Improving the Characterization of Radiologically Isolated Syndrome Suggestive of Multiple Sclerosis

OBJECTIVE: To improve the characterization of asymptomatic subjects with brain magnetic resonance imaging (MRI) abnormalities highly suggestive of multiple sclerosis (MS), a condition named as "radiologically isolated syndrome" (RIS). METHODS: Quantitative MRI metrics such as brain volumes and magnetization transfer (MT) were assessed in 19 subjects previously classified as RIS, 20 demographically-matched relapsing-remitting MS (RRMS) patients and 20 healthy controls (HC). Specific measures were: white matter (WM) lesion volumes (LV), total and regional brain volumes, and MT ratio (MTr) in lesions, normal-appearing WM (NAWM) and cortex. RESULTS: LV was similar in RIS and RRMS, without differences in distribution and frequency at lesion mapping. Brain volumes were similarly lower in RRMS and RIS than in HC (p<0.001). Lesional-MTr was lower in RRMS than in RIS (p = 0.048); NAWM-MTr and cortical-MTr were similar in RIS and HC and lower (p<0.01) in RRMS. These values were particularly lower in RRMS than in RIS in the sensorimotor and memory networks. A multivariate logistic regression analysis showed that 13/19 RIS had ≥70% probability of being classified as RRMS on the basis of their brain volume and lesional-MTr values. CONCLUSIONS: Macroscopic brain damage was similar in RIS and RRMS. However, the subtle tissue damage detected by MTr was milder in RIS than in RRMS in clinically relevant brain regions, suggesting an explanation for the lack of clinical manifestations of subjects with RIS. This new approach could be useful for narrowing down the RIS individuals with a high risk of progression to MS

The combination therapy with alfacalcidol and risedronate improves the mechanical property in lumbar spine by affecting the material properties in an ovariectomized rat model of osteoporosis

<p>Abstract</p> <p>Background</p> <p>We conducted the present study to investigate the therapeutic effects of a combination treatment of alfacalcidol (ALF) and risedronate (RIS) on the bone mechanical properties of bone and calcium (Ca) metabolism using an ovariectomized (OVX) rat model of osteoporosis.</p> <p>Methods</p> <p>Female Wistar rats were OVX- or sham-operated at 40 weeks of age. Twelve weeks post-surgery, rats were randomized into seven groups: 1) sham + vehicle, 2) OVX + vehicle, 3) OVX + ALF 0.025 μg/kg/day, 4) OVX + ALF 0.05 μg, 5) OVX + RIS 0.3 mg, 6) OVX + RIS 3.0 mg, 7) OVX + ALF 0.025 μg + RIS 0.3 mg. Each drug was administered orally five times a week for 12 weeks. After treatment, we evaluated the mechanical properties of the lumbar vertebra and femoral midshaft. In the lumbar vertebra, structural and material analyses were performed using micro-computed tomography (micro-CT) and microbeam X-ray diffraction (micro-XRD), respectively. Biochemical markers in serum and urine were also determined.</p> <p>Results</p> <p>(1) With respect to improvement in the mechanical strength of the lumbar spine and the femoral midshaft, the combination treatment of ALF and RIS at their sub-therapeutic doses was more effective than each administered as a monotherapy; (2) In the suppression of bone resorption and the amelioration of microstructural parameters, the effects of ALF and RIS were considered to be independent and additive; (3) The improvement of material properties, such as microstructural parameters and the biological apatite (Bap) c-axis orientation, contributed to the reinforcement of spinal strength; and (4) The combination treatment of ALF and RIS normalized urinary Ca excretion, suggesting that this treatment ameliorated the changes in Ca metabolism.</p> <p>Conclusion</p> <p>These results demonstrate that the combination treatment of ALF and RIS at their sub-therapeutic doses can improve the mechanical properties of the spine as well as the femur and ameliorate changes in Ca metabolism in an animal model of osteoporosis, suggesting that the combination treatment of ALF and RIS has a therapeutic advantage over each monotherapy for the treatment of osteoporosis.</p

An Outline of a Progressive Resolution to the Euro-area Sovereign Debt Overhang: How a Five year Suspension of the Debt Burden Could Overthrow Austerity

The present study puts forward a plan for solving the sovereign debt crisis in the euro area (EA) in line with the interests of the working classes and the social majority. Our main strategy is for the European Central Bank (ECB) to acquire a significant part of the outstanding sovereign debt (at market prices) of the countries in the EA and convert it to zero-coupon bonds. No transfers will take place between individual states; taxpayers in any EA country will not be involved in the debt restructuring of any foreign eurozone country. Debt will not be forgiven: individual states will agree to buy it back from the ECB in the future when the ratio of sovereign debt to GDP has fallen to 20 percent. The sterilization costs for the ECB are manageable. This model of an unconventional monetary intervention would give progressive governments in the EA the necessary basis for developing social and welfare policies to the benefit of the working classes. It would reverse present-day policy priorities and replace the neoliberal agenda with a program of social and economic reconstruction, with the elites paying for the crisis. The perspective taken here favors social justice and coherence, having as its priority the social needs and the interests of the working majority

Generalized Derivations on Power Values of Lie Ideals in Prime and Semiprime Rings

LetRbe a 2-torsion free ring and letLbe a noncentral Lie ideal ofR, and letF:R→RandG:R→Rbe two generalized derivations ofR. We will analyse the structure ofRin the following cases: (a)Ris prime andF(um)=G(un)for allu∈Land fixed positive integersm≠n; (b)Ris prime andF((upvq)m)=G((vrus)n)for allu,v∈Land fixed integersm,n,p,q,r,s≥1; (c)Ris semiprime andF((uv)n)=G((vu)n)for allu,v∈[R,R]and fixed integern≥1; and (d)Ris semiprime andF((uv)n)=G((vu)n)for allu,v∈Rand fixed integern≥1

Comparison of surface chlorophyll, primary production, and satellite imagery in hydrographically different sounds off southern New England

Block Island Sound (BIS) and Rhode Island Sound (RIS) are adjacent inner continental shelf ecosystems with contrasting hydrographic regimes. BIS exhibits more energetic tidal mixing, and water column stratification remains weak but persists year-round due to nearby estuarine exchange flow; RIS is less influenced by estuaries, and more seasonal with strong stratification in summer. We compared annual cycles of phytoplankton biomass and primary production in BIS and RIS using measurements (surface chlorophyll, 14C primary production), primary production models (Webb/Platt and BZE models), and satellite ocean color products. During 22 mo of sampling, measured surface chlorophyll was not significantly different between BIS (mean = 1.86 mg m-3) and RIS (1.69 mg m-3), and bimodal peaks of phytoplankton biomass and production occurred concurrently in both Sounds. In contrast, a 12 yr ocean-color based chlorophyll time series indicated higher long-term average surface chlorophyll in the more well-mixed system (BIS, mean = 1.50 mg m-3; RIS, mean = 0.86 mg m-3). BIS annual primary production (318 to 329 g C m-2 yr-1) was higher than RIS (239 to 256 g C m-2 yr-1; p \u3c 0.001). These differences were most apparent during the summer, concurrent with the largest differences in water column stratification. Phytoplankton bloom phenology was driven by physical processes, with chlorophyll significantly related to water column stratification (r = -0.51, p = 0.01), depth of the euphotic zone (r = -0.54, p = 0.05), and surface water salinity (r = 0.54, p = 0.04). Primary production was correlated with surface water temperature (r = 0.57, p = 0.03) but the mechanisms underlying production differences between the Sounds remain unresolved. We hypothesize that different hydrographies give rise to different productivity between the Sounds

Epidemiological analysis of hospitalisations due to recurrent stroke in the Silesian Province, Poland, between 2009 and 2015

Background and aim. There is a lack of recent epidemiological studies on recurrent stroke (RS) in Poland. The aim of this study was to analyse all hospitalisations related to RS in Silesia – an industrial region covering 12% of the Polish population.Material and methods. We carried out statistical analysis of data contained in stroke questionnaires transferred to the Polish National Health Fund by hospitals in Silesia, Poland, between 2009 and 2015.Results. In the analysed period, the number of RS hospitalisations in Silesia was 18,063 (22.2% of all acute strokes). The percentage of RS significantly decreased during the period under consideration (p &lt; 0.001). The same observation concerned recurrent ischaemic stroke (RIS), but not recurrent haemorrhagic stroke (RHS). The median hospitalisation time was 14 days for RHS, and 11 days for RIS. Large-artery atherosclerosis and cardioembolisms were significantly more often recognised in RIS than in first-ever ischaemic stroke (FIS) (consecutively, 38.2% vs 36.0%, and 21% vs 18.1%; p &lt; 0.001). The in-hospital mortality rate was significantly higher for RS than for first-ever stroke (18.4% vs 17.2%; p &lt; 0.001). The same observation wasdone for RIS vs FIS (16.2% vs 13.9%; p &lt; 0.001), and for RHS vs FHS (39.8% vs 36%; p = 0.004). The rtPA therapy was applied to 5.3% of FIS and 3.2% of RIS patients (p &lt; 0.001).Conclusions. This is the first such comprehensive and long-term analysis of recurrent stroke in Silesia, Poland. It could help in the implementation of appropriate educational programmes, and thus help to improve the health status of society

Intrarenal Resistance Index as a Prognostic Parameter in Patients with Liver Cirrhosis Compared with Other Hepatic Scoring Systems

Background and Aims: Patients with advanced liver cirrhosis who develop renal dysfunction have a poor prognosis. Elevated intrarenal resistance indices (RIs) due to renal vascular constriction have been described before in cirrhotic patients. In the current study, we prospectively investigated the course of intrarenal RIs and compared their prognostic impact with those of the Model for End-Stage Liver Disease (MELD) and the Child-Pugh scores. Methods: Sixty-three patients with liver cirrhosis underwent a baseline visit which included a sonographic examination and laboratory tests. Forty-four patients were prospectively monitored. The end points were death or survival at the day of the follow-up visit. Results: In 28 patients, a follow-up visit was performed after 22 8 months (group 1). Sixteen patients died during follow-up after 12 8 months (group 2). Group 2 patients showed a significantly higher baseline RI (0.76 +/- 0.05) than group 1 patients (RI = 0.72 +/- 0.06; p < 0.05). As shown by receiver operating characteristic analysis, the RI and the MELD score achieved similar sensitivity and specificity {[}area under the curve (AUC): 0.722; 95% confidence interval (95% CI): 0.575-0.873 vs. AUC: 0.724; 95% CI: 0.575-0.873, z = 0.029, n.s.] in predicting survival and were superior to the Child-Pugh score (AUC: 0.677; 96% Cl: 0.518-0.837). Conclusion: The RI is not inferior in sensitivity and specificity to the MELD score. Cirrhotic patients with elevated RIs have impaired short- and long-term survival. The RI may help identify high-risk patients that require special therapeutic care. Copyright (C) 2012 S. Karger AG, Base

Effect on bone turnover markers of once-yearly intravenous infusion of zoledronic acid versus daily oral risedronate in patients treated with glucocorticoids

Objective. Long-term glucocorticoid use is accompanied by rapid bone loss; however, early treatment with bisphosphonates prevents bone loss and reduces fracture risk. The aim of this study was to examine the effects of two bisphosphonates, i.v. zoledronic acid (ZOL) versus oral risedronate (RIS), on bone turnover markers (BTMs) in subjects with glucocorticoid-induced osteoporosis (GIO). Methods. Patients were randomly stratified according to the duration of pre-study glucocorticoid therapy [prevention subpopulation (ZOL, n = 144; RIS, n = 144) ≤3 months, treatment subpopulation (ZOL, n = 272; RIS, n = 273) >3 months]. Changes in β-C-terminal telopeptides of type 1 collagen (β-CTx), N-terminal telopeptide of type I collagen (NTx), procollagen type 1 N-terminal propeptide (P1NP) and bone-specific alkaline phosphatase (BSAP) from baseline were measured on day 10 and months 3, 6 and 12. Results. At most time points, there were significantly greater reductions (P < 0.05) in the concentrations of serum β-CTx, P1NP and BSAP and urine NTx in subjects on ZOL compared with RIS in both males and females of the treatment and prevention subpopulations. In pre- and post-menopausal women, there were significantly greater reductions in the concentrations of BTMs with ZOL compared with RIS. At 12 months, ZOL had significantly greater reductions compared with RIS (P < 0.05) for β-CTx, P1NP, BSAP and NTx levels, independent of glucocorticoid dose. Conclusions. Once-yearly i.v. infusion of ZOL 5 mg was well tolerated in different subgroups of GIO patients. ZOL was non-inferior to RIS and even superior to RIS in the response of BTMs in GIO patients. Trial registration: ClinicalTrials.gov, http://clinicaltrials.gov, NCT0010062

Robust Target Positioning for Reconfigurable Intelligent Surface Assisted MIMO Radar Systems

The direction of arrival (DOA) based multiple-input multiple-output (MIMO) radar technique has been widely utilized for ubiquitous positioning due to its advantage of simple implementability. On the other hand, reconfigurable intelligent surface (RIS) has received considerable attention, which can be deployed on the walls and objects to strengthen the positioning performance. However, RIS is usually not equipped with a perception module, which results in the tremendous challenge for RIS-assisted positioning. To tackle this challenge, this paper propose the fundamental problem of DOA-based target positioning in RIS-assisted MIMO radar system. Unlike conventional DOA estimation systems, the beneficial role of RIS is investigated in MIMO radar system, where a nonconvex $\ell _{p}$ promoting function is exploited to estimate DOA task. By adjusting the reflecting elements of the RIS, the proximal projection iterative strategy is developed to obtain the feasible solution. Both theoretical analysis and simulation results illustrate that the proposed scheme can achieve remarkable positioning performance and shed light on the benefits offered by the adoption of the RIS in terms of positioning performance