Sacrococcygeal germ-cell tumours - the Red Cross War Memorial Children's hospital experience, 1980 - 1996

Objective. To document the experience of Red Cross War Memorial Children's Hospital in the treatment of sacrococcygeal germ-eell tumours.Patients. Twenty-seven patients with sacrococcygeal germ-cell tumours were treated in our hospital from 1980 to 1996.Design. A retrospective review of these patients' records was undertaken.Results. There were 19 female and 8 male patients. Seventeen (63%) presented in the neonatal period, 13 on the first day of life. Complete surgical resection of the tumour was achieved in all patients with mature or immature teratomas (20 patients) and in 2 neonates with malignant tumours. The first of these 2 neonates, with a malignant teratoma, was not given chemotherapy and remains well 10 years later. The second, with a yolk-sac tumour, also received no initial chemotherapy. He relapsed at the age of 9 months and was successfully treated with repeat excision and chemotherapy. All 5 patients first diagnosed after the age of 1 year had malignant tumours. These patients had incomplete surgical resection (3) or biopsy only (2), and 3 were successfully treated with chemotherapy. One patient relapsed with yolksac tumour after initial complete resection cif a mature teratoma. She was successfully treated with repeat surgery and chemotherapy

The 'Switch' study protocol: a randomised-controlled trial of switching to an alternative tumour-necrosis factor (TNF)-inhibitor drug or abatacept or rituximab in patients with rheumatoid arthritis who have failed an initial TNF-inhibitor drug

Background: Rheumatoid Arthritis (RA) is one of the most common autoimmune diseases, affecting approximately 1% of the UK adult population. Patients suffer considerable pain, stiffness and swelling and can sustain various degrees of joint destruction, deformity, and significant functional decline. In addition, the economic burden due to hospitalisation and loss of employment is considerable, with over 50% of patients being work-disabled within 10 years of diagnosis. Despite several biologic disease modifying anti-rheumatic drugs (bDMARD) now available, there is a lack of data to guide biologic sequencing. In the UK, second-line biologic treatment is restricted to a single option, rituximab. The aim of the SWITCH trial is to establish whether an alternative-mechanism-TNF-inhibitor (TNFi) or abatacept are as effective as rituximab in patients with RA who have failed an initial TNFi drug. Methods/Design: SWITCH is a pragmatic, phase IV, multi-centre, parallel-group design, open-label, randomised, controlled trial (RCT) comparing alternative-mechanism-TNFi and abatacept with rituximab in patients with RA who have failed an initial TNFi drug. Participants are randomised in a 1:1:1 ratio to receive alternative mechanism TNFi, (monoclonal antibodies: infliximab, adalimumab, certolizumab or golimumab or the receptor fusion protein, etanercept), abatacept or rituximab during the interventional phase (from randomisation up to week 48). Participants are subsequently followed up to a maximum of 96 weeks, which constitutes the observational phase. The primary objective is to establish whether an alternative-mechanism-TNFi or abatacept are non-inferior to rituximab in terms of disease response at 24 weeks post randomisation. The secondary objectives include the comparison of alternative-mechanism-TNFi and abatacept to rituximab in terms of disease response, quality of life, toxicity, safety and structural and bone density outcomes over a 12-month period (48 weeks) and to evaluate the cost-effectiveness of switching patients to alternative active therapies compared to current practice. Discussion: SWITCH is a well-designed trial in this therapeutic area that aims to develop a rational treatment algorithm to potentially inform personalised treatment regimens (as opposed to switching all patients to only one available (and possibly unsuccessful) therapy), which may lead to long-term improved patient outcomes and gains in population health

Elasticity in ecosystem services: Exploring the variable relationship between ecosystems and human well-being

Although ecosystem services are increasingly recognized as benefits people obtain from nature, we still have a poor understanding of how they actually enhance multidimensional human well-being, and how well-being is affected by ecosystem change. We develop a concept of “ecosystem service elasticity” (ES elasticity) that describes the sensitivity of human well-being to changes in ecosystems. ES Elasticity is a result of complex social and ecological dynamics and is context dependent, individually variable, and likely to demonstrate nonlinear dynamics such as thresholds and hysteresis. We present a conceptual framework that unpacks the chain of causality from ecosystem stocks through flows, goods, value, and shares to contribute to the well-being of different people. This framework builds on previous conceptualizations, but places multidimensional well-being of different people as the final element. This ultimately disaggregated approach emphasizes how different people access benefits and how benefits match their needs or aspirations. Applying this framework to case studies of individual coastal ecosystem services in East Africa illustrates a wide range of social and ecological factors that can affect ES elasticity. For example, food web and habitat dynamics affect the sensitivity of different fisheries ecosystem services to ecological change. Meanwhile high cultural significance, or lack of alternatives enhance ES elasticity, while social mechanisms that prevent access can reduce elasticity. Mapping out how chains are interlinked illustrates how different types of value and the well-being of different people are linked to each other and to common ecological stocks. We suggest that examining chains for individual ecosystem services can suggest potential interventions aimed at poverty alleviation and sustainable ecosystems while mapping out of interlinkages between chains can help to identify possible ecosystem service trade-offs and winners and losers. We discuss conceptual and practical challenges of applying such a framework and conclude on its utility as a heuristic for structuring interdisciplinary analysis of ecosystem services and human wellbeing.This paper results from the project Sustainable Poverty Alleviation from Coastal Ecosystem Services (SPACES) project number NE-K010484-1, funded by the Ecosystem Services for Poverty Alleviation (ESPA) programme. The ESPA programme is funded by the Department for International Development (DFID), the Economic and Social Research Council (ESRC), and the Natural Environment Research Council (NERC).

Insights into the chemical composition of Equisetum hyemale by high resolution Raman imaging

Equisetaceae has been of research interest for decades, as it is one of the oldest living plant families, and also due to its high accumulation of silica up to 25% dry wt. Aspects of silica deposition, its association with other biomolecules, as well as the chemical composition of the outer strengthening tissue still remain unclear. These questions were addressed by using high resolution (<1 μm) Confocal Raman microscopy. Two-dimensional spectral maps were acquired on cross sections of Equisetum hyemale and Raman images calculated by integrating over the intensity of characteristic spectral regions. This enabled direct visualization of differences in chemical composition and extraction of average spectra from defined regions for detailed analyses, including principal component analysis (PCA) and basis analysis (partial least square fit based on model spectra). Accumulation of silica was imaged in the knobs and in a thin layer below the cuticula. In the spectrum extracted from the knob region as main contributions, a broad band below 500 cm−1 attributed to amorphous silica, and a band at 976 cm−1 assigned to silanol groups, were found. From this, we concluded that these protrusions were almost pure amorphous, hydrated silica. No silanol group vibration was detected in the silicified epidermal layer below and association with pectin and hemicelluloses indicated. Pectin and hemicelluloses (glucomannan) were found in high levels in the epidermal layer and in a clearly distinguished outer part of the hypodermal sterome fibers. The inner part of the two-layered cells revealed as almost pure cellulose, oriented parallel along the fiber

Limited contribution of permafrost carbon to methane release from thawing peatlands

Models predict that thaw of permafrost soils at northern high-latitudes will release tens of billions of tonnes of carbon (C) to the atmosphere by 21001-3. The effect on the Earth's climate depends strongly on the proportion of this C which is released as the more powerful greenhouse gas methane (CH4), rather than carbon dioxide (CO2)1,4; even if CH4 emissions represent just 2% of the C release, they would contribute approximately one quarter of the climate forcing5. In northern peatlands, thaw of ice-rich permafrost causes surface subsidence (thermokarst) and water-logging6, exposing substantial stores (10s of kg C m-2, ref. 7) of previously-frozen organic matter to anaerobic conditions, and generating ideal conditions for permafrost-derived CH4 release. Here we show that, contrary to expectations, although substantial CH4 fluxes (>20 g CH4 m 2 yr-1) were recorded from thawing peatlands in northern Canada, only a small amount was derived from previously-frozen C (<2 g CH4 m-2 yr-1). Instead, fluxes were driven by anaerobic decomposition of recent C inputs. We conclude that thaw-induced changes in surface wetness and wetland area, rather than the anaerobic decomposition of previously-frozen C, may determine the effect of permafrost thaw on CH4 emissions from northern peatlands

Thiothymidine combined with UVA as a potential novel therapy for bladder cancer

BACKGROUND: Thiothymidine (S4TdR) can be incorporated into DNA and sensitise cells to DNA damage and cell death following exposure to UVA light. Studies were performed to determine if the combination of S4TdR and UVA could be an effective treatmentfor bladder cancer. METHODS: Uptake and incorporation of S4TdR was determined in rat and human bladder tumour cell lines. Measures of DNA crosslinking and apoptosis were also performed. In vivo activity of the combination of S4TdR and UVA was investigated in an orthotopic model of bladder cancer in rats. RESULTS: Thiothymidine (200 uM) replaced up to 0.63% of thymidine in rat and tumour bladder cancer cells. The combination of S4TdR (10–200 uM) and UVA (1–5 kJm-2) caused apoptosis and cell death at doses that were not toxic alone. Addition of raltitrexed (Astra Zeneca, Alderley Edge, Cheshire, UK) increased the incorporation of S4TdR into DNA (up to 20-fold at IC5) and further sensitised cells to UVA. Cytotoxic effect was associated with crosslinking of DNA, at least partially to protein. Intravenous administration of S4TdR, in combination with UVA delivered directly to the bladder, resulted in an antitumour effect in three of five animals treated. CONCLUSION: These data indicate that the combination of S4TdR and UVA has potential as a treatment for bladder cancer, and give some insight into the mechanism of action. Further work is necessary to optimise the delivery of the two components

B Cell Activating Factor (BAFF) and T Cells Cooperate to Breach B Cell Tolerance in Lupus-Prone New Zealand Black (NZB) Mice

The presence of autoantibodies in New Zealand Black (NZB) mice suggests a B cell tolerance defect however the nature of this defect is unknown. To determine whether defects in B cell anergy contribute to the autoimmune phenotype in NZB mice, soluble hen egg lysozyme (sHEL) and anti-HEL Ig transgenes were bred onto the NZB background to generate double transgenic (dTg) mice. NZB dTg mice had elevated levels of anti-HEL antibodies, despite apparently normal B cell functional anergy in-vitro. NZB dTg B cells also demonstrated increased survival and abnormal entry into the follicular compartment following transfer into sHEL mice. Since this process is dependent on BAFF, BAFF serum and mRNA levels were assessed and were found to be significantly elevated in NZB dTg mice. Treatment of NZB sHEL recipient mice with TACI-Ig reduced NZB dTg B cell survival following adoptive transfer, confirming the role of BAFF in this process. Although NZB mice had modestly elevated BAFF, the enhanced NZB B cell survival response appeared to result from an altered response to BAFF. In contrast, T cell blockade had a minimal effect on B cell survival, but inhibited anti-HEL antibody production. The findings suggest that the modest BAFF elevations in NZB mice are sufficient to perturb B cell tolerance, particularly when acting in concert with B cell functional abnormalities and T cell help

Medical students' and facilitators' experiences of an Early Professional Contact course: Active and motivated students, strained facilitators

Background: Today, medical students are introduced to patient contact, communication skills, and clinical examination in the preclinical years of the curriculum with the purpose of gaining clinical experience. These courses are often evaluated from the student perspective. Reports with an additional emphasis on the facilitator perspective are scarce. According to constructive alignment, an influential concept from research in higher education, the learning climate between students and teachers is also of great importance. In this paper, we approach the learning climate by studying both students' and facilitators' course experiences.\ud \ud In 2001, a new "Early Professional Contact" longitudinal strand through term 1–4, was introduced at the Sahlgrenska Academy, University of Gothenburg, Sweden. General practitioners and hospital specialists were facilitators.\ud \ud The aim of this study was to assess and analyse students' and clinical facilitators' experiences of the Early Professional Contact course and to illuminate facilitators' working conditions.\ud \ud Methods: Inspired by a Swedish adaptation of the Course Experience Questionnaire, an Early Professional Contact Questionnaire was constructed. In 2003, on the completion of the first longitudinal strand, a student and facilitator version was distributed to 86 students and 21 facilitators. In the analysis, both Chi-square and the Mann-Whitney tests were used.\ud \ud Results: Sixty students (70%) and 15 facilitators (71%) completed the questionnaire. Both students and facilitators were satisfied with the course. Students reported gaining [inspiration] for their future work as doctors along with increased confidence in meeting patients. They also reported increased motivation for biomedical studies. Differences in attitudes between facilitators and students were found. Facilitators experienced a greater workload, less reasonable demands and less support, than students.\ud \ud Conclusion: In this project, a new Early Professional Contact course was analysed from both student and facilitator perspectives. The students experienced the course as providing them with a valuable introduction to the physician's professional role in clinical practice. In contrast, course facilitators often experienced a heavy workload and lack of support, despite thorough preparatory education. A possible conflict between the clinical facilitator's task as educator and member of the workplace is suggested. More research is needed on how doctors combine their professional tasks with work as facilitators