproteins (HDL), and elevated levels of triglyceride-rich very low density lipoproteins is associated with an increased risk for coronary heart disease. The atherogenicity of small, dense LDL is believed to be one of the main reasons for this association. This particle contains less phospholipids (PL) and unesterified cholesterol than large LDL, and the apoB-100 appears to occupy a more extensive area at its surface. Although there are experiments that suggest a metabolic pathway leading to the overproduction of small, dense LDL, no clear molecular model exists to explain its association with atherogenesis. A current hypothesis is that small, dense LDL, because of its higher affinity for proteoglycans, is entrapped in the intima extracellular matrix and is more susceptible to oxidative modifications than large LDL. Here we describe how a specific reduction of approximately 50% of the PL of a normal buoyant LDL by immobilized phospholipase A2(PLA2) (EC 3.1.1.4) produces smaller and denser particles without inducing significant lipoprotein aggregation (<5%). These smaller LDL particles display a higher tendency to form nonsoluble complexes with proteoglycans and glycosaminoglycans than the parent LDL. Binding parameters of LDL and glycosaminoglycans and proteoglycans produced by human arterial smooth muscle cells were measured at near to physiological conditions. The PLA2-modified LDL has about 2 times higher affinity for the sulfated polysaccharides than control LDL. In addition, incubation of human plasma in the presence of PLA2 generated smaller LDL and HDL particles compared with the control plasma incubated without PLA2. These in vitro results indicate that the reduction of surface PL characteristic of small, dense LDL subfractions, besides contributing to its small size and density, may enhance its tendency to be retained by proteoglycans.
Tissue Stabilizer Reverse Mounting in Minimally Invasive Direct Coronary Artery Bypass, a Simple Tool in Difficult Times

The simple reverse mounting of an Octopus arm over a rib retractor can give more arm length by up to 5 cm inside the chest cavity which could prove to be very useful in patients with huge chest cavities, i.e. chronic obstructive pulmonary disease, high body mass index, allowing more flexibility and better maneuverability of the stabilizer arm during MIDCAB.
CASTLE: A Framework for Integrating Cognitive Models into Virtual Environments

CASTLE is a software framework that links various types of cognitive models to various virtual environment simulators, such as those used for military training. It supplies cognitive models with perceptual information about the virtual environment, and simulates the effects in the virtual environment of actions invoked by cognitive models, while imposing human-like limitations on perception and action.
An interaction visualisation tool for a learning management system

Interaction design in a Learning Management System is the art of instigating interactions and facilitating communication between learners. In order to instigate interactions we need to first analyse and model these online interactions. This paper describes an automated, scalable, multi-browser, real-time visualisation software tool, which depicts the structure and design of the interaction between the students in an asynchronous conference. It gives an in-depth explanation of the tool and illustrates the purpose and management of interactions between the students in a. learning environment. The data examined in this study included a purposive sample of asynchronous, online discussion postings of students in our institution captured via forums and discussion-boards in a Moodle environment for the purpose of testing the software. This innovative tool is embedded into the Moodle environment and can be used by educators to evaluate students' activities and identify online behaviors and interaction patterns in the networked learning environment. Information provided by the software tool can be used for motivating the students and building an online socio-learning community.
Changes in Left Main Bifurcation Geometry After a Single-Stent Crossover Technique: An Intravascular Ultrasound Study Using Direct Imaging of Both the Left Anterior Descending and the Left Circumflex Coronary Arteries Before and After Intervention

Background—We assessed geometric changes responsible for acute lumen loss at the left circumflex coronary artery (LCX) ostium after crossover stenting from the left anterior descending coronary artery (LAD) to the left main artery. Methods and Results—Twenty-three left main artery bifurcation lesions with a preprocedural angiographic diameter stenosis <50% at the LCX ostium were evaluated using prestenting and poststenting intravascular ultrasound pullbacks from both the LAD and the LCX. At the minimal lumen area (MLA) sites within the LCX ostium and at the LCX carina, the lumen, stent, plaque+media (P+M), and external elastic membrane (EEM) areas were measured; the EEM eccentricity was calculated at the LCX carina. The change in MLA within the LCX ostium (&Dgr;L), the change in EEM area at the MLA site (&Dgr;V), and the change in P+M area at the MLA site (&Dgr;P) were calculated. The MLA within the LCX ostium significantly decreased from 5.4 mm2 (first and third quartiles, 4.3 mm2, 7.2 mm2) prestenting to 4.0 mm2 (3.0 mm2, 4.8 mm2) poststenting (P<0.001). The percent change in MLA within the LCX ostium correlated with changes in EEM eccentricity (r=−0.414, P=0.049) and percent change in EEM area at the MLA site (r=0.626, P=0.001). A smaller distal carina angle between the LAD and the LCX before stenting was associated with a greater percent reduction in lumen (r=0.472, P=0.023) and EEM (r=0.402, P=0.048) after stenting. In 18 lesions with >10% reduction of MLA within the LCX ostium despite the lack of direct relationship between &Dgr;L and &Dgr;P at the MLA site, &Dgr;P closely correlated with the ratio of &Dgr;V to &Dgr;L (r=−0.953, P<0.001), suggesting that an increase in plaque at the LCX ostium contributed to the MLA loss relative to the decrease in EEM area. Conclusions—Lumen loss at the LCX ostium frequently occurred after crossover stenting from the distal LM to the LAD. The main mechanism was carina shift that was associated with a narrow angle between the LAD and LCX.
Rôle du pharmacien dans la prévention du dopage par la prise de médicaments et de certains compléments alimentaires

De nombreux medicaments, complements alimentaires et denrees alimentaires pour sportifs renferment des substances interdites et peuvent faire l’objet, soit de detournement d’usage a des fins d’amelioration des performances, soit de dopage par inadvertance faisant courir un risque de sanction pour le sportif lors d’un controle antidopage. Chaque pharmacien est un acteur incontournable de la lutte contre ce fleau et se doit de s’armer des connaissances essentielles en matiere de dopage pour jouer pleinement son role de prevention et d’education.
Redox Molecules and Cancer Prevention: The Importance of Understanding the Role of the Antioxidant Network

Abstract: Cancer has a complex etiology with multiple risk factors that involve the interplay between genetic and environmental influences. There is compelling evidence that dietary plant foods appear to be protective against certain type of cancers. Among a number of mechanistic hypotheses, diet-derived antioxidants have been proposed to contribute to explain these findings. However, contrasting results from intervention trials have raised strong concerns about the influence of antioxidants on human health. A vulnerable point of the research on antioxidants is the lack of information on the effect of the whole array of dietary antioxidants in cancer prevention because so far mainly single molecules have been investigated. Total antioxidant capacity (TAC) considers the single antioxidant activity as well as the synergistic interactions of the redox molecules present in complex matrixes, giving an insight into the assessment of the non-enzymatic antioxidant network. This article will outline the state of art of the research on TAC and cancer, describing the plasma non-enzymatic antioxidant network and its association with diet. The feasibility of TAC assessment as an innovative tool for investigating the association between dietary antioxidants, oxidative stress, and cancer will be also discussed.
DISEÑO DE INTERVENCIÓN DE ACTIVIDAD FÍSICA EN ADULTOS MAYORES

La definicion de adulto mayor segun las Naciones Unidas es toda aquella persona >60 anos. En Mexico los adultos mayores representan el 10.5% de la poblacion y solo el 24.1% declara hacer ejercicio. El ejercicio fisico en el adulto mayor se ha relacionado con menores tasas de obesidad, mortalidad y de morbilidad, mejora la calidad de vida, ademas, es un factor clave para la prevencion y tratamiento de enfermedades. Existen 4 tipos diferentes de ejercicios: aerobico, fortalecimiento, flexibilidad y balance, los cuales cada uno de ellos tiene sus recomendaciones minimas para alcanzar los beneficios antes mencionados. Los adultos mayores deben tener un plan de ejercicio especifico que describa como, cuando y donde se realizara el ejercicio tomando en cuenta que el plan debe ser adaptado considerando las diferencias en las condiciones de salud y limitaciones fisicas de los mismos. En este trabajo se propone un programa de intervencion fisica para adultos mayores basado en ejercicios y recomendaciones geriatricas identificadas.
A library based fitting method for visual reflectance spectroscopy of human skin

The diffuse reflectance spectrum of human skin in the visible region (400–800 nm) contains information on the concentrations of chromophores such as melanin and haemoglobin. This information may be extracted by fitting the reflectance spectrum with an optical diffusion based analytical expression applied to a layered skin model. With the use of the analytical expression, it is assumed that light transport is dominated by scattering. For port wine stain (PWS) and highly pigmented human skin, however, this assumption may not be valid resulting in a potentially large error in visual reflectance spectroscopy (VRS). Monte Carlo based techniques can overcome this problem but are currently too computationally intensive to be combined with previously used fitting procedures. The fitting procedure presented herein is based on a library search which enables the use of accurate reflectance spectra based on forward Monte Carlo simulations or diffusion theory. This allows for accurate VRS to characterize chromophore concentrations in PWS and highly pigmented human skin. The method is demonstrated using both simulated and measured reflectance spectra. An additional advantage of the method is that the fitting procedure is very fast.
Food expenditure and nutritional quality over the Great Recession

Food expenditure and nutritional quality over the Great Recession. Published by the Institute for Fiscal Studies (IFS) and written by Rachel Griffith, Martin O’Connell and Kate Smith (2013). In this briefing note, the IFS document how the food purchases of households in the UK have changed over this period of recession and food price rises. They followed the same households over time, which allowed them to control for fixed differences in households’ food purchasing behaviour. They show that, on average, real food expenditure (i.e. nominal expenditure on food divided by the food component of the consumer price index) declined and that households bought fewer calories and have switched to cheaper calories. This has coincided with a switch towards more calorie-dense types of food and substitution to more calorific food products within food types.
Drug survival rates for tumour necrosis factor‐α antagonists in psoriasis

screening. Over a 3-month period 113 skin tumours were photographed as clinical and dermatoscopic images. A clinician used a pocket dermatoscope and a phone with a 3.2-megapixel (Mp) in-built camera to acquire the images. The 322 clinical and 278 dermatoscopic images were then transmitted via a virtual private network for online assessment. The latest smartphones on the high street come equipped with 12-Mp cameras (personal communication) and will probably reduce to negligible the 7% of images deemed inadequate for diagnosis in the study. Satisfactory levels of accuracy in diagnosis and concordance between remote diagnosis and FTF consultation were achieved but note that clinical image tele-evaluation was better than teledermatoscopy. The importance of this paper is that it implies usefulness of this technology. With increasing referrals to lesion clinics, departments may feel under pressure to limit consultations or reduce follow-up rates. It may be feasible in the future to consider ‘virtual’ consultations with a patient or general practitioner taking images on their high-resolution camera phone with or without a dermatoscope and submitting them with a text history to a dermatologist or specialist nurse via MMS (multimedia messaging service). This might enable one to reassure patients who have obviously benign lesions and triage those patients with lesions suspected as being cancerous or indeterminate for an FTF consultation. However, it is crucial to remember that even between experienced dermatologists there is interobserver variability in teledermatoscopy. Studies with large numbers of patients usually show diagnostic inferiority to clinical examination for pigmented and nonpigmented lesions. Medicolegal issues regarding confidentiality, security and storage of photographs and inaccurate or delayed diagnosis will need to be addressed. Teledermatology has shown its use in war zones and mobile teledermatology in Africa. However, further larger-scale clinical studies with economic assessments demonstrating cost–effectiveness will be needed before mobile teledermatology becomes widely adopted in societies where access to a dermatologist is a fairly straightforward process.