RNA interference-mediated c-MYC inhibition prevents cell growth and decreases sensitivity to radio- and chemotherapy in childhood medulloblastoma cells

BACKGROUND: With current treatment strategies, nearly half of all medulloblastoma (MB) patients die from progressive tumors. Accordingly, the identification of novel therapeutic strategies remains a major goal. Deregulation of c-MYC is evident in numerous human cancers. In MB, over-expression of c-MYC has been shown to cause anaplasia and correlate with unfavorable prognosis. METHODS: To study the role of c-MYC in MB biology, we down-regulated c-MYC expression by using small interfering RNA (siRNA) and investigated changes in cellular proliferation, cell cycle analysis, apoptosis, telomere maintenance, and response to ionizing radiation (IR) and chemotherapeutics in a representative panel of human MB cell lines expressing different levels of c-MYC (DAOY wild-type, DAOY transfected with the empty vector, DAOY transfected with c-MYC, D341, and D425). RESULTS: siRNA-mediated c-MYC down-regulation resulted in an inhibition of cellular proliferation and clonogenic growth, inhibition of G1-S phase cell cycle progression, and a decrease in human telomerase reverse transcriptase (hTERT) expression and telomerase activity. On the other hand, down-regulation of c-MYC reduced apoptosis and decreased the sensitivity of human MB cells to IR, cisplatin, and etoposide. This effect was more pronounced in DAOY cells expressing high levels of c-MYC when compared with DAOY wild-type or DAOY cells transfected with the empty vector. CONCLUSION: In human MB cells, in addition to its roles in growth and proliferation, c-MYC is also a potent inducer of apoptosis. Therefore, targeting c-MYC might be of therapeutic benefit when used sequentially with chemo- and radiotherapy rather than concomitantly.

Language ideologies: the formation and legitimisation of New Zealand English

New Zealand English first emerged at the beginning of the 19th century as a result of the dialect contact of British (51%), Scottish (27.3%) and Irish (22%) migrants (Hay and Gordon 2008:6). This variety has subsequently developed into an autonomous and legitimised national variety and enjoys a distinct socio-political status, recognition and codification. In fact, a number of dictionaries of New Zealand English have been published1 and the variety is routinely used as the official medium on TV, radio and other media. This however, has not always been the case, as for long only British standard norms were deemed suitable for media broadcasting. While there is some work already on lay commentary about New Zealand English (see for example Gordon 1983, 1994; Hundt 1998), there is much more to be done especially concerning more recent periods of the history of this variety and the ideologies underlying its development and legitimisation. Consequently, the current project aims at investigating the metalinguistic discourses during the period of transition from a British norm to a New Zealand norm in the media context, this will be done by focusing on debates about language in light of the advent of radio and television. The main purpose of this investigation is thus to examine the (language) ideologies that have shaped and underlain these discourses (e.g. discussions about the appropriateness of New Zealand English vis à vis external, British models of language) and their related practices in these media (e.g. broadcasting norms). The sociolinguistic and pragmatic effects of these ideologies will also be taken into account. Furthermore, a comparison will be carried out, at a later stage in the project, between New Zealand English and a more problematic and less legitimised variety: Estuary English. Despite plenty of evidence of media and other public discourses on Estuary English, in fact, there has been very little metalinguistic analysis of this evidence, nor examinations of the underlying ideologies in these discourses. The comparison will seek to discover whether similar themes emerge in the ideologies played out in publish discourses about these varieties, themes which serve to legitimise one variety, whilst denying such legitimacy to the other.

Contact, Mobility and Authenticity: Language Ideologies in Koineisation

New Zealand English first emerged at the beginning of the 19th century as a result of the dialect contact of British (51%), Scottish (27.3%) and Irish (22%) migrants (Hay and Gordon 2008:6). This variety has subsequently developed into an autonomous and legitimised national variety and enjoys a distinct socio-political status, recognition and codification. In fact, a number of dictionaries of New Zealand English have been published1 and the variety is routinely used as the official medium on TV, radio and other media. This however, has not always been the case, as for long only British standard norms were deemed suitable for media broadcasting. While there is some work already on lay commentary about New Zealand English (see for example Gordon 1983, 1994; Hundt 1998), there is much more to be done especially concerning more recent periods of the history of this variety and the ideologies underlying its development and legitimisation. Consequently, the current project aims at investigating the metalinguistic discourses during the period of transition from a British norm to a New Zealand norm in the media context, this will be done by focusing on debates about language in light of the advent of radio and television. The main purpose of this investigation is thus to examine the (language) ideologies that have shaped and underlain these discourses (e.g. discussions about the appropriateness of New Zealand English vis à vis external, British models of language) and their related practices in these media (e.g. broadcasting norms). The sociolinguistic and pragmatic effects of these ideologies will also be taken into account. Furthermore, a comparison will be carried out, at a later stage in the project, between New Zealand English and a more problematic and less legitimised variety: Estuary English. Despite plenty of evidence of media and other public discourses on Estuary English, in fact, there has been very little metalinguistic analysis of this evidence, nor examinations of the underlying ideologies in these discourses. The comparison will seek to discover whether similar themes emerge in the ideologies played out in publish discourses about these varieties, themes which serve to legitimise one variety, whilst denying such legitimacy to the other.

A model for radiofrequency electromagnetic field predictions at outdoor and indoor locations in the context of epidemiological research

We present a geospatial model to predict the radiofrequency electromagnetic field from fixed site transmitters for use in epidemiological exposure assessment. The proposed model extends an existing model toward the prediction of indoor exposure, that is, at the homes of potential study participants. The model is based on accurate operation parameters of all stationary transmitters of mobile communication base stations, and radio broadcast and television transmitters for an extended urban and suburban region in the Basel area (Switzerland). The model was evaluated by calculating Spearman rank correlations and weighted Cohen's kappa (kappa) statistics between the model predictions and measurements obtained at street level, in the homes of volunteers, and in front of the windows of these homes. The correlation coefficients of the numerical predictions with street level measurements were 0.64, with indoor measurements 0.66, and with window measurements 0.67. The kappa coefficients were 0.48 (95%-confidence interval: 0.35-0.61) for street level measurements, 0.44 (95%-CI: 0.32-0.57) for indoor measurements, and 0.53 (95%-CI: 0.42-0.65) for window measurements. Although the modeling of shielding effects by walls and roofs requires considerable simplifications of a complex environment, we found a comparable accuracy of the model for indoor and outdoor points.

Experience and attitudes towards CAM--a survey of internal and psychosomatic patients in a German university hospital

Complementary and alternative medicine (CAM) is popular in Germany. In a consecutive survey the experiences with CAM and the need for a CAM consultation among inpatients of the departments of cardiology (CL), gastroenterology (GE), oncology (OL) and psychosomatics (PS) of the University Hospital Freiburg (FUH) were questionned. Exclusion criteria were inability to understand the questions or a Karnofsky Index < 30%. Four hundred thirty-five patients were included. Three hundred and fifty patients, 100 each in the departments of CL, GE and OL, and 50 in PS answered the questionnaires. Eighty-five patients (20%) refused. Among the 350 patients 26% had previously visited a CAM physician and 19% had visited a CAM therapist (Heilpraktiker). Information about CAM was obtained mainly by television, radio and family members. Frequently used therapies for the current disease were physical training (21%), diet (19%), massage (19%), vitamins/trace elements (19%), herbs (13%), acupuncture (10%) and homeopathy (7%). The highest frequency of CAM use had PS patients, followed by GE, OL and CL patients. High effectivity (> or = 70%) for the current disease, rated on a scale of 4 degrees, had for CL patients physical exercise and massage, for GE patients herbal treatment and for OL patients diet. Physical exercise, diet, massage and herbal treatment generally had better ratings than homeopathy, acupuncture and vitamins. 65% would welcome a CAM center and 53% asked for a consultation about CAM at FUH. OL and GE patients had the strongest (58%), PS patients a lower (52%) and patients with cardiovascular diseases the lowest (43%) interest in a CAM consultation. Twenty-five percent believed, that CAM can help to cope better with their disease. Predictors for a positive attitude towards CAM were young age, aversion to chemical medications (Spearman correlation r = 0.22), desire to participate in therapeutic decisions (r = 0.29), motivation to change, if recommended, the life style (r = 0.31) and desire for a holistic treatment (r = 0.37).

An Architecture to offer Cloud-Based Radio Access Network as a Service

This paper addresses the novel notion of offering a radio access network as a service. Its components may be instantiated on general purpose platforms with pooled resources (both radio and hardware ones) dimensioned on-demand, elastically and following the pay-per-use principle. A novel architecture is proposed that supports this concept. The architecture's success is in its modularity, well-defined functional elements and clean separation between operational and control functions. By moving much processing traditionally located in hardware for computation in the cloud, it allows the optimisation of hardware utilization and reduction of deployment and operation costs. It enables operators to upgrade their network as well as quickly deploy and adapt resources to demand. Also, new players may easily enter the market, permitting a virtual network operator to provide connectivity to its users.

Patients' information-seeking activity is associated with treatment compliance in inflammatory bowel disease patients

BACKGROUND Despite the chronic and relapsing nature of inflammatory bowel diseases (IBD), at least 30% to 45% of the patients are noncompliant to treatment. IBD patients often seek information about their disease. AIM To examine the association between information-seeking activity and treatment compliance among IBD patients. To compare information sources and concerns between compliant and noncompliant patients. METHODS We used data from the Swiss IBD cohort study, and from a qualitative survey conducted to assess information sources and concerns. Crude and adjusted odds ratios (OR) for noncompliance were calculated. Differences in the proportions of information sources and concerns were compared between compliant and noncompliant patients. RESULTS A total of 512 patients were included. About 18% (n = 99) of patients were reported to be noncompliant to drug treatment and two-thirds (n = 353) were information seekers. The OR for noncompliance among information seekers was 2.44 (95%CI: 1.34-4.41) after adjustment for confounders and major risk factors. General practitioners were 15.2% more often consulted (p = 0.019) among compliant patients, as were books and television (+13.1%; p = 0.048), whereas no difference in proportions was observed for sources such as internet or gastroenterologists. Information on tips for disease management were 14.2% more often sought among noncompliant patients (p = 0.028). No difference was observed for concerns on research and development on IBD or therapies. CONCLUSION In Switzerland, IBD patients noncompliant to treatment were more often seeking disease-related information than compliant patients. Daily management of symptoms and disease seemed to be an important concern of those patients.

Radio-guided surgery: advantages of a new portable γ-camera (Sentinella(®) ) for intraoperative real time imaging and detection of sentinel lymph nodes in cutaneous malignancies

The histological status of the sentinel lymph node (SLN) is one of the most relevant prognostic factors for the overall survival of patients with cutaneous malignancies, independent of tumour depth of the primary tumour.