Miracle-dz/UniFAR-FTUs huggingface dataset:
The continual reassessment method for dose-finding studies: a tutorial

The Continual Reassessment Method (CRM), along with other adaptive dose-finding study designs, has gained popularity since its proposal by O'Quigley. Several of the reasons it has been embraced by clinical trialists is that it tends to incur fewer toxic events, and more accurately estimate the maximum tolerated dose as compared to the standard Phase I dose escalation designs. Many variations have been published and discussed in the statistical literature, but there has not been as much practical advice for choosing design parameters and implementing the CRM. As a result, the CRM has not been as widely utilized as it could be for dose-finding studies. The goal of this paper is to provide a tutorial for those unfamiliar with the CRM who are either statisticians considering using the CRM for the first time, or investigators with some statistical background. This paper presents the original CRM, and then some of its modified versions. It also explains the specifications that define a CRM design, along with simulated examples of CRMs and standard designs, for illustration.
Sucrose‐predictive cues evoke greater phasic dopamine release than saccharin‐predictive cues

Cues that have been paired with food evoke dopamine in nucleus accumbens (NAc) and drive approach behavior. This cue‐evoked dopamine signaling could contribute to overconsumption of food. One manner in which individuals try to restrict caloric intake is through the consumption of foods containing artificial (non‐nutritive) sweeteners. We were interested in whether cues paired with a non‐nutritive sweetener (saccharin) would evoke similar dopamine release as cues paired with a nutritive sweetener (sucrose). We trained food‐restricted rats to associate distinct cues with sucrose or saccharin pellets. In the first group of rats, training sessions with each pellet took place on different days, maximizing the opportunity for rats to detect nutritional differences. After training, voltammetry recordings in NAc core revealed that sucrose cues evoked greater phasic dopamine release than saccharin cues. In a second group of rats, on each training day, sucrose and saccharin pellets were presented in pseudorandom order within the same session, to mask nutritional differences. In this condition, the difference in dopamine between sucrose and saccharin cues was attenuated, but not abolished. These results suggest that sucrose‐paired cues will more powerfully motivate behavior than saccharin‐paired cues. The differing responses to each cue seem to be driven by overall preference with both the nutritional value that the pellets predict as well as other factors, such as taste, contributing. Synapse 2012. © 2011 Wiley Periodicals, Inc.
St. John's Wort and Antidepressant Drug Interactions in the Elderly

There is increasing interest in and use of the herbal preparation St. John's wort. Hypericin, the major active ingre dient, has many psychoactive properties. The agent is sold in the US as a nutritional supplement and is recommended for numerous conditions, including depression, anxiety, insomnia, and inflammation. We report a series of five cases of clinically diagnosed central serotonergic syndrome among elderly patients who combined prescription antide pressants with St. John's wort. Older adults are large consumers of both over-the-counter and prescription medications. They are particularly vulnerable to interactions between medications and products sold as nutritional or herbal supplements. St. John's wort requires further evaluation due to potential for drug interactions with central ner vous system agents and for more definitive therapeutic indications. (J Geriatr Psychiatry Neurol 1999; 12:7-10).
A web-based system for automating a disciplined personal software process (PSP)

In this paper, we describe PSP-DROPS (PSF Data RepOsitory and Presentation System), an automated Web-based tool to support teaching the Personal Software Process (PSP) technique, at Embry-Riddle Aeronautical University. PSP is a disciplined personal software process used in software development. Last year, PSP was incorporated into our first two programming, courses (CS1 and CS2). Using PPS-DROPS, students can receive on-line instructions for recording, their data, which cuts down the work load of managing and analyzing process data. Most importantly, the analyzed result can be presented to the students graphically anywhere that has the World Wide Web, (WWW) access. The user friendly environment by PSP-DROPS facilitates and motivates the students to practice PSP for improving, their academic work.
Normal saline and mucous plugging.

cialist in the medical critical care/pulmonary unit at Christiana Care Health System in Newark, Delaware. history of smoking along with chronic respiratory diseases such as cystic fibrosis, chronic obstructive pulmonary disease, asthma, and bronchiectasis. Other patient-related factors that may contribute include smoking, immobility, sedation, muscle weakness, and dehydration. A mucous plug occurs when excessive, tenacious mucous secretion blocks or “plugs” the airway lumen. Several mechanisms can improve secretion management and prevent mucous plugging.
Determination of ethambutol MICs for Mycobacterium tuberculosis and Mycobacterium avium isolates by resazurin microtitre assay.

OBJECTIVES To test susceptibilities of Mycobacterium tuberculosis (MTB) isolates to ethambutol by the Löwenstein-Jensen (LJ) proportion method and resazurin microtitre assay (REMA) and to evaluate REMA for the determination of ethambutol MICs for MTB and Mycobacterium avium isolates. METHODS A total of 50 MTB and 20 M. avium isolates were tested to determine the MICs of ethambutol by REMA and agar dilution method. MTB isolates were also tested by the LJ proportion method. RESULTS REMA provided ethambutol susceptibility results for all the isolates within 8-9 days. For MTB isolates, REMA showed 96.7% sensitivity, 100.0% specificity and 98.0% accuracy when LJ proportion results were taken as 'gold standard'. For both MTB and M. avium isolates, the MICs determined by REMA were lower than those determined in agar medium, indicating that MIC values determined by REMA are closer to the actual MICs for the isolates. CONCLUSIONS REMA can be used as a rapid and inexpensive method for mycobacterial drug susceptibility testing against ethambutol. In comparison with the agar method, the MICs determined by REMA can more accurately be correlated with achievable plasma concentrations of antimycobacterial agents.
Safety and Efficacy of Etanercept in a Cohort of Patients with Juvenile Idiopathic Arthritis Under 4 Years of Age

Objective. To evaluate safety, tolerability, and efficacy of etanercept in a cohort of patients with juvenile idiopathic arthritis (JIA) under 4 years of age. Methods. Data were collected at every visit during treatment with etanercept in 25 children who began treatment at a mean age of 3 years (range 18–48 months). Safety endpoints included the incidence of any adverse events. Efficacy endpoints included the American College of Rheumatology (ACR) Pediatric 30, 50, and 70 criteria for improvement. Results. Data from 25 patients with JIA treated with etanercept for a mean period of 23 months were analyzed. All patients received concomitant medications: 24 methotrexate, 3 cyclosporin A, and 10 corticosteroids. After the first 6 months of treatment, 15 (71.4%) patients achieved an ACR Pedi30 response and at the last observation 20 (80%) achieved ACR Pedi30. ACR Pedi50 and 70 responses were, respectively, 62% and 43% at 6 months and 72% and 64% at the last followup. Five patients (20%) discontinued etanercept for lack of efficacy. Two (8%) developed adverse events, both primary varicella zoster virus (VZV) infections (both not vaccinated). One was hospitalized because of a necrotizing fasciitis secondary to VZV infection. No cases of tuberculosis, opportunistic infections, or malignancies were reported. Conclusion. In our cohort of patients etanercept proved to be safe and efficacious in the majority of children. The response in toddlers was similar to that in older children. We observed only 1 case of severe infection that required hospitalization and stopped treatment temporarily.
Atlas régional Région du Tadla Azilal Maroc

L’Atlas regional de la region du Tadla-Azilal au Maroc a ete realise a la suite d’un Programme d’Action Integree Volubilis soutenu par le Comite Mixte Interuniversitaire Franco-Marocain de 2005 a 2008 associant ESO-Angers (UMR CNRS 6590) de l’Universite d’Angers (France), l’Universite Sultan Moulay Slimane de Beni Mellal (Maroc) et le LATES de l’EHESS de Paris (France). L'atlas permet de mettre en perspective les elements a valoriser et ceux a preserver et ainsi participer a apporter des reponses concretes pour l’amenagement et le developpement de cette region. Apres un etat des lieux historique, physique et humain, sont developpes les dynamiques et enjeux specifiques aux trois unites regionales (montagne, piemont plaine) et les enjeux transversaux autour de l'eau, de la question migratoire, des risques et des patrimoines reconnus et potentiels.
A novel CMOS constant-bandwidth variable-gain amplifier for WiMAX receivers

In this study, a novel variable-gain amplifier (VGA) is proposed. A mathematical analysis of the circuit is given. The proposed circuit keeps a constant current flowing through the load transistors and provides a constant bandwidth over the voltage gain range. The circuit is designed with TSMC 180 nm CMOS technology, using 1.8 V single supply voltage and simulated with Cadence Analog Virtuoso.
Narrativa prototipo de la depresión. Una validación convergente en sujetos depresivos

Resumen El presente estudio tiene como proposito establecer la identiÞcacion que un grupo de sujetos masculinos deprimidos hace con la narrativa prototipo de la depresion en comparacion con un grupo de sujetos femeninos deprimidos. La muestra se conformo con 65 sujetos depresivos y 65 no depresivos para cada grupo segun el genero con edades entre los 16 y 40 anos. Los participantes fueron derivados de diferentes centros de atencion psicologica de la ciudad de Bucaramanga. No se aplicaron criterios de inclusion adicionales salvo capacidad de comprension lectora que les facilitara el manejo de los instrumentos psicologicos aplicados. El estudio siguio un diseno correlacional transversal. El procedimiento incluyo la aplicacion de la entrevista estructurada SCID, el test de Hamilton y la narrativa prototipo de la depresion de Goncalves. Se aplico el estadistico Ji cuadrado para conÞrmar las hipotesis de identiÞcacion con la narrativa prototipo de la depresion en los sujetos depresivos y lo opuesto en los no depresivos en cada grupo segun el genero, por medio de un estudio de casos y controles. Los hallazgos demuestran que e grupo masculino y el femenino de sujetos depresivos puestos en comparacion, se identiÞcan con la narrativa prototipo de la depresion en tanto que los no depresivos en cada genero, no lo hacen. Se concluye que tanto los varones como las mujeres deprimidos del estudio se identiÞcan con la narrativa prototipo de la depresion salvo que en grados superiores en el segundo grupo. [Alvarez LY Narrativa prototipo de la depresion. Una validacion convergente en sujetos depresivos. MedUNAB 2007; 10:19-23]. Palabras clave: Narrativa prototipo, depresiUn, validaciUn convergente.
Évaluation de l'efficacité de l'information délivrée par les sages-femmes de l'unité de médecine de la procréation aux patientes suivies pour une surveillance de l'ovulation

Introduction : En France de nombreux couples ont recours a l'AMP, et plus specifiquement a l'optimisation de l'ovulation. Dans le service d'AMP du CHU de Grenoble, un entretien est realise par les sages femmes aupres des patientes afin de les informer de la physiologie entourant la conception naturelle. Notre objectif a ete d'evaluer l'impact de cet entretien en terme d'apport de connaissances pour les patientes, par rapport a leurs connaissances anterieures. Materiel et methode : Il s'agit d'une etude comparative avant-apres, realisee par questionnaire aupres de 36 patientes, suivies dans le service d'AMP du CHU de Grenoble du 11 octobre 2010 au 14 mars 2011. L'objectif principal, etait d'evaluer la performance de l'information transmise par les sages femmes aux patientes en surveillance de l'ovulation. L'objectif secondaire etait d'evaluer leurs connaissances initiales des patientes. Resultats : La difference des moyennes entre les 2 questionnaires est statistiquement significative car on retrouve un p = 0.002. Concernant les connaissances initiales des patientes 63.89% ont un score superieur a 10/20 au 1er questionnaire. De plus, 100% des patientes qui n'ont pas obtenu 10/20 au premier questionnaire, ont gagne des points a la note finale du deuxieme questionnaire (gain de 0.11 a 13.33 points). La moyenne des gains etant de 4.76 points. Discussion et conclusion : La prise en charge des couples infertiles par la sage-femme apparait comme une necessite. Elle permet d'identifier et corriger les erreurs "inconscientes" faites par les couples depuis des annees. Il serait interessant de realiser une etude pour evaluer le gain de cet entretien en terme de survenue de grossesse.
Prospects for the Use of Multiplayer Online Games in Psychological Rehabilitation

The aim of this paper is to describe the potential role of Multiplayer Online Games (MOGs) in e-therapy. E-therapy is defined as the provision of psychological therapy and consultation over the Internet. An increasing number of MOGs are now being designed specifically for therapeutical applications, and several support groups, have been already developed in commercial MOGs such as Second Life and Entropia. From the technological viewpoint, the goal of this approach is to combine the use of Internet and Virtual Reality (VR) to create distributed virtual environments (VEs) that are used to enhance the remote communication between therapists and patients. We speculate that MOGs can convey higher feelings of presence and social presence than traditional e-therapy tools such as email or chat. Embodiment by means of avatars has the potential to facilitate the clinical communication process, to positively influence group processes and cohesiveness in group-based therapies and to create higher levels of interpersonal trust. Potential caveats related to the use of MOGs in therapy are also discussed.
Effect of mineral addition in water or feed on heart rate in broilers under chronic and acute heat stress

Se evaluaron en ambiente semicontrolado, los efectos de adicion de minerales en agua o alimento sobre parametros productivos y frecuencia cardiaca (FC) en pollos de engorde de 28-35 d y 36 d bajo estres calorico cronico (ECC) y estres calorico agudo (ECA), respectivamente. Se uso un total de 192 pollos, segun peso, distribuidos en 6 corrales y 4 salas, asignandose 8 pollos/corral: cuatro machos y cuatro hembras. A los 21 d, para las medidas individuales, de los 8 pollos se seleccionaron 2 machos y 2 hembras, identificandolos como macho pesado, macho liviano, hembra pesada y hembra liviana. Para FC, se escogieron 48 pollos. El ensayo incluyo 3 tratamientos (T): T1: Alimento balanceado (AB); T2: AB con adicion mineral y T3: AB con adicion mineral en agua. El diseno utilizado fue completamente al azar con 4 repeticiones/tratamiento. La composicion del suplemento mineral fue: NaHCO3 (0,83%); NH4Cl (0,07%) y; NaCl (0,30%) con un balance electrolitico de 240 mEq/kg. Se evaluo consumo de alimento (CAL), consumo de agua (CAG), ganancia de peso (GP), conversion alimenticia (CA), temperatura corporal (TC), nivel de AbstrAct
Health-related Quality of Life of Patients with Endometrial Cancer Who are Disease-free Following External Irradiation

Health-related quality of life (HQoL) is assessed through the patients' own evaluation of the impact that a disease and its treatment may have on some of the physical, psychological and social aspects of their lives. The purpose of this study is to describe the HQoL of patients with endometrial cancer who are free of disease after undergoing external irradiation. An HQoL questionnaire was designed and validated, and consisted of the EORTC QLQ-C30 and 80 additional questions. The patients provided self-reported assessments at the end of radiotherapy, and 1, 3, 6, 12, 18 and 24 months later. Forty-nine out of 66 potential subjects participated in the study, which was confined to the period during which the women were disease free. Most patients experience physical side effects at the end of treatment and up to 6 months thereafter; 10% of the patients have chronic local symptoms and a large number of the patients think about their treatment even two years later. The patients' overall evaluation of their quality of life is lower than that of a matched population of healthy women.
Type I Keratin 17 Protein Is Phosphorylated on Serine 44 by p90 Ribosomal Protein S6 Kinase 1 (RSK1) in a Growth- and Stress-dependent Fashion*

Background: Keratin 17 (K17) provides structural support and regulates cell growth, apoptosis, and immune responses in skin epithelia. Results: K17-Ser44 is dynamically phosphorylated by RSK1 in skin keratinocytes undergoing growth or stress. Conclusion: K17 is regulated by Ser44 phosphorylation in vivo. Significance: K17-Ser44 phosphorylation provides a novel biomarker reflecting growth or stress situations in keratinocytes. Keratin 17 (K17) is a type I intermediate filament protein that is constitutively expressed in ectoderm-derived epithelial appendages and robustly induced in epidermis following injury, during inflammation, and in chronic diseases such as psoriasis and cancer. Mutations within K17 are responsible for two rare diseases related to ectodermal dysplasias. Studies in K17-null mice uncovered several roles for K17, including structural support, resistance to TNFα-induced apoptosis, regulation of protein synthesis, and modulation of cytokine expression. Yet, little is known about the regulation of K17 protein via post-translational modification. Here, we report that serine 44 in the N-terminal head domain of K17 (K17-Ser44) is phosphorylated in response to extracellular stimuli (serum, EGF, and the phorbol ester 12-O-tetradecanoylphorbol-13-acetate) that alter skin keratinocyte growth, and to cellular stresses (sorbitol-induced hyperosmotic shock, UV irradiation, and hydrogen peroxide-induced oxidative stress). It also occurs in basaloid skin tumors in situ. Upon its stimulation in skin keratinocytes, K17-Ser44 phosphorylation is induced rapidly but stays on transiently. The majority of the phosphorylated K17-Ser44 pool is polymer-bound and is not obviously related to a change in filament organization. The amino acid sequence surrounding K17-Ser44 matches the consensus for the AGC family of basophilic kinases. We show that p90 RSK1, an AGC kinase involved in the regulation of cell survival and proliferation, phosphorylates K17-Ser44 in skin keratinocytes. These findings confirm and expand the tight link that has emerged between K17 up-regulation and growth and stress responses in the skin epithelium.
Chapter 8 Interspeci fi c Mycorrhizal Networks and Non-networking Hosts : Exploring the Ecology of the Host Genus Alnus

While the dominant ectomycorrhizal (ECM) fungi in most temperate and tropical forests have low host specificity, a commonly cited exception to this pattern is the ECM fungal community associated with the host genus Alnus. In this chapter, we discuss multiple hypotheses that have been put forth to explain the specificity of the Alnus ECM symbiosis and consider their strengths and weaknesses in light of current research on the topic. In addition to reviewing the range of suggested explanations, we also propose and discuss a new alternative explanation of Alnus ECM specificity involving three-way interactions among Alnus plants, ECM fungi, and Frankia bacteria. With specific regard to common mycorrhizal networks (CMNs), we believe they may play an important role in the specificity observed in the Alnus ECM system. To understand that role in the larger context of research on Alnus ECM fungal communities, we begin our chapter with a synopsis of the studies documenting the unique specificity pattern. From there, we discuss why it appears to be advantageous for Alnus plants not to participate in interspecific CMNs. Finally, we elaborate on how specificity may be established and maintained in the Alnus ECM system and suggest what we consider to be promising future research directions.
Current and emerging drugs for acute bacterial skin and skin structure infections: an update

Introduction: Antibiotic resistance, the emergence of multidrug-resistant bacteria and the exponential rise of methicillin-resistant Staphylococcus aureus (MRSA) acute bacterial skin and skin structure infections (ABSSSI) pose a great threat to the public health. In order to combat these threats, development of new antibiotics is vital and measures to decrease antibiotic resistance should be prioritized. Areas covered: This manuscript provides an overview of the current FDA-approved antibiotics and the antibiotics in development for MRSA ABSSSI. Expert opinion: A great need exists currently for novel antibiotics to combat multidrug-resistant MRSA. As clinicians, it is imperative to implement proper management in order to reduce antibiotic resistance.
Observer Bias in Acellular Pertussis Vaccine Trials

To the Editor. We wish to comment on the recently published article1 that evaluates the impact of observer bias on the estimate of clinical efficacy of one acellular pertussis vaccine. The authors report that, in the Erlangen trial, the observed incidence in unblinded unvaccinated children (DT) was only 13%, compared with an expected figure of approximately 40%. To determine potential observer bias, the authors analyzed the trial physicians' cough referral rates and used these rates to divide the physicians into three categories indicating their compliance to the trial protocol, which required referral of any cough lasting >7 days. Physicians who had reported an at least 20% incidence of cough were classified as “highly compliant. ” The authors then recalculated vaccine efficacy for each compliance category and found that the estimated efficacy greatly varied among the categories and that it was inversely proportional to the physician's referral rate, concluding that a bias had occurred. Because no correlation was found between the cough referral rate and the proportion of unvaccinated (DT) children in each physician's study subject group, the authors concluded that the bias did not depend on unblinded conditions and that a similar bias was thus likely to have occurred in all of the recently conducted pertussis trials. Although the evidence for the Erlangen trial is convincing, extending the conclusions …
Artificial Cohort Generation Based on Statistics of Real Cohorts for GMM-Based Speaker Verification

This paper discusses speaker verification (SV) using Gaussian mixture models (GMMs), where only utterances of enrolled speakers are required. Such an SV system can be realized using artificially generated cohorts instead of real cohorts from speaker databases. This paper presents a rational approach to set GMM parameters for artificial cohorts based on statistics of GMM parameters for real cohorts. Equal error rates for the proposed method are about 10% less than those for the previous method, where GMM parameters for artificial cohorts were set in an ad hoc manner.
In vitro activity of cefbuperazone against Bacteroides spp

The activity of cefbuperazone was tested in vitro against 287 clinical isolates of Bacteroides spp. Cefbuperazone showed good activity against B. fragilis, B. vulgatus, and other Bacteroides species, comparable to that of cefoxitin. It was relatively ineffective against B. distasonis and the B. thetaiotaomicron-ovatus group and was not active against cefoxitin-resistant Bacteroides spp.