From The Hague to Geneva: The protection of civilians and refugees in the perspective of legal history, 1899-1951

The presentation proposed here shall focus on international (and as far as possible some cases of national) legal protection of civilians and refugees between the first Hague Convention of 1899 and the Geneva Convention for the Protection of Refugees in 1951. An analysis of international legal texts as well as, if possible, some exemplary national constitutions will form the core of the presentation, which will try to find out, to what extent not only the civilian population remaining close to front-line fighting, but also under occupation was supposed to be protected by legal norms, but also to what extent the issue of forcing civilian to leave their homes became part of the international legal discourse as well as of international legal norms.

Clinical relevance of DPYD variants c.1679T>G, c.1236G>A/HapB3, and c.1601G>A as predictors of severe fluoropyrimidine-associated toxicity: a systematic review and meta-analysis of individual patient data

BACKGROUND The best-known cause of intolerance to fluoropyrimidines is dihydropyrimidine dehydrogenase (DPD) deficiency, which can result from deleterious polymorphisms in the gene encoding DPD (DPYD), including DPYD*2A and c.2846A>T. Three other variants-DPYD c.1679T>G, c.1236G>A/HapB3, and c.1601G>A-have been associated with DPD deficiency, but no definitive evidence for the clinical validity of these variants is available. The primary objective of this systematic review and meta-analysis was to assess the clinical validity of c.1679T>G, c.1236G>A/HapB3, and c.1601G>A as predictors of severe fluoropyrimidine-associated toxicity. METHODS We did a systematic review of the literature published before Dec 17, 2014, to identify cohort studies investigating associations between DPYD c.1679T>G, c.1236G>A/HapB3, and c.1601G>A and severe (grade ≥3) fluoropyrimidine-associated toxicity in patients treated with fluoropyrimidines (fluorouracil, capecitabine, or tegafur-uracil as single agents, in combination with other anticancer drugs, or with radiotherapy). Individual patient data were retrieved and analysed in a multivariable analysis to obtain an adjusted relative risk (RR). Effect estimates were pooled by use of a random-effects meta-analysis. The threshold for significance was set at a p value of less than 0·0167 (Bonferroni correction). FINDINGS 7365 patients from eight studies were included in the meta-analysis. DPYD c.1679T>G was significantly associated with fluoropyrimidine-associated toxicity (adjusted RR 4·40, 95% CI 2·08-9·30, p<0·0001), as was c.1236G>A/HapB3 (1·59, 1·29-1·97, p<0·0001). The association between c.1601G>A and fluoropyrimidine-associated toxicity was not significant (adjusted RR 1·52, 95% CI 0·86-2·70, p=0·15). Analysis of individual types of toxicity showed consistent associations of c.1679T>G and c.1236G>A/HapB3 with gastrointestinal toxicity (adjusted RR 5·72, 95% CI 1·40-23·33, p=0·015; and 2·04, 1·49-2·78, p<0·0001, respectively) and haematological toxicity (adjusted RR 9·76, 95% CI 3·03-31·48, p=0·00014; and 2·07, 1·17-3·68, p=0·013, respectively), but not with hand-foot syndrome. DPYD*2A and c.2846A>T were also significantly associated with severe fluoropyrimidine-associated toxicity (adjusted RR 2·85, 95% CI 1·75-4·62, p<0·0001; and 3·02, 2·22-4·10, p<0·0001, respectively). INTERPRETATION DPYD variants c.1679T>G and c.1236G>A/HapB3 are clinically relevant predictors of fluoropyrimidine-associated toxicity. Upfront screening for these variants, in addition to the established variants DPYD*2A and c.2846A>T, is recommended to improve the safety of patients with cancer treated with fluoropyrimidines. FUNDING None.

Humanitarian intervention and the issue of state sovereignty in the discourse of legal experts between the 1830s and the First World War

This article discusses the tensions between the principle of state sovereignty and the idea of a "humanitarian intervention" (or a intervention on humanitarian grounds) as they resulted from the debate of leading legal scholars in the 19th and early 20th century. While prominent scholars such as Johann Caspar Bluntschli, Gustave Rolin Jaequemyns or Aegidius Arntz spoke out in favour of a form of "humanitarian interventions", others such as August Wilhelm Heffter or Pasquale Fiore were much more critical and in many cases spoke out in favour of absolute state sovereignty.

Prognostic Relevance of Palliative Primary Tumor Removal in 37,793 Metastatic Colorectal Cancer Patients: A Population-Based, Propensity Score-Adjusted Trend Analysis

OBJECTIVE To assess whether palliative primary tumor resection in colorectal cancer patients with incurable stage IV disease is associated with improved survival. BACKGROUND There is a heated debate regarding whether or not an asymptomatic primary tumor should be removed in patients with incurable stage IV colorectal disease. METHODS Stage IV colorectal cancer patients were identified in the Surveillance, Epidemiology, and End Results database between 1998 and 2009. Patients undergoing surgery to metastatic sites were excluded. Overall survival and cancer-specific survival were compared between patients with and without palliative primary tumor resection using risk-adjusted Cox proportional hazard regression models and stratified propensity score methods. RESULTS Overall, 37,793 stage IV colorectal cancer patients were identified. Of those, 23,004 (60.9%) underwent palliative primary tumor resection. The rate of patients undergoing palliative primary cancer resection decreased from 68.4% in 1998 to 50.7% in 2009 (P < 0.001). In Cox regression analysis after propensity score matching primary cancer resection was associated with a significantly improved overall survival [hazard ratio (HR) of death = 0.40, 95% confidence interval (CI) = 0.39-0.42, P < 0.001] and cancer-specific survival (HR of death = 0.39, 95% CI = 0.38-0.40, P < 0.001). The benefit of palliative primary cancer resection persisted during the time period 1998 to 2009 with HRs equal to or less than 0.47 for both overall and cancer-specific survival. CONCLUSIONS On the basis of this population-based cohort of stage IV colorectal cancer patients, palliative primary tumor resection was associated with improved overall and cancer-specific survival. Therefore, the dogma that an asymptomatic primary tumor never should be resected in patients with unresectable colorectal cancer metastases must be questioned.

The relevance of sport-related behaviour patterns in the family for the sport participation of youth in Switzerland

Despite various efforts to promote sport participation among youth, social inequalities still exist. An explanation for these social inequalities could be traced back to transgenerational transmission of sport-related values and behaviour patterns in a family (Baur, 1989). Therefore, children’s socialisation to sport is strongly influenced by the parents’ sport-related values and sport behaviour (Burrmann, 2005). However, findings of previous studies are inconsistent, and the daily sport-related behaviour patterns of families have often not been taken into account. The paper deals with the question, to what extent sport participation of youth is influenced by factors such as the importance of sport, the self-evidence of regular sport activity, mutual support, shared sport activities, sport-related health-awareness and communication about sport in the family. In order to pursue this research question, socialisation theories were used as theoretical framework (Hurrelmann, 2006). Based on this approach, a quantitative online survey where 4’039 adolescents and young adults from the ages of 15 to 30 (n = 4’039, M = 21.48, SD = 4.64) answered questions according their sport participation and the sport-related patterns of their families. Furthermore, a qualitative study that included guideline-based interviews with adolescents and young adults (n = 13) were undertaken. Content analysis was used to analyse the interviews. Initial findings of the multiple regression analysis reveal that the most important predictors of sport participation of youth are communication about sport (β = .18, p < .001), mutual support (β = .13, p < .001), regular sport activity (β = .10, p < .01) and the importance of sport in the family (β = .10, p < .01). By means of content analysis, more in-depth information could be identified. The promotion of sport through sport-related behaviour patterns in the family appears to be a successful strategy to develop a durable sport commitment in youth. References Baur, J. (1989). Körper- und Bewegungskarrieren [Body and exercise careers]. Schorndorf: Hofmann. Burrmann, U. (2005). Zur Vermittlung und intergenerationalen "Vererbung" von Sport(vereins)engagements in der Herkunftsfamilie [On placing and "inheriting" intergenerational sport(club) commitment in the family of origin]. Sport und Gesellschaft, 2, 125–154. Hurrelmann, K. (2006). Einführung in die Sozialisationstheorie [Introduction to socialisation theory] (9th ed.). Studium Paedagogik. Weinheim: Beltz.

Clinical relevance of polymorphic DNA copy number variation (CNV) in African American women with stage I-II breast cancer

Objectives. The chief goal of this study was to analyze copy number variation (CNV) in breast cancer tumors from 25 African American women with early stage breast cancer (BC) using molecular inversion probes (MIP) in order to: (1) compare the degree of CNV in tumors compared to normal lymph nodes, and (2) determine whether gains and/or losses of genes in specific chromosomes differ between pathologic subtypes of breast cancer defined by known prognostic markers, (3) determine whether gains/losses in CN are associated with known oncogenes or tumor suppressor genes, and (4) determine whether increased gains/losses in CN for specific chromosomes were associated with differences in breast cancer recurrence. ^ Methods. Twenty to 37 nanograms of DNA extracted from 25 formalin-fixed paraffin embedded (FFPE) tumor samples and matched normal lymph nodes were added to individual tubes. Oligonucleotide probes with recognition sequences at each terminus were hybridized with a genomic target sequence to form a circular structure. Probes are released from genomic DNA obtained from FFPE samples, and those which have been correctly "circularized" in the proper allele/nucleotide reaction combination are amplified using polymerase chain reaction (PCR) primers. Amplicons were fluorescently labeled and the tag sequences released from the genome homology regions by treatment with uracil-N-glycosylase to cleave the probe at the site where uracils are present, and detected using a complementary tag array developed by Affymetrix. ^ Results. Analysis of CN gains and losses from tumors and normal tissues showed marked differences in tumors with numerous chromosomes affected. Similar changes were not observed in normal lymph nodes. When tumors were stratified into four groups based on expression or lack of expression of the estrogen receptor and HER2/neu, distinct patterns of CNV for different chromosomes were observed. Gains or losses in CN for specific chromosomes correlated with amplifications/deletions of particular oncogenes or tumor suppressor genes (i.e. such as found on chromosome 17) known to be associated with aggressive tumor phenotype and poor prognosis. There was a trend for increases in CN observed for chromosome 17 to correlate inversely with time to recurrence of BC (p=0.14 for trend). CNV was also observed for chromosomes 5, 8, 10, 11, and 16, which are known sites for several breast cancer susceptibility alleles. ^ Conclusions. This study is the first to validate the MIP technique, to correlate differences in gene expression with known prognostic tumor markers, and to correlate significant increases/decreases in CN with known tumor markers associated with prognosis. The results of this study may have far reaching public health implications towards identifying new high-risk groups based on genomic differences in CNP, both with respect to prognosis and response to therapy, and to eventually identify new therapeutic targets for prevention and treatment of this disease. ^

Making Abortion Services Accessible in the Wake of Legal Reforms: A Framework and Six Case Studies

Contiene Informe completo y resumen.

Neutrality in the choice of number of firms or level of fixed costs in calibrating an Armington-Krugman-Melitz encompassing module for applied general equilibrium models

This paper shows how an Armington-Krugman-Melitz encompassing module based on Dixon and Rimmer (2012) can be calibrated, and clarifies the choice of initial levels for two kinds of number of firms, or parameter values for two kinds of fixed costs, that enter a Melitz-type specification can be set freely to any preferred value, just as the cases we derive quantities from given value data assuming some of the initial prices to be unity. In consequence, only one kind of additional information, which is on the shape parameter related to productivity, just is required in order to incorporate Melitz-type monopolistic competition and heterogeneous firms into a standard applied general equilibrium model. To be a Krugman-type, nothing is needed. This enables model builders in applied economics to fully enjoy the featured properties of the theoretical models invented by Krugman (1980) and Melitz (2003) in practical policy simulations at low cost.

The relevance of seed size in modulating leaf physiology and early plant performance in two tree species

he size of seeds and the microsite of seed dispersal may affect the early establishment of seedlings through different physiological processes. Here, we examined the effects of seed size and light availability on seedling growth and survival, and whether such effects were mediated by water use efficiency. Acorns of Quercus petraea and the more drought-tolerant Quercus pyrenaica were sowed within and around a tree canopy gap in a sub-Mediterranean forest stand. We monitored seedling emergence and measured predawn leaf water potential (Ψpd), leaf nitrogen per unit area (Na), leaf mass per area, leaf carbon isotope composition (δ13C) and plant growth at the end of the first summer. Survival was measured on the next year. Path analysis revealed a consistent pattern in both species of higher δ13C as Ψpd decreased and higher δ13C as seedlings emerged later in the season, indicating an increase in 13C as the growing season is shorter and drier. There was a direct positive effect of seed size on δ13C in Q. petraea that was absent in Q. pyrenaica. Leaf δ13C had no effect on growth but the probability of surviving until the second year was higher for those seedlings of Q. pyrenaica that had lower δ13C on the first year. In conclusion, leaf δ13C is affected by seed size, seedling emergence time and the availability of light and water, however, leaf δ13C is irrelevant for first year growth, which is directly dependent on the amount of seed reserves.

Evaluation of a User-Adapted Spoken Language Dialogue System: Measuring the Relevance of the Contextual Information Sources

We present an evaluation of a spoken language dialogue system with a module for the management of userrelated information, stored as user preferences and privileges. The flexibility of our dialogue management approach, based on Bayesian Networks (BN), together with a contextual information module, which performs different strategies for handling such information, allows us to include user information as a new level into the Context Manager hierarchy. We propose a set of objective and subjective metrics to measure the relevance of the different contextual information sources. The analysis of our evaluation scenarios shows that the relevance of the short-term information (i.e. the system status) remains pretty stable throughout the dialogue, whereas the dialogue history and the user profile (i.e. the middle-term and the long-term information, respectively) play a complementary role, evolving their usefulness as the dialogue evolves.

Relevance of motion-related assessment metrics in laparoscopic surgery

INTRODUCTION: Motion metrics have become an important source of information when addressing the assessment of surgical expertise. However, their direct relationship with the different surgical skills has not been fully explored. The purpose of this study is to investigate the relevance of motion-related metrics in the evaluation processes of basic psychomotor laparoscopic skills, as well as their correlation with the different abilities sought to measure. METHODS: A framework for task definition and metric analysis is proposed. An explorative survey was first conducted with a board of experts to identify metrics to assess basic psychomotor skills. Based on the output of that survey, three novel tasks for surgical assessment were designed. Face and construct validation study was performed, with focus on motion-related metrics. Tasks were performed by 42 participants (16 novices, 22 residents and 4 experts). Movements of the laparoscopic instruments were registered with the TrEndo tracking system and analyzed. RESULTS: Time, path length and depth showed construct validity for all three tasks. Motion smoothness and idle time also showed validity for tasks involving bi-manual coordination and tasks requiring a more tactical approach respectively. Additionally, motion smoothness and average speed showed a high internal consistency, proving them to be the most task-independent of all the metrics analyzed. CONCLUSION: Motion metrics are complementary and valid for assessing basic psychomotor skills, and their relevance depends on the skill being evaluated. A larger clinical implementation, combined with quality performance information, will give more insight on the relevance of the results shown in this study.

Relevance of the glottal pulse and the vocal tract in gender detection

Gender detection is a very important objective to improve efficiency in tasks as speech or speaker recognition, among others. Traditionally gender detection has been focused on fundamental frequency (f0) and cepstral features derived from voiced segments of speech. The methodology presented here consists in obtaining uncorrelated glottal and vocal tract components which are parameterized as mel-frequency coefficients. K-fold and cross-validation using QDA and GMM classifiers showed that better detection rates are reached when glottal source and vocal tract parameters are used in a gender-balanced database of running speech from 340 speakers.