T1-weighted MRI as a substitute to CT for refocusing planning in MR-guided focused ultrasound.

Precise focusing is essential for transcranial MRI-guided focused ultrasound (TcMRgFUS) to minimize collateral damage to non-diseased tissues and to achieve temperatures capable of inducing coagulative necrosis at acceptable power deposition levels. CT is usually used for this refocusing but requires a separate study (CT) ahead of the TcMRgFUS procedure. The goal of this study was to determine whether MRI using an appropriate sequence would be a viable alternative to CT for planning ultrasound refocusing in TcMRgFUS. We tested three MRI pulse sequences (3D T1 weighted 3D volume interpolated breath hold examination (VIBE), proton density weighted 3D sampling perfection with applications optimized contrasts using different flip angle evolution and 3D true fast imaging with steady state precision T2-weighted imaging) on patients who have already had a CT scan performed. We made detailed measurements of the calvarial structure based on the MRI data and compared those so-called 'virtual CT' to detailed measurements of the calvarial structure based on the CT data, used as a reference standard. We then loaded both standard and virtual CT in a TcMRgFUS device and compared the calculated phase correction values, as well as the temperature elevation in a phantom. A series of Bland-Altman measurement agreement analyses showed T1 3D VIBE as the optimal MRI sequence, with respect to minimizing the measurement discrepancy between the MRI derived total skull thickness measurement and the CT derived total skull thickness measurement (mean measurement discrepancy: 0.025; 95% CL (-0.22-0.27); p = 0.825). The T1-weighted sequence was also optimal in estimating skull CT density and skull layer thickness. The mean difference between the phase shifts calculated with the standard CT and the virtual CT reconstructed from the T1 dataset was 0.08 ± 1.2 rad on patients and 0.1 ± 0.9 rad on phantom. Compared to the real CT, the MR-based correction showed a 1 °C drop on the maximum temperature elevation in the phantom (7% relative drop). Without any correction, the maximum temperature was down 6 °C (43% relative drop). We have developed an approach that allows for a reconstruction of a virtual CT dataset from MRI to perform phase correction in TcMRgFUS.

Global Education in the Shifting Classroom: Refocusing the Teacher Lens Through Study Abroad

Academic exchange programmes provide opportunities for teacher candidates to study at educational institutions abroad wherein they are able to learn more about different cultures, teaching practices, and build cross-cultural relationships. This paper is an exploration into my teacher candidate experience abroad. The relevant research on this topic indicates that teacher certification should take an active role in creating opportunities for teacher candidates to participate in educational experiences abroad because of their benefits. The knowledge that a teacher gains through abroad experiences is one of the strongest factors in helping to build authentic global classrooms. In addition, these programmes allow for fuller understanding of a global context and the chance to understand someone else’s story. This review and synthesis of literature and research findings prepares a foundation for how teacher candidates, and hopefully, how policy makers can work toward creating a more inclusive global classroom for students.

Qualitative analysis by online nuclear magnetic resonance using Carr-Purcell-Meiboom-Gill sequence with low refocusing flip angles

The Carr-Purcell-Meiboom-Gill (CPMG) pulse sequence has been used in many applications of magnetic resonance imaging (MRI) and low-resolution NMR (LRNMR) spectroscopy. Recently. CPMG was used in online LRNMR measurements that use long RF pulse trains, causing an increase in probe temperature and, therefore, tuning and matching maladjustments. To minimize this problem, the use of a low-power CPMG sequence based on low refocusing pulse flip angles (LRFA) was studied experimentally and theoretically. This approach has been used in several MRI protocols to reduce incident RF power and meet the specific absorption rate. The results for CPMG with LRFA of 3 pi/4 (CPMG(135)), pi/2 (CPMG(90)) and pi/4 (CPMG(45)) were compared with conventional CPMG with refocusing pi pulses. For a homogeneous field, with linewidth equal to Delta nu = 15 Hz, the refocusing flip angles can be as low as pi/4 to obtain the transverse relaxation time (T(2)) value with errors below 5%. For a less homogeneous magnetic field. Delta nu = 100 Hz, the choice of the LRFA has to take into account the reduction in the intensity of the CPMG signal and the increase in the time constant of the CPMG decay that also becomes dependent on longitudinal relaxation time (T(1)). We have compared the T(2) values measured by conventional CPMG and CPMG(90) for 30 oilseed species, and a good correlation coefficient, r = 0.98, was obtained. Therefore, for oilseeds, the T(2) measurements performed with pi/2 refocusing pulses (CPMG(90)), with the same pulse width of conventional CPMG, use only 25% of the RF power. This reduces the heating problem in the probe and reduces the power deposition in the samples. (C) 2011 Elsevier B.V. All rights reserved.

Use of Carr-Purcell pulse sequence with low refocusing flip angle to measure T-1 and T-2 in a single experiment

The Carr-Purcell pulse sequence, with low refocusing flip angle, produces echoes midway between refocusing pulses that decay to a minimum value dependent on T*(2). When the refocusing flip angle was pi/2 (CP90) and tau > T*(2), the signal after the minimum value, increased to reach a steady-state free precession regime (SSFP), composed of a free induction decay signal after each pulse and an echo, before the next pulse. When tau < T*(2), the signal increased from the minimum value to the steady-state regime with a time constant (T*) = 2T(1)T(2)/(T-1 + T-2). identical to the time constant observed in the SSFP sequence, known as the continuous wave free precession (CWFP). The steady-state amplitude obtained with M-cp90 = M0T2/(T-1+T-2) was identical to CWFP. Therefore, this sequence was named CP-CWFP because it is a Carr-Purcell sequence that produces results similar to the CWFP. However, CP-CWFP is a better sequence for measuring the longitudinal and transverse relaxation times in single scan, when the sample exhibits T-1 similar to T-2. Therefore, this sequence can be a useful method in time domain NMR and can be widely used in the agriculture, food and petrochemical industries because those samples tend to have similar relaxation times in low magnetic fields. (C) 2011 Elsevier Inc. All rights reserved.

Refocusing regulatory exclusivities: Regulatory data protection and marketing exclusivity as forms of pharmaceutical innovation policy

Protection of innovation in the pharmaceutical industry has traditionally been realised through protection of inventions via patents. However, in the European Union regulatory exclusivities restricting market entry of generic products confer tailored, industry specific protection for final, marketable products. This paper retraces the protection conferred by the different forms of exclusivity and assesses them in the light of recent transparency policies of the European Medicines Agency. The purpose of the paper is to argue for rethinking the role of regulatory data as a key tool of innovation policy and for refocusing the attention from patents to the existing regulatory framework. After detailed assessment of the exclusivity regime, the paper identifies key areas of improvement calling for reassessment so as to promote better functioning of the regime as an incentive for accelerated innovation. While economic and public health analysis necessarily provide final answers as to necessity of reform, this paper provides a legal perspective to the issue, appraising the current regulatory framework and identifying areas for further analysis.

An archaeobotanical perspective on Holocene plant-use practices in lowland northern New Guinea

Existing archaeobotanical and palynological records of plant use in the northern New Guinea lowlands are reviewed in light of recent work at Kuk and theoretical refocusing on plant use practice. A practice-based approach is supported as the most useful way of investigating the highly problematical area of tropical plant food production. The existing direct record of past plant use in lowland New Guinea is considered woefully inadequate to achieve this task, as is that in Near Oceania and Island Southeast Asia. Archaeobotanical methods exist to fill the void, but full implementation requires a change in general archaeological and palaeoecological practice.

Grau de diversificação nas empresas do mercado de capitais ibérico

Dissertação de Mestrado em Ciências Económicas e Empresariais.

Echo-time independent signal modulations for strongly coupled systems in triple echo localization schemes: an extension of S-PRESS editing.

The double spin-echo point resolved spectroscopy sequence (PRESS) is a widely used method and standard in clinical MR spectroscopy. Existence of important J-modulations at constant echo times, depending on the temporal delays between the rf-pulses, have been demonstrated recently for strongly coupled spin systems and were exploited for difference editing, removing singlets from the spectrum (strong-coupling PRESS, S-PRESS). A drawback of this method for in vivo applications is that large signal modulations needed for difference editing occur only at relatively long echo times. In this work we demonstrate that, by simply adding a third refocusing pulse (3S-PRESS), difference editing becomes possible at substantially shorter echo times while, as applied to citrate, more favorable lineshapes can be obtained. For the example of an AB system an analytical description of the MR signal, obtained with this triple refocusing sequence (3S-PRESS), is provided.

B1-insensitive T2 preparation for improved coronary magnetic resonance angiography at 3 T.

At 3 T, the effective wavelength of the RF field is comparable to the dimension of the human body, resulting in B1 standing wave effects and extra variations in phase. This effect is accompanied by an increase in B0 field inhomogeneity compared to 1.5 T. This combination results in nonuniform magnetization preparation by the composite MLEV weighted T2 preparation (T2 Prep) sequence used for coronary magnetic resonance angiography (MRA). A new adiabatic refocusing T2 Prep sequence is presented in which the magnetization is tipped into the transverse plane with a hard RF pulse and refocused using a pair of adiabatic fast-passage RF pulses. The isochromats are subsequently returned to the longitudinal axis using a hard RF pulse. Numerical simulations predict an excellent suppression of artifacts originating from B1 inhomogeneity while achieving good contrast enhancement between coronary arteries and surrounding tissue. This was confirmed by an in vivo study, in which coronary MR angiograms were obtained without a T2 Prep, with an MLEV weighted T2 Prep and the proposed adiabatic T2 Prep. Improved quantitative and qualitative coronary MRA image measurement was achieved using the adiabatic T2 Prep at 3 T.

Three-dimensional magnetic resonance myocardial motion tracking from a single image plane.

Three-dimensional imaging for the quantification of myocardial motion is a key step in the evaluation of cardiac disease. A tagged magnetic resonance imaging method that automatically tracks myocardial displacement in three dimensions is presented. Unlike other techniques, this method tracks both in-plane and through-plane motion from a single image plane without affecting the duration of image acquisition. A small z-encoding gradient is subsequently added to the refocusing lobe of the slice-selection gradient pulse in a slice following CSPAMM acquisition. An opposite polarity z-encoding gradient is added to the orthogonal tag direction. The additional z-gradients encode the instantaneous through plane position of the slice. The vertical and horizontal tags are used to resolve in-plane motion, while the added z-gradients is used to resolve through-plane motion. Postprocessing automatically decodes the acquired data and tracks the three-dimensional displacement of every material point within the image plane for each cine frame. Experiments include both a phantom and in vivo human validation. These studies demonstrate that the simultaneous extraction of both in-plane and through-plane displacements and pathlines from tagged images is achievable. This capability should open up new avenues for the automatic quantification of cardiac motion and strain for scientific and clinical purposes.

Improving T2 -weighted imaging at high field through the use of kT -points.

PURPOSE: At high magnetic field strengths (B0 ≥ 3 T), the shorter radiofrequency wavelength produces an inhomogeneous distribution of the transmit magnetic field. This can lead to variable contrast across the brain which is particularly pronounced in T2 -weighted imaging that requires multiple radiofrequency pulses. To obtain T2 -weighted images with uniform contrast throughout the whole brain at 7 T, short (2-3 ms) 3D tailored radiofrequency pulses (kT -points) were integrated into a 3D variable flip angle turbo spin echo sequence. METHODS: The excitation and refocusing "hard" pulses of a variable flip angle turbo spin echo sequence were replaced with kT -point pulses. Spatially resolved extended phase graph simulations and in vivo acquisitions at 7 T, utilizing both single channel and parallel-transmit systems, were used to test different kT -point configurations. RESULTS: Simulations indicated that an extended optimized k-space trajectory ensured a more homogeneous signal throughout images. In vivo experiments showed that high quality T2 -weighted brain images with uniform signal and contrast were obtained at 7 T by using the proposed methodology. CONCLUSION: This work demonstrates that T2 -weighted images devoid of artifacts resulting from B1 (+) inhomogeneity can be obtained at high field through the optimization of extended kT -point pulses. Magn Reson Med 71:1478-1488, 2014. © 2013 Wiley Periodicals, Inc.

Identity, non-identity, and near-identity: Addressing the complexity of coreference

This article examines the mainstream categorical definition of coreference as "identity of reference." It argues that coreference is best handled when identity is treated as a continuum, ranging from full identity to non-identity, with room for near-identity relations to explain currently problematic cases. This middle ground is needed to account for those linguistic expressions in real text that stand in relations that are neither full coreference nor non-coreference, a situation that has led to contradictory treatment of cases in previous coreference annotation efforts. We discuss key issues for coreference such as conceptual categorization, individuation, criteria of identity, and the discourse model construct. We redefine coreference as a scalar relation between two (or more) linguistic expressions that refer to discourse entities considered to be at the same granularity level relevant to the linguistic and pragmatic context. We view coreference relations in terms of mental space theory and discuss a large number of real life examples that show near-identity at different degrees.

L’expérience vécue à domicile par les conjointes de partenaires atteints de la démence de type Alzheimer au moment des soins d’hygiène

Suite à une recension des écrits sur les soins d’hygiène des personnes atteintes de démence de type Alzheimer (DTA), force est de constater la rareté, voire l’absence de recherches sur la question des soins d’hygiène (SH) dispensés à domicile par les conjointes. Pourtant, la conjointe à domicile est confrontée aux mêmes difficultés que les intervenants des établissements de santé et doit ainsi faire face aux comportements, parfois difficiles de la personne atteinte. Dans la pratique, les infirmières questionnent peu les difficultés rencontrées par les aidantes au moment des soins d’hygiène, ce qui permet difficilement de prendre conscience de leurs sentiments d’isolement et de détresse et de les réduire, le cas échéant. Pour pallier cette lacune, la présente recherche vise à comprendre l’expérience que vivent des conjointes d’hommes atteints de DTA lorsqu’elles leur dispensent des SH à domicile. Un second objectif vise à identifier les dimensions qui sont associées à cette expérience. Une approche de recherche qualitative est utilisée. Les participantes ont été recrutées par l’entremise des Sociétés Alzheimer de Laval et des Laurentides. La stratégie de collecte des données a impliqué la réalisation de deux entrevues individuelles, face à face, de même que l’administration d’un court questionnaire portant sur les aspects sociodémographiques. La démarche retenue pour l’analyse de l’ensemble de données est inspirée de l’approche proposée par Miles et Huberman (2003). Les résultats permettent d’abord de mettre en évidence des profils de conjointes qui, tout en étant variables, présentent certaines similarités. Eu égard aux SH, toutes ont à consacrer des efforts soutenus, quotidiens et intenses. Elles doivent faire montre de patience et compter sur des capacités personnelles les amenant à ressentir des sentiments positifs malgré les situations difficiles. Les résultats montrent par ailleurs que la dispensation des SH provoque aussi des sentiments négatifs associés au fardeau que ces soins impliquent. Les conjointes mettent toutefois en œuvre une variété de stratégies d’adaptation au stress telles la résolution de problème, la recherche de soutien social et le recadrage. Cinq ensembles de dimensions personnelles et contextuelles sont associés à l’expérience des aidantes : 1) En ce qui a trait aux caractéristiques personnelles des conjointes, l’avancement en âge et l’état de santé physique ou psychologique influencent négativement l’expérience lors des SH. Par contre, les ressources personnelles intrinsèques (acceptation de la réalité, capacité de trouver un sens à l’évènement, habileté à improviser et sens de l’humour) sont utilisées de manière naturelle ou acquise; 2) Les caractéristiques personnelles du conjoint (année du diagnostic, pertes d’autonomie et troubles de comportement) affectent négativement l’expérience vécue; 3) La relation conjugale présente un intérêt important puisqu’il apparaît qu’une relation conjugale pré-diagnostic positive semble favoriser des sentiments positifs chez la conjointe en ce qui a trait aux SH; 4) Les dimensions familiales ont un impact favorable, étant donné le soutien psychologique reçu de la famille; 5) Les dimensions macro-environnementales, incluant l’aide reçue du réseau informel plus large de même que du réseau formel, ainsi que les divers aménagements matériels de l’environnement physique du couple, ressortent enfin comme ayant un impact positif. Au terme de l’analyse des résultats, l’auteure est en mesure de proposer une synthèse de l’expérience des conjointes. La discussion aborde quatre enjeux qui se dégagent des résultats observés : impacts des difficultés rencontrées lors des SH dans la décision d’hébergement, réticence des aidantes à faire appel aux ressources du réseau formel pour obtenir de l’aide eu égard aux SH, importance des ressources personnelles des aidantes et potentiel de l’approche relationnelle humaine (human caring) pour faire face aux défis que pose la dispensation des SH.

La politique allemande de la France telle que perçue par la presse française (1919-1926)

La France est souvent perçue comme la principale garante du traité de Versailles. Le révisionnisme français envers l’ordre établi par le traité, contrairement au même courant chez les responsables allemands, est un sujet peu étudié. Il a été abordé par quelques auteurs, tels George-Henri Soutou et Stanislas Jeannesson, mais la question mérite davantage d’élaboration. Grâce à l’analyse de la presse française, ce mémoire vérifie l’existence d’une volonté de rendre le traité de paix plus favorable à la France. Une Machtpolitik ainsi qu’un révisionnisme français sont apparents de 1919 à 1923 avec, comme zénith, l’occupation de la Ruhr. Les années suivantes virent la situation de la France se détériorer sur les plans politique, économique et diplomatique. La dégradation de sa posture inclina la France à se tourner vers une conciliation qui émanait de l’esprit du traité de Versailles. La couverture de l’actualité internationale de trois journaux français (Le Temps, L’Action française et L’Humanité) avant et après l’invasion de la Ruhr est analysée. On constate l’existence d’un révisionnisme français qui mène, après son échec en 1924, à un recentrage de la politique allemande de la France. En liant la perception des différents journaux à leur idéologie, nous avons aussi expliqué les variations dans leurs analyses des mêmes événements. L’étude de la presse, conjuguée aux sources secondaires, révèle un discours teinté d’une volonté révisionniste. Elle porte à croire, aussi, que le traité de Versailles ne fut réellement défendu en France qu’après l’échec de la politique de puissance et du révisionnisme français.

Efecto de la hipoxia-reoxigenación y las radiaciones ionizantes en la captación de glucosa en líneas tumorales de seno y colon cocultivadas con células endoteliales.

La captación de glucosa y su conversión en lactato juega un papel fundamental en el metabolismo tumoral, independientemente de la concentración de oxígeno presente en el tejido (efecto Warburg). Sin embrago, dicha captación varía de un tipo tumoral a otro, y dentro del mismo tumor, situación que podría depender de las características microambientales tumorales (fluctuaciones de oxígeno, presencia de otros tipos celulares) y de factores estresores asociados a los tratamientos. Se estudió el efecto de la hipoxia-reoxigenación (HR) y las radiaciones ionizantes (RI) sobre la captación de glucosa, en cultivos de líneas tumorales MCF-7 y HT-29, cultivadas de forma aislada o en cocultivo con la línea celular EAhy296. Se encontró que la captación de glucosa en HR es diferente para lo descrito en condiciones de hipoxia permanente y que es modificada en el cocultivo. Se identificaron poblaciones celulares dentro de la misma línea celular, de alta y baja captación de glucosa, lo que implicaría una simbiosis metabólica de la célula como respuesta adaptativa a las condiciones tumorales. Se evaluó la expresión de NRF2 y la translocación nuclear de NRF2 y HIF1a, como vías de respuesta a estrés celular e hipoxia. La translocación nuclear de las proteínas evaluadas explicaría el comportamiento metabólico de las células tumorales de seno, pero no de colon, por lo cual deben existir otras vías metabólicas implicadas. Las diferencias en el comportamiento de las células tumorales en HR en relación con hipoxia permitirá realizar planeaciones dosimétricas más dinámicas, que reevalúen las condiciones de oxigenación tumoral constantemente.