Low back pain, quality of life and function in people with incomplete spinal cord injury in USA, UK and Greece

This thesis was submitted for the degree of Doctor of Philosophy and awarded by Brunel University.BACKGROUND: Pain is a common consequence of Spinal Cord Injury (SCI). While research into pain in SCI is vast, examining musculoskeletal pain (MSKP) and low back pain (LBP) are limited. This thesis aims to investigate these categories of pain in incomplete SCI (iSCI). The experience of pain is known to affect quality of life (QoL) and function. The impact of the experience of pain, particularly of LBP, on both the QoL and function are examined in this research. While research in similar fields is predominantly conducted in single nation populations this research is set out to study three different nations. METHOD: The following were part of this study: • A systematic literature review on the prevalence on chronic back pain (BP), LBP and MSKP in SCI. • A translation, and preliminary validation, into Greek of the Spinal Cord Independence Measure (SCIM version III). • A cross-national survey conducted in the USA, UK and Greece. Questionnaires included the short-form McGill Pain questionnaire (SF-MPQ), EQ-5D and the SCIM III. They were collected either online or via post and 219 questionnaires were analysed. RESULTS: The papers included in the systematic literature review were considerably heterogeneous not allowing meta-analysis to be made. 95% confidence intervals (CI) for the total number of participants in the studies were used. Among people with pain the prevalence of chronic MSKP (CMSKP) was 49% (95%CI 44%, 55%), of chronic BP (CBP) was 47% (95%CI 43%, 50%) and chronic LBP (CLBP) was 49% (95%CI 44%, 55%). GR-SCIM III maintains its unidimensionality and has acceptable internal consistency (α=0.78). Concurrent/criterion validity for the two cross-examined subscales were strong for “self-care” (ρ=-0.78) and moderate for “mobility” (ρ=-0.58). Unidimensionality was also confirmed for the English version of SCIM III, which had accepted internal consistency (α=0.79) and strong concurrent/criterion validity for “self-care” (ρ=-0.75) and moderate for “mobility” (ρ=-0.45). The survey results showed that the prevalence of current LBP is 67.9% (95%CI 61%, 73%) and of MSKP is 38.8% (95%CI 32%, 45%). LBP was of moderate intensity and most commonly described as “aching”. People who report pain, LBP or MSKP reported worse QoL. The impact of LBP on QoL was greater than that of pain in general or MSKP. The increased intensity of LBP correlated with worse function. Among the three participating countries, people from the UK had the worst experience of pain and LBP, classified themselves with the worst health status and reported the worst functional independence. CONCLUSION: This study offers the first systematic review on CLBP, CBP and CMSKP in SCI. It is unique in using SCIM III by self-report and into Greek. The results show that LBP is highly present in iSCI affecting both QoL and function. Both the GR-SCIM III and the SCIM III are reliable for use, however studies are needed to examine further their psychometric properties. The findings of the study fit with features of the currently used patients’ rehabilitation models.This research is funded by the EPSR

The transmittable through stinging microbiota differs between honeybees and wasps: a potentially greater microbial risk of the wasp sting for humans

The present research investigated whether accidental contact through stinging with honeybees, wasps, and hornets could represent a microbial hazard for humans. It has been previously suggested that such contact may transmit pathogens causing infections that could even be fatal for some susceptible individuals. Stinging simulation experiments were performed in the lab with live insects collected from the environment in Lemnos Island (north-eastern Greece), while different selective agar media targeting some clinically important bacteria (i.e., Staphylococcus aureus, Streptococcus pyogenes, Enterococcus faecalis/faecium, and Pseudomonas aeruginosa) were used as substrates for microbial recovery and identification. Results revealed none of the target pathogenic bacterial species in the honeybee samples, with bacilli, staphylococci, and micrococci dominating their surveyed microbiota. However, most of the suspect colonies isolated from wasps and hornets belonged to important hygienic indicators (i.e., enterococci, Proteus mirabilis, and coliforms), implying possible contact of these insects with fecal origin materials. To sum up, the microbiota that may be transmitted to humans through stinging appears to differ between honeybees and wasps/hornets, while the isolation from the latter samples of some other important opportunistic pathogens, such as Enterobacter spp. and Klebsiella spp., also known for multidrug resistance, could be an additional reason of concern

Common non-synonymous SNPs associated with breast cancer susceptibility: findings from the Breast Cancer Association Consortium.

Candidate variant association studies have been largely unsuccessful in identifying common breast cancer susceptibility variants, although most studies have been underpowered to detect associations of a realistic magnitude. We assessed 41 common non-synonymous single-nucleotide polymorphisms (nsSNPs) for which evidence of association with breast cancer risk had been previously reported. Case-control data were combined from 38 studies of white European women (46 450 cases and 42 600 controls) and analyzed using unconditional logistic regression. Strong evidence of association was observed for three nsSNPs: ATXN7-K264R at 3p21 [rs1053338, per allele OR = 1.07, 95% confidence interval (CI) = 1.04-1.10, P = 2.9 × 10(-6)], AKAP9-M463I at 7q21 (rs6964587, OR = 1.05, 95% CI = 1.03-1.07, P = 1.7 × 10(-6)) and NEK10-L513S at 3p24 (rs10510592, OR = 1.10, 95% CI = 1.07-1.12, P = 5.1 × 10(-17)). The first two associations reached genome-wide statistical significance in a combined analysis of available data, including independent data from nine genome-wide association studies (GWASs): for ATXN7-K264R, OR = 1.07 (95% CI = 1.05-1.10, P = 1.0 × 10(-8)); for AKAP9-M463I, OR = 1.05 (95% CI = 1.04-1.07, P = 2.0 × 10(-10)). Further analysis of other common variants in these two regions suggested that intronic SNPs nearby are more strongly associated with disease risk. We have thus identified a novel susceptibility locus at 3p21, and confirmed previous suggestive evidence that rs6964587 at 7q21 is associated with risk. The third locus, rs10510592, is located in an established breast cancer susceptibility region; the association was substantially attenuated after adjustment for the known GWAS hit. Thus, each of the associated nsSNPs is likely to be a marker for another, non-coding, variant causally related to breast cancer risk. Further fine-mapping and functional studies are required to identify the underlying risk-modifying variants and the genes through which they act.BCAC is funded by Cancer Research UK (C1287/A10118, C1287/A12014) and by the European Community’s Seventh Framework Programme under grant agreement n8 223175 (HEALTH-F2–2009-223175) (COGS). Meetings of the BCAC have been funded by the European Union COST programme (BM0606). Genotyping of the iCOGS array was funded by the European Union (HEALTH-F2-2009-223175), Cancer Research UK (C1287/A10710), the Canadian Institutes of Health Research for the ‘CIHR Team in Familial Risks of Breast Cancer’ program and the Ministry of Economic Development, Innovation and Export Trade of Quebec (PSR-SIIRI-701). Additional support for the iCOGS infrastructure was provided by the National Institutes of Health (CA128978) and Post-Cancer GWAS initiative (1U19 CA148537, 1U19 CA148065 and 1U19 CA148112—the GAME-ON initiative), the Department of Defence (W81XWH-10-1-0341), Komen Foundation for the Cure, the Breast Cancer Research Foundation, and the Ovarian Cancer Research Fund. The ABCFS and OFBCR work was supported by grant UM1 CA164920 from the National Cancer Institute (USA). The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centers in the Breast Cancer Family Registry (BCFR), nor does mention of trade names, commercial products or organizations imply endorsement t by the US Government or the BCFR. The ABCFS was also supported by the National Health and Medical Research Council of Australia, the New South Wales Cancer Council, the Victorian Health Promotion Foundation (Australia) and the Victorian Breast Cancer Research Consortium. J.L.H. is a National Health and Medical Research Council (NHMRC) Senior Principal Research Fellow and M.C.S. is a NHMRC Senior Research Fellow. The OFBCR work was also supported by the Canadian Institutes of Health Research ‘CIHR Team in Familial Risks of Breast Cancer’ program. The ABCS was funded by the Dutch Cancer Society Grant no. NKI2007-3839 and NKI2009-4363. The ACP study is funded by the Breast Cancer Research Trust, UK. The work of the BBCC was partly funded by ELAN-Programme of the University Hospital of Erlangen. The BBCS is funded by Cancer Research UK and Breakthrough Breast Cancer and acknowledges NHS funding to the NIHR Biomedical Research Centre, and the National Cancer Research Network (NCRN). E.S. is supported by NIHR Comprehensive Biomedical Research Centre, Guy’s & St. Thomas’ NHS Foundation Trust in partnership with King’s College London, UK. Core funding to the Wellcome Trust Centre for Human Genetics was provided by the Wellcome Trust (090532/Z/09/Z). I.T. is supported by the Oxford Biomedical Research Centre. The BSUCH study was supported by the Dietmar-Hopp Foundation, the Helmholtz Society and the German Cancer Research Center (DKFZ). The CECILE study was funded by the Fondation de France, the French National Institute of Cancer (INCa), The National League against Cancer, the National Agency for Environmental l and Occupational Health and Food Safety (ANSES), the National Agency for Research (ANR), and the Association for Research against Cancer (ARC). The CGPS was supported by the Chief Physician Johan Boserup and Lise Boserup Fund, the Danish Medical Research Council and Herlev Hospital.The CNIO-BCS was supported by the Genome Spain Foundation the Red Temática de Investigación Cooperativa en Cáncer and grants from the Asociación Española Contra el Cáncer and the Fondo de Investigación Sanitario PI11/00923 and PI081120). The Human Genotyping-CEGEN Unit, CNIO is supported by the Instituto de Salud Carlos III. D.A. was supported by a Fellowship from the Michael Manzella Foundation (MMF) and was a participant in the CNIO Summer Training Program. The CTS was initially supported by the California Breast Cancer Act of 1993 and the California Breast Cancer Research Fund (contract 97-10500) and is currently funded through the National Institutes of Health (R01 CA77398). Collection of cancer incidence e data was supported by the California Department of Public Health as part of the statewide cancer reporting program mandated by California Health and Safety Code Section 103885. HAC receives support from the Lon V Smith Foundation (LVS39420). The ESTHER study was supported by a grant from the Baden Württemberg Ministry of Science, Research and Arts. Additional cases were recruited in the context of the VERDI study, which was supported by a grant from the German Cancer Aid (Deutsche Krebshilfe). The GENICA was funded by the Federal Ministry of Education and Research (BMBF) Germany grants 01KW9975/5, 01KW9976/8, 01KW9977/0 and 01KW0114, the Robert Bosch Foundation, Stuttgart, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr University Bochum (IPA), as well as the Department of Internal Medicine , Evangelische Kliniken Bonn gGmbH, Johanniter Krankenhaus Bonn, Germany. The HEBCS was supported by the Helsinki University Central Hospital Research Fund, Academy of Finland (132473), the Finnish Cancer Society, The Nordic Cancer Union and the Sigrid Juselius Foundation. The HERPACC was supported by a Grant-in-Aid for Scientific Research on Priority Areas from the Ministry of Education, Science, Sports, Culture and Technology of Japan, by a Grant-in-Aid for the Third Term Comprehensive 10-Year strategy for Cancer Control from Ministry Health, Labour and Welfare of Japan, by a research grant from Takeda Science Foundation , by Health and Labour Sciences Research Grants for Research on Applying Health Technology from Ministry Health, Labour and Welfare of Japan and by National Cancer Center Research and Development Fund. The HMBCS was supported by short-term fellowships from the German Academic Exchange Program (to N.B), and the Friends of Hannover Medical School (to N.B.). Financial support for KARBAC was provided through the regional agreement on medical training and clinical research (ALF) between Stockholm County Council and Karolinska Institutet, the Stockholm Cancer Foundation and the Swedish Cancer Society. The KBCP was financially supported by the special Government Funding (EVO) of Kuopio University Hospital grants, Cancer Fund of North Savo, the Finnish Cancer Organizations, the Academy of Finland and by the strategic funding of the University of Eastern Finland. kConFab is supported by grants from the National Breast Cancer Foundation , the NHMRC, the Queensland Cancer Fund, the Cancer Councils of New South Wales, Victoria, Tasmania and South Australia and the Cancer Foundation of Western Australia. The kConFab Clinical Follow Up Study was funded by the NHMRC (145684, 288704, 454508). Financial support for the AOCS was provided by the United States Army Medical Research and Materiel Command (DAMD17-01-1-0729), the Cancer Council of Tasmania and Cancer Foundation of Western Australia and the NHMRC (199600). G.C.T. and P.W. are supported by the NHMRC. LAABC is supported by grants (1RB-0287, 3PB-0102, 5PB-0018 and 10PB-0098) from the California Breast Cancer Research Program. Incident breast cancer cases were collected by the USC Cancer Surveillance Program (CSP) which is supported under subcontract by the California Department of Health. The CSP is also part of the National Cancer Institute’s Division of Cancer Prevention and Control Surveillance, Epidemiology, and End Results Program, under contract number N01CN25403. LMBC is supported by the ‘Stichting tegen Kanker’ (232-2008 and 196-2010). The MARIE study was supported by the Deutsche Krebshilfe e.V. (70-2892-BR I), the Federal Ministry of Education Research (BMBF) Germany (01KH0402), the Hamburg Cancer Society and the German Cancer Research Center (DKFZ). MBCSG is supported by grants from the Italian Association ciation for Cancer Research (AIRC) and by funds from the Italian citizens who allocated a 5/1000 share of their tax payment in support of the Fondazione IRCCS Istituto Nazionale Tumori, according to Italian laws (INT-Institutional strategic projects ‘5 × 1000’). The MCBCS was supported by the NIH grants (CA122340, CA128978) and a Specialized Program of Research Excellence (SPORE) in Breast Cancer (CA116201), the Breast Cancer Research Foundation and a generous gift from the David F. and Margaret T. Grohne Family Foundation and the Ting Tsung and Wei Fong Chao Foundation. MCCS cohort recruitment was funded by VicHealth and Cancer Council Victoria. The MCCS was further supported by Australian NHMRC grants 209057, 251553 and 504711 and by infrastructure provided by Cancer Council Victoria. The MEC was supported by NIH grants CA63464, CA54281, CA098758 and CA132839. The work of MTLGEBCS was supported by the Quebec Breast Cancer Foundation, the Canadian Institutes of Health Research (grant CRN-87521) and the Ministry of Economic Development, Innovation and Export Trade (grant PSR-SIIRI-701). MYBRCA is funded by research grants from the Malaysian Ministry of Science, Technology and Innovation (MOSTI), Malaysian Ministry of Higher Education (UM.C/HlR/MOHE/06) and Cancer Research Initiatives Foundation (CARIF). Additional controls were recruited by the Singapore Eye Research Institute, which was supported by a grant from the Biomedical Research Council (BMRC08/1/35/19,tel:08/1/35/19./550), Singapore and the National medical Research Council, Singapore (NMRC/CG/SERI/2010). The NBCS was supported by grants from the Norwegian Research council (155218/V40, 175240/S10 to A.L.B.D., FUGE-NFR 181600/ V11 to V.N.K. and a Swizz Bridge Award to A.L.B.D.). The NBHS was supported by NIH grant R01CA100374. Biological sample preparation was conducted the Survey and Biospecimen Shared Resource, which is supported by P30 CA68485. The OBCS was supported by research grants from the Finnish Cancer Foundation, the Sigrid Juselius Foundation, the Academy of Finland, the University of Oulu, and the Oulu University Hospital. The ORIGO study was supported by the Dutch Cancer Society (RUL 1997-1505) and the Biobanking and Biomolecular Resources Research Infrastructure (BBMRI-NLCP16). The PBCS was funded by Intramural Research Funds of the National Cancer Institute, Department of Health and Human Services, USA. pKARMA is a combination of the KARMA and LIBRO-1 studies. KARMA was supported by Ma¨rit and Hans Rausings Initiative Against Breast Cancer. KARMA and LIBRO-1 were supported the Cancer Risk Prediction Center (CRisP; www.crispcenter.org), a Linnaeus Centre (Contract ID 70867902) financed by the Swedish Research Council. The RBCS was funded by the Dutch Cancer Society (DDHK 2004-3124, DDHK 2009-4318). SASBAC was supported by funding from the Agency for Science, Technology and Research of Singapore (A∗STAR), the US National Institute of Health (NIH) and the Susan G. Komen Breast Cancer Foundation KC was financed by the Swedish Cancer Society (5128-B07-01PAF). The SBCGS was supported primarily by NIH grants R01CA64277, R01CA148667, and R37CA70867. Biological sample preparation was conducted the Survey and Biospecimen Shared Resource, which is supported by P30 CA68485. The SBCS was supported by Yorkshire Cancer Research S305PA, S299 and S295. Funding for the SCCS was provided by NIH grant R01 CA092447. The Arkansas Central Cancer Registry is fully funded by a grant from National Program of Cancer Registries, Centers for Disease Control and Prevention (CDC). Data on SCCS cancer cases from Mississippi were collected by the Mississippi Cancer Registry which participates in the National Program of Cancer Registries (NPCR) of the Centers for Disease Control and Prevention (CDC). The contents of this publication are solely the responsibility of the authors and do not necessarily represent the official views of the CDC or the Mississippi Cancer Registry. SEARCH is funded by a programme grant from Cancer Research UK (C490/A10124) and supported by the UK National Institute for Health Research Biomedical Research Centre at the University of Cambridge. The SEBCS was supported by the BRL (Basic Research Laboratory) program through the National Research Foundation of Korea funded by the Ministry of Education, Science and Technology (2012-0000347). SGBCC is funded by the National Medical Research Council Start-up Grant and Centre Grant (NMRC/CG/NCIS /2010). The recruitment of controls by the Singapore Consortium of Cohort Studies-Multi-ethnic cohort (SCCS-MEC) was funded by the Biomedical Research Council (grant number: 05/1/21/19/425). SKKDKFZS is supported by the DKFZ. The SZBCS was supported by Grant PBZ_KBN_122/P05/2004. K. J. is a fellow of International PhD program, Postgraduate School of Molecular Medicine, Warsaw Medical University, supported by the Polish Foundation of Science. The TNBCC was supported by the NIH grant (CA128978), the Breast Cancer Research Foundation , Komen Foundation for the Cure, the Ohio State University Comprehensive Cancer Center, the Stefanie Spielman Fund for Breast Cancer Research and a generous gift from the David F. and Margaret T. Grohne Family Foundation and the Ting Tsung and Wei Fong Chao Foundation. Part of the TNBCC (DEMOKRITOS) has been co-financed by the European Union (European Social Fund – ESF) and Greek National Funds through the Operational Program ‘Education and Life-long Learning’ of the National Strategic Reference Framework (NSRF)—Research Funding Program of the General Secretariat for Research & Technology: ARISTEIA. The TWBCS is supported by the Institute of Biomedical Sciences, Academia Sinica and the National Science Council, Taiwan. The UKBGS is funded by Breakthrough Breast Cancer and the Institute of Cancer Research (ICR). ICR acknowledges NHS funding to the NIHR Biomedical Research Centre. Funding to pay the Open Access publication charges for this article was provided by the Wellcome Trust.This is the advanced access published version distributed under a Creative Commons Attribution License 2.0, which can also be viewed on the publisher's webstie at: http://hmg.oxfordjournals.org/content/early/2014/07/04/hmg.ddu311.full.pdf+htm

Fine-Scale Mapping of the 4q24 Locus Identifies Two Independent Loci Associated with Breast Cancer Risk

Background: A recent association study identified a common variant (rs9790517) at 4q24 to be associated with breast cancer risk. Independent association signals and potential functional variants in this locus have not been explored. Methods: We conducted a fine-mapping analysis in 55,540 breast cancer cases and 51,168 controls from the Breast Cancer Association Consortium. Results: Conditional analyses identified two independent association signals among women of European ancestry, represented by rs9790517 [conditional P = 2.51 × 10−4; OR, 1.04; 95% confidence interval (CI), 1.02–1.07] and rs77928427 (P = 1.86 × 10−4; OR, 1.04; 95% CI, 1.02–1.07). Functional annotation using data from the Encyclopedia of DNA Elements (ENCODE) project revealed two putative functional variants, rs62331150 and rs73838678 in linkage disequilibrium (LD) with rs9790517 (r2 ≥ 0.90) residing in the active promoter or enhancer, respectively, of the nearest gene, TET2. Both variants are located in DNase I hypersensitivity and transcription factor–binding sites. Using data from both The Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC), we showed that rs62331150 was associated with level of expression of TET2 in breast normal and tumor tissue. Conclusion: Our study identified two independent association signals at 4q24 in relation to breast cancer risk and suggested that observed association in this locus may be mediated through the regulation of TET2. Impact: Fine-mapping study with large sample size warranted for identification of independent loci for breast cancer risk

Genetic variation at CYP3A is associated with age at menarche and breast cancer risk : a case-control study

Abstract Introduction We have previously shown that a tag single nucleotide polymorphism (rs10235235), which maps to the CYP3A locus (7q22.1), was associated with a reduction in premenopausal urinary estrone glucuronide levels and a modest reduction in risk of breast cancer in women age ≤50 years. Methods We further investigated the association of rs10235235 with breast cancer risk in a large case control study of 47,346 cases and 47,570 controls from 52 studies participating in the Breast Cancer Association Consortium. Genotyping of rs10235235 was conducted using a custom Illumina Infinium array. Stratified analyses were conducted to determine whether this association was modified by age at diagnosis, ethnicity, age at menarche or tumor characteristics. Results We confirmed the association of rs10235235 with breast cancer risk for women of European ancestry but found no evidence that this association differed with age at diagnosis. Heterozygote and homozygote odds ratios (ORs) were OR = 0.98 (95% CI 0.94, 1.01; P = 0.2) and OR = 0.80 (95% CI 0.69, 0.93; P = 0.004), respectively (P trend = 0.02). There was no evidence of effect modification by tumor characteristics. rs10235235 was, however, associated with age at menarche in controls (P trend = 0.005) but not cases (P trend = 0.97). Consequently the association between rs10235235 and breast cancer risk differed according to age at menarche (P het = 0.02); the rare allele of rs10235235 was associated with a reduction in breast cancer risk for women who had their menarche age ≥15 years (ORhet = 0.84, 95% CI 0.75, 0.94; ORhom = 0.81, 95% CI 0.51, 1.30; P trend = 0.002) but not for those who had their menarche age ≤11 years (ORhet = 1.06, 95% CI 0.95, 1.19, ORhom = 1.07, 95% CI 0.67, 1.72; P trend = 0.29). Conclusions To our knowledge rs10235235 is the first single nucleotide polymorphism to be associated with both breast cancer risk and age at menarche consistent with the well-documented association between later age at menarche and a reduction in breast cancer risk. These associations are likely mediated via an effect on circulating hormone levels

Dissecting Ras signalling in melanoma development using zebrafish

EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Risk-aware Data Usage Control

Distributed environments such as Internet of Things, have an increasing need of introducing access and usage control mechanisms, to manage the rights of performing specific operations and regulate the access to the plethora of information daily generated by an enormous network of interconnected devices. Defining policies which are specific to these distributed environments could be a challenging and tedious task, mainly due to the large set of attributes that should be considered, leading often to unforeseen conflicts or unconsidered conditions and misconfigurations. This thesis presents the study, design and implementation of a risk-aware security policy enforcement mechanism, which aims at providing a way of simplifying the process of writing, managing and enforcing security policies in highly dynamic and heterogeneous environments such as the Internet of Things. Usage Control model was exploited in order to allow the fine-grained policy based management of system resources, based on dynamic monitoring and evaluation of object, subject, and environmental attributes. The proposed mechanism is based on the construction of an hierarchy of the attributes which participate in the security policy, while the notion of risk is introduced by assigning a risk level to those attributes based on the values that they can acquire at the time of the access request or during the access session. Those risk values are then aggregated, aiming at computing one single risk value that is able to characterize the total risk of a given access request. The construction of the hierarchy and the assignment of the risk values are handled as a Multi-Criteria Decision Making problem and the utilized algorithms are the Analytic Hierarchy Process, the fuzzy Analytic Hierarchy Process and a variation of TOPSIS. This single value can then be utilized in order to define one-attribute policies, which lessens both the evaluation time and the coding complexity, avoiding thus potential errors during the policy writing process. Moreover, this study presents the integration of the risk-aware Usage Control framework to a Software-Defined Network architecture and the validation of the proposed solution through its application to a Smart Building environment. The conducted experiments have shown that the evaluation time was decreased significantly by the use of one-attribute policies while at the same time the final decision of granting or denying the access was in most of the cases the same as the one that would have been made evaluating a policy which contains the full range of attributes. In addition, with respect to the integration of the framework to the Software-Defined Networks, the achieved timings of installing or revoking a traffic flow do not present an overhead able to compromise the user's experience or the network processes, proving thus a proof of the feasibility of the proposed solution. Last but not least, this thesis presents the application of a risk-aware security policy enforcement mechanism in constrained and dynamic networks based on a combination of Attribute Based and Role Based access control. The framework exploits and combines the benefits of those two models and enhances them with the possibility of considering and evaluating risk-aware policies

Are fundamental rights the answer to the deficiencies of EU copyright law, discussed in a European context?

Die vorliegende Arbeit zielt auf die Untersuchung der Rolle der Grundrechte innerhalb des urheberrechtlichen Systems der EU ab. Angesichts der Tatsache, dass der geltende umfassende Rechtstext der letzten Jahre für das EU Urheberrecht die Richtlinie 2001/29/EG zur Harmonisierung bestimmter Aspekte des Urheberrechts und der verwandten Schutzrechte in der Informationsgesellschaft („InfoSoc Richtlinie“) war, beginnt die Analyse mit den Besonderheiten der Grundrechteordnung, die auf der Richtlinie beruhen. Das wesentliche Problem der InfoSoc Richtlinie ist die Reihe von Ausnahmen und Beschränkungen, die zu einem fragmentierten und strengen internen System führte, das als effektives Instrument zum Gleichgewicht der widerstrebenden Interessen zwischen den Rechtsinhabern und Nutzern nicht funktionieren konnte. Daher wurde wegen der mangelnden Flexibilität des Systems von dem EuGH und dem EGMR eine neue Tendenz entwickelt: beide Gerichte haben immer öfter auf die Grundrechte zurückgegriffen, um entweder das problematische interne System der Ausnahmen und Beschränkungen zu interpretieren oder die entgegenstehenden Rechte der Copyright-Inhaber und Dritter auszugleichen. Die Einführung des Systems der Grundrechte als externe Grenze zum Umfang des Urheberrechts hat Fragen über die exakte Rolle dieser Ordnung im EU-Urheberrecht aufgeworfen. Verschiedene Meinungen sind dazu ausgedrückt worden. Während dieser lebendigen Diskussion wenige Monate bevor der EuGH die Antwort auf ein relevantes Vorabentscheidungsersuchen gab, das das Grundrechtsregime keine externe begrenzende Rolle im Urheberrecht in der EU einnimmt und dass seine Rolle nur interpretativ ist, wurde die neue Copyright-Richtlinie über das Urheberrecht im digitalen Binnenmarkt verabschiedet. Die neue Richtlinie verändert die bisherige Struktur indem sie versucht, neue Lösungen zu den bisherigen Mängeln der alten zu finden. Dennoch erhält die neue Richtlinie trotz ihrer erfreulichen neue Bestimmungen Ähnlichkeiten mit der InfoSoc Richtlinie. Die Schlussfolgerung ist undeutlich, wird das neue System in der Lage sein, den Herausforderungen, die der digitale Binnenmarkt stellt, zu entsprechen oder soll die Rolle der Grundrechte überdacht werden? Was jetzt zu tun ist, ist die Interpretation der neuen Bestimmungen des EuGH und ihre Durchführung von den Mitgliedsstaaten.The present thesis aims at examining the role of fundamental rights regime in the EU copyright law system. Given that the past years the applicable comprehensive legal text on EU copyright law was the InfoSoc Directive, the analysis starts with the particularities of the regime based on the respective Directive. The main flaw of the regulation under the InfoSoc Directive was the optional list of exceptions and limitations and the application of the three-step-test, which led to a fragmented and strict internal system. Resultantly, the system could not function as a sufficient tool for the balance of the competing interests between the right holders and the users. Consequently, a new tendency has been developed by the ECtHR and the ECJ: both courts resorted even more often to the fundamental rights regime in order to either interpret the problematic internal system of exceptions and limitations or to balance the conflicting rights of the copyright owners and the users. The advent of the fundamental rights regime as an external limit to the copyright protection scope has raised questions on the exact role of the regime in the EU copyright system. A few months before the ECJ’s answer to the relevant preliminary questions on whether is no externally limiting role of fundamental rights regime in the EU copyright system, the new Copyright Directive in the Digital Single Market was adopted. The Directive changed the preceding landscape and attempted to give solutions to its flaws as well as structure a solid internal balancing system and reinforce users’ rights. However, the DSM Directive despite of its welcome new provisions maintains connections to the preceding system of the InfoSoc Directive. The conclusion is blurred. Will the new system be able to correspond to the challenges that the digital single market places or should the role of fundamental rights regime be reconsidered? What is left to be observed is the interpretation of the new provisions by the ECJ and their implementation by the Member States

Weather types at Athens and Thessaloniki and their relationship to circulation types

The present PhD thesis is a contribution to the study of weather types that occur over two Greek stations, Athens and Thessaloniki. More specifically, the aim of the study is to distinguish primary weather patterns so that the investigation into the relationship between weather patterns and circulation types will be more effective. For this purpose, data of several surface meteorological parameters have been employed in addition to NCEP/NCAR data referring to the 500hPa level and finally the calendar of an automatic classification of circulation types according to Maheras et al (2000a). On the first step, the Besancenot (1990) classification of weather types has been applied for both of the stations. A new classification of weather types has been created as a result of the low or even zero frequencies of occurrence for some of the Besancenot weather types as well as the very high percentage of occurrence of the “unfavorable conditions” weather type. The new grouping of weather types reflects better the conditions over the two Greek stations. Twelve weather types have been created for the cold and eleven for the warm period of the year. Significant differences are observed mainly due to the particular characteristics of each meteorological parameter at each of the stations. Rainy days are more in Thessaloniki whereas the overall amount of precipitation is higher in Athens. During the warm period the days that are related with episodes of discomfort feeling are relatively higher in Thessaloniki. Furthermore, a new method for the automatic classification of weather types is presented which combines meteorological parameters, reflecting air mass characteristics at the surface, with synoptic conditions prevailing over an area. Five quantitative meteorological parameters are used in the procedure: temperature, precipitation, relative humidity, wind velocity and sunshine duration. In addition, two qualitative variables related to the prevailing circulation type and whether it is cyclonic or anticyclonic are also included. Weather types are defined using a relatively new method of cluster analysis, Two-Step Cluster Analysis, which allows the simultaneous use of both quantitative and qualitative variables. For Athens, six weather types are created, whereas for Thessaloniki five are produced. For both stations, only two weather types are related to anticyclonic situations. The majority of the identified weather types correspond to a distinctive and well-defined synoptic situation. Each weather type differs from the others, not only in terms of the circulation conditions referring to it, but also with reference to meteorological variables such as temperature and precipitation. Finally, Discriminant Analysis is applied in order to determine the relationships between circulation types in the middle troposphere and prevailing weather types. By means of a Stepwise Discriminant Analysis model, the most important variables from the 500 hPa level are found and are used to generate the necessary functions that can discriminate weather types over the two stations. The first function discriminates the days into cyclonic and anticyclonic ones, the second function dissociates two of the most predominant weather types according to the position (latitude and longitude) of the center of the circulation type while the rest of the functions use appropriate grid points parameters in order to separate the rest of the weather types with regard to their thermo-dynamical characteristics. The results of the evaluation of the aforementioned procedure are considered to be very satisfactory (>80%).Η παρούσα διδακτορική διατριβή αποτελεί μια συμβολή στη μελέτη των τύπων καιρού που επικρατούν σε δυο σταθμούς της ελληνικής περιοχής, την Αθήνα και τη Θεσσαλονίκη. Βασικός στόχος της μελέτης είναι η δημιουργία νέων κατατάξεων τύπων καιρού και η εύρεση των σχέσεων που τους συνδέουν με τους τύπους κυκλοφορίας. Για την επίτευξη του στόχου αυτού, χρησιμοποιήθηκαν δεδομένα που αναφέρονται σε μετεωρολογικές παραμέτρους στην επιφάνεια των σταθμών, δεδομένα NCEP/NCAR από την ισοβαρική στάθμη των 500hPa καθώς και το ημερολόγιο της αυτόματης κατάταξης τύπων κυκλοφορίας των Maheras et al (2000a). Στο πρώτο στάδιο της μελέτης εφαρμόσθηκε η κατάταξη τύπων καιρού του Besancenot (1990) στους δυο σταθμούς. Οι μικρές ή ακόμη και μηδενικές συχνότητες εμφάνισης κάποιων τύπων καιρού καθώς και τα ιδιαίτερα υψηλά ποσοστά επικράτησης του «κακού» τύπου καιρού οδήγησαν στη δημιουργία μιας νέας εμπειρικής κατάταξης τύπων καιρού με καλύτερη προσαρμογή στα ελληνικά δεδομένα. Προέκυψαν 12 τύποι καιρού για την ψυχρή και 11 για τη θερμή περίοδο του έτους. Οι δύο σταθμοί παρουσιάζουν σημαντικές διαφορές οι οποίες διέπονται από τα ιδιαίτερα χαρακτηριστικά κάθε παραμέτρου σε κάθε σταθμό. Οι ημέρες με μεγάλες ταχύτητες ανέμου είναι περισσότερες στην Αθήνα, ενώ οι ημέρες με χαμηλές θερμοκρασίες είναι περισσότερες στη Θεσσαλονίκη. Οι ημέρες βροχής είναι περισσότερες στη Θεσσαλονίκη ωστόσο τα συνολικά ποσά βροχής είναι μεγαλύτερα στην Αθήνα. Τη θερμή περίοδο είναι σχετικά αυξημένες οι ημέρες που συνδέονται με επεισόδια δυσφορίας στη Θεσσαλονίκη. Ακολούθως, προτείνεται μια μεθοδολογία για την αυτόματη κατάταξη των τύπων καιρού. Οι τύποι αυτοί συνδυάσουν πέντε επιφανειακές μετεωρολογικές μεταβλητές με δυο ποιοτικές μεταβλητές, οι οποίες σχετίζονται με τον επικρατών τύπο κυκλοφορίας και με τη κατηγοριοποίηση του σε κυκλωνικό ή αντικυκλωνικό. Οι τύποι καθορίζονται μέσω της ανάλυσης κατά συστάδες σε δύο βήματα (Two - Step Cluster Analysis, TSCA). Για την Αθήνα δημιουργήθηκαν 6 τύποι καιρού για την ψυχρή - υγρή περίοδο, τρείς για τη θερμή - ξηρή και πέντε για τη μεταβατική ενώ για τη Θεσσαλονίκη προέκυψαν πέντε, τρείς και πέντε, αντίστοιχα. Στην πλειοψηφία τους οι τύποι καιρού που αναγνωρίστηκαν αντιστοιχούν σε διακριτές και καλώς ορισμένες συνοπτικές καταστάσεις. Κάθε τύπος καιρού διαφέρει από τους υπόλοιπους όχι μόνο αναφορικά με τις συνθήκες κυκλοφορίας κατά την επικράτησή του, αλλά και σε σχέση με μετεωρολογικές μεταβλητές όπως η θερμοκρασία και η βροχόπτωση. Η Διαχωριστική Ανάλυση (Discriminant Analysis, DA) εφαρμόσθηκε με κύριο στόχο να βρεθούν οι σχέσεις που συνδέουν τους τύπους κυκλοφορίας της μέσης τροπόσφαιρας με τους τύπους καιρού. Μέσω μιας κλιμακωτής διαχωριστικής ανάλυσης (stepwise DA), αρχικά απομονώθηκαν οι σημαντικότερες μεταβλητές από τη στάθμη των 500 hPa και χρησιμοποιήθηκαν προκειμένου να παραχθούν οι απαραίτητες συναρτήσεις οι οποίες είναι ικανές να διαχωρίσουν τους τύπους καιρού στους δυο σταθμούς μελέτης. Η πρώτη διαχωριστική συνάρτηση διαχωρίζει τις ημέρες σε κυκλωνικές ή αντικυκλωνικές, η δεύτερη διαχωρίζει δύο από τους επικρατούντες τύπους καιρού σε σχέση με τη θέση (γεωγραφικό πλάτος και μήκος) του κέντρου του τύπου κυκλοφορίας και οι υπόλοιπες συναρτήσεις απομονώνουν κατάλληλα επιλεγμένα κομβικά σημεία και διαχωρίζουν τους εναπομείναντες τύπους καιρού σε σχέση με τα θερμοδυναμικά χαρακτηριστικά τους. Τα ποσοστά ορθής κατάταξης των τύπων καιρού είναι ιδιαίτερα υψηλά (>80%)