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

HIF-independent synthetic lethality between CDK4/6 inhibition and VHL loss across species

This is the author accepted manuscript. The final version is available from AAAS via the DOI in this recordData and materials availability: The full dataset of the dsRNA screen in Drosophila S2R+cells is available at www.flyrnai.org/screensummary. All other data needed to evaluate the conclusions in the paper are present in the paper or the Supplementary Materials.Inactivation of the VHL tumor suppressor gene is the signature initiating event in clear cell renal cell carcinoma (ccRCC), the most common form of kidney cancer, and causes the accumulation of hypoxia-inducible factor 2α (HIF-2α). HIF-2α inhibitors are effective in some ccRCC cases, but both de novo and acquired resistance have been observed in the laboratory and in the clinic. Here, we identified synthetic lethality between decreased activity of cyclin-dependent kinases 4 and 6 (CDK4/6) and VHL inactivation in two species (human and Drosophila) and across diverse human ccRCC cell lines in culture and xenografts. Although HIF-2α transcriptionally induced the CDK4/6 partner cyclin D1, HIF-2α was not required for the increased CDK4/6 requirement of VHL−/− ccRCC cells. Accordingly, the antiproliferative effects of CDK4/6 inhibition were synergistic with HIF-2α inhibition in HIF-2α–dependent VHL−/− ccRCC cells and not antagonistic with HIF-2α inhibition in HIF-2α–independent cells. These findings support testing CDK4/6 inhibitors as treatments for ccRCC, alone and in combination with HIF-2α inhibitors.National Cancer InstituteDana-Farber Cancer InstituteHoward Hughes Medical InstituteNational Institute of General Medical Science

Beta-lactamic resistance profiles in porphyromonas, prevotella, and parvimonas species isolated from acute endodontic infections

Susceptibility to beta-lactamic agents has changed among anaerobic isolates from acute endodontic infections. The aim of the present study was to determine the prevalence of the cfxAlcfxA2 gene in Prevotella spp., Porphyromonas spp., and Parviomonas micra strains and show its phenotypic expression. Root canal samples from teeth with acute endodontic infections were collected and Porphyromonas, Prevotella, and Parvimonas micra strains were isolated and microbiologically identified with conventional culture techniques. The susceptibility of the isolates was determined by the minimum inhibitory concentration of benzylpenicillin, amoxicillin, and amoxicillin + clavulanate using the E-test method (AB BIODISK, Solna, Sweden). The presence of the cfxAlcfxA2 gene was determined through primer-specific polymerase chain reaction. The nitrocefin test was used to determine the expression of the lactamase enzyme. Prevotella disiens, Prevotella oralis, Porphyromonas gin givalis, and P micra strains were susceptible to benzylpenicillin, amoxicillin, and amoxicillin + clavulanate. The cfxA/cfxA2 gene was detected in 2 of 29 isolates (6.9%). Simultaneous detection of the cfxAlcfxA2 gene and lactamase production was observed for 1 Prevotella buccalis strain. The gene was in 1 P micra strain but was not expressed. Three strains were positive for lactamase production, but the cfxAlcfxA2 gene was not detected through polymerase chain reaction. There is a low prevalence of the cfxAl cfxA2 gene and its expression in Porphyromonas spp., Prevotella spp., and P. micra strains isolated from acute endodontic infections. Genetic and phenotypic screening must be performed simultaneously to best describe additional mechanisms involved in lactamic resistance for strict anaerobes403339344FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DO RIO GRANDE DO SUL - FAPERGSFederal University of Rio Grande do Su

Decrease in n-acetylaspartate following concussion may be coupled to decrease in creatine

Objectives: To assess the time course changes in brain N-acetylaspartate (NAA) and creatine (Cr) in athletes who suffered a sport-related concussion. Participants: Eleven non-consecutive concussed athletes and 11 sex and age-matched control volunteers. Main outcome measures: At 3, 15, 30 and 45 days post-injury, athletes were examined by proton Magnetic Resonance Spectroscopy (1H-MRS) for the determination of NAA,(Cr) and choline (Cho). 1H-MRS data recorded in the control group were used for comparison. Results: Compared to controls (2.18 ± 0.19), athletes showed an NAA/Cr increase at 3 (2.71 ± 0.16; p < 0.01) and 15 days (2.54 ± 0.21; p < 0.01), followed by a decrease and subsequent normalization at 30 (1.95 ± 0.16, p < 0.05) and 45 days(2.17 ± 0.20; p <0.05) post-concussion. NAA/Cho decreased at 3, 15 and 30 days post-injury (p < 0.01 compared to controls), with no differences from controls at 45 days post-concussion. Significant increase in the Cho/Cr after 3 (+33%, p < 0.01) and 15 (+31.5%, p < 0.01) days post-injury was observed, whilst no differences compared to controls were recorded at 30 and 45 days post-impact. Conclusions: This cohort of athletes indicates that concussion may cause concomitant decrease in cerebral NAA and Cr. This occurrence provokes longer time of metabolism normalization, as well as longer resolution time of concussion-associated clinical symptoms

High dose intermittent sorafenib shows improved efficacy over conventional continuous dose in renal cell carcinoma

<p>Abstract</p> <p>Background</p> <p>Renal cell carcinoma (RCC) responds to agents that inhibit vascular endothelial growth factor (VEGF) pathway. Sorafenib, a multikinase inhibitor of VEGF receptor, is effective at producing tumor responses and delaying median progression free survival in patients with cytokine refractory RCC. However, resistance to therapy develops at a median of 5 months. In an effort to increase efficacy, we studied the effects of increased sorafenib dose and intermittent scheduling in a murine RCC xenograft model.</p> <p>Methods</p> <p>Mice bearing xenografts derived from the 786-O RCC cell line were treated with sorafenib according to multiple doses and schedules: 1) Conventional dose (CD) continuous therapy; 2) high dose (HD) intermittent therapy, 3) CD intermittent therapy and 4) HD continuous therapy. Tumor diameter was measured daily. Microvessel density was assessed after 3 days to determine the early effects of therapy, and tumor perfusion was assessed serially by arterial spin labeled (ASL) MRI at day 0, 3, 7 and 10.</p> <p>Results</p> <p>Tumors that were treated with HD sorafenib exhibited slowed tumor growth as compared to CD using either schedule. HD intermittent therapy was superior to CD continous therapy, even though the total dose of sorafenib was essentially equivalent, and not significantly different than HD continuous therapy. The tumors exposed to HD sorafenib had lower microvessel density than the untreated or the CD groups. ASL MRI showed that tumor perfusion was reduced to a greater extent with the HD sorafenib at day 3 and at all time points thereafter relative to CD therapy. Further the intermittent schedule appeared to maintain RCC sensitivity to sorafenib as determined by changes in tumor perfusion.</p> <p>Conclusions</p> <p>A modification of the sorafenib dosing schedule involving higher dose intermittent treatment appeared to improve its efficacy in this xenograft model relative to conventional dosing. MRI perfusion imaging and histologic analysis suggest that this benefit is related to enhanced and protracted antiangiogenic activity. Thus, better understanding of dosing and schedule issues may lead to improved therapeutic effectiveness of VEGF directed therapy in RCC and possibly other tumors.</p

Regulation of TCL1 expression in B- and T-cell lymphomas and reactive lymphoid tissues

Chromosomal rearrangements observed in T-cell prolymphocytic leukemia involve the translocation of one T-cell receptor gene to either chromosome 14q32 or Xq28, deregulating the expression of cellular proto-oncogenes of unknown function, such as TCL1 or its homologue, MTCP1. In the human hematopoietic system, TCL1 expression is predominantly observed in developing B lymphocytes, whereas its overexpression in T cells causes mature T-cell proliferation in transgenic mice. In this study, using a newly generated monoclonal antibody against recombinant TCL1 protein, we extended our analysis mainly by immunohistochemistry and also by fluorescence-activated cell sorting and Western blot to a large tumor lymphoma data bank including 194 cases of lymphoproliferative disorders of B- and T-cell origin as well as reactive lymphoid tissues. The results obtained show that in reactive lymphoid tissues, TCL1 is strongly expressed by a subset of mantle zone B lymphocytes and is expressed to a lesser extent by follicle center cells and by scattered interfollicular small lymphocytes. In B-cell neoplasia, TCL1 was expressed in the majority of the cases, including lymphoblastic lymphoma, chronic lymphocytic leukemia, mantle cell lymphoma, follicular lymphoma, Burkitt lymphoma, diffuse large B-cell lymphoma (60%), and primary cutaneous B cell lymphoma (55%). TCL1 expression was observed in both the cytoplasmic and nuclear compartments, as confirmed by Western blot analysis. Conversely, TCL1 was not expressed in Hodgkin/Reed-Sternberg cells, multiple myelomas, marginal zone B-cell lymphomas, CD30+ anaplastic large cell lymphoma, lymphoblastic T-cell lymphoma, peripheral T-cell lymphoma, and mycosis fungoides. These data indicate that TCL1 is expressed in more differentiated B cells, under both reactive and neoplastic conditions, from antigen committed B cells and in germinal center B cells and is down-regulated in the latest stage of B-cell differentiation

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

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