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Although modern clinical management strategies have improved the outcome of paediatric patients with severe autoimmune and inflammatory diseases over recent decades, a proportion will experience ongoing or recurrent/relapsing disease activity despite multiple therapies often leading to irreversible organ damage, and compromised quality of life, growth/development and long-term survival. Autologous and allogeneic haematopoietic stem cell transplantation (HSCT) have been used successfully to induce disease control and often apparent cure of severe treatment-refractory autoimmune diseases (ADs) in children. However, transplant-related outcomes are disease-dependent and long-term outcome data are limited in respect to efficacy and safety. Moreover, balancing risks of HSCT against AD prognosis with continually evolving non-transplant options is challenging. This review appraises published literature on HSCT strategies and outcomes in individual paediatric ADs. We also provide a summary of the European Society for Blood and Marrow Transplantation (EBMT) Registry, where 343 HSCT procedures (176 autologous and 167 allogeneic) have been reported in 326 children (

International audience; PMIP contributed to the Intergovernmental Panel on Climate Change (IPCC) Assessment Reports (ARs) by placing current climate change into a wider context, evaluating climate model performance in very different climatic states, and constraining climate sensitivity based on paleoclimates.

Modelling studies are evaluated by comparing the simulation outputs to an observational reference. In climate science, the number and complexity of the models and the mass of data have led the community to develop standardised methods and automated tools, such as the Climate Variability Diagnostic Package or the ESMValTool. However, these tools are mostly designed to evaluate simulations of the instrumental period. Different methods are required to compare paleoclimate simulations to palaeodata. For example, new variables are being modelled, such as vegetation, ice sheet extent, or isotopic ratio, and are used for the evaluation. Changing boundary conditions in transient simulations further complicate the evaluation process: traditional indices that characterise circulation (e.g. monsoon) or modes of variability (e.g. NAO, ENSO) need to be adapted, while new ones are needed to investigate modes of longer timescale and abrupt events. Finally, the palaeodata also present challenges: various type of uncertainty, complex relation to climate variables, and different spatio-temporal representativeness compared to model outputs. Here, we summarise the challenges of model-data comparison in paleo-climate studies. We then review some of the different methods and tools already developed by the community, such as biome comparison and Bayesian approaches to quantify model-data deviation. We finally discuss the implementation of an evaluation framework which aims to provide both adaptable tools to the community and automated standardised analyses.

The mid-Holocene (6,000 years ago) is a standard experiment for the evaluation of the simulated response of global climate models using paleoclimate reconstructions. The latest mid-Holocene simulations are a contribution by the Palaeoclimate Model Intercomparison Project (PMIP4) to the current phase of the Coupled Model Intercomparison Project (CMIP6). Here we provide an initial analysis and evaluation of the results of the experiment for the mid-Holocene. We show that state-of-the-art models produce climate changes that are broadly consistent with theory and observations, including increased summer warming of the northern hemisphere and associated shifts in tropical rainfall. Many features of the PMIP4-CMIP6 simulations were present in the previous generation (PMIP3-CMIP5) of simulations. The PMIP4-CMIP6 ensemble for the mid-Holocene has a global mean temperature change of -0.3 K, which is -0.2 K cooler that the PMIP3-CMIP5 simulations predominantly as a result of the prescription of realistic greenhouse gas concentrations in PMIP4-CMIP6. Neither this difference nor the improvement in model complexity and resolution seems to improve the realism of the simulations. Biases in the magnitude and the sign of regional responses identified in PMIP3-CMIP5, such as the amplification of the northern African monsoon, precipitation changes over Europe and simulated aridity in mid-Eurasia, are still present in the PMIP4-CMIP6 simulations. Despite these issues, PMIP4-CMIP6 and the mid-Holocene provide an opportunity both for quantitative evaluation and derivation of\ud emergent constraints on climate sensitivity and feedback strength.

These updated EBMT guidelines review the clinical evidence, registry activity and mechanisms of action of haematopoietic stem cell transplantation (HSCT) in multiple sclerosis (MS) and other immune-mediated neurological diseases and provide recommendations for patient selection, transplant technique, follow-up and future development. The major focus is on autologous HSCT (aHSCT), used in MS for over two decades and currently the fastest growing indication for this treatment in Europe, with increasing evidence to support its use in highly active relapsing remitting MS failing to respond to disease modifying therapies. aHSCT may have a potential role in the treatment of the progressive forms of MS with a significant inflammatory component and other immune-mediated neurological diseases, including chronic inflammatory demyelinating polyneuropathy, neuromyelitis optica, myasthenia gravis and stiff person syndrome. Allogeneic HSCT should only be considered where potential risks are justified. Compared with other immunomodulatory treatments, HSCT is associated with greater short-term risks and requires close interspeciality collaboration between transplant physicians and neurologists with a special interest in these neurological conditions before, during and after treatment in accredited HSCT centres. Other experimental cell therapies are developmental for these diseases and patients should only be treated on clinical trials.

Contains fulltext : 174409.pdf (Publisher’s version ) (Open Access)

This interdisciplinary study examines whether instances, variants, and translations of the human rights term كرامة (karāma, 'dignity') in the Leeds Parallel Corpus of Arabic-English Constitutions imply a shared understanding of the term from source to target text (i.e. from Arabic to English). Our approach combines quantitative and qualitative techniques from Corpus Linguistics and Arabic legal translation and contributes to theory and practice in the emerging field of computer-assisted legal linguistics and translation. Our research methodology includes: specification of morphological variants of كرامة in the Arabic corpus; close scrutiny of parallel concordance lines; and analysis of the semantic prosody of target terms through collocation discovery. In total, we identify 65 instances of كرامة (or one of its variants) in the Arabic data, where raw frequency of the term is highest in the constitutions of Egypt and Sudan, and missing in the constitution of Palestine. We find that while the indefinite noun كرامة is always translated as ‘dignity’ in English, the definite form (الكرامة, al-karāma) is often rendered via a qualifying adjective plus the word 'treatment'. We also find that the combination of الكرامة and negation leads to qualification of ‘treatment’ with notions of humiliation and cruelty. This is further evidenced via collocation discovery over the Arabic and English sub-corpora of 19 constitutions. This suggests a common understanding of كرامة and dignity as an inviolable human right across these different languages and cultures, fostered perhaps by the theological significance of these terms.

Human impacts prior to the Industrial Revolution are not well constrained. We investigate whether the decline in global atmospheric CO2 concentration by 7–10 ppm in the late 1500s and early 1600s which globally lowered surface air temperatures by 0.15∘C, were generated by natural forcing or were a result of the large-scale depopulation of the Americas after European arrival, subsequent land use change and secondary succession. We quantitatively review the evidence for (i) the pre-Columbian population size, (ii) their per capita land use, (iii) the post-1492 population loss, (iv) the resulting carbon uptake of the abandoned anthropogenic landscapes, and then compare these to potential natural drivers of global carbon declines of 7–10 ppm. From 119 published regional population estimates we calculate a pre-1492 CE population of 60.5 million (interquartile range, IQR 44.8–78.2 million), utilizing 1.04 ha land per capita (IQR 0.98–1.11). European epidemics removed 90% (IQR 87–92%) of the indigenous population over the next century. This resulted in secondary succession of 55.8 Mha (IQR 39.0–78.4 Mha) of abandoned land, sequestering 7.4 Pg C (IQR 4.9–10.8 Pg C), equivalent to a decline in atmospheric CO2 of 3.5 ppm (IQR 2.3–5.1 ppm CO2). Accounting for carbon cycle feedbacks plus LUC outside the Americas gives a total 5 ppm CO2 additional uptake into the land surface in the 1500s compared to the 1400s, 47–67% of the atmospheric CO2 decline. Furthermore, we show that the global carbon budget of the 1500s cannot be balanced until large-scale vegetation regeneration in the Americas is included. The Great Dying of the Indigenous Peoples of the Americas resulted in a human-driven global impact on the Earth System in the two centuries prior to the Industrial Revolution.

Interannual variability of African rainfall impacts local and global communities, but its past behavior and response in future climate projections are poorly understood. This is primarily due to short instrumental records and a lack of long high-resolution palaeoclimate proxy records. Here we present an annually resolved 91,000 year Early Pleistocene record of hydroclimate from the early hominin-bearing Makapansgat Valley, South Africa. Changes in speleothem annual band thickness are dominated by precession over four consecutive orbital cycles with strong millennial-scale periodicity. The frequency of interannual variability (2.0–6.5 yr oscillations) does not change systematically, yet its amplitude is modulated by the orbital forcing. These long-term characteristics of interannual variability are reproduced with transient climate model simulations of water balance for South Africa from the Late Pleistocene to Recent. Based on these results, we suggest that the frequency of interannual variations in southern African rainfall is likely to be stable under anthropogenic warming, but that the size of year-to-year variations may increase. We see an orbitally forced increase in the amplitude of interannual climate variability between 1.8 Ma and 1.7 Ma coincident with the first evidence for the Acheulean stone tool technology.

Autologous haematopoietic stem cell transplantation (AHSCT) is an emerging therapeutic option for refractory Crohn’s disease (CD). The ASTIC trial of AHSCT failed to meet its stringent composite primary endpoint, but 1-year follow-up data demonstrate sustained efficacy. The real-world use and outcomes of AHSCT for CD are unknown. Using the EBMT registry, we evaluated long-term outcomes for patients (pts) undergoing AHSCT for CD in Europe.

In this paper, we augment the Boundary Annotated Qur?an dataset published at LREC 2012 (Brierley et al 2012; Sawalha et al 2012a) with automatically generated phonemic transcriptions of Arabic words. We have developed and evaluated a comprehensive grapheme-phoneme mapping from Standard Arabic \ensuremath> IPA (Brierley et al under review), and implemented the mapping in Arabic transcription technology which achieves 100% accuracy as measured against two gold standards: one for Qur?anic or Classical Arabic, and one for Modern Standard Arabic (Sawalha et al [1]). Our mapping algorithm has also been used to generate a pronunciation guide for a subset of Qur?anic words with heightened prosody (Brierley et al 2014). This is funded research under the EPSRC " Working Together" theme.

Semantic Pathways is a corpus exploration tool with a unique visual interface in which keyword extraction and keyword-based document clustering have been implemented in order to facilitate insight forming. Semantic Pathways combines corpus comparison techniques from Corpus Linguistics with aesthetically-driven design and interaction to produce fluidly interactive information exploration. In addition, users can access Semantic Pathways via the command line, where integration with Python and NLTK offers additional benefits. We describe system operation from the user’s perspective, and then use the tool for corpus comparison of different varieties of English with the LOB and Brown corpora as test and reference sets, demonstrating its novelty in gisting an entire document collection and speedy and intuitive exploration of lexical usage across the document set.

Prosodic phrasing is the means by which speakers of any given language break up an utterance into meaningful chunks. The term ‘prosody’ itself refers to the tune or intonation of an utterance and therefore prosodic phrases literally signal the end of one tune and the beginning of another. This study uses phrase break annotations in the Aix-MARSEC Corpus of spoken English as a “gold standard” for measuring the degree of correspondence between prosodic phrases and the discrete syntactic grouping of prepositional phrases, where the latter is defined via a chunk parse rule using nltk_lite’s regular expression chunk parser. A three-way comparison is also introduced between “gold standard”, chunk parse rule and human judgement in the form of intuitive predictions about phrasing. Results show that even with a discrete syntactic grouping and a small sample of text (around 1400 words), problems arise for this rule-based method due to uncategorical behaviour in parts of speech. Lack of correspondence between intuitive prosodic phrases and corpus annotations highlights the optional nature of certain boundary types. Finally, there are clear indications, supported by corpus annotations, that significant prosodic phrase boundaries occur within sentences and not just at full stops.

The goal of automatic phrase break prediction is to identify prosodic-syntactic boundaries in text which correspond to the way a native speaker might process or chunk that same text as speech. This is treated as a classification task in machine learning and output predictions from language models are evaluated against a ‘gold standard’: human-labelled prosodic phrase break annotations in transcriptions of recorded speech - the speech corpus. Despite the introduction of rigorous metrics such as precision and recall, the evaluation of phrase break models is still problematic because prosody is inherently variable; morphosyntactic analysis and prosodic annotations for a given text are not representative of the range of parsing and phrasing strategies available to, and exhibited by, native speakers. This article recommends creating automatically-generated POS tagged and prosodically annotated variants of a text to enrich the gold standard and enable more robust ‘noise-tolerant’ evaluation of language models.

This special issue containing 24 papers emerged from a PAGES supported meeting "Palaeoclimate Modelling Intercomparison Project Phase 3 (PMIP3) Towards IPCC AR5" which took place from the 6 11 May 2012 in Crewe UK.