A metastatic neuroendocrine anaplastic small cell tumor in a patient with multiple endocrine neoplasia type 1 syndrome : assessment of disease status and response to doxorubicin, cyclophosphamide, etoposide chemotherapy through scintigraphic imaging with 111In-pentetreotide

Extrapulmonary small cell and small cell neuroendocrine tumors of unknown primary site are, in general, aggressive neoplasms with a short median survival. Like small cell lung cancer (SCLC), they often are responsive to chemotherapy and radiotherapy. Small cell lung cancer and well differentiated neuroendocrine carcinomas of the gastrointestinal tract and pancreas tend to express somatostatin receptors. These tumors may be localized in patients by scintigraphic imaging using radiolabeled somatostatin analogues. A patient with an anaplastic neuroendocrine small cell tumor arising on a background of multiple endocrine neoplasia type 1 syndrome is reported. The patient had a known large pancreatic gastrinoma and previously treated parathyroid adenopathy. At presentation, there was small cell cancer throughout the liver and skeleton. Imaging with a radiolabeled somatostatin analogue, 111In- pentetreotide (Mallinckrodt Medical B. V., Petten, Holland), revealed all sites of disease detected by routine biochemical and radiologic methods. After six cycles of chemotherapy with doxorubicin, cyclophosphamide, and etoposide, there was almost complete clearance of the metastatic disease. 111In-pentetreotide scintigraphy revealed uptake consistent with small areas of residual disease in the liver, the abdomen (in mesenteric lymph nodes), and posterior thorax (in a rib). The primary gastrinoma present before the onset of the anaplastic small cell cancer showed no evidence of response to the treatment. The patient remained well for 1 year and then relapsed with brain, lung, liver, and skeletal metastases. Despite an initial response to salvage radiotherapy and chemotherapy with carboplatin and dacarbazine, the patient died 6 months later.

Association between maternal depressive symptoms in the early postnatal period and responsiveness in feeding at child age 2 years

Maternal depression is a known risk factor for poor outcomes for children. Pathways to these poor outcomes relate to reduced maternal responsiveness or sensitivity to the child. Impaired responsiveness potentially impacts the feeding relationship and thus may be a risk factor for inappropriate feeding practices. The aim of this study was to examine the longitudinal relationships between self-reported maternal post-natal depressive symptoms at child age 4 months and feeding practices at child age 2 years in a community sample. Participants were Australian first-time mothers allocated to the control group of the NOURISH randomized controlled trial when infants were 4 months old. Complete data from 211 mothers (of 346 allocated) followed up when their children were 2 years of age (51% girls) were available for analysis. The relationship between Edinburgh Postnatal Depression Scale (EPDS) score (child age 4 months) and child feeding practices (child age 2 years) was tested using hierarchical linear regression analysis adjusted for maternal and child characteristics. Higher EPDS score was associated with less responsive feeding practices at child age 2 years: greater pressure [β = 0.18, 95% confidence interval (CI): 0.04–0.32, P = 0.01], restriction (β = 0.14, 95% CI: 0.001–0.28, P = 0.05), instrumental (β = 0.14, 95% CI: 0.005–0.27, P = 0.04) and emotional (β = 0.15, 95% CI: 0.01–0.29, P = 0.03) feeding practices (ΔR2 values: 0.02–0.03, P < 0.05). This study provides evidence for the proposed link between maternal post-natal depressive symptoms and lower responsiveness in child feeding. These findings suggest that the provision of support to mothers experiencing some levels of depressive symptomatology in the early post-natal period may improve responsiveness in the child feeding relationship.

Learner-focused evaluation cycles : facilitating learning using feedforward, concurrent and feedback evaluation

There is a growing trend to offer students learning opportunities that are flexible, innovative and engaging. As educators embrace student-centred agile teaching and learning methodologies, which require continuous reflection and adaptation, the need to evaluate students’ learning in a timely manner has become more pressing. Conventional evaluation surveys currently dominate the evaluation landscape internationally, despite recognition that they are insufficient to effectively evaluate curriculum and teaching quality. Surveys often: (1) fail to address the issues for which educators need feedback, (2) constrain student voice, (3) have low response rates and (4) occur too late to benefit current students. Consequently, this paper explores principles of effective feedback to propose a framework for learner-focused evaluation. We apply a three-stage control model, involving feedforward, concurrent and feedback evaluation, to investigate the intersection of assessment and evaluation in agile learning environments. We conclude that learner-focused evaluation cycles can be used to guide action so that evaluation is not undertaken simply for the benefit of future offerings, but rather to benefit current students by allowing ‘real-time’ learning activities to be adapted in the moment. As a result, students become co-producers of learning and evaluation becomes a meaningful, responsive dialogue between students and their instructors.

Educating for digital futures : what the learning strategies of digital content professionals can teach higher education

Beginning in the second half of the 20th century, ICTs transformed many societies from industrial societies in which manufacturing was the central focus, into knowledge societies in which dealing effectively with data and information has become a central element of work (Anderson, 2008). To meet the needs of the knowledge society, universities must reinvent their structures and processes, their curricula and pedagogic practices. In addition to this, of course higher education is itself subject to the sweeping influence of ICTs. But what might effective higher education look like in the 21st century? In designing higher education systems and learning experiences which are responsive to the learning needs of the future and exploit the possibilities offered by ICTs, we can learn much from the existing professional development strategies of people who are already successful in 21st century fields, such as digital media. In this study, I ask: (1) what are the learning challenges faced by digital media professionals in the 21st century? (2) what are the various roles of formal and informal education in their professional learning strategies at present? (3) how do they prefer to acquire needed capabilities? In-depth interviews were undertaken with successful Australian digital media professionals working in micro businesses and SMEs to answer these questions. The strongest thematic grouping that emerged from the interviews related to the need for continual learning and relearning because of the sheer rate of change in the digital media industries. Four dialectical relationships became apparent from the interviewees’ commentaries around the learning imperatives arising out of the immense and continual changes occurring in the digital content industries: (1) currency vs best practice (2) diversification vs specialisation of products and services (3) creative outputs vs commercial outcomes (4) more learning opportunities vs less opportunity to learn. These findings point to the importance of ‘learning how to learn’ as a 21st century capability. The interviewees were ambivalent about university courses as preparation for professional life in their fields. Higher education was described by several interviewees as having relatively little value-add beyond what one described as “really expensive credentialling services.” For all interviewees in this study, informal learning strategies were the preferred methods of acquiring the majority of knowledge and skills, both for ongoing and initial professional development. Informal learning has no ‘curriculum’ per se, and tends to be opportunistic, unstructured, pedagogically agile and far more self-directed than formal learning (Eraut, 2004). In an industry impacted by constant change, informal learning is clearly both essential and ubiquitous. Inspired by the professional development strategies of the digital media professionals in this study, I propose a 21st century model of the university as a broad, open learning ecology, which also includes industry, professionals, users, and university researchers. If created and managed appropriately, the university learning network becomes the conduit and knowledge integrator for the latest research and industry trends, which students and professionals alike can access as needed.

An extracellular signal-regulated kinase 2 survival pathway mediates resistance of human mesothelioma cells to asbestos-induced injury

We hypothesized that normal human mesothelial cells acquire resistance to asbestos-induced toxicity via induction of one or more epidermal growth factor receptor (EGFR) - linked survival pathways (phosphoinositol-3-kinase/AKT/ mammalian target of rapamycin and extracellular signal - regulated kinase [ERK] 1/2) during simian virus 40 (SV40) transformation and carcinogenesis. Both isolated HKNM-2 mesothelial cells and a telomerase-immortalized mesothelial line (LP9/TERT-1) were more sensitive to crocidolite asbestos toxicity than an SV40 Tag-immortalized mesothelial line (MET5A) and malignant mesothelioma cell lines (HMESO and PPM Mill). Whereas increases in phosphorylation of AKT (pAKT) were observed in MET5A cells in response to asbestos, LP9/TERT-1 cells exhibited dose-related decreases in pAKT levels. Pretreatment with an EGFR phosphorylation or mitogen-activated protein kinase kinase 1/2 inhibitor abrogated asbestos-induced phosphorylated ERK (pERK) 1/2 levels in both LP9/TERT-1 and MET5A cells as well as increases in pAKT levels in MET5A cells. Transient transfection of small interfering RNAs targeting ERK1, ERK2, or AKT revealed that ERK1/2 pathways were involved in cell death by asbestos in both cell lines. Asbestos-resistant HMESO or PPM Mill cells with high endogenous levels of ERKs or AKT did not show dose-responsive increases in pERK1/ERK1, pERK2/ERK2, or pAKT/AKT levels by asbestos. However, small hairpin ERK2 stable cell lines created from both malignant mesothelioma lines were more sensitive to asbestos toxicity than shERK1 and shControl lines, and exhibited unique, tumor-specific changes in endogenous cell death - related gene expression. Our results suggest that EGFR phosphorylation is causally linkedto pERK and pAKT activation by asbestos in normal and SV40 Tag - immortalized human mesothelial cells. They also indicate that ERK2 plays a role in modulating asbestos toxicity by regulating genes critical to cell injury and survival that are differentially expressed in human mesotheliomas.

Developing cultural responsiveness in environmental design students through digital storytelling and photovoice

As the Latino population in the United States grows, it will become increasingly important for undergraduate students in environmental design and related disciplines to become more culturally responsive and learn how to understand and address challenges faced by population groups, such as Latino youth. To this end, we involved environmental design undergraduate students at the University of Colorado in a service-learning class to mentor Latino youth in the creation of multimedia narratives using photovoice and digital storytelling techniques. The introduction of technology was used as a bridge between the two groups and to provide a platform for the Latino youth to reveal their community experiences. Based on focus group results, we describe the impact on the undergraduate students and provide recommendations for similar programs that can promote cultural responsiveness through the use of digital technology and prepare environmental design students to work successfully in increasingly diverse communities.

Experience, recursive awareness and understanding in autism spectrum disorders : insights of parents and teachers in Singapore

Provision of an individually responsive education requires a comprehensive understanding of the inner worlds of learners, such as their feelings and thoughts. However, this is difficult to achieve when learners, such as those with Autism Spectrum Disorders (ASD) and cognitive difficulties, have problems with communication. To address this issue, the current exploratory descriptive study sought the views of 133 Singaporean parents and teachers of school-age learners with ASD and cognitive difficulties regarding the inner experience of their children and students. The findings highlight the variety of abilities and difficulties found in how these learners experience their own mental states and understand those of others. These abilities and difficulties are characterized according to type of mental state and analysed in line with three qualia, those of experience, recursive awareness and understanding. The findings indicate that learners show a greater awareness of their own mental states compared to their ability to understand these same mental states in others. Educational implications are discussed.

Improving public spaces for young people : the contribution of participatory research

The objectives of this chapter are to examine the contribution of public spaces to the wellbeing of young people and how participatory action research can be used as a process tool for contextually responsive, collaborative, iterative and multi-method community level practice. The addition of a spatial frame to practice can open up unexpected alliances and opportunities for enhancing the wellbeing of people.

Understanding VET teachers’challenges in providing quality education to international students

In the past fifteen years, increasing attention has been given to the role of Vocational Education and Training (VET) in attracting large numbers of international students and its contribution to the economic development of Australia. This trend has given rise to many challenges in vocational education, especially with regard to providing quality education that ensures international students stay in Australia is a satisfactory experience. Teaching and learning are continuously scrutinised, and teaching quality and student assessment are subject to regular audit (Takerei, 2010). VET teachers are key stakeholders in international education and share responsibility for ensuring international students gain quality learning experiences and positive outcomes; however, their experiences are generally not well understood. Therefore, this paper reports on a study which responded to this research gap and investigated particular challenges that VET teachers experience when teaching international students. The research participants were 15 teachers from several public and private VET institutions in Brisbane, Australia. The method involved responsive interviewing and inductive data analysis to identify and categorize teachers’ challenges and dilemmas. After briefly outlining the background of the research approach, this paper presents findings about challenges that VET teachers’ experienced while teaching international students. The aim of the paper is to explore VET teachers’ perspectives in order to contribute essential understandings that contribute to a holistic approach to vocational education of international students. It reveals that the teachers experienced challenges of three main types: professional, personal and educational.

Biological markers of stress in pediatric acute burn injury

BACKGROUND Burns and their associated wound care procedures evoke significant stress and anxiety, particularly for children. Little is known about the body's physiological stress reactions throughout the stages of re-epithelialization following an acute burn injury. Previously, serum and urinary cortisol have been used to measure stress in burn patients, however these measures are not suitable for a pediatric burn outpatient setting. AIM To assess the sensitivity of salivary cortisol and sAA in detecting stress during acute burn wound care procedures and to investigate the body's physiological stress reactions throughout burn re-epithelialization. METHODS Seventy-seven participants aged four to thirteen years who presented with an acute burn injury to the burn center at the Royal Children's Hospital, Brisbane, Australia, were recruited between August 2011 and August 2012. RESULTS Both biomarkers were responsive to the stress of burn wound care procedures. sAA levels were on average 50.2U/ml higher (p<0.001) at 10min post-dressing removal compared to baseline levels. Salivary cortisol levels showed a blunted effect with average levels at ten minutes post dressing removal decreasing by 0.54nmol/L (p<0.001) compared to baseline levels. sAA levels were associated with pain (p=0.021), no medication (p=0.047) and Child Trauma Screening Questionnaire scores at three months post re-epithelialization (p=0.008). Similarly, salivary cortisol was associated with no medication (p<0.001), pain scores (p=0.045) and total body surface area of the burn (p=0.010). CONCLUSION Factors which support the use of sAA over salivary cortisol to assess stress during morning acute burn wound care procedures include; sensitivity, morning clinic times relative to cortisol's diurnal peaks, and relative cost.

Progesterone activates multiple innate immune pathways inChlamydia trachomatis-Infected endocervical cells

Problem Susceptibility to Chlamydia trachomatis infection is increased by oral con- traceptives and modulated by sex hormones. We therefore sought to determine the effects of female sex hormones on the innate immune response to C. trachomatis infection. Method of study ECC-1 endometrial cells, pre-treated with oestradiol or progesterone, were infected with C. trachomatis and the host transcriptome analysed by Illumina Sentrix HumanRef-8 microarray. Primary endocervical epithe- lial cells, prepared at either the proliferative or secretory phase of the menstrual cycle, were infected with C. trachomatis and cytokine gene expression determined by quantitative RT-PCR analysis. Results Chlamydia trachomatis yield from progesterone-primed ECC-1 cells was significantly reduced compared with oestradiol-treated cells. Genes upregulated in progesterone-treated and Chlamydia-infected cells only included multiple CC and CXC chemokines, IL-17C, IL-29, IL-32, TNF-a, DEFB4B, LCN2, S100A7-9, ITGAM, NOD2, JAK1, IL-6ST, type I and II interferon receptors, numerous interferon-stimulated genes and STAT6. CXCL10, CXCL11, CX3CL1 and IL-17C, which were also upregu- lated in infected secretory-stage primary cells, and there was a trend towards higher levels of immune mediators in infected secretory-phase compared with proliferative-phase cells. Conclusion Progesterone treatment primes multiple innate immune pathways in hormone-responsive epithelial cells that could potentially increase resis- tance to chlamydial infection.

The role of the Eph and ephrin proteins in prostate cancer

Prostate cancer is the most commonly diagnosed malignancy and the second leading cause of cancer related deaths in Australian men. Treatment in the early stages of the disease involves surgery, radiation and/or hormone therapy. However, in late stages of the disease these treatments are no longer effective and only palliative care is available. Therefore, there is a focus on exploration of novel therapies to increase survival and treatment efficacy. Advanced prostate cancer is characterised by bone or other distant metastasis. Spreading of the primary tumour to a secondary location is a complex process requiring an initial loss in cell-cell adhesion followed by increased cell migration and invasion. One gene family that has been known to affect cell-to-cell contact in other model systems are the Eph receptor tyrosine kinases. They are the largest family of receptor tyrosine kinases made up of 14 vertebrate Eph receptors that bind to nine cell membrane bound ephrin ligands. Eph-ephrin interaction is crucial in regulating cell behaviour in developmental processes and it is now thought that the underlying mechanisms involved in development may also be involved in cancer. Aberrant expression has been reported in many human malignancies including prostate cancer. Furthermore, expression has been linked with metastasis and poor prognosis in other tumour models. This study explores the potential role of the Eph receptor family in prostate cancer, in particular the roles of EphA2, EphA3 and ephrin-A5. Gene expression profiles were established for the Eph family in a series of prostate cancer cell lines using quantitative real time RT-PCR. A smaller subset of the most prominently expressed genes was chosen to screen a cohort of clinical samples. Elevated levels of EphA2, EphA3 and their ligands, ephrin-A1 and ephrin-A5 were observed in individual cell lines. Interestingly high EphA3 expression was observed in the androgen responsive cell lines while EphA2 was more prominent in the androgen independent cell lines. However, studies using 5-dihydrotestosterone suggest that EphA3 expression in not regulated by androgen. Cells expressing EphA2 showed a greater ability for migration and invasion while cells expressing EphA3 showed poor migration and invasion. Forced expression of EphA2 in the LNCaP cell line resulted in a more invasive phenotype while forced expression of EphA3 in the PC-3 cell line suggests a possible negative effect for EphA3 on cell migration and invasion. Cell signalling studies show activation of EphA2 decreases activity of proteins thought to be involved in pathways regulating cell movement including Akt, Src and FAK. Changes to the activation status of Rho family members, including RhoA and Rac1, associated with reorganisation of the actin cytoskeleton, an important part of cell migration was also observed. As a result, activation of EphA2 in PC-3 cells resulted in a less invasive phenotype. A novel finding in this study was the discovery of a combination of two EphA2 Mabs able to activate EphA2. Preliminary results show a potential for this antibody combination to reduce prostate cancer invasion in vitro. A unique aspect of Eph-ephrin interaction is the resulting bi-directional signalling that occurs through both the receptor and ligand. In this study a potential role for ephrin-A5 mediated signalling in prostate cancer was observed. LNCaP cells express high levels of EphA3 and its high affinity ligand ephrin-A5. In stripe assays, used to study guidance cues, LNCaP cells show strong attraction/migration to EphA3-Fc stripes but not ephrin-A5-Fc stripes suggesting ephrin-A5 mediated reverse cell signalling is involved. Knockdown of ephrin-A5 using shRNA resulted in a decrease in attraction/migration to EphA3-Fc stripes. Furthermore a reduction in proliferation was also observed in vitro. A subcutaneous xenograft model using ephrin-A5 shRNA cells versus controls showed a decrease in tumour formation. This study demonstrates a difference in EphA2 and EphA3 function in prostate cancer migration/invasion and a potential role for ephrin-A5 in prostate cancer cell adhesion and growth.

Sounds From The Empty City (soundtrack)

These wordless songs were composed as music first, and soundtrack second. There is a difference. A soundtrack will always be connected with whatever it is accompanying. Music doesn’t neccessarily need to reference anything else. The Empty City transformed a picture book into a non-verbal performance combining the live and animated. Without spoken words the show would dance on the dangerous intersection of music, image and action. In both theatre and film (and this production drew on both traditions) soundtrack and music are often added on at the end when everything’s been pre-determined, a passive, responsive mode for such a powerful artform. It’s literally added in ‘post’. In The Empty City, music was present from its inception and grew with the show. It was active in process and product. It frequently led rehearsals and shaped other key decisions in virtual and live performance. Rather than tailor-make music towards pre-determined moments, independent compositions created without specific reference to narrative experimented with the creation of a flock of small musical pieces. I was interested in seeing how they flew and where they roosted, rather than having them born and raised in (narrative) captivity. The sonic palette is largely acoustic, incorporating ukulele, prepared piano and supported by a range of other elements tending towards electronica. Eventually more than seventy pieces of music were made for this show, twice the number used. These pieces were then placed in relation to the emerging scenes, then adapted in duration, texture and progression to develop a relationship with the scene. In this way, music (even when it’s synced) has a conversation with a performance, an exchange that may result in surprise rather than fulfillment of expectation. Leitmotif emerged from loops and layers, as the pieces of music ‘conversed’ with each other, rather than being premeditated and imposed. Nineteen of these tracks are compiled for this release, which finds the compositions (which progressed through many versions) poised at the moment between their fullest iteration as ‘music’ and their editing and full incorporation into a sychronised soundtrack. They are released as the began: as 'music-alone' (Kivy) In picture-book writing, the mutual interplay of text and image is sometimes referred to as interanimation , and this is the kind of symbiosis this project sought in the creation of the soundtrack. Reviewers of the noted the important role of the soundtrack in two separate productions of The Empty City: “The original score…takes centre stage” (Borhani, 2013) “…swept up in its repetition of sounds and images, like a Bach fugue” (Zampatti, 2013)

Integrin αvβ3 mediates upregulation of epidermal growth-factor receptor expression and activity in human ovarian cancer cells

Upon overexpression of integrin αvβ3 and its engagement by vitronectin, we previously showed enhanced adhesion, proliferation, and motility of human ovarian cancer cells. By studying differential expression of genes possibly related to these tumor biological events, we identified the epidermal growth-factor receptor (EGF-R) to be under control of αvβ3 expression levels. Thus in the present study we characterized αvβ3-dependent changes of EGF-R and found significant upregulation of its expression and activity which was reflected by prominent changes of EGF-R promoter activity. Upon disruption of DNA-binding motifs for the transcription factors p53, ETF, the repressor ETR, p50, and c-rel, respectively, we sought to identify DNA elements contributing to αvβ3-mediated EGF-R promoter induction. Both, the p53- and ETF-mutant, while exhibiting considerably lower EGF-R promoter activity than the wild type promoter, retained inducibility by αvβ3. Mutation of the repressor motif ETR, as expected, enhanced EGF-R promoter activity with a further moderate increase upon αvβ3 elevation. The p50-mutant displayed EGF-R promoter activity almost comparable to that of the wild type promoter with no impairment of induction by αvβ3. However, the activity of an EGF-R promoter mutant displaying a disrupted c-rel-binding motif did not only prominently decline, but, moreover, was not longer responsive to enhanced αvβ3, involving this DNA element in αvβ3-dependent EGF-R upregulation. Moreover, αvβ3 did not only increase the EGF-R but, moreover, also led to obvious co-clustering on the cancer cell surface. By studying αvβ3/EGF-R-effects on the focal adhesion kinase (FAK) and the mitogen activated protein kinases (MAPK) p44/42 (erk−1/erk−2), having important functions in synergistic crosstalk between integrins and growth-factor receptors, we found for both significant enhancement of expression and activity upon αvβ3/VN interaction and cell stimulation by EGF. Upregulation of the EGF-R by integrin αvβ3, both receptor molecules with a well-defined role as targets for cancer treatment, might represent an additional mechanism to adapt synergistic receptor signaling and crosstalk in response to an altered tumor cell microenvironment during ovarian cancer progression.

Fostering rapid transitions to education for sustainable development through a whole-system approach to curriculum and organizational change

Despite decades of attempts to embed sustainability within higher education, literature clearly suggests that highly regulated disciplines such as engineering have been relatively slow to incorporate sustainability knowledge and skill areas, and are generally poorly prepared to do so. With current efforts, it is plausible that sustainability could take another two decades to be embedded within the curriculum. Within this context, this paper presents a whole system approach to implement systematic, intentional and timely curriculum renewal that is responsive to emerging challenges and opportunities, encompassing curriculum and organizational change. The paper begins by considering the evolution of curriculum renewal processes, documenting a number of whole system considerations that have been empirically distilled from literature, case studies, pilot trials, and a series of workshops with built environment educators from around the world over the last decade. The paper outlines a whole-of-institution curriculum renewal approach to embedding sustainability knowledge and skills within the DNA of the institutional offerings. The paper concludes with a discussion of research and practice implications for the field of education research, within and beyond higher education.