Human Rhinovirus at Naturally Occurring COPD Exacerbation

Chronic obstructive pulmonary disease (COPD) is an inflammatory condition of the lung caused by an abnormal response to particles and noxious gases, primarily cigarette smoke. Patients suffer daily symptoms and can have episodes of worsening symptoms termed acute exacerbations. Exacerbations are associated with impaired quality of life, faster lung function decline, higher mortality and increased risk of hospitalisation. The aetiology of COPD exacerbations is controversial; however respiratory viral and bacterial infections are an important feature of exacerbations. This study utilised real-time qPCR to measure prevalence and load of human rhinovirus (HRV) in stable COPD and during the time-course of naturally occurring exacerbations and their recovery. HRV was assessed in association with upper respiratory tract (URT) symptoms namely cold symptoms and sore throats, secondary bacterial infection, patient reported outcomes and exacerbation frequency. Additionally, respiratory syncytial virus (RSV) was semi-quantitatively examined in stable COPD and at exacerbation. The original contribution of this work to the field is that HRV prevalence and load are highest at exacerbation presentation and decrease during recovery. HRV load is higher in the presence of URT symptoms compared to the load without, and the load remains higher for longer with both symptoms compared to only one. This study described novel evidence for the development of secondary bacterial infection after HRV infection in natural exacerbations, and demonstrated that HRV infection is associated with patient reported outcomes. Patients with HRV had higher exacerbation frequencies compared to those without HRV. RSV prevalence did not change significantly between stable COPD and exacerbation. The findings from this thesis have important implications in terms of exacerbation therapy. The evidence provided may allow appropriate targeting of therapeutic interventions therefore reducing exacerbation severity and frequency. These findings emphasise the importance of rapid development of therapeutic targets for the prevention and treatment of HRV infection in COPD patients

Advanced Multilevel Node Separator Algorithms

A node separator of a graph is a subset S of the nodes such that removing S and its incident edges divides the graph into two disconnected components of about equal size. In this work, we introduce novel algorithms to find small node separators in large graphs. With focus on solution quality, we introduce novel flow-based local search algorithms which are integrated in a multilevel framework. In addition, we transfer techniques successfully used in the graph partitioning field. This includes the usage of edge ratings tailored to our problem to guide the graph coarsening algorithm as well as highly localized local search and iterated multilevel cycles to improve solution quality even further. Experiments indicate that flow-based local search algorithms on its own in a multilevel framework are already highly competitive in terms of separator quality. Adding additional local search algorithms further improves solution quality. Our strongest configuration almost always outperforms competing systems while on average computing 10% and 62% smaller separators than Metis and Scotch, respectively

Arsenicosis, possibly from contaminated groundwater, associated with noncirrhotic intrahepatic portal hypertension.

BACKGROUND AND AIMS: Idiopathic noncirrhotic intrahepatic portal hypertension (NCIPH), a chronic microangiopathy of the liver caused by arsenicosis from use of contaminated groundwater, was reported from Asia. This study aimed to see, if in the twenty-first century, arsenicosis was present in NCIPH patients at our hospital and, if present, to look for groundwater contamination by arsenic in their residential locality. METHODS: Twenty-seven liver biopsy proven NCIPH patients, 25 portal hypertensive controls with hepatitis B or C related cirrhosis and 25 healthy controls, matched for residential locality, were studied. Eighty-four percent to 96 % of study subjects belonged to middle or lower socioeconomic category. Arsenicosis was looked for by estimation of arsenic levels in finger/toe nails and by skin examination. Arsenic levels in nails and in ground water (in NCIPH patients with arsenicosis) was estimated by mass spectrometry. RESULTS: Nail arsenic levels were raised in five (10 %) portal hypertensive study subjects [two NCIPH patients (both had skin arsenicosis) and three portal hypertensive controls]. All of these five patients were residents of West Bengal or Bangladesh. Skin arsenicosis was noted in three NCIPH patients (11 %) compared to none of disease/healthy controls. Ground water from residential locality of one NCIPH patient with arsenicosis (from Bangladesh) showed extremely high level of arsenic (79.5 μg/L). CONCLUSIONS: Arsenicosis and microangiopathy of liver, possibly caused by environmental contamination continues in parts of Asia. Further studies are needed to understand the mechanisms of such 'poverty-linked thrombophilia'

Assessment of a novel, capsid-modified adenovirus with an improved vascular gene transfer profile

<p>Background: Cardiovascular disorders, including coronary artery bypass graft failure and in-stent restenosis remain significant opportunities for the advancement of novel therapeutics that target neointimal hyperplasia, a characteristic of both pathologies. Gene therapy may provide a successful approach to improve the clinical outcome of these conditions, but would benefit from the development of more efficient vectors for vascular gene delivery. The aim of this study was to assess whether a novel genetically engineered Adenovirus could be utilised to produce enhanced levels of vascular gene expression.</p> <p>Methods: Vascular transduction capacity was assessed in primary human saphenous vein smooth muscle and endothelial cells using vectors expressing the LacZ reporter gene. The therapeutic capacity of the vectors was compared by measuring smooth muscle cell metabolic activity and migration following infection with vectors that over-express the candidate therapeutic gene tissue inhibitor of matrix metalloproteinase-3 (TIMP-3).</p> <p>Results: Compared to Adenovirus serotype 5 (Ad5), the novel vector Ad5T*F35++ demonstrated improved binding and transduction of human vascular cells. Ad5T*F35++ mediated expression of TIMP-3 reduced smooth muscle cell metabolic activity and migration in vitro. We also demonstrated that in human serum samples pre-existing neutralising antibodies to Ad5T*F35++ were less prevalent than Ad5 neutralising antibodies.</p> <p>Conclusions: We have developed a novel vector with improved vascular transduction and improved resistance to human serum neutralisation. This may provide a novel vector platform for human vascular gene transfer.</p&gt

Cauchyness and convergence in fuzzy metric spaces

[EN] In this paper we survey some concepts of convergence and Cauchyness appeared separately in the context of fuzzy metric spaces in the sense of George and Veeramani. For each convergence (Cauchyness) concept we find a compatible Cauchyness (convergence) concept. We also study the relationship among them and the relationship with compactness and completeness (defined in a natural sense for each one of the Cauchy concepts). In particular, we prove that compactness implies p-completeness.Almanzor Sapena acknowledges the support of Ministry of Economy and Competitiveness of Spain under grant TEC2013-45492-R. Valentín Gregori acknowledges the support of Ministry of Economy and Competitiveness of Spain under grant MTM 2012-37894-C02-01.Gregori Gregori, V.; Miñana, J.; Morillas, S.; Sapena Piera, A. (2017). Cauchyness and convergence in fuzzy metric spaces. Revista de la Real Academia de Ciencias Exactas Físicas y Naturales Serie A Matemáticas. 111(1):25-37. https://doi.org/10.1007/s13398-015-0272-0S25371111Alaca, C., Turkoglu, D., Yildiz, C.: Fixed points in intuitionistic fuzzy metric spaces. Chaos Solitons Fractals 29, 1073–1078 (2006)Edalat, A., Heckmann, R.: A computational model for metric spaces. Theor. Comput. Sci. 193, 53–73 (1998)Engelking, R.: General topology. PWN-Polish Sci. Publ, Warsawa (1977)Fang, J.X.: On fixed point theorems in fuzzy metric spaces. Fuzzy Sets Syst. 46(1), 107–113 (1992)George, A., Veeramani, P.: On some results in fuzzy metric spaces. Fuzzy Sets Syst. 64, 395–399 (1994)George, A., Veeramani, P.: Some theorems in fuzzy metric spaces. J. Fuzzy Math. 3, 933–940 (1995)George, A., Veeramani, P.: On some results of analysis for fuzzy metric spaces. Fuzzy Sets Syst. 90, 365–368 (1997)Grabiec, M.: Fixed points in fuzzy metric spaces. Fuzzy Sets Syst. 27, 385–389 (1989)Gregori, V., Romaguera, S.: Some properties of fuzzy metric spaces. Fuzzy Sets Syst. 115, 485–489 (2000)Gregori, V., Romaguera, S.: On completion of fuzzy metric spaces. Fuzzy Sets Syst. 130, 399–404 (2002)Gregori, V., Romaguera, S.: Characterizing completable fuzzy metric spaces. Fuzzy Sets Syst. 144, 411–420 (2004)Gregori, V., López-Crevillén, A., Morillas, S., Sapena, A.: On convergence in fuzzy metric spaces. Topol. Appl. 156, 3002–3006 (2009)Gregori, V., Miñana, J.J.: Some concepts realted to continuity in fuzzy metric spaces. In: Proceedings of the conference in applied topology WiAT’13, pp. 85–91 (2013)Gregori, V., Miñana, J.-J., Sapena, A.: On Banach contraction principles in fuzzy metric spaces (2015, submitted)Gregori, V., Miñana, J.-J.: std-Convergence in fuzzy metric spaces. Fuzzy Sets Syst. 267, 140–143 (2015)Gregori, V., Miñana, J.-J.: Strong convergence in fuzzy metric spaces Filomat (2015, accepted)Gregori, V., Miñana, J.-J., Morillas, S.: Some questions in fuzzy metric spaces. Fuzzy Sets Syst. 204, 71–85 (2012)Gregori, V., Miñana, J.-J., Morillas, S.: A note on convergence in fuzzy metric spaces. Iran. J. Fuzzy Syst. 11(4), 75–85 (2014)Gregori, V., Morillas, S., Sapena, A.: On a class of completable fuzzy metric spaces. Fuzzy Sets Syst. 161, 2193–2205 (2010)Gregori, V., Morillas, S., Sapena, A.: Examples of fuzzy metric spaces and applications. Fuzzy Sets Syst. 170, 95–111 (2011)Kramosil, I., Michalek, J.: Fuzzy metric and statistical metric spaces. Kybernetika 11, 326–334 (1975)Mihet, D.: On fuzzy contractive mappings in fuzzy metric spaces. Fuzzy Sets Syst. 158, 915–921 (2007)Mihet, D.: Fuzzy $$\varphi$$ φ -contractive mappings in non-Archimedean fuzzy metric spaces. Fuzzy Sets Syst. 159, 739–744 (2008)Mihet, D.: A Banach contraction theorem in fuzzy metric spaces. Fuzzy Sets Syst. 144, 431–439 (2004)Mishra, S.N., Sharma, N., Singh, S.L.: Common fixed points of maps on fuzzy metric spaces Internat. J. Math. Math. Sci. 17(2), 253–258 (1994)Morillas, S., Sapena, A.: On Cauchy sequences in fuzzy metric spaces. In: Proceedings of the conference in applied topology (WiAT’13), pp. 101–108 (2013)Ricarte, L.A., Romaguera, S.: A domain-theoretic approach to fuzzy metric spaces. Topol. Appl. 163, 149–159 (2014)Sherwood, H.: On the completion of probabilistic metric spaces. Z.Wahrschein-lichkeitstheorie verw. Geb. 6, 62–64 (1966)Sherwood, H.: Complete Probabilistic Metric Spaces. Z. Wahrschein-lichkeitstheorie verw. Geb. 20, 117–128 (1971)Tirado, P.: On compactness and G-completeness in fuzzy metric spaces. Iran. J. Fuzzy Syst. 9(4), 151–158 (2012)Tirado, P.: Contraction mappings in fuzzy quasi-metric spaces and [0,1]-fuzzy posets. Fixed Point Theory 13(1), 273–283 (2012)Vasuki, R., Veeramani, P.: Fixed point theorems and Cauchy sequences in fuzzy metric spaces. Fuzzy Sets Syst. 135(3), 415–417 (2003)Veeramani, P.: Best approximation in fuzzy metric spaces. J. Fuzzy Math. 9, 75–80 (2001

Habitat Selection and Temporal Abundance Fluctuations of Demersal Cartilaginous Species in the Aegean Sea (Eastern Mediterranean)

Predicting the occurrence of keystone top predators in a multispecies marine environment, such as the Mediterranean Sea, can be of considerable value to the long-term sustainable development of the fishing industry and to the protection of biodiversity. We analysed fisheries independent scientific bottom trawl survey data of two of the most abundant cartilaginous fish species (Scyliorhinus canicula, Raja clavata) in the Aegean Sea covering an 11-year sampling period. The current findings revealed a declining trend in R. clavata and S. canicula abundance from the late ′90 s until 2004. Habitats with the higher probability of finding cartilaginous fish present were those located in intermediate waters (depth: 200–400 m). The present results also indicated a preferential species' clustering in specific geographic and bathymetric regions of the Aegean Sea. Depth appeared to be one of the key determining factors for the selection of habitats for all species examined. With cartilaginous fish species being among the more biologically sensitive fish species taken in European marine fisheries, our findings, which are based on a standardized scientific survey, can contribute to the rational exploitation and management of their stocks by providing important information on temporal abundance trends and habitat preferences

Sprint interval and sprint continuous training increases circulating CD34+ cells and cardio-respiratory fitness in young healthy women

The improvement of vascular health in the exercising limb can be attained by sprint interval training (SIT). However, the effects on systemic vascular function and on circulating angiogenic cells (CACs) which may contribute to endothelial repair have not been investigated. Additionally, a comparison between SIT and sprint continuous training (SCT) which is less time committing has not been made

Spondylarthritis presenting with an allergic immediate systemic reaction to adalimumab in a woman: a case report

<p>Abstract</p> <p>Introduction</p> <p>The efficacy of adalimumab, a fully human anti-tumor necrosis factor α recombinant antibody, has dramatically improved the quality of life of patients with rheumatoid and psoriatic arthritis and Crohn's disease. Because it is fully human, one should not expect immune reactions to this molecule. Adverse reactions to adalimumab are limited mainly to injection site reactions and are very common. Immediate systemic reactions are rarely reported.</p> <p>Case presentation</p> <p>We report the case of a 61-year-old Caucasian woman who was treated with adalimumab for spondylarthritis and developed injection site reactions after the sixth dose. After a two-month suspension, she recommenced therapy and experienced two systemic reactions. The first occurred after one hour with itching of the palms and soles and angioedema of the tongue and lips. Thirty minutes after the next dose the patient had itching of the palms and soles with diffusion to her whole body, angioedema of the lips, dizziness and visual disturbances. A skin-prick test and intra-dermal tests with adalimumab gave strong positive results at the immediate reading. However, serum-specific immunoglobulin E (IgE) to adalimumab were not detectable by using Phadia solid phase, especially harvested for this case, in collaboration with our Immunology and Allergy Laboratory Unit. Her total IgE concentration was 6.4 kU/L.</p> <p>Conclusion</p> <p>We describe what is, to the best of our knowledge, the first reported case of immediate systemic reaction to adalimumab studied with a skin test giving positive results and a serum-specific IgE assay giving negative results. The mechanism of the reaction must be immunologic but not IgE-mediated.</p