Network measures in civil air transport: A case study of Lufthansa

Network analysis has already a long history in operations research and quantitative social science research. In the past, much attention has been paid to shortest-route algorithms (for example, the travelling salesman problem), where the spatial configuration of networks was put in the centre of empirical investigation. Integer programming, linear and nonlinear programming turned out to offer a proper analytical toolbox. In recent years, we have seen several new trends, in particular, the rise of hub-and-spoke systems in liberalized networks, the emergence of dynamic adjustments to new competitive conditions and the increase in complexity in international networks. Furthermore, it appears that in the past decades many social, spatial and economic systems show an organized pattern characterized by network features, such as transportation, telecommunication, information or energy systems. As a consequence, much attention has recently been paid to the study of network properties emerging in many social, spatial and economic fields, as witnessed by the vast amount of literature published in the past years. Air transport is a prominent example of modern network constellations and will be addressed in this paper from a connectivity perspective. Air transport shows indeed clear network features, which impact on the way single airline carriers operate. The abundant scientific literature on airline networks has addressed this topic in terms of theoretical modelling and empirical measurements on different typologies of airline network configurations. This strand of recent research aimed to measure the network structure in relation to the effects of: (a) the market deregulation in United States in 1978 and in the European Union in the 1990s, (b) new trends in recent airline business strategies denoted as \u2018low cost\u2019 principles. Low cost carriers developed rather fast after the deregulation policy, by acquiring a competitive network advantage on traditional airlines, which consequently seemed to reorganise rapidly their airline network to respond to the new market dynamics. In this context, interesting research has emerged that mainly addressed the issue of describing and classifying networks by means of geographical concentration indices of traffic or flight frequency. These measures, such as the Gini concentration index or the Theil index, provide a proper measure of frequency or traffic concentration of the main airports in a simple, well-organized network. However, if a real-world network structure is complex, including multi-hub or mixed point-to-point and hub-spokes connections, the concentration indices may record high values for all types of structure, but fail to clearly discriminate between different network shapes. There is a need for a more appropriate measurement of connectivity structures in complex networks. Starting from the above considerations and research challenges, the present paper aims to investigate the scientific potential and applicability of a series of network connectivity/concentration indices, in order to properly typify and map out complex airline network configurations. Specifically, these various network indicators will be adopted and tested to describe the main properties \u2013 in terms of the network connectivity and configuration \u2013 of Lufthansa\u2019s airline system

The surgical treatment of pituitary adenomas in the eighth decade

BACKGROUND The surgical treatment of pituitary adenomas in elderly patients (i.e., over 70 years of age) is a special problem because of the increased rate of perioperative complications and the reduced tolerance of postoperative fluid and electrolyte imbalance. Therefore, the unquestionable progress in the pharmacological and radiotherapy may not allow these patients the option of radical surgical treatment, We report our experience with the transsphenoidal procedure for pituitary adenomas in aged patients in an attempt to contribute to a better definition of the actual role of surgery. METHODS Transsphenoidal surgery was performed in 11 patients over 70 years of age affected by various histological types of pituitary micro- and macroadenomas, ranging from Hardy Grade I through IIIc, Special care was dedicated to the postoperative treatment, in particular to water and electrolyte balances, and to the immediate treatment of any pathological variation of these parameters. RESULTS We had no mortality and no postoperative adjunctive morbidity, All the patients recovered well from the operation with an average hospital stay of 20 days. The tumor removal was complete in six cases and partial in the remaining five. With an average follow-up of 2 years, we did observe only one case of symptomatic recurrence of the disease. CONCLUSIONS Transsphenoidal surgery in the elderly is feasible and quite safe in the hands of an experienced team, if special care is devoted to the preoperative selection of patients and to the postoperative treatment of fluid and electrolyte imbalanc

Cox-2 Inhibition Enhances the Activity of Sunitinib in Human Renal Cell Carcinoma Xenografts

Background: Sunitinib (Su), a tyrosine kinase inhibitor of VEGFR, is effective at producing tumour response in clear cell renal cell carcinoma (cRCC), but resistance to therapy is inevitable. As COX-2 is a known mediator of tumour growth, we explored the potential benefit of COX-2 inhibition in combination with VEGFR inhibition in attempts at delaying tumour progression on Su. Methods: COX-2 expression was compared with areas of hypoxia in tumours that progressed on Su vs untreated tumours. Mice bearing human cRCC xenografts were treated with Su and the COX-2 inhibitor, celecoxib, and the effects on tumour growth were assessed. Sequential vs concurrent regimens were compared. Results: COX-2 expression was increased in cRCC xenografts in areas of tumour hypoxia. The combination of Su and celecoxib achieved longer times to tumour progression compared to treatment with either agent alone or to untreated control animals in four models. This effect was seen with concurrent but not with sequential therapy. Conclusion: COX-2 inhibition can extend the effectiveness of VEGFR inhibition. This effect is dependent on the timing of therapy. Clinical trials combining Su and COX-2 inhibitors should be considered as a means delaying time to progression on sunitinib in patients with metastatic cRCC

p63 expression in normal skin and usual cutaneous carcinomas

Background: p63 is a p53 homologue that is mapped to chromosome 3q27. This gene encodes six different isoforms, which have either transactivating or dominant negative effects on p53-reporter genes. It has been described that in contrast to p53, p63 seems not to be associated with tumor predisposition, as neither p63 knockout mouse models nor germline p63 mutations are related to an increased risk of tumorigenesis. It has been demonstrated that p63 is a reliable keratinocyte stem cell marker and that it is involved in the maintenance of the stem cell population. Scant data on p63 expression in normal skin, basal cell carcinomas (BCCs), keratoacanthomas and squamous cell carcinomas (SCCs) have been reported. We herein evaluated p63 expression in 16 BCCs, one keratoacanthoma and 13 SCCs. Methods: Immunohistochemistry according to the streptavidinbiotin-peroxidase technique, using the antibody 4A4 raised against all p63 isoforms, was performed. p63 expression was evaluated in epidermal cells and skin appendages. Semi-quantitative evaluation (–, π, ππ, πππ) of p63 expression in BCCs, keratoacanthoma and SCCs was carried out. Only nuclear expression was considered as specific. Results: p63 was expressed in the nuclei of epidermal basal and suprabasal cells, in the cells of the germinative hair matrix and the external root sheath of hair follicles, in the basal cells of the sebaceous gland and in the myoepithelial/basal cells of the sweat glands. All terminally differentiated cells were negative for p63. All BCCs showed ππto πππ immunoreactivity. At variance, keratoacanthomas and grade I and II SCCs showed variable p63 reactivity in a basal layerlike distribution, whereas undifferentiated cells of grade III SCCs showed ππto πππ positivity. A grade IV spindle SCC showed π immunoreactivity. The SCCs in situ showed remarkable expression of p63 in all cell layers. Terminally differentiated squamous cells were either negative or showed only focal immunoreactivity in the carcinomas. Conclusions: p63 is consistently expressed in the basal cells of epidermis and cutaneous appendages, including the basal/ myoepithelial cells of sweat glands. Based on our findings, the balance of probabilities favors that p63 might play a role in the pattern of differentiation and in the oncogenesis of usual carcinomas of the skin.Fundação para a Ciência e a Tecnologia (FCT) - SFRH/BD/5386/2001. Fundação para a Ciência e a Tecnologia (FCT) – Programa Operacional “Ciência, Tecnologia, Inovação” (POCTI)

WNT signaling regulates self-renewal and differentiation of prostate cancer cells with stem cell characteristics

Prostate cancer cells with stem cell characteristics were identified in human prostate cancer cell lines by their ability to form from single cells self-renewing prostaspheres in non-adherent cultures. Prostaspheres exhibited heterogeneous expression of proliferation, differentiation and stem cell-associated makers CD44, ABCG2 and CD133. Treatment with WNT inhibitors reduced both prostasphere size and self-renewal. In contrast, addition of Wnt3a caused increased prostasphere size and self-renewal, which was associated with a significant increase in nuclear Β-catenin, keratin 18, CD133 and CD44 expression. As a high proportion of LNCaP and C4-2B cancer cells express androgen receptor we determined the effect of the androgen receptor antagonist bicalutamide. Androgen receptor inhibition reduced prostasphere size and expression of PSA, but did not inhibit prostasphere formation. These effects are consistent with the androgen-independent self-renewal of cells with stem cell characteristics and the androgen-dependent proliferation of transit amplifying cells. As the canonical WNT signaling effector Β-catenin can also associate with the androgen receptor, we propose a model for tumour propagation involving a balance between WNT and androgen receptor activity. That would affect the self-renewal of a cancer cell with stem cell characteristics and drive transit amplifying cell proliferation and differentiation. In conclusion, we provide evidence that WNT activity regulates the self-renewal of prostate cancer cells with stem cell characteristics independently of androgen receptor activity. Inhibition of WNT signaling therefore has the potential to reduce the self-renewal of prostate cancer cells with stem cell characteristics and improve the therapeutic outcome.Peer reviewe

Quantitative Observation of Magnetic Flux Distribution in New Magnetic Films for Future High Density Recording Media

International audienceOff-axis electron holography was used to observe and quantify the magnetic microstructure of a perpendicular magnetic anisotropic (PMA) recording media. Thin foils of PMA materials exhibit an interesting up and down domain configuration. These domains are found to be very stable and were observed at the same time with their stray field, closing magnetic flux in the vacuum. The magnetic moment can thus be determined locally in a volume as small as few tens of cubic nanometers

Calibration of multi-layered probes with low/high magnetic moments

We present a comprehensive method for visualisation and quantification of the magnetic stray field of magnetic force microscopy (MFM) probes, applied to the particular case of custom-made multi-layered probes with controllable high/low magnetic moment states. The probes consist of two decoupled magnetic layers separated by a non-magnetic interlayer, which results in four stable magnetic states: ±ferromagnetic (FM) and ±antiferromagnetic (A-FM). Direct visualisation of the stray field surrounding the probe apex using electron holography convincingly demonstrates a striking difference in the spatial distribution and strength of the magnetic flux in FM and A-FM states. In situ MFM studies of reference samples are used to determine the probe switching fields and spatial resolution. Furthermore, quantitative values of the probe magnetic moments are obtained by determining their real space tip transfer function (RSTTF). We also map the local Hall voltage in graphene Hall nanosensors induced by the probes in different states. The measured transport properties of nanosensors and RSTTF outcomes are introduced as an input in a numerical model of Hall devices to verify the probe magnetic moments. The modelling results fully match the experimental measurements, outlining an all-inclusive method for the calibration of complex magnetic probes with a controllable low/high magnetic moment

Prognostic factor from MR spectroscopy in rat with astrocytic tumour during radiation therapy

Objective: To investigate the relationship between the tumour volume and metabolic rates of astrocytic tumours using MR spectroscopy (MRS) during radiation therapy (RT). Methods: 12 healthy male Sprague-Dawley® rats (Sprague–Dawley Animal Company, Madison, WI) were used, and a tumour model was created through injecting C6 tumour cells into the right caudate nuclei of the rats. Tumours grew for 18 days after the injection and before the imaging study and radiation treatment. MRS was performed with two-dimensional multivoxel point-resolved spectroscopy sequence using a GE Signa VH/i 3.0-T MR scanner (GE Healthcare, Milwaukee, WI) equipped with rat-special coil. RT was given on the 19th day with a dose of 4 Gy in one single fraction. The image examinations were performed before RT, and on the 4th, 10th, 14th and 20th days after treatment, respectively. GE FuncTool software package (GE Healthcare) was used for post-processing of spectrum. Results: Metabolic ratios of serial MRS decrease progressively with time after RT. Choline-containing components (Cho)/creatine and creatine phosphate (Cr) ratios immediately prior to RT differed significantly from those on the 10th, 14th and 20th days after RT; both Cho/N-acetyl aspartate (NAA) ratios and NAA/Cr ratios immediately prior to RT differed significantly from those on the 14th and 20th days after RT. A positive correlation between changes of tumour volume and changes of Cho/Cr, lipid and lactate/Cr and glutamate plus glutamine/Cr ratio was observed on the 4th day after RT. Conclusion: MRS provides potential in monitoring tumour response during RT, and the imaging biomarkers predict the response of astrocytic tumours to treatment. Advances in knowledge: MRS is combined with both tumour size and Ki-67 labelling index to access tumour response to radiation.ECU Open Access Publishing Support Fun

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts