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Purpose: Many breast cancer (BC) survivors continue to be seen by specialists for routine follow-up care despite growing evidence that transitioning appropriate BC survivors to primary care is safe and effective. We describe the formative evaluation of an initiative involving the development and implementation of sustainable models of follow-up care for BC survivors across 14 Regional Cancer Centers (RCC) in Ontario, Canada., Methods: After extensive consultation, each RCC received catalyst funding for the initiative. Detailed work plans were developed locally and submitted to Cancer Care Ontario. Each region had a designated lead and support from primary care. Funding could be used to develop any aspect of the model. Formative evaluation of each model was conducted with descriptive analysis of the model created, including summative description of how resources were used, the number of survivors transitioned, and preliminary results from patient surveys of experience at transition., Results: Each region developed a unique model that included clearly identified structures and processes of care. All regions used survivorship care plans and patient education materials. Three main models of follow-up care were developed: (1) direct to primary care, (2) transition clinic, and (3) shared care. A total of 3,418 BC survivors transitioned between March 2012 and September 2013. Patient experience surveys were distributed by 12 regions, gathering responses from 752 BC survivors, with 85% reporting that they felt adequately prepared for the transition., Conclusion: Using the approach described, wide-scale transition of appropriate BC survivors from oncology-led practice is feasible over a fairly short timeframe., (Copyright © 2015 by American Society of Clinical Oncology.)

During long bone development and post-natal growth, the cartilaginous model of the skeleton is progressively replaced by bone, a process known as endochondral ossification. In the primary spongiosa, osteoclasts degrade the mineralized cartilage produced by hypertrophic chondrocytes to generate cartilage trabeculae that osteoblasts embed in bone matrix. This leads to the formation of the trabecular bone network of the secondary spongiosa that will undergo continuous remodeling. Osteoclasts are specialized in mineralized tissue degradation, with the combined ability to solubilize hydroxyapatite and to degrade extracellular matrix proteins. We reported previously that osteoclasts lacking Dock5 could not degrade bone due to abnormal podosome organization and absence of sealing zone formation. Consequently, adult Dock5(-/-) mice have increased trabecular bone mass. We used Dock5(-/-) mice to further investigate the different functions of osteoclast during endochondral bone formation. We show that long bones are overall morphologically normal in developing and growing Dock5(-/-) mice. We demonstrate that Dock5(-/-) mice also have normal hypertrophic cartilage and cartilage trabecular network. Conversely, trabecular bone volume increased progressively in the secondary spongiosa of Dock5(-/-) growing mice as compared to Dock5(+/+) animals, even though their osteoclast numbers were the same. In vitro, we show that Dock5(-/-) osteoclasts do present acidic compartments at the ventral plasma membrane and produce normal amounts of active MMP9, TRAP and CtsK for matrix protein degradation but they are unable to solubilize minerals. These observations reveal that contrarily to bone resorption, the ability of osteoclasts to dissolve minerals is dispensable for the degradation of mineralized hypertrophic cartilage during endochondral bone formation., (Copyright © 2014 Elsevier Inc. All rights reserved.)

The inducible proto-oncogenic (c-Fos:c-Jun)/AP-1 transcription complex binds 12-O-tetradecanoylphorbol 13-acetate (TPA)-responsive elements (TRE) in its target genes. It is tightly controlled at multiple levels to avoid the deleterious effects of its inappropriate activation. In particular, SUMOylation represses its transactivation capacity in transient reporter assays using constitutively expressed proteins. This led to the presumption that (c-Fos:c-Jun)/AP-1 SUMOylation would be required to turn-off transcription of its target genes, as proposed for various transcription factors. Instead, thanks to the generation of an antibody specific for SUMO-modified c-Fos, we provide here direct evidence that SUMOylated c-Fos is present on a stably integrated reporter TPA-inducible promoter at the onset of transcriptional activation and colocalizes with RNA polymerase II within chromatin. Interestingly, (c-Fos:c-Jun)/AP-1 SUMOylation limits reporter gene induction, as well as the appearance of active transcription-specific histone marks on its promoter. Moreover, non-SUMOylatable mutant (c-Fos:c-Jun)/AP-1 dimers accumulate to higher levels on their target promoter, suggesting that SUMOylation might facilitate the release of (c-Fos:c-Jun)/AP-1 from promoters. Finally, activation of GADD153, an AP-1 target gene, is also associated with a rapid increase in SUMOylation at the level of its TRE and c-Fos SUMOylation dampens its induction by TPA. Taken together, our data suggest that SUMOylation could serve to buffer transcriptional activation of AP-1 target genes.

Clinical researchers make use of experimental models for mental disorders. In many cases, these models use stimuli that are relevant to the disorder under scrutiny, which allows one to experimentally investigate the factors that contribute to the development of the disorder. For example, one might use spiders or spider-like stimuli in the study of specific phobia. More broadly, researchers often make use of real-world stimuli such as images of animals, geometrical shapes or emotional words. However, these stimuli are often limited in their experimental controllability and their applicability to the disorder in question. We present a novel set of animal-like stimuli, called Fribbles, for use within behavioural research. Fribbles have desirable properties for use in research because they are similar to real-world stimuli, but due to their novelty, participants will not have had previous experience with them. They also have known properties that can be experimentally manipulated. We present an investigation into similarity between Fribbles in order to illustrate their utility in research that relies on comparisons between similar stimuli. Fribbles offer both experimental control and generalisability to the real world, although some consideration must be made concerning the properties that influence similarity between Fribbles when selecting them along a dimension of similarity.

Cadherins are homophilic cell-cell adhesion molecules implicated in many fundamental processes, such as morphogenesis, cell growth, and differentiation. They accumulate at cell-cell contact sites and assemble into large macromolecular complexes named adherens junctions (AJs). Cadherin targeting and function are regulated by various cellular processes, many players of which remain to be uncovered. Here we identify the small GTPase Rab35 as a new regulator of cadherin trafficking and stabilization at cell-cell contacts in C2C12 myoblasts and HeLa cells. We find that Rab35 accumulates at cell-cell contacts in a cadherin-dependent manner. Knockdown of Rab35 or expression of a dominant-negative form of Rab35 impaired N- and M-cadherin recruitment to cell-cell contacts, their stabilization at the plasma membrane, and association with p120 catenin and led to their accumulation in transferrin-, clathrin-, and AP-2-positive intracellular vesicles. We also find that Rab35 function is required for PIP5KIγ accumulation at cell-cell contacts and phosphatidyl inositol 4,5-bisphosphate production, which is involved in cadherin stabilization at contact sites. Finally, we show that Rab35 regulates myoblast fusion, a major cellular process under the control of cadherin-dependent signaling. Taken together, these results reveal that Rab35 regulates cadherin-dependent AJ formation and myoblast fusion.

Attosecond experiments involving focusing of attosecond light pulses can suffer from a spread of the attosecond radiation both in space and time due to optical aberrations. We present a detailed numerical study of the distortions induced in the most common focusing geometries that make use of parabolic, spherical, toroidal and ellipsoidal mirrors. We deduce the consequences on the pulse duration and possible issues that could arise in applications of attosecond pulses. This should serve as a guideline for setting up attosecond focusing optics.

Electromyographical (EMG) signals have been frequently used to estimate human muscular torques. In the field of human-assistive robotics, these methods provide valuable information to provide effectively support to the user. However, their usability is strongly limited by the necessity of complex user-dependent and session-dependent calibration procedures, which confine their use to the laboratory environment. Nonetheless, an accurate estimate of muscle torque could be unnecessary to provide effective movement assistance to users. The natural ability of human central nervous system of adapting to external disturbances could compensate for a lower accuracy of the torque provided by the robot and maintain the movement accuracy unaltered, while the effort is reduced. In order to explore this possibility, in this paper we study the reaction of ten healthy subjects to the assistance provided through a proportional EMG control applied by an elbow powered exoskeleton. This system gives only a rough estimate of the user muscular torque but does not require any specific calibration. Experimental results clearly show that subjects adapt almost instantaneously to the assistance provided by the robot and can reduce their effort while keeping full control of the movement under different dynamic conditions (i.e., no alterations of movement accuracy are observed).

We present an automated segmentation method based on the analysis of plantar pressure signals recorded from two synchronized wireless foot insoles. Given the strict limits on computational power and power consumption typical of wearable electronic components, our aim is to investigate the capability of a Hidden Markov Model machine-learning method, to detect gait phases with different levels of complexity in the processing of the wearable pressure sensors signals. Therefore three different datasets are developed: raw voltage values, calibrated sensor signals and a calibrated estimation of total ground reaction force and position of the plantar center of pressure. The method is tested on a pool of 5 healthy subjects, through a leave-one-out cross validation. The results show high classification performances achieved using estimated biomechanical variables, being on average the 96%. Calibrated signals and raw voltage values show higher delays and dispersions in phase transition detection, suggesting a lower reliability for online applications.

We report on a simple method allowing one to decompose the duration of arbitrary ultrashort light pulses, potentially distorted by space-time coupling, into four elementary durations. Such a decomposition shows that, in linear optics, a spatio-temporal pulse can be stretched with respect to its Fourier limit by only three independent phenomena: nonlinear frequency dependence of the spectral phase over the whole spatial extent of the pulse, spectral amplitude inhomogeneities in space, and spectral phase inhomogeneities in space. We illustrate such a decomposition using numerical simulations of complex spatio-temporal femtosecond and attosecond pulses. Finally we show that the contribution of two of these three effects to the pulse duration is measurable without any spectral phase characterization.

The temporal coherence of an injection-seeded transient 18.9 nm molybdenum soft x-ray laser was measured using a wavefront division interferometer and compared to model simulations. The seeded laser is found to have a coherence time similar to that of the unseeded amplifier, ~1 ps, but a significantly larger degree of temporal coherence. The measured coherence time for the unseeded amplifier is only a small fraction of the pulsewidth, while in the case of the seeded laser it approaches full temporal coherence. The measurements confirm that the bandwidth of the solid target amplifiers is significantly wider than that of soft x-ray lasers that use gaseous targets, an advantage for the development of sub-picosecond soft x-ray lasers.

Objectives: (i) To define the current state of oral medicine clinical practice internationally, and (ii) to make recommendations for future modeling of the practice of oral medicine., Materials and Methods: A survey was designed by an international panel of oral medicine experts to assess the current state of oral medicine practice internationally. The survey was sent to oral medicine experts across the world, and responses were electronically stored and analyzed using descriptive statistics., Results: Two hundred respondents completed the survey representing 40 countries from six continents. The two most common settings for an oral medicine practice were in a hospital and a dental school. More than 88% of respondents considered management of oral mucosal disease, salivary dysfunction, oral manifestations of systemic diseases, and facial pain in the definition of oral medicine., Conclusions: (i) Oral medicine clinicians diagnose and manage a wide variety of orofacial conditions; (ii) There are significant differences in the definition of oral medicine clinical practice from country to country; (iii) India has the largest expansion of oral medicine services as defined by escalating numbers of clinicians within the specialty as compared with other countries; (iv) oral medicine practitioners have a wide range of professional responsibilities., (© 2011 John Wiley & Sons A/S.)

We report on the advanced amplitude and phase control of attosecond radiation allowed by specifically-designed multilayer XUV mirrors. We first demonstrate that such mirrors can compensate for the intrinsic chirp of the attosecond emission over a large bandwidth of more than 20 eV. We then show that their combination with metallic foils introduces a third-order dispersion that is adjustable through the mirror's incidence angle. This results in a controllable beating allowing the radiation to be shaped from a single to a series of sub-100 as pulses.

In this work, we present the development of an in-shoe device to monitor plantar pressure distribution for gait analysis. The device consists in a matrix of 64 sensitive elements, integrated with in-shoe electronics and battery which provide an high-frequency data acquisition, wireless transmission and an average autonomy of 7 hours in continuous working mode. The device is presented along with its experimental characterization and a preliminary validation on a healthy subject.

Electromyography (EMG) has been frequently proposed as the driving signal for controlling powered exoskeletons. Lot of effort has been spent to design accurate algorithms for muscular torque estimation, while very few studies attempted to understand to what extent an accurate torque estimate is indeed necessary to provide effective movement assistance through powered exoskeletons. In this study, we focus on the latter aspect by using a simple and "low-accuracy" torque estimate, an EMG-proportional control, to provide assistance through an elbow exoskeleton. Preliminary results show that subjects adapt almost instantaneously to the assistance provided by the exoskeleton and can reduce their effort while keeping full control of the movement.

In this article, we report that usual multilayer mirror configurations to focus attosecond pulses generate geometric aberrations and can significantly stretch pulses. The numerical simulations show that the effects can be strong enough to delay some parts of the pulses of an attosecond pulse train and make them interfere with the next pulses of the train. The influence of the numerical aperture on the pulse duration is also studied, showing that such effects can occur even with very low numerical apertures.

We demonstrate the use of a binary diffractive optical element in a very simple setup to convert the multilobed beam from a low fill factor array of coherent laser diodes into a quasi-Gaussian beam. The phase profile of the grating is determined with a phase retrieval algorithm. Experimentally, the conversion efficiency reaches more than 44%. We also establish that this setup can be used to make an effective measurement of the coherency of the laser array.

A new and alternative method to measure the interaction force between the user and a lower-limb gait rehabilitation exoskeleton is presented. Instead of using a load cell to measure the resulting interaction force, we propose a distributed measure of the normal interaction pressure over the whole contact area between the user and the machine. To obtain this measurement, a soft silicone tactile sensor is inserted between the limb and commonly used connection cuffs. The advantage of this approach is that it allows for a distributed measure of the interaction pressure, which could be useful for rehabilitation therapy assessment purposes, or for control. Moreover, the proposed solution does not change the comfort of the interaction; can be applied to connection cuffs of different shapes and sizes; and can be manufactured at a low cost. Preliminary results during gait assistance tasks show that this approach can precisely detect changes in the pressure distribution during a gait cycle.

Background: Competency-based education (CBE) has emerged in the health professions to address criticisms of contemporary approaches to training. However, the literature has no clear, widely accepted definition of CBE that furthers innovation, debate, and scholarship in this area., Aim: To systematically review CBE-related literature in order to identify key terms and constructs to inform the development of a useful working definition of CBE for medical education., Methods: We searched electronic databases and supplemented searches by using authors' files, checking reference lists, contacting relevant organizations and conducting Internet searches. Screening was carried out by duplicate assessment, and disagreements were resolved by consensus. We included any English- or French-language sources that defined competency-based education. Data were analyzed qualitatively and summarized descriptively., Results: We identified 15,956 records for initial relevancy screening by title and abstract. The full text of 1,826 records was then retrieved and assessed further for relevance. A total of 173 records were analyzed. We identified 4 major themes (organizing framework, rationale, contrast with time, and implementing CBE) and 6 sub-themes (outcomes defined, curriculum of competencies, demonstrable, assessment, learner-centred and societal needs). From these themes, a new definition of CBE was synthesized., Conclusion: This is the first comprehensive systematic review of the medical education literature related to CBE definitions. The themes and definition identified should be considered by educators to advance the field.

This work describes the neuro-robotics paradigm: the fusion of neuroscience and robotics. The fusion of neuroscience and robotics, called neuro-robotics, is fundamental to develop robotic systems to be used in functional support, personal assistance and neuro-rehabilitation. While usually the robotic device is considered as a "tool" for neuroscientific studies, a breakthrough is obtained if the two scientific competences and methodologies converge to develop innovative platforms to go beyond robotics by including novel models to design better robots. This paper describes three robotic platforms developed at the ARTS lab of Scuola Superiore Sant'Anna, implementing neuro-robotic design paradigm.

We use low coherence interferometry to investigate the depth structure of a complex multilayer stack reflector. The probing instrument is an interferometer based on a Fresnel's bi-mirror illuminated by relatively wide-band synchrotron undulator light near 13.5 nm. Simulations clearly confirm that our test object generates two back propagated signals that behave as if reflected on two effective planes. First results in this spectral range may open the way to a new physical approach to extreme ultraviolet sample characterization in the form of line-scan optical coherence tomography.

Headaches are a significant component of many facial pain syndromes. These facial pain/headache syndromes often have various etiologies, including neurologic, vascular, musculoskeletal, or combinations of vascular/musculoskeletal origins. Referred rhinologic headache, however, can be overlooked as a cause of facial pain in the dental literature. We report a case of nasal mucosal headache that presented as facial pain and include a review of the literature.

Burning mouth syndrome is a complicated, poorly understood, predominantly oral condition that affects more than 1 million people in the United States. Women are particularly affected by the condition; they are diagnosed with symptoms seven times more frequently than males. Burning mouth syndrome is characterized by a burning, painful sensation of the oral mucosa that most commonly involves the anterior tongue. Many precipitating factors to burning mouth syndrome have been proposed, and treatment addressing these factors has had limited success. Patients with burning mouth syndrome are more likely to be evaluated by physicians, and therefore it is advantageous for the physician to be familiar with this oral condition. This paper reviews burning mouth syndrome, associated causative factors, and treatment strategies for the physician.

Signs and symptoms of contact allergic reactions affecting the oral mucosa may mimic other common oral disorders, making diagnosis difficult. Patients frequently seek multiple consultations and do not receive the correct diagnosis or effective management. As intraoral contact allergy may be more prevalent than previously believed, a review of this topic is warranted. This article emphasizes signs and symptoms that suggest intraoral contact allergy, and the authors discuss the allergens that most frequently affect the oral mucosa.

Lupus erythematosus, or LE, is a connective tissue disease that affects a number of organ systems. Patients with this condition can experience several other serious conditions--bleeding, infection, endocarditis, adrenal insufficiency and mucocutaneous disease--that can affect the provision of dental care. The authors describe considerations for managing dental treatment of patients with LE.

The spleen plays an important role in the body's defense mechanism against microbial infections. However, trauma or diseases sometimes make removal of this important organ necessary, which predisposes patients to certain infections. This increased risk of infection and the underlying reason for the organ's removal both may affect the provision of dental care. This article reviews the structure and function of the spleen, conditions that may require its removal or cause its dysfunction, and provides considerations for dentists who care for asplenic patients.

An increasing number of Americans are living with end-stage renal disease. This disease has many implications for dentistry, in terms of oral manifestations and management of afflicted patients. The authors present pertinent information to help dentists treat patients who exhibit the oral and systemic manifestations of renal disease, from the onset of renal impairment through hemodialysis.

In this study the authors attempted to restore the coagulative fibrinolytic homeostasis that is compromised in peripheral vascular disease. Eleven patients with arterial disease, eleven with venous disease and seven healthy volunteers underwent oral treatment using 3 g of propionyl-L-carnitine divided into thrice daily doses for a period of 20 days. (1 g t.i.d.). This quaternaria amine is able to correct tissue hypoxia by increasing ATP and energy production and has the capacity to prevent alterations in endothelial membrane permeability. The authors observed a significant increase of t-PA synthesis on the 10th day of therapy in the arterial disease and control groups. All three groups showed a significant increase in t-PA synthesis on the 20th day of therapy. A significant decrease in PAI-1 activity was observed on the 10th and on the 20th day of therapy in both the patient groups, but not in the control group. Although the exact pathological mechanisms of peripheral vascular disease are complex and in many aspects still unknown, it is now absolutely certain that there is a pathogenetic role of functional imbalances. An important part is played by the reduction in t-PA synthesis and the increase in PAI-1 activity, and the authors conclude that it is necessary to use pharmaceutical substances to restore proper equilibrium.