Antibody signatures in patients with histopathologically defined multiple sclerosis patterns

Early active multiple sclerosis (MS) lesions can be classified histologically into three main immunopathological patterns of demyelination (patterns I-III), which suggest pathogenic heterogeneity and may predict therapy response. Patterns I and II show signs of immune-mediated demyelination, but only pattern II is associated with antibody/complement deposition. In pattern III lesions, which include Baló's concentric sclerosis, primary oligodendrocyte damage was proposed. Serum antibody reactivities could reflect disease pathogenesis and thus distinguish histopathologically defined MS patterns. We established a customized microarray with more than 700 peptides that represent human and viral antigens potentially relevant for inflammatory demyelinating CNS diseases, and tested sera from 66 patients (pattern I n = 12; II n = 29; III n = 25, including 8 with Baló's), healthy controls, patients with Sjögren's syndrome and stroke patients. Cell-based assays were performed for aquaporin 1 (AQP1) and AQP4 antibody detection. No single peptide showed differential binding among study cohorts. Because antibodies can react with different peptides from one protein, we also analyzed groups of peptides. Patients with pattern II showed significantly higher reactivities to Nogo-A peptides as compared to patterns I (p = 0.02) and III (p = 0.02). Pattern III patients showed higher reactivities to AQP1 (compared to pattern I p = 0.002, pattern II p = 0.001) and varicella zoster virus (VZV, compared to pattern II p = 0.05). In patients with Baló's, AQP1 reactivity was also significantly higher compared to patients without Baló's (p = 0.04), and the former revealed distinct antibody signatures. Histologically, Baló's patients showed loss of AQP1 and AQP4 in demyelinating lesions, but no antibodies binding conformational AQP1 or AQP4 were detected. In summary, higher reactivities to Nogo-A peptides in pattern II patients could be relevant for enhanced axonal repair and remyelination. Higher reactivities to AQP1 peptides in pattern III patients and its subgroup of Baló's patients possibly reflect astrocytic damage. Finally, latent VZV infection may cause peripheral immune activation

Effect of vitamin D on bone mineral density of elderly patients with osteoporosis responding poorly to bisphosphonates

BACKGROUND: Bisphosphonates are indicated in the prevention and treatment of osteoporosis. However, bone mineral density (BMD) continues to decline in up to 15% of bisphosphonate users. While randomized trials have evaluated the efficacy of concurrent bisphosphonates and vitamin D, the incremental benefit of vitamin D remains uncertain. METHODS: Using data from the Canadian Database of Osteoporosis and Osteopenia (CANDOO), we performed a 2-year observational cohort study. At baseline, all patients were prescribed a bisphosphonate and counseled on vitamin D supplementation. After one year, patients were divided into two groups based on their response to bisphosphonate treatment. Non-responders were prescribed vitamin D 1000 IU daily. Responders continued to receive counseling on vitamin D. RESULTS: Of 449 patients identified, 159 were non-responders to bisphosphonates. 94% of patients were women. The mean age of the entire cohort was 74.6 years (standard deviation = 5.6 years). In the cohort of non-responders, BMD at the lumbar spine increased 2.19% (p < 0.001) the year after vitamin D was prescribed compared to a decrease of 0.55% (p = 0.36) the year before. In the cohort of responders, lumbar spine BMD improved 1.45% (p = 0.014) the first year and 1.11% (p = 0.60) the second year. The difference between the two groups was statistically significant the first year (p < 0.001) but not the second (p = 0.60). Similar results were observed at the femoral neck but were not statistically significant. CONCLUSION: In elderly patients with osteoporosis not responding to bisphosphonates, vitamin D 1000 IU daily may improve BMD at the lumbar spine

Randomized comparison of the effects of the vitamin D(3 )adequate intake versus 100 mcg (4000 IU) per day on biochemical responses and the wellbeing of patients

BACKGROUND: For adults, vitamin D intake of 100 mcg (4000 IU)/day is physiologic and safe. The adequate intake (AI) for older adults is 15 mcg (600 IU)/day, but there has been no report focusing on use of this dose. METHODS: We compared effects of these doses on biochemical responses and sense of wellbeing in a blinded, randomized trial. In Study 1, 64 outpatients (recruited if summer 2001 25(OH)D <61 nmol/L) were given 15 or 100 mcg/day vitamin D in December 2001. Biochemical responses were followed at subsequent visits that were part of clinical care; 37 patients completed a wellbeing questionnaire in December 2001 and February 2002. Subjects for Study 2 were recruited if their 25(OH)D was <51 nmol/L in summer 2001. 66 outpatients were given vitamin D; 51 completed a wellbeing questionnaire in both December 2002 and February 2003. RESULTS: In Study 1, basal summer 25-hydroxyvitamin D [25(OH)D] averaged 48 ± 9 (SD) nmol/L. Supplementation for more than 6 months produced mean 25(OH)D levels of 79 ± 30 nmol/L for the 15 mcg/day group, and 112 ± 41 nmol/L for the 100 mcg/day group. Both doses lowered plasma parathyroid hormone with no effect on plasma calcium. Between December and February, wellbeing score improved more for the 100-mcg/day group than for the lower-dosed group (1-tail Mann-Whitney p = 0.036). In Study 2, 25(OH)D averaged 39 ± 9 nmol/L, and winter wellbeing scores improved with both doses of vitamin D (two-tail p < 0.001). CONCLUSION: The highest AI for vitamin D brought summertime 25(OH)D to >40 nmol/L, lowered PTH, and its use was associated with improved wellbeing. The 100 mcg/day dose produced greater responses. Since it was ethically necessary to provide a meaningful dose of vitamin D to these insufficient patients, we cannot rule out a placebo wellbeing response, particularly for those on the lower dose. This work confirms the safety and efficacy of both 15 and 100 mcg/day vitamin D(3 )in patients who needed additional vitamin D

A discharge summary adapted to the frail elderly to ensure transfer of relevant information from the hospital to community settings: a model

<p>Abstract</p> <p>Background</p> <p>Elderly patients admitted to Geriatric Assessment Units (GAU) typically have complex health problems that require multi-professional care. Considering the scope of human and technological resources solicited during hospitalization, as well as the many risks and discomforts incurred by the patient, it is important to ensure the communication of pertinent information for quality follow-up care in the community setting. Conventional discharge summaries do not adequately incorporate the elements specific to an aging clientele.</p> <p>Objective</p> <p>To develop a discharge summary adapted to the frail elderly patient (D-SAFE) in order to communicate relevant information from hospital to community services.</p> <p>Methods</p> <p>The items to be included in the D-SAFE have been determined by means of a modified Delphi method through consultation with clinical experts from GAUs (11 physicians and 5 pharmacists) and the community (10 physicians and 5 pharmacists). The consensus analysis and the level of agreement among the experts were reached using a modified version of the RAND^®/University of California at Los Angeles appropriateness method.</p> <p>Results</p> <p>A consensus was reached after two rounds of consultation for all the items evaluated, where none was judged «inappropriate». Among the items proposed, four were judged to be « uncertain » and were eliminated from the final D-SAFE, which was divided into two sections: the medical discharge summary (22 main items) and the discharge prescription (14 main items).</p> <p>Conclusions</p> <p>The D-SAFE was developed as a more comprehensive tool specifically designed for GAU inpatients. Additional research to validate its acceptability and practical impact on the continuity of care is needed before it can be recommended for use on a broader scale.</p

Ground Vibration Tests on PILATUS PC-21 Aircraft

The Swiss company Pilatus Aircraft Ltd. is developing the new trainer aircraft PC-21. Before first flight, ground vibration tests were performed on the prototype of this aircraft by DLR. The main objective of the tests were to provide a reliable data base for validating the mathematical model of the aircraft for aeroelastic analyses. The aircraft was investigated in three configurations with full and empty tanks and with additional external tanks. Both phase resonance and phase separation methods were applied. The measurements provided the normal modes and the respective modal parameters in the frequency range up to 80 Hz including nonlinearity investigations

Influence and characterisation of weak non-linearities in swept-sine modal testing

The European aircraft industry is constantly calling for a reduction in the testing time of new aircraft without diminishing the accuracy of the data. As a consequence, substantial changes in the testing strategy of ground vibration tests (GVTs), were proposed and applied during the last couple of years (Fargette et al., Tasks for improvements in ground vibration testing of large aircraft, in: Proc. of IFASD, CASA/AIAE, 2001, pp. 121-133; G. Gloth, et al., Sound and Vibration 35 (11) (2001) 14-18). The basic idea is to combine the benefits of the very reliable but time-consuming phase resonance method (sine dwell) with the application of phase separation techniques to data stemming from broad-band excitation at various excitation points. The authors recommend the use of swept-sine excitation which provides a high excitation level compared to random excitation and a short testing time compared to stepped-sine excitation. The modes of the structure are identified from the resulting frequency response functions (FRFs) by means of phase separation techniques in parallel to the on-going measurement. In the practice of modal testing it is often observed that structures do not behave in a perfectly linear manner. This article investigates the influence of non-linear structural dynamics behaviour on the measurement results. An expansion of the test concept of swept-sine excitation is proposed which introduces a combined approach for linearity checks as well. The plotting of modal parameters like the eigenfrequency as a function of the excitation level is the manner in which non-linear phenomena in GVTs are presently explored. Traditionally these linearity functions are produced by harmonically exciting one single normal mode on different levels of excitation. The goal to extract as much information as possible from the FRF data can be complemented by computing plots of amplitude-dependent modal parameters for modes which have been identified at various excitation levels during the swept-sine testing, depending on the excitation point and the exciter force. The article expounds how the excitation level can be determined in the case of swept-sine excitation. It gives examples of linearity plots from numerical simulations and complex, large aerospace structures. The plots are compared with curves that stem from the phase resonance testing

Modal Survey Test on the European Robotic Arm ERA

This test report describes the performance and the results of a dedicated Modal Survey Test on the Flight Model of the European Robotic Arm ERA, which was performed prior to the strength verification of the spacecraft by means of a Boosted Modal Survey Test. The test was part of the overall ERA-FM system level verification programme. The main objective of the test was to provide a reliable data base to update the respective mathematical model of the spacecraft and to provide the necessary input data for the Boosted Modal Survey Test. The measurements included the normal modes and the modal parameters in the frequency range up to 100 Hz. The test results are correlated with the analytical predictions. Special emphasis is given to nonlinear behaviour of the spacecraft

Analysis of swept-sine runs during modal identification

Experimental modal analysis of large aerospace structures in Europe combine nowadays the benefits of the very reliable but time-consuming phase resonance method and the application of phase separation techniques evaluating frequency response functions (FRF). FRFs of a test structure can be determined by a variety of means. Applied excitation signal waveforms include harmonic signals like stepped-sine excitation, periodic signals like multi-sine excitation, transient signals like impulse and swept-sine excitation, and stochastic signals like random. The current article focuses on slow swept-sine excitation which is a good trade-off between magnitude of excitation level needed for large aircraft and testing time. However, recent ground vibration tests (GVTs) brought up that reliable modal data from swept-sine test runs depend on a proper data processing. The article elucidates the strategy of modal analysis based on swept-sine excitation. The standards for the application of slowly swept sinusoids defined by the international organisation for standardisation in ISO 7626 part 2 are critically reviewed. The theoretical background of swept-sine testing is expounded with particular emphasis to the transition through structural resonances. The effect of different standard procedures of data processing like tracking filter, fast Fourier transform (FFT), and data reduction via averaging are investigated with respect to their influence on the FRFs and modal parameters. Particular emphasis is given to FRF distortions evoked by unsuitable data processing. All data processing methods are investigated on a numerical example. Their practical usefulness is demonstrated on test data taken from a recent GVT on a large aircraft. The revision of ISO 7626 part 2 is suggested regarding the application of slow swept-sine excitation. Recommendations about the proper FRF estimation from slow swept-sine excitation are given in order to enable the optimisation on these applications for future modal survey tests of large aerospace structures