Frequent activating FGFR2 mutations in endometrial carcinomas parallel germline mutations associated with craniosynostosis and skeletal dysplasia syndromes

Endometrial carcinoma is the most common gynecological malignancy in the United States. Although most women present with early disease confined to the uterus, the majority of persistent or recurrent tumors are refractory to current chemotherapies. We have identified a total of 11 different FGFR2 mutations in 3/10 (30%) of endometrial cell lines and 19/187 (10%) of primary uterine tumors. Mutations were seen primarily in tumors of the endometrioid histologic subtype (18/115 cases investigated, 16%). The majority of the somatic mutations identified were identical to germline activating mutations in FGFR2 and FGFR3 that cause Apert Syndrome, Beare-Stevenson Syndrome, hypochondroplasia, achondroplasia and SADDAN syndrome. The two most common somatic mutations identified were S252W (in eight tumors) and N550K (in five samples). Four novel mutations were identified, three of which are also likely to result in receptor gain-of-function. Extensive functional analyses have already been performed on many of these mutations, demonstrating they result in receptor activation through a variety of mechanisms. The discovery of activating FGFR2 mutations in endometrial carcinoma raises the possibility of employing anti-FGFR molecularly targeted therapies in patients with advanced or recurrent endometrial carcinoma.

The subjective experience of negative symptoms : characteristics of emotional withdrawal

According to the diagnosis of schizophrenia in the DSM-IV-TR (American Psychiatric Association, 2000), negative symptoms are those personal characteristics that are thought to be reduced from normal functioning, while positive symptoms are aspects of functioning that exist as an excess or distortion of normal functioning. Negative symptoms are generally considered to be a core feature of people diagnosed with schizophrenia. However, negative symptoms are not always present in those diagnosed, and a diagnosis can be made with only negative or only positive symptoms, or with a combination of both. Negative symptoms include an observed loss of emotional expression (affective flattening), loss of motivation or self directedness (avolition), loss of speech (alogia), and also a loss of interests and pleasures (anhedonia). Positive symptoms include the perception of things that others do not perceive (hallucinations), and extraordinary explanations for ordinary events (delusions) (American Psychiatric Association, 2000). Both negative and positive symptoms are derived from watching the patient and thus do not consider the patient’s subjective experience. However, aspects of negative symptoms, such as observed affective flattening are highly contended. Within conventional psychiatry, the absence of emotional expression is assumed to coincide with an absence of emotional experience. Contrasting research findings suggests that patients who were observed to score low on displayed emotional expression, scored high on self ratings of emotional experience. Patients were also observed to be significantly lower on emotional expression when compared with others (Aghevli, Blanchard, & Horan, 2003; Selton, van der Bosch, & Sijben, 1998). It appears that there is little correlation between emotional experience and emotional expression in patients, and that observer ratings cannot help us to understand the subjective experience of the negative symptoms. This chapter will focus on research into the subjective experiences of negative symptoms. A framework for these experiences will be used from the qualitative research findings of the primary author (Le Lievre, 2010). In this study, the primary author found that subjective experiences of the negative symptoms belonged to one of the two phases of the illness experience; “transitioning into emotional shutdown” or “recovering from emotional shutdown”. This chapter will use the six themes from the phase of “transitioning into emotional shutdown”. This phase described the experience of turning the focus of attention away from the world and onto the self and the past, thus losing contact with the world and others (emotional shutdown). Transitioning into emotional shutdown involved; “not being acknowledged”, “relational confusion”, “not being expressive”, “reliving the past”, “detachment”, and “no sense of direction” (Le Lievre, 2010). Detail will be added to this framework of experience from other qualitative research in this area. We will now review the six themes that constitute a “transition into emotional shutdown” and corresponding previous research findings.

A people-to-people recommendation system using Tensor Space Models

Existing recommendation systems often recommend products to users by capturing the item-to-item and user-to-user similarity measures. These types of recommendation systems become inefficient in people-to-people networks for people to people recommendation that require two way relationship. Also, existing recommendation methods use traditional two dimensional models to find inter relationships between alike users and items. It is not efficient enough to model the people-to-people network with two-dimensional models as the latent correlations between the people and their attributes are not utilized. In this paper, we propose a novel tensor decomposition-based recommendation method for recommending people-to-people based on users profiles and their interactions. The people-to-people network data is multi-dimensional data which when modeled using vector based methods tend to result in information loss as they capture either the interactions or the attributes of the users but not both the information. This paper utilizes tensor models that have the ability to correlate and find latent relationships between similar users based on both information, user interactions and user attributes, in order to generate recommendations. Empirical analysis is conducted on a real-life online dating dataset. As demonstrated in results, the use of tensor modeling and decomposition has enabled the identification of latent correlations between people based on their attributes and interactions in the network and quality recommendations have been derived using the 'alike' users concept.

Design and implementation of a virtual world training simulation of ICU first hour handover processes

Nursing training for an Intensive Care Unit (ICU) is a resource intensive process. High demands are made on staff, students and physical resources. Interactive, 3D computer simulations, known as virtual worlds, are increasingly being used to supplement training regimes in the health sciences; especially in areas such as complex hospital ward processes. Such worlds have been found to be very useful in maximising the utilisation of training resources. Our aim is to design and develop a novel virtual world application for teaching and training Intensive Care nurses in the approach and method for shift handover, to provide an independent, but rigorous approach to teaching these important skills. In this paper we present a virtual world simulator for students to practice key steps in handing over the 24/7 care requirements of intensive care patients during the commencing first hour of a shift. We describe the modelling process to provide a convincing interactive simulation of the handover steps involved. The virtual world provides a practice tool for students to test their analytical skills with scenarios previously provided by simple physical simulations, and live on the job training. Additional educational benefits include facilitation of remote learning, high flexibility in study hours and the automatic recording of a reviewable log from the session. To the best of our knowledge, we believe this is a novel and original application of virtual worlds to an ICU handover process. The major outcome of the work was a virtual world environment for training nurses in the shift handover process, designed and developed for use by postgraduate nurses in training.

Benign Epilepsy with Centro-temporal Spikes: Spike Triggered fMRI Shows Somato-sensory Cortex Activity

Summary:  Objective: We performed spike triggered functional MRI (fMRI) in a 12 year old girl with Benign Epilepsy with Centro-temporal Spikes (BECTS) and left-sided spikes. Our aim was to demonstrate the cerebral origin of her interictal spikes. Methods: EEG was recorded within the 3 Tesla MRI. Whole brain fMRI images were acquired, beginning 2–3 seconds after spikes. Baseline fMRI images were acquired when there were no spikes for 20 seconds. Image sets were compared with the Student's t-test. Results: Ten spike and 20 baseline brain volumes were analysed. Focal activiation was seen in the inferior left sensorimotor cortex near the face area. The anterior cingulate was more active during baseline than spikes. Conclusions: Left sided epileptiform activity in this patient with BECTS is associated with fMRI activation in the left face region of the somatosensory cortex, which would be consistent with the facial sensorimotor involvement in BECT seizures. The presence of BOLD signal change in other regions raises the possibility that the scalp recorded field of this patient with BECTs may reflect electrical change in more than one brain region.

Myoinositol Abnormalities in Temporal Lobe Epilepsy

Purpose: This study used magnetic resonance spectroscopy (MRS) to examine metabolite abnormalities in the temporal and frontal lobe of patients with temporal lobe epilepsy (TLE) of differing severity. Methods: We investigated myoinositol in TLE by using short-echo MRS in 34 TLE patients [26 late onset (LO-TLE), eight hippocampal sclerosis (HS-TLE)], and 16 controls. Single-voxel short-echo (35 ms) MR spectra of temporal and frontal lobes were acquired at 1.5 T and analyzed by using LCModel. Results: The temporal lobe ipsilateral to seizure origin in HS-TLE, but not LO-TLE, had reduced N-acetylaspartate (NA) and elevated myoinositol (MI; HS-TLE NA, 7.8 ± 1.9 mM, control NA, 9.2 ± 1.3 mM; p < 0.05; HS-TLE MI, 6.1 ± 1.6 mM, control mI 4.9 ± 0.8 mM, p< 0.05). Frontal lobe MI was low in both patient groups (LO-TLE, 4.3 ± 0.8 mM; p < 0.05; HS-TLE, 3.6 ±.05 mM; p < 0.001; controls, 4.8 ± 0.5 mM). Ipsilateral frontal lobes had lower MI (3.8 ± 0.7 mM; p < 0.01) than contralateral frontal lobes (4.3 ± 0.8 mM; p < 0.05). Conclusions: MI changes may distinguish between the seizure focus, where MI is increased, and areas of seizure spread where MI is decreased.

Design overview of USDL

Enabling web-based service networks and ecosystems requires a way of describing services by a "commercial envelope" as discussed in Chapter 1. A uniform conception of services across all walks of life (including technical services) is required capturing business, operational and technical aspects. Therefore, our proposed Unified Service Description Language (USDL) particularly draws from and generalizes the best-of-breed approaches presented in Part I. The following chapter presents the design rationale of USDL where the different aspects are put in a framework of descriptions requirements. This is followed by the subsequent chapters of this part that provide details on specific aspects such as pricing or legal issues.

Health professionals’ perspectives on information provision for patients with brain tumours and their families

A significant number of patients diagnosed with primary brain tumours report unmet information needs. Using concept mapping methodology, this study aimed to identify strategies for improving information provision, and to describe factors that health professionals understood to influence their provision of information to patients with brain tumours and their families. Concept mapping is a mixed methods approach that uses statistical methods to represent participants’ perceived relationships between elements as conceptual maps. These maps, and results of associated data collection and analyses, are used to extract concepts involved in information provision to these patients. Thirty health professionals working across a range of neuro-oncology roles and settings participated in the concept mapping process. Participants rated a care coordinator as the most important strategy for improving brain tumour care, with psychological support as a whole rated as the most important element of care. Five major themes were identified as facilitating information provision: health professionals’ communication skills, style and attitudes; patients’ needs and preferences; perceptions of patients’ need for protection and initiative; rapport and continuity between patients and health professionals; and the nature of the health care system. Overall, health professionals conceptualised information provision as ‘individualised’, dependent on these interconnected personal and environmental factors.

Perceptions of clinical safety climate of the multicultural nursing workforce in Saudi Arabia : a cross-sectional survey

Purpose The purpose of this study is to explore the safety climate perceptions of the multicultural nursing workforce, and to investigate the influence of diversity of the multicultural nursing workforce on clinical safety in a large tertiary hospital in Saudi Arabia. Background Working in a multicultural environment is challenging. Each culture has its own unique characteristics and dimensions that shape the language, lifestyle, beliefs, values, customs, traditions, and patterns of behaviour, which expatriate nurses must come to terms with. However, cultural diversity in the health care environment can potentially affect the quality of care and patient safety. Method A mixed-method case study (survey, interview and document analysis) was employed. A primary study phase entailed the administration of the Safety Climate Survey (SCS). A population sampling strategy was used and 319 nurses participated, yielding a 76.8% response rate. Descriptive and inferential statistics (Kruskal–Wallis test) were used to analyse survey data. Results The data revealed the nurses’ perceptions of the clinical safety climate in this multicultural environment was unsafe, with a mean score of 3.9 out of 5. No significant difference was found between the age groups, years of nursing experience and their perceptions of the safety climate in this context. A significant difference was observed between the national background categories of nurses and perceptions of safety climate. Conclusion Cultural diversity within the nursing workforce could have a significant influence on perceptions of clinical safety. These findings have the potential to inform policy and practice related to cultural diversity in Saudi Arabia.