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  • 1
    Article
    Article
    2017
    ISSN: 0034-3404 
    Language: English
    In: Regional studies, 2017-01-02, Vol.51 (1), p.9-18
    Description: Contesting European regions. Regional Studies. A regional or 'meso'-level of regulation and policy-making has emerged in Europe. This cannot adequately be explained by functional imperatives or drivers. A constructivist perspective sees the region as the outcome of political contestation over the definition and meaning of territory. Six competing conceptual frames for regionalism are proposed: integrative; competitive; welfare; identity; government; and the region as a refraction of social and economic interests. Any given case will reflect a balance among these conceptions. Such an understanding permits a combination of comparative analysis with an understanding of individual cases and avoids both dismissal of territory and territorial determinism.
    Subject(s): Comparative analysis ; Determinism ; Dismissal ; Economic policy ; Europe ; Identity ; Maßstabsänderung ; Meaning ; Policy making ; reescalamiento ; Regionalism ; regionalismo ; Regionalismus ; Regionen ; regiones ; Regions ; Regulation ; rescaling ; régionalisme ; régions ; rééchelonnement ; Territory ; 再尺度化 ; 区域主义
    ISSN: 0034-3404
    E-ISSN: 1360-0591
    Source: International Bibliography of the Social Sciences (IBSS)
    Source: Business Source Ultimate
    Source: Taylor & Francis Open Access
    Source: EconLit with Full Text
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  • 2
    Book
    Book
    2017
    ISBN: 147441642X  ISBN: 9781474416429 
    Language: English
    Description: Michael Keating argues that what matters to Scotland is not independence but the powers and taxes that the Scottish Parliament and Government control, and how they use them - a vital question after the referendum as new powers are devolved from Westminster. There is popular support for a social and economic settlement on Nordic lines, combining economic performance with social justice, but can Scotland achieve this notoriously difficult ideal? This is the first study to delve into these issues in detail. It will be of interest to those concerned with the future of Scotland and in what a non-sovereign nation or region can do in a complex and interdependent world.
    Subject(s): Political Science
    ISBN: 147441642X
    ISBN: 9781474416429
    Source: eBook Academic Collection - Worldwide
    Source: Cambridge Core All Books
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  • 3
    Article
    Article
    2017
    ISSN: 1350-1763 
    Language: English
    In: Journal of European public policy, 2017-04-11, Vol.24 (4), p.615-632
    Description: European federalism must be conceived at multiple levels, not just that of the state and the EU. A regional level has emerged below and across the states, as a result of spatial rescaling: the migration of functional systems, political change and the institutionalization of the regional level. The sub-state region remains a contested space, both as to its territorial boundary and its control. The EU itself has used the regional level for the framing and implementation of its own policies. Regional politics are characterized by inter-regional competition. Demands for recognition and autonomy from below have added another dimension. There is not a uniform regional level of politics or policy but a variety of constructions of the region. Federalism helps us understand this changing dynamic, if it is seen not as a specific form of government but as a general principle of order, combining unity with diversity.
    Subject(s): Autonomy ; Competition ; Federalism ; Framing ; Implementation ; Institutionalization ; Migration ; Political change ; Politics ; regions ; rescaling
    ISSN: 1350-1763
    E-ISSN: 1466-4429
    Source: International Bibliography of the Social Sciences (IBSS)
    Source: Taylor & Francis Open Access
    Source: Get It Now
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  • 4
    Book
    Book
    2017
    ISBN: 147441642X  ISBN: 9781474416429 
    Language: English
    Description: The ambition of the Scottish Government is to create a wealthier and fairer nation. Following the devolution acts of 1998, 2012 and 2016, it has extensive powers and resources to fulfill its ambition. This interdisciplinary collection of essays asks how it can be achieved, given the range of powers available, economic constraints, institutions and public support. Looking at economic policy, taxation and welfare, it provides a realistic analysis of the opportunities and constraints facing a small, devolved nation. After years of debate on what powers Scotland should have, this book examines how they might be used to shape the country's future.
    Subject(s): Scotland-Economic conditions
    ISBN: 147441642X
    ISBN: 9781474416429
    Source: eBook Academic Collection - Worldwide
    Source: Cambridge Core All Books
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  • 5
    Language: English
    In: Clinical cancer research, 2017-07-15, Vol.23 (14), p.3734-3743
    Description: Ibrutinib inhibits Bruton tyrosine kinase (BTK) by irreversibly binding to the Cys-481 residue in the enzyme. However, ibrutinib also inhibits several other enzymes that contain cysteine residues homologous to Cys-481 in BTK. Patients with relapsed/refractory or previously untreated chronic lymphocytic leukemia (CLL) demonstrate a high overall response rate to ibrutinib with prolonged survival. Acalabrutinib, a selective BTK inhibitor developed to minimize off-target activity, has shown promising overall response rates in patients with relapsed/refractory CLL. A head-to-head comparison of ibrutinib and acalabrutinib in CLL cell cultures and healthy T cells is needed to understand preclinical biologic and molecular effects. Using samples from patients with CLL, we compared the effects of both BTK inhibitors on biologic activity, chemokine production, cell migration, BTK phosphorylation, and downstream signaling in primary CLL lymphocytes and on normal T-cell signaling to determine the effects on other kinases. Both BTK inhibitors induced modest cell death accompanied by cleavage of PARP and caspase-3. Production of CCL3 and CCL4 chemokines and pseudoemperipolesis were inhibited by both drugs to a similar degree. These drugs also showed similar inhibitory effects on the phosphorylation of BTK and downstream S6 and ERK kinases. In contrast, off-target effects on SRC-family kinases were more pronounced with ibrutinib than acalabrutinib in healthy T lymphocytes. Both BTK inhibitors show similar biological and molecular profile in primary CLL cells but appear different on their effect on normal T cells. .
    Subject(s): acalabrutinib ; Agammaglobulinaemia Tyrosine Kinase ; apoptosis ; Benzamides - administration & dosage ; Benzamides - adverse effects ; Biological effects ; Bruton tyrosine kinase ; Bruton's tyrosine kinase ; Cancer ; Carbon tetrachloride ; Caspase ; Caspase 3 - genetics ; Caspase-3 ; CCL3 protein ; CCL4 protein ; Cell death ; Cell Line, Tumor ; Cell migration ; Chemokines ; Chronic lymphatic leukemia ; chronic lymphocytic leukemia ; Downstream ; Downstream effects ; Drug Resistance, Neoplasm - genetics ; Drugs ; Experimental design ; Extracellular signal-regulated kinase ; Homology ; Humans ; ibrutinib ; Inhibitors ; Kinases ; Leukemia ; Leukemia, Lymphocytic, Chronic, B-Cell - drug therapy ; Leukemia, Lymphocytic, Chronic, B-Cell - genetics ; Leukemia, Lymphocytic, Chronic, B-Cell - pathology ; Leukocyte migration ; Lymphatic leukemia ; Lymphocytes ; Lymphocytes T ; Patients ; Phosphorylation ; Poly (ADP-Ribose) Polymerase-1 - antagonists & inhibitors ; Poly (ADP-Ribose) Polymerase-1 - genetics ; Poly(ADP-ribose) polymerase ; Protein Kinase Inhibitors - administration & dosage ; Protein Kinase Inhibitors - adverse effects ; Protein-tyrosine kinase ; Protein-Tyrosine Kinases - antagonists & inhibitors ; Protein-Tyrosine Kinases - genetics ; Pyrazines - administration & dosage ; Pyrazines - adverse effects ; Pyrazoles - administration & dosage ; Pyrazoles - adverse effects ; Pyrimidines - administration & dosage ; Pyrimidines - adverse effects ; Signal Transduction - drug effects ; Signaling ; src-Family Kinases - antagonists & inhibitors ; T-Lymphocytes - drug effects ; Tyrosine
    ISSN: 1078-0432
    E-ISSN: 1557-3265
    Source: HighWire Press (Free Journals)
    Source: Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals
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  • 6
    Article
    Article
    2019
    ISSN: 0032-3179 
    Language: English
    In: The Political quarterly (London. 1930), 2019-04, Vol.90 (S2), p.167-176
    Description: Byline: Michael Keating
    Subject(s): EU membership ; Government & Law ; Political Science ; Social Sciences
    ISSN: 0032-3179
    E-ISSN: 1467-923X
    Source: International Bibliography of the Social Sciences (IBSS)
    Source: Hellenic Academic Libraries Link
    Source: Academic Search Ultimate
    Source: Web of Science - Social Sciences Citation Index – 2019〈img src="http://exlibris-pub.s3.amazonaws.com/fromwos-v2.jpg" /〉
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  • 7
    Article
    Article
    2008
    ISSN: 0140-2382 
    Language: English
    In: West European politics, 2008-01-01, Vol.31 (1-2), p.60-81
    Description: For many years, territorial politics was neglected in political science under the influence of a modernist paradigm according to which territory gives way to function as a principle of social and political organisation. In the last 30 years it has received more attention as territorial political movements have made an impact. This has provoked a reconsideration not just of the present but also of the past, as scholars have identified the persistence of territorial politics even within unitary states. There is a continuing separation of the study of local and urban from regional politics, although the respective literatures address similar issues and use similar concepts. The 'new regionalism' literature examines the emergence of territorial systems of action under the impact of state transformation and transnational integration. There are marked differences in territorial politics in western and east-central Europe, not because of primordial ethnic characteristics, but because of the evolution of the state in the post-war era.
    Subject(s): Europe ; European integration ; Globalization ; Interest groups ; Local politics ; Modernism ; Multi-level governance ; Political activism ; Political movements ; Political science ; Politics ; Public Policy ; Regionalism ; Social organization ; Territoriality
    ISSN: 0140-2382
    E-ISSN: 1743-9655
    Source: International Bibliography of the Social Sciences (IBSS)
    Source: Get It Now
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  • 8
    Language: English
    In: Clinical cancer research, 2017-05-01, Vol.23 (9), p.2154-2158
    Description: Ibrutinib is an active therapy with an acceptable safety profile for patients with chronic lymphocytic leukemia (CLL), including high-risk patients with del17p or with mutations. Ibrutinib is broadly indicated for the treatment of patients with CLL and specifically including those with 17p deletion. The optimal use of ibrutinib in combination with other agents remains controversial. We report the long-term outcome [median follow-up of 47 months (range, 36-51 months)] of 40 patients with high-risk CLL, treated on the first ibrutinib combination trial with rituximab (IR). The majority of patients (36/40) were previously treated. Median age was 65 years, and 21 patients (52%) had 17p deletion. Median duration on treatment was 41 months (range, 2-51 months), and median number of treatment cycles was 42 (range, 2-49). Overall response rate was 95%, and 9 patients (23%) attained a complete remission. Twenty-one patients discontinued treatment, 10 due to disease progression, 9 for other causes, and 2 due to stem cell transplantation; the remaining 19 patients continue on ibrutinib. Median progression-free survival for all patients was 45 months, which was significantly shorter in the subgroup of patients with del17p ( = 21, 32.3 months, = 0.02). Fourteen patients (35%) died, five from progressive disease, five from infections, and four from other causes. Median overall survival has not been reached. IR combination therapy leads to durable remissions in high-risk CLL; the possible benefit from the addition of rituximab is currently explored in a randomized trial. .
    Subject(s): Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols - administration & dosage ; Antineoplastic Combined Chemotherapy Protocols - adverse effects ; Cancer ; Cell survival ; Chronic lymphatic leukemia ; chronic lymphocytic leukemia ; CLL ; Clonal deletion ; deletion 17p ; Disease-Free Survival ; Experimental design ; Fatalities ; Female ; Follow-Up Studies ; Humans ; Ibrutinib ; Immunotherapy ; Leukemia ; Leukemia, Lymphocytic, Chronic, B-Cell - drug therapy ; Leukemia, Lymphocytic, Chronic, B-Cell - pathology ; Lymphatic leukemia ; Male ; Medical treatment ; Middle Aged ; Monoclonal antibodies ; Mutation ; p53 Protein ; Patients ; Pyrazoles - administration & dosage ; Pyrazoles - adverse effects ; Pyrimidines - administration & dosage ; Pyrimidines - adverse effects ; Remission ; Remission Induction ; Risk ; Risk groups ; Rituximab ; Rituximab - administration & dosage ; Rituximab - adverse effects ; Stem cell transplantation ; Survival ; Targeted cancer therapy ; Therapy ; Transplantation
    ISSN: 1078-0432
    E-ISSN: 1557-3265
    Source: HighWire Press (Free Journals)
    Source: Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals
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  • 9
    Language: English
    In: Blood, 2016-01-21, Vol.127 (3), p.303-309
    Description: Accurate identification of patients likely to achieve long-progression-free survival (PFS) after chemoimmunotherapy is essential given the availability of less toxic alternatives, such as ibrutinib. Fludarabine, cyclophosphamide, and rituximab (FCR) achieved a high response rate, but continued relapses were seen in initial reports. We reviewed the original 300 patient phase 2 FCR study to identify long-term disease-free survivors. Minimal residual disease (MRD) was assessed posttreatment by a polymerase chain reaction-based ligase chain reaction assay (sensitivity 0.01%). At the median follow-up of 12.8 years, PFS was 30.9% (median PFS, 6.4 years). The 12.8-year PFS was 53.9% for patients with mutated immunoglobulin heavy chain variable (IGHV) gene (IGHV-M) and 8.7% for patients with unmutated IGHV (IGHV-UM). 50.7% of patients with IGHV-M achieved MRD-negativity posttreatment; of these, PFS was 79.8% at 12.8 years. A plateau was seen on the PFS curve in patients with IGHV-M, with no relapses beyond 10.4 years in 42 patients (total follow-up 105.4 patient-years). On multivariable analysis, IGHV-UM (hazard ratio, 3.37 [2.18-5.21]; P 〈 .001) and del(17p) by conventional karyotyping (hazard ratio, 7.96 [1.02-61.92]; P = .048) were significantly associated with inferior PFS. Fifteen patients with IGHV-M had 4-color MRD flow cytometry (sensitivity 0.01%) performed in peripheral blood, at a median of 12.8 years posttreatment (range, 9.5-14.7). All were MRD-negative. The high rate of very long-term PFS in patients with IGHV-M after FCR argues for the continued use of chemoimmunotherapy in this patient subgroup outside clinical trials; alternative strategies may be preferred in patients with IGHV-UM, to limit long-term toxicity. •FCR-treated chronic lymphocytic leukemia patients with mutated IGHV gene achieve long-term PFS, with a plateau on the PFS curve.•MRD-negativity posttreatment is highly predictive of long-term PFS, particularly in patients with mutated IGHV gene.
    Subject(s): Adolescent ; Adult ; Aged ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols - therapeutic use ; Cause of Death ; Clinical Trials and Observations ; Cyclophosphamide - administration & dosage ; Female ; Humans ; Immunoglobulin Heavy Chains - genetics ; Incidence ; Leukemia, Lymphocytic, Chronic, B-Cell - diagnosis ; Leukemia, Lymphocytic, Chronic, B-Cell - drug therapy ; Leukemia, Lymphocytic, Chronic, B-Cell - genetics ; Leukemia, Lymphocytic, Chronic, B-Cell - mortality ; Male ; Middle Aged ; Mutation ; Neoplasm Staging ; Neoplasm, Residual ; Neoplasms, Second Primary - epidemiology ; Neoplasms, Second Primary - etiology ; Neoplasms, Second Primary - mortality ; Prognosis ; Recurrence ; Remission Induction ; Retreatment ; Rituximab - administration & dosage ; Survival Analysis ; Treatment Outcome ; Vidarabine - administration & dosage ; Vidarabine - analogs & derivatives ; Young Adult
    ISSN: 0006-4971
    E-ISSN: 1528-0020
    Source: Alma/SFX Local Collection
    Source: American Society of Hematology
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  • 10
    Language: English
    In: Acta haematologica, 2018-09, Vol.140 (1), p.51-54
    Description: The immunoglobulin heavy chain gene (IgHV) mutation status correlates with the clinical outcome of patients with chronic lymphocytic leukemia (CLL) treated with chemoimmunotherapy. Why the survival rate of patients with unmutated IgHV is worse than that of patients with mutated IgHV is unknown. CLL cells with unmutated IgHV were thought to originate from naïve B lymphocytes, whereas CLL cells with mutated IgHV were thought to arise from B cells that have undergone somatic hypermutation (SHM). Cell surface protein expression profile and gene expression studies showing that all CLL cells, regardless of their IgHV mutation status, are of postgerminal center origin, negated this hypothesis. We hereby propose that all CLL cells undergo SHM and their proliferation rate determines their IgHV mutation status. DNA breaks, accumulated during SHM, are restored by various DNA repair mechanisms. In rapidly dividing cells DNA breaks are repaired by the efficient high-fidelity homology-directed DNA repair apparatus, whereas in slowly dividing cells they are repaired by the inefficient low-fidelity nonhomology end-joining repair mechanism. Accordingly, a low IgHV mutation rate is found in rapidly dividing cells whereas a high mutation rate is typically found in slowly dividing cells. Thus, the proliferation rate of CLL cells determines the IgHV mutation status and patients’ clinical outcome.
    Subject(s): DNA Breaks ; DNA End-Joining Repair ; Humans ; Immunoglobulin Heavy Chains - genetics ; Leukemia, Lymphocytic, Chronic, B-Cell - diagnosis ; Mutation ; Prognosis ; Review
    ISSN: 0001-5792
    E-ISSN: 1421-9662
    Source: Karger Journals Archiv (DFG Nationallizenzen)
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