Extramedullary relapse of IgA-lambda myeloma after recent bortezomib therapy: a case report

Intracranial plasmacytomas are an uncommon presentation of extramedullary relapse of multiple myeloma. The optimal management of extramedullary plasmacytomas remains unclear, with initial reports of bortezomib showing promising clinical results. We describe a case of multiple extracellular, including intracranial, plasmacytoma, with no evidence of marrow involvement, in a patient with relapsed IgA multiple myeloma. To our knowledge, this is the first reported case of a patient with rapid extramedullary relapse of disease despite recent exposure to bortezomib and dexamethasone

Travelling for Umrah:destination attributes, destination image, and post-travel intentions

This paper examines the links between cosmopolitanism, self-identity, and a desire for social interaction perceived destination image and behavioural intentions. A model tested using a sample of 538 Iranian visitors to Mecca for the purpose of Umrah. The result from the structural model suggests that destination attributes influence perceived destination image. Further, such tourists are likely to revisit or recommend Islamic destinations if their experience matches their perceived image of the destination. This implies that, while the religious characteristics of the destination remain important, destination managers cannot disregard the tangential, non-religious attributes of a destination which are crucial in order to satisfy more conventional tourist desires. As such, this study suggests that those managing religious travel destinations should endeavour to foster a welcoming image, where experience, interaction and tolerance are at the forefront of the destination’s offering

Contrasting responses of mean and extreme snowfall to climate change

Snowfall is an important element of the climate system, and one that is expected to change in a warming climate. Both mean snowfall and the intensity distribution of snowfall are important, with heavy snowfall events having particularly large economic and human impacts. Simulations with climate models indicate that annual mean snowfall declines with warming in most regions but increases in regions with very low surface temperatures. The response of heavy snowfall events to a changing climate, however, is unclear. Here I show that in simulations with climate models under a scenario of high emissions of greenhouse gases, by the late twenty-first century there are smaller fractional changes in the intensities of daily snowfall extremes than in mean snowfall over many Northern Hemisphere land regions. For example, for monthly climatological temperatures just below freezing and surface elevations below 1,000 metres, the 99.99th percentile of daily snowfall decreases by 8% in the multimodel median, compared to a 65% reduction in mean snowfall. Both mean and extreme snowfall must decrease for a sufficiently large warming, but the climatological temperature above which snowfall extremes decrease with warming in the simulations is as high as −9 °C, compared to −14 °C for mean snowfall. These results are supported by a physically based theory that is consistent with the observed rain–snow transition. According to the theory, snowfall extremes occur near an optimal temperature that is insensitive to climate warming, and this results in smaller fractional changes for higher percentiles of daily snowfall. The simulated changes in snowfall that I find would influence surface snow and its hazards; these changes also suggest that it may be difficult to detect a regional climate-change signal in snowfall extremes.National Science Foundation (U.S.) (Grant AGS-1148594)United States. National Aeronautics and Space Administration (ROSES Grant 09-IDS09-0049

Inhibition abilities and functional brain connectivity in school-aged term-born and preterm-born children

Background Inhibition abilities are known to have impact on self-regulation, behavior, and academic success, and they are frequently impaired in children born preterm. We investigated the possible contributions of resting-state functional brain connectivity to inhibition following preterm birth. Methods Forty-four preterm and 59 term-born participants aged 8–13 years were administered two inhibition tasks and resting-state functional MRI was performed. Functional connectivity (FC) networks were compared between groups using network-based statistics. Associations of FCNs and inhibition abilities were investigated through multivariate linear regression models accounting for the interaction between birth status and inhibition. Results NBS revealed weaker FC in children born preterm compared to term-born peers in connections between motor and supplementary motor regions, frontal lobe, precuneus, and insula. Irrespective of birth status, connections between the cerebellum, frontal, and occipital lobes and inter-lobar, subcortical, intra-hemispheric long-range connections were positively correlated with one of the two inhibition tasks. Conclusions Preterm birth results in long-term alterations of FC at network level but these FCN alterations do not specifically account for inhibition problems in children born very preterm. Impact Irrespective of birth status, significant associations were found between the subdomain of response inhibition and functional connectivity in some subnetworks. A group comparisons of functional brain connectivity measured by rsfMRI in school-aged children born very preterm and at term. The investigation of network-level functional connectivity at rest does not appear adequate to explain differences in inhibition abilities between children born very preterm and at term, hence other imaging techniques might be more suited to explore the underlying neural mechanisms of inhibition abilities in school-aged children born very preterm

Blood-Based Protein Changes in Childhood Are Associated With increased risk for later psychotic disorder: evidence from a nested case–control study of the ALSPAC Longitudinal Birth Cohort

The identification of early biological changes associated with the psychotic disorder (PD) is important as it may provide clues to the underlying pathophysiological mechanisms. We undertook the first proteomic profiling of blood plasma samples of children who later develop a PD. Participants were recruited from the UK Avon Longitudinal Study of Parents and Children (ALSPAC) cohort who also participated in psychiatric assessment interviews at age 18. Protein expression levels at age 11 were compared between individuals who developed PD at age 18 (n = 37) with population-based age-matched controls (n = 38). Sixty out of 181 plasma proteins profiled were found to be differentially expressed (P < .05) in children with an outcome of the PD. Thirty-four of these proteins were found to be differentially expressed following correction for multiple comparisons. Pathway analysis implicated the complement and coagulation cascade. A second, targeted proteomic approach was used to verify these findings in age 11 plasma from subjects who reported psychotic experiences at age 18 (n = 40) in comparison to age-matched controls (n = 66). Our findings indicate that the complement and coagulation system is dysregulated in the blood during childhood before the development of the PD

Scaffolding development and the human condition

This paper addresses the concept of semiotic scaffolding by considering it in light of questions arising from the contemporary challenge to the humanities. This challenge comes from a mixture of scientistic demands, opportunism on the part of Western governments in thrall to neo-liberalism, along with crass economic utilitarianism. In this paper we attempt to outline what a theory of semiotic scaffolding may offer to an understanding of the humanities’ contemporary role, as well as what the humanities might offer to the elucidation of semiotic scaffolding. We argue that traditional humanist positions adopted in defence of the humanities fail to articulate the enhancement of humanity that semiotic scaffolding represents. At the same time, we note that the concept of scaffolding is sometimes in danger of taking on a functionalist perspective which understanding the humanities modus operandi is likely to dispel. Putting forward these arguments, we draw on the work of Peirce, Cassirer and Sebeok in elucidating the structural and ‘future-orientated’ benefits of the scaffolding process as it suffuses the humanities

Assessing variations of extreme indices inducing weather-hazards on critical infrastructures over Europe?the INTACT framework

Extreme weather events are projected to be more frequent and severe across the globe because of global warming. This poses challenging problems for critical infrastructures, which could be dramatically affected (or disrupted), and may require adaptation plans to the changing climate conditions. The INTACT FP7-European project evaluated the resilience and vulnerability of critical infrastructures to extreme weather events in a climate change scenario. To identify changes in the hazard induced by climate change, appropriate extreme weather indicators (EWIs), as proxies of the main atmospheric features triggering events with high impact on the infrastructures, were defined for a number of case studies and different approaches were analyzed to obtain local climate projections. We considered the influence of weighting and bias correction schemes on the delta approach followed to obtain the resulting projections, considering data from the Euro-CORDEX ensemble of regional future climate scenarios over Europe. The aim is to provide practitioners, decision-makers, and administrators with appropriate methods to obtain actionable and plausible results on local/regional future climate scenarios. Our results show a small sensitivity to the weighting approach and a large sensitivity to bias correcting the future projections.This work has been carried out within the activities of INTACT project, receiving funding from the European Union Seventh Framework Programme (FP7/2007-2013) under grant agreement n° FP7-SEC-2013-1-606799. The information and views set out in this paper are those of the authors and do not necessarily reflect the opinion of the European Union. We acknowledge the World Climate Research Programme's Working Group on Regional Climate, and the Working Group on Coupled Modelling, former coordinating body of CORDEX and responsible panel for CMIP5

Systemic inflammatory response predicts outcome in patients undergoing resection for ductal adenocarcinoma head of pancreas

The aim of the present study was to examine the relationship between the clinicopathological status, the pre- and postoperative systemic inflammatory response and survival in patients undergoing potentially curative resection for ductal adenocarcinoma of the head of the pancreas. Patients (n=65) who underwent resection of ductal adenocarcinoma of the head of pancreas between 1993 and 2001, and had pre- and postoperative measurements of C-reactive protein, were included in the study. The majority of patients had stage III disease (International Union Against Cancer Criteria, IUCC), positive circumferential margin involvement (R1), tumour size greater than 25 mm with perineural and lymph node invasion and died within the follow-up period. On multivariate analysis, tumour size (hazard ratio (HR) 2.10, 95% confidence interval (CI) 1.20–3.68, P=0.009), vascular invasion (HR 2.58, 95% CI 1.48–4.50, P<0.001) and postoperative C-reactive protein (HR 2.00, 95% CI 1.14–3.52, P=0.015) retained independent significance. Those patients with a postoperative C-reactive protein ⩽10 mg l−1 had a median survival of 21.5 months compared with 8.4 months in those patients with a C-reactive protein >10 mg l−1 (P<0.001). The results of the present study indicate that, in patients who have undergone potentially curative resection for ductal adenocarcinoma of the head of pancreas, the presence of a systemic inflammatory response predicts poor outcome