Treatment of Adult Patients with Relapsed/Refractory B-Cell Philadelphia-Negative Acute Lymphoblastic Leukemia

The majority of adult patients affected by B-cell acute lymphoblastic leukemia (B-ALL) will relapse after an initial response, while approximately 20% will display primary resistant disease. Patients suffering from relapsed/refractory B-ALL have a very poor outcome. Allogeneic hematopoietic cell transplantation (HCT) still represents the only curative approach, but is not so frequently feasible, because of patient’s fitness, donor availability, and the ability to achieve a remission prior to HCT. The estimated remission rates with conventional cytotoxic agents are around 30%, but they are short-lived. These disappointing results led to the introduction of new immunologic-based treatments—blinatumomab and inotuzumab. They produced a substantial improvement in terms of response rates, with the ability, in most cases, to induce a minimal residual disease (MRD)-negative status. Similarly, T cells engineered to express a CD19-specific chimeric antigen receptor (CAR-T) have yielded sensational results among patients with relapsed/refractory B-ALL, with unexpectedly high MRD-negative complete remissions rates. However, the first studies looking at long-term outcomes after CAR-T infusions told us that a significant fraction of such responses are not durable, and may benefit from a consolidation approach such as an allogeneic HCT

How Fast are the Tourism Countries Growing? The cross-country evidence

Specializing in tourism is an option available to a number of less developed countries and regions. But is it a good option? To answer this question, we have compared the relative growth performance of 14 “tourism countries” within a sample of 143 countries, observed during the period 1980-95. Using standard OLS cross-country growth regressions, we have documented that the tourism countries grow significantly faster than all the other sub-groups considered in our analysis (OECD, Oil, LDC, Small). Moreover, we have shown that the reason why they are growing faster is neither that they are poorer than the average; nor that they have particularly high saving/investment propensities; nor that they are very open to trade. In other words, the positive performance of the tourism countries is not significantly accounted for by the traditional growth factors of the Mankiw, Romer and Weil type of models. Tourism specialization appears to be an independent determinant. A corollary of our findings is that the role played by the tourism sector should not be ignored by the debate about whether smallness is harmful for growth (e.g. Easterly and Kraay (2000), who conclude that there is no growth disadvantage in smallness). Half of the thirty countries classified as microstates in this literature are heavily dependent on tourism. Once this distinction is adopted, it is easy to see that the small tourism countries perform much better than the remaining small countries. In our findings, smallness per se can be bad for growth, while the opposite is true when smallness goes together with a specialization in tourism.Economic growth, Convergence, Tourism specialization, Sustainable development

How Fast are Small Tourist Countries Growing? The 1980-2003 Evidence

We analyze the empirical relationship between growth, country size and tourism specialization by using a dataset covering the period 1980-2003. We find that tourism countries grow significantly faster than all the other sub-groups considered in our analysis. Tourism appears to be an independent determining factor for growth, and the reason for that is neither because they are poorer than the average, nor because they are very open to trade. Another finding of our paper is that small states are fast-growing only when they are highly specialized in tourism. In contrast with some previous conclusions in the literature, smallness per se is not good for growth.Small States, Growth, Tourism, Cross Country Comparisons

Non-Destructive Inspection of Impact Damage in Composite Aircraft Panels by Ultrasonic Guided Waves and Statistical Processing.

This paper discusses a non-destructive evaluation (NDE) technique for the detection of damage in composite aircraft structures following high energy wide area blunt impact (HEWABI) from ground service equipment (GSE), such as heavy cargo loaders and other heavy equipment. The test structures typically include skin, co-cured stringers, and C-frames that are bolt-connected onto the skin with shear ties. The inspection exploits the waveguide geometry of these structures by utilizing ultrasonic guided waves and a line scan approach. Both a contact prototype and a non-contact prototype were developed and tested on realistic test panels subjected to impact in the laboratory. The results are presented in terms of receiver operating characteristic curves that show excellent probability of detection with low false alarm rates for defects located in the panel skin and stringers

On the number of limit cycles in asymmetric neural networks

The comprehension of the mechanisms at the basis of the functioning of complexly interconnected networks represents one of the main goals of neuroscience. In this work, we investigate how the structure of recurrent connectivity influences the ability of a network to have storable patterns and in particular limit cycles, by modeling a recurrent neural network with McCulloch-Pitts neurons as a content-addressable memory system. A key role in such models is played by the connectivity matrix, which, for neural networks, corresponds to a schematic representation of the "connectome": the set of chemical synapses and electrical junctions among neurons. The shape of the recurrent connectivity matrix plays a crucial role in the process of storing memories. This relation has already been exposed by the work of Tanaka and Edwards, which presents a theoretical approach to evaluate the mean number of fixed points in a fully connected model at thermodynamic limit. Interestingly, further studies on the same kind of model but with a finite number of nodes have shown how the symmetry parameter influences the types of attractors featured in the system. Our study extends the work of Tanaka and Edwards by providing a theoretical evaluation of the mean number of attractors of any given length $L$ for different degrees of symmetry in the connectivity matrices.Comment: 35 pages, 12 figure

CXCR4 pos circulating progenitor cells coexpressing monocytic and endothelial markers correlating with fibrotic clinical features are present in the peripheral blood of patients affected by systemic sclerosis

There is still controversy regarding the role of circulating endothelial and progenitor cells (CECs/CEPs) in the pathogenesis of systemic sclerosis (SSc). Using a sequential Boolean gating strategy based on a 4-color flow cytometric protocol, an increased number of CD31(pos)/CD184(pos)(CXCR4)/CD34(pos)/CD45(pos) and CD31(pos)/CD117(pos) (c-kit-R) /CD34(pos)/ CD45(pos) hematopoietic circulating progenitor cells (HCPCs) was detected in SSc patients compared with healthy subjects. In SSc, no circulating mature and progenitor endothelial cells were observed, while an enhanced generation of erythroid progenitor cells was found to be correlated with the presence of CD117+ HCPCs. The presence of freshly detected CXCR4posHCPC was correlated either to the in vitro cultured spindle-shaped endothelial like cells (SELC) with an endo/myelomonocytic profile or to SDF-1 and VEGF serum level. These data are related to more fibrotic clinical features of the disease, thus supporting a possible role of these cells in fibrosis