Vulnerability assessment and feasibility analysis of seismic strengthening of school buildings

The majority of structures in seismic-prone areas worldwide are structures that have been designed either without seismic design considerations, or using codes of practice that are seriously inadequate in the light of current seismic design principles. In Cyprus, after a series of earthquakes that occurred between 1995 and 1999, it was decided to carry out an unprecedented internationally seismic retrofitting of all school buildings, taking into account the sensitivity of the society towards these structures. In this paper representative school buildings are analysed in both their pristine condition and after applying retrofitting schemes typical of those implemented in the aforementioned large-scale strengthening programme. Non-linear analysis is conducted on calibrated analytical models of the selected buildings and fragility curves are derived for typical reinforced concrete and unreinforced masonry structures. These curves are then used to carry out a feasibility study, including both benefit-cost and life-cycle analysis, and evaluate the effectiveness of the strengthening programme

Extending displacement-based earthquake loss assessment (DBELA) for the computation of fragility curves

This paper presents a new procedure to derive fragility functions for populations of buildings that relies on the displacement-based earthquake loss assessment (DBELA) methodology. In the method proposed herein, thousands of synthetic buildings have been produced considering the probabilistic distribution describing the variability in geometrical and material properties. Then, their nonlinear capacity has been estimated using the DBELA method and their response against a large set of ground motion records has been estimated. Global limit states are used to estimate the distribution of buildings in each damage state for different levels of ground motion, and a regression algorithm is applied to derive fragility functions for each limit state. The proposed methodology is demonstrated for the case of ductile and non-ductile Turkish reinforced concrete frames with masonry infills

Performance-Based Seismic Design and Assessment of Bridges

Current trends in the seismic design and assessment of bridges are discussed, with emphasis on two procedures that merit some particular attention, displacement-based procedures and deformation-based procedures. The available performance-based methods for bridges are critically reviewed and a number of critical issues are identified, which arise in all procedures. Then two recently proposed methods are presented in some detail, one based on the direct displacement-based design approach, using equivalent elastic analysis and properly reduced displacement spectra, and one based on the deformation-based approach, which involves a type of partially inelastic response-history analysis for a set of ground motions and wherein pier ductility is included as a design parameter, along with displacement criteria. The current trends in seismic assessment of bridges are then summarised and the more rigorous assessment procedure, i.e. nonlinear dynamic response-history analysis, is used to assess the performance of bridges designed to the previously described procedures. Finally some comments are offered on the feasibility of including such methods in the new generation of bridge codes

Machine learning techniques for the estimation of limit state thresholds and bridge-specific fragility analysis of R/C bridges

Based on past earthquake events, bridges are the most critical and usually the most vulnerable components of road and rail transport systems, while bridge damage is related to substantial direct and indirect losses. In view of this, the need for direct and reliable assessment of bridge vulnerability has emerged, and several methodologies have been developed using probabilistic analysis for the derivation of fragility curves. A new framework for the derivation of bridge-specific fragility curves is proposed herein, introducing machine learning techniques for a reliable estimation of limit state thresholds of the most critical component of the bridge system (which in standard -ductility based- design is the piers), in terms of a widely used engineering demand parameter, i.e. displacement of control point. A set of parameters affecting the seismic capacity and the failure modes of bridge piers is selected, including geometry, material properties, and reinforcement ratios for cylindrical piers. Training and test sets are generated from multiple inelastic pushover analyses of the pier component, and Artificial Neural Networks (ANN) analysis is performed to derive closed-form relationships for the estimation of limit state thresholds. The latter are compared with closed-form relationships available in the literature, highlighting the effect of machine learning techniques on the reliable estimation of bridge fragility curves for all damage states

Fingolimod: therapeutic mechanisms and ocular adverse effects.

Fingolimod is an oral immunomodulating drug used in the management of relapsing-remitting multiple sclerosis (RRMS). We aim to review the published literature on ocular manifestations of fingolimod therapy and their possible underlying mechanisms. The therapeutic effects of fingolimod are mediated via sphingosine receptors, which are found ubiquitously in various organs, including lymphoid cells, central nervous system, cardiac myocytes, and smooth muscle cells. Fingolimod-associated macular oedema (FAME) is the most common ocular side effect but retinal haemorrhages and retinal vein occlusion can occur. The visual consequences appear to be mild and, in cases of FAME, resolution is often attained with discontinuation of therapy. However, in cases of retinal vein occlusion, discontinuation of fingolimod alone may not be sufficient and intra-vitreal therapy may be required. We also propose a pragmatic service pathway for monitoring patients on fingolimod therapy, which includes stratifying them by risk and visual acuity

Interferon β-1a in relapsing multiple sclerosis: four-year extension of the European IFNβ-1a Dose-C omparison Study

Background: Multiple sclerosis (MS) is a chronic disease requiring long-term monitoring of treatment. Objective: To assess the four-year clinical efficacy of intramuscular (IM) IFNb-1a in patients with relapsing MS from the European IFNb-1a Dose-C omparison Study. Methods: Patients who completed 36 months of treatment (Part 1) of the European IFNb-1a Dose-C omparison Study were given the option to continue double-blind treatment with IFNb-1a 30 mcg or 60 mcg IM once weekly (Part 2). Analyses of 48-month data were performed on sustained disability progression, relapses, and neutralizing antibody (NA b) formation. Results: O f 608/802 subjects who completed 36 months of treatment, 493 subjects continued treatment and 446 completed 48 months of treatment and follow-up. IFNb-1a 30 mcg and 60 mcg IM once weekly were equally effective for up to 48 months. There were no significant differences between doses over 48 months on any of the clinical endpoints, including rate of disability progression, cumulative percentage of patients who progressed (48 and 43, respectively), and annual relapse rates; relapses tended to decrease over 48 months. The incidence of patients who were positive for NAbs at any time during the study was low in both treatment groups. Conclusion: C ompared with 60-mcg IM IFNb-1a once weekly, a dose of 30 mcg IM IFNb-1a once weekly maintains the same clinical efficacy over four years

Treatment with the immunomodulator FTY720 does not promote spontaneous bacterial infections after experimental stroke in mice

Background: FTY720, an immunomodulator derived from a fungal metabolite which reduces circulating lymphocyte counts by increasing the homing of lymphocytes to the lymph nodes has recently gained interest in stroke research. The aim of this study was to evaluate the protective efficacy of FTY720 in cerebral ischemia in two different application paradigms and to gather first data on the effect of FTY720 on the rate of spontaneous bacterial infections in experimental stroke. Methods: Middle cerebral artery occlusion (MCAO) in C57BL/6 mice (strain J, groups of 10 animals) was performed with two different durations of ischemia (90 min and 3 h) and FTY720 was applied 2 h after vessel occlusion to study the impact of reperfusion on the protective potency of FTY720. Lesion size was determined by TTC staining. Mice treated with FTY720 or vehicle were sacrificed 48 h after 90 min MCAO to determine the bacterial burden in lung and blood. Results: FTY720 1 mg/kg significantly reduced ischemic lesion size when administered 2 h after the onset of MCAO for 3 h (45.4 +/- 22.7 mm3 vs. 84.7 +/- 23.6 mm3 in control mice, p = 0.001) and also when administered after reperfusion, 2 h after the onset of MCAO for 90 min (31.1 +/- 28.49 mm3 vs. 69.6 +/- 27.2 mm3 in control mice, p = 0.013). Bacterial burden of lung homogenates 48 h after stroke did not increase in the group treated with the immunomodulator FTY720 while there was no spontaneous bacteremia 48 h after MCAO in treated and untreated animals. Conclusions: Our results corroborate the experimental evidence of the protective effect of FTY720 seen in different rodent stroke models. Interestingly, we found no increase in bacterial lung infections even though FTY720 strongly reduces the number of circulating leukocytes

Recent developments in multiple sclerosis therapeutics

Multiple sclerosis, the most common neurologic disorder of young adults, is traditionally considered to be an inflammatory, autoimmune, demyelinating disease of the central nervous system. Based on this understanding, the initial therapeutic strategies were directed at immune modulation and inflammation control. These approaches, including high-dose corticosteroids for acute relapses and long-term use of parenteral interferon-β, glatiramer acetate or natalizumab for disease modification, are at best moderately effective. Growing evidence supports that, while an inflammatory pathology characterizes the early relapsing stage of multiple sclerosis, neurodegenerative pathology dominates the later progressive stage of the disease. Multiple sclerosis disease-modifying therapies currently in development attempt to specifically target the underlying pathology at each stage of the disease, while avoiding frequent self-injection. These include a variety of oral medications and monoclonal antibodies to reduce inflammation in relapsing multiple sclerosis and agents intended to promote neuroprotection and neurorepair in progressive multiple sclerosis. Although newer therapies for relapsing MS have the potential to be more effective and easier to administer than current therapies, they also carry greater risks. Effective treatments for progressive multiple sclerosis are still being sought

Lymphocyte Modulation with FTY720 Improves Hemorrhagic Shock Survival in Swine

The inflammatory response to severe traumatic injury results in significant morbidity and mortality. Lymphocytes have recently been identified as critical mediators of the early innate immune response to ischemia-reperfusion injury. Experimental manipulation of lymphocytes following hemorrhagic shock may prevent secondary immunologic injury in surgical and trauma patients. The objective of this study is to evaluate the lymphocyte sequestration agent FTY720 as an immunomodulator following experimental hemorrhagic shock in a swine liver injury model. Yorkshire swine were anesthetized and underwent a grade III liver injury with uncontrolled hemorrhage to induce hemorrhagic shock. Experimental groups were treated with a lymphocyte sequestration agent, FTY720, (n = 9) and compared to a vehicle control group (n = 9). Animals were observed over a 3 day survival period after hemorrhage. Circulating total leukocyte and neutrophil counts were measured. Central lymphocytes were evaluated with mesenteric lymph node and spleen immunohistochemistry (IHC) staining for CD3. Lung tissue infiltrating neutrophils were analyzed with myeloperoxidase (MPO) IHC staining. Relevant immune-related gene expression from liver tissue was quantified using RT-PCR. The overall survival was 22.2% in the vehicle control and 66.7% in the FTY720 groups (p = 0.081), and reperfusion survival (period after hemorrhage) was 25% in the vehicle control and 75% in the FTY720 groups (p = 0.047). CD3+ lymphocytes were significantly increased in mesenteric lymph nodes and spleen in the FTY720 group compared to vehicle control, indicating central lymphocyte sequestration. Lymphocyte disruption significantly decreased circulating and lung tissue infiltrating neutrophils, and decreased expression of liver immune-related gene expression in the FTY720 treated group. There were no observed infectious or wound healing complications. Lymphocyte sequestration with FTY720 improves survival in experimental hemorrhagic shock using a porcine liver injury model. These results support a novel and clinically relevant lymphocyte immunomodulation strategy to ameliorate secondary immune injury in hemorrhagic shock