Prognosis for patients suffering from malignant glioma has not substantially improved. Specific immunotherapy as a novel treatment concept critically depends on target antigens, which are highly ...overexpressed in the majority of gliomas, but the number of such antigens is still very limited. SOX2 was identified by screening an expression database for transcripts that are overexpressed in malignant glioma, but display minimal expression in normal tissues. Expression of SOX2 mRNA was further investigated in tumour and normal tissues by real-time PCR. Compared to cDNA from pooled normal brain, SOX2 was overexpressed in almost all (9 out of 10) malignant glioma samples, whereas expression in other, non-malignant tissues was almost negligible. SOX2 protein expression in glioma cell lines and tumour tissues was verified by Western blot and immunofluorescence. Immunohistochemistry demonstrated SOX2 protein expression in all malignant glioma tissues investigated ranging from 6 to 66% stained tumour cells. Human leucocyte antigen-A(*)0201-restricted SOX2-derived peptides were tested for the activation of glioma-reactive CD8+ cytotoxic T lymphocytes (CTLs). Specific CTLs were raised against the peptide TLMKKDKYTL and were capable of lysing glioma cells. The abundant and glioma-restricted overexpression of SOX2 and the generation of SOX2-specific and tumour-reactive CTLs may recommend this antigen as target for T-cell-based immunotherapy of glioma.
Issue Title: Policy sciences for sustainable development Planned adaptation to climate change denotes actions undertaken to reduce the risks and capitalize on the opportunities associated with global ...climate change. This paper summarizes current thinking about planned adaptation. It starts with an explanation of key adaptation concepts, a description of the diversity of adaptation contexts, and a discussion of key prerequisites for effective adaptation. On the basis of this introduction, major approaches to climate impact and adaptation assessment and their evolution are reviewed. Finally, principles for adaptation assessment are derived from decision-analytical considerations and from the experience with past adaptation assessments.PUBLICATION ABSTRACT
The term ‘vulnerability’ is used in many different ways by various scholarly communities. The resulting disagreement about the appropriate definition of vulnerability is a frequent cause for ...misunderstanding in interdisciplinary research on climate change and a challenge for attempts to develop formal models of vulnerability. Earlier attempts at reconciling the various conceptualizations of vulnerability were, at best, partly successful. This paper presents a generally applicable conceptual framework of vulnerability that combines a nomenclature of vulnerable situations and a terminology of vulnerability concepts based on the distinction of four fundamental groups of vulnerability factors. This conceptual framework is applied to characterize the vulnerability concepts employed by the main schools of vulnerability research and to review earlier attempts at classifying vulnerability concepts. None of these one-dimensional classification schemes reflects the diversity of vulnerability concepts identified in this review. The wide range of policy responses available to address the risks from global climate change suggests that climate impact, vulnerability, and adaptation assessments will continue to apply a variety of vulnerability concepts. The framework presented here provides the much-needed conceptual clarity and facilitates bridging the various approaches to researching vulnerability to climate change.
▶ Countries most vulnerable for climate change are generally least responsible for it. ▶ The inequity is most pronounced for climate impacts on food security and human health. ▶ International ...adaptation funding should be informed by sector-specific criteria.
While it is generally asserted that those countries who have contributed least to anthropogenic climate change are most vulnerable to its adverse impacts some recently developed indices of vulnerability to climate change come to a different conclusion. Confirmation or rejection of this assertion is complicated by the lack of an agreed metric for measuring countries’ vulnerability to climate change and by conflicting interpretations of vulnerability. This paper presents a comprehensive semi-quantitative analysis of the disparity between countries’ responsibility for climate change, their capability to act and assist, and their vulnerability to climate change for four climate-sensitive sectors based on a broad range of disaggregated vulnerability indicators. This analysis finds a double inequity between responsibility and capability on the one hand and the vulnerability of food security, human health, and coastal populations on the other. This double inequity is robust across alternative indicator choices and interpretations of vulnerability. The main cause for the higher vulnerability of poor nations who have generally contributed little to climate change is their lower adaptive capacity. In addition, the biophysical sensitivity and socio-economic exposure of poor nations to climate impacts on food security and human health generally exceeds that of wealthier nations. No definite statement can be made on the inequity associated with climate impacts on water supply due to large uncertainties about future changes in regional water availability and to conflicting indicators of current water scarcity. The robust double inequity between responsibility and vulnerability for most climate-sensitive sectors strengthens the moral case for financial and technical assistance from those countries most responsible for climate change to those countries most vulnerable to its adverse impacts. However, the complex and geographically heterogeneous patterns of vulnerability factors for different climate-sensitive sectors suggest that the allocation of international adaptation funds to developing countries should be guided by sector-specific or hazard-specific criteria despite repeated requests from participants in international climate negotiations to develop a generic index of countries’ vulnerability to climate change.
A critical issue for policymakers in defining mitigation strategies for climate change is the availability of appropriate evaluation tools. The development of climate impact response functions ...(CIRFs) is our reaction to this challenge. CIRFs depict the response of selected climate-sensitive impact sectors across a wide range of plausible futures. They consist of a limited number of climate-change-related dimensions and sensitivities of sector-specific impact models. The concept of CIRFs is defined and the procedure to develop them is presented. The use of climate change scenarios derived from various GCM experiments and the adopted impact assessment models are explained. The CIRFs presented here consider climate change impacts on natural vegetation, crop production, and water availability. They are part of the ICLIPS integrated assessment framework based on the tolerable windows approach. CIRFs can be applied both in `forward' and in `inverse' mode. In the latter, they help to translate thresholds for climate impacts perceived by stakeholders (so-called impact guardrails) into constraints for climate variables (so-called climate windows). This enables the results of detailed impact models to be incorporated into intertemporally optimizing integrated assessment models, such as the ICLIPS model. PUBLICATION ABSTRACT
de Bruin et al. (Clim Change, 2009) report on an expert assessment aimed at prioritizing adaptation options in several climate-sensitive sectors of the Netherlands. Their results show that even in a ...country with high economic, institutional and technical capacity, it is not currently feasible to prioritize national-level adaptation options based on social cost-benefit analysis because of methodological difficulties and insufficient quantitative data. Multi-criteria analysis based on qualitative indicators can help prioritizing adaptation options but the analysis detected strong conflicts between priority and feasibility criteria. The specific results of the ranking exercise should be treated with caution due to weaknesses in the selection of adaptation options and the definition of evaluation criteria. The authors assert that their methods can be transferred to other regions but substantial modifications are likely required in developing countries with large current climate risks, fewer economic resources, and substantial social inequalities.
There is substantial need to improve the outcome of patients with high-risk acute myeloid leukemia (AML). The clinical trial reported here investigated a new approach of up-front allogeneic ...hematopoietic stem cell transplantation (HSCT), provided a median of 40 days (range 22-74) after diagnosis, in twenty-six consecutive patients with newly-diagnosed high-risk AML characterized by poor-risk cytogenetics (n = 19) or inadequate blast clearance by induction chemotherapy (IC, n = 7). The median age was 49 years (range 17-68). During IC-induced aplasia after the 1st (n = 11) or 2nd (n = 15) cycle, patients received allogeneic peripheral blood stem cells (PBSC) from related (n = 11) or unrelated (n = 15) donors following a fludarabine-based reduced-intensity regimen. Seventeen patients were not in remission before HSCT with a median marrow blast count of 34% (range 6-70). All patients achieved rapid engraftment and went into remission with complete myeloid and lymphatic chimerism. Grades II to IV acute GvHD occurred in 14 (56%) and extensive chronic GvHD was documented in 8 (35%) patients. The probability of disease-free survival was 61% with only three patients relapsing 5, 6 and 7 months after transplantation, respectively. Up-front allogeneic HSCT as part of primary induction therapy seems to be an effective strategy in high-risk AML patients and warrants further investigation.
OBJECTIVES To elucidate the contribution of microsatellite polymorphisms of TNFa and TNFb alleles to the pathogenesis of systemic sclerosis (SSc) by comparing the allele distribution among ...populations with different HLA susceptibility genes in SSc. METHODS TNFa and TNFb microsatellite polymorphisms were determined by PCR in 54 Japanese and 50 German SSc patients and in normal controls. HLA-DR genotyping was carried out by PCR-SSCP. RESULTS The frequency of TNFa13 was significantly increased in Japanese SSc (p=0.011, OR=8.53, 95% confidence intervals (95%CI)=2.46, 32.51, and p<1.0 × 10E-5, OR=10.35, 95%CI=4.88, 22.09) and SSc with antitopoisomerase I antibody (a-Scl-70) (p=0.021, OR=33.25, 95%CI=3.39, 800.76, and p<1.0 × 10E-5, OR=24.42, 95%CI=8.40, 72.83), compared with the German patient group and German controls, respectively. This increase was not only attributable to a higher prevalence of TNFa13 in Japanese compared with Germans (p=0.005, OR=3.55, 95%CI=1.60, 7.85) but was also caused by an increase in SSc, especially in the a-Scl-70 positive patients (p=0.028, OR=6.88, 95%CI=1.16, 22.60) compared with Japanese controls. TNFa13 was positively in linkage disequilibrium with HLA-DRB1*1502 (LD=0.053,t=2.69). Association analysis indicated that both TNFa13 and DRB1*1502 might have comparable probabilities of being susceptibility factors for SSc with a-Scl-70 in Japanese. Prevalences of TNFa6 and 13 were significantly increased and prevalences of TNFa2, and 7 were significantly decreased in Japanese controls as compared with German controls. CONCLUSION TNFa13 is a genetic marker for SSc with a-Scl-70 in Japanese patients. Various differences in the prevalences of TNFa alleles between Japanese and German controls were established.
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