In this study, two types of relays are considered. Conventional amplify and forward relays this website in which all relays amplify their received signal and forward it to the destination in a round-robin fashion. In addition, decode and forward relays in which the relays that correctly detect the source signal will forward the corresponding fading gain to the destination in pre-determined orthogonal time slots are studied. The optimum decoder for both communication systems is derived and performance analysis are conducted. The exact average bit error probability (ABEP) over Rayleigh fading channels is obtained in closed-form for a source equipped
with two transmit antennas and arbitrary number of relays. Furthermore, simple and general asymptotic expression for the ABEP is derived and analyzed. Numerical results are also provided, sustained by simulations which corroborate the exactness Selleck DMXAA of the theoretical analysis. It is shown that both schemes perform nearly the same and the advantages and disadvantages
of each are discussed.”
“Development of assays to screen milk for economically motivated adulteration with foreign proteins has been stalled since 2008 due to strong international reactions to the melamine poisoning incident in China and the surveillance emphasis placed on low molecular weight nitrogen-rich adulterants. New screening assays are still needed to detect high molecular weight foreign protein adulterants and characterize this understudied potential risk. A rapid turbidimetric method was developed to screen milk powder for adulteration with insoluble plant proteins. Milk powder samples spiked with 0.03-3% by weight of soy, pea, rice, and wheat protein isolates were
extracted in 96-well plates, and resuspended pellet solution absorbance was measured. Limits of detection ranged from 100 to 200 mu g, or 0.1-0.2% of the sample weight, and adulterant pellets were visually apparent even at similar to 0.1%. Extraction recoveries ranged from 25 to 100%. Assay sensitivity and simplicity indicate that it would be ideally suitable to rapidly screen milk samples in resource NU7026 in vivo poor environments where adulteration with plant protein is suspected.”
“BackgroundAlopecia areata (AA) is a common dermatological problem that manifests as sudden loss of hair without any inflammation or scarring. Various cytokines are implicated in the pathogenesis of this disease. Macrophage migration inhibitory factor (MIF) is located at an upstream position in the events leading to the possible dysregulated immuno-inflammatory responses, and the high level of this cytokine in AA may suggest a role of MIF in the pathogenesis of AA. MethodsThis case-control study was carried out on 31 AA patients with different grades of severity and 15 apparently healthy subjects. Serum MIF level was measured by ELISA, and was correlated with the clinical severity of the disease using SALT (severity of alopecia tool) scoring system.
Thus, children with intermediate or premutation range fragile X cytosine-guanine-guanine expansions may be more susceptible than children without such expansions to other processes, both genetic and environmental, that contribute to neurodevelopmental disability.”
“We investigated the growth and the CA4P in vivo cell lipid composition of the mycelium and of the yeast-like form of Mucor hiemalis VKMF-1431 obtained under aerobic conditions by treatment with
the morphogenetic agents itraconazole, exogenous triacylglycerols (TAGs), and trehalose. The sporangiospores of a 20-day culture were inoculated on the medium with glucose. Under these conditions, the fungus produced both mycelium and yeast-like cells. It was established that, upon the germination of old (20-day) sporangiospores, selleck inhibitor the fungus predominantly used the mycelium development strategy in the presence of trehalose and TAGs. It was characterized by a low ratio between the two bulk membrane lipids (PEA/PC) and increased levels of PC and polyunsaturated fatty
acids (FA). Compared to the mycelium, the yeast cell morphotype obtained on the medium with glucose was distinguished by an elevated PEA/PC ratio, lowered TAG, free sterol (FS) and esterified sterol (ES) levels, a decreased ES/FS ratio that correlated with the reserve sterol pool size, and a lowered content of unsaturated fatty acids (the linoleic and the gamma-linolenic acid). These peculiarities LOXO-101 of the lipid composition of yeastlike cells correlated with the intensity of yeastlike growth. Light and electron microscopy revealed differences between the above cell morphotypes. With itraconazole, yeast-like cells were characterized by the destruction of the endoplasmic reticulum membranes and formation of a large number of vacuoles. The suggestion was confirmed that the
state/age of inoculum sporangiospores exerts an influence on the capacity for dimorphism in mucorous fungi such as M. hiemalis. The data obtained testify to an involvement of lipids in the process of adaptation to environmental factors and to their regulatory role in morphogenetic processes associated with the formation of alternative morphotypes of the mucorous fungus.”
“Monozygotic (MZ) twinning is generally considered to be rare in species other than human. We inspected sex ratios in European zoo-bred ring-tailed lemurs (Lemur catta), revealing a significant excess of same-sex twins. Of 94 pairs, 60 (64%) were either both males or both females (p = .004). Application of the Weinberg differential rule argues that 27% of all twins in this species are MZ pairs.
The objectives of this paper were to evaluate the effect of photoperiod on flowering date of the model species for legume crops, Medicago truncatula and to describe genetic architecture of this trait in multiple mapping populations. The effect of photoperiod (12 and 18 h) was analysed on eight lines. Quantitative variation
in three recombinant inbred lines (RILs) populations involving four parental lines was evaluated, and QTL detection was carried out. Flowering occurred earlier in long than in short photoperiods. Modelling the rate of progression Apoptosis inhibitor to flowering with temperature and photoperiod gave high R(2), with line-specific parameters that indicated differential responses of the lines to both photoperiod and temperature. QTL detection showed a QTL on chromosome 7 that was common to all populations and seasons. Taking advantage of the multiple mapping populations, it was condensed into a single QTL with a support interval of only 0.9 cM. In a bioanalysis, six candidate genes were identified in this interval. buy 3-Methyladenine This design also indicated other genomic regions that were involved in flowering date variation more specifically in one population or one season. The analysis on three different mapping populations detected more QTLs than on a single population, revealed more alleles and gave a more precise position of the QTLs that were
common to several populations and/or seasons. Identification of candidate genes was a result of integration of QTL analysis and genomics in M. truncatula.”
“Genetic diversity between synthetic cultivars (Syn5, Syn7), inbred lines (D-3, D-5, E-1/2, G(1/1), G(1/2)) and ecotypes (E16, E51, E182, E231) of lucerne (Medicago sativa L.) was studied using the RAPD-PCR method. The plants differed in the efficiency of seed set and in the yield of green mass. The ecotypes E182 and E231 and the synthetic population Syn5 showed the highest fertility. Additionally, Syn5 also showed
the highest efficiency of seed set and the yield of green mass. Among the inbred lines, D3 was characterised by the highest yield of green mass and E1/2 by the highest fertility. An optimal combination of yield and biomass was observed for the synthetic population Syn5, obtained by crossing the lines D-3, D-5 and G(1/1), C59 as demonstrated using comparative analysis. A total of 338 polymorphic products were generated using 20 arbitrary primers. Cluster analysis using the Unweighted-Pair Group Method with Arithmetic Mean (UPGMA) in the Molecular image Gel Doc (TM) XR (Bio-Rad) software based on the Dice’s coefficient of genetic similarity showed a division of the studied forms into two groups based on genetic similarity. The ecotype E16 formed one of the groups whereas all of the other ecotypes observed in this study clustered into the second group. A high level of polymorphism among the studied lucerne forms was detected indicating an interesting gene pool awaiting future exploration.
In the present work we demonstrate that the fungal pathogen Botrytis cinerea also
can secrete mannitol, and that overexpression of MTD in zonal geranium (Pelargonium x hortorum) in turn provides increased resistance to B. cinerea. These results are not only an important validation of previous work, but support the idea that MTD-overexpression might be used to engineer a broad variety p38 MAPK assay of plants for resistance to mannitol-secreting fungal pathogens like B. cinerea for which specific resistance is lacking.”
“To determine the rate and factors associated with the successful Induction of Labor (IOL) in nulliparous patients undergoing scheduled IOL at 41 weeks of gestational age (GA) with an unfavorable cervix.\n\nThis was a retrospective analysis that included nulliparous patients who presented to the Labor and Delivery unit at the Bronx Lebanon Hospital Center between 2011 and 2012 for
elective IOL at 41 weeks of GA. The Bishop score was assessed upon admission and IOL agents were used in compliance with ACOG guidelines in different combinations, based on the obstetrical team preference.\n\nLabor and Delivery Unit of the Bronx Lebanon selleck chemicals Hospital.\n\nNulliparous patients with 41 weeks of pregnancy for elective induction of labor.\n\nSeventy-six patients were included in the study. GA was confirmed using a combination of the last menstrual period and a dating sonogram during pregnancy.\n\nThis was a retrospective chart review that included nulliparous patients who presented to the Labor and Delivery unit at the Bronx Lebanon Hospital Center between October 2011 and October 2012 for elective IOL at 41 weeks of gestational age with an unfavorable cervix defined as a Bishop score of 6 or less.\n\nThe overall successful rate of IOL in a combination of different maternal factors with different agents for induction in nulliparous patients undergoing scheduled IOL with an unfavorable Bishop score at 41 weeks of GA was 51.32 %.\n\nFactors associated with successful IOL were younger age [22.3 years vs. 25.1(p = 0.015)], lower BMI [25 vs. 28.1(p = 0.46)] and lower
maternal weight [64.75 kg vs. 74.02 (p = 0.28)]. Maternal height was not a contributing factor; GDC-0068 cell line the artificial rupture of membranes, epidural anesthesia and the prostaglandins used did not contribute. Use of cervical balloon and oxytocin was associated with failed IOL.\n\nPatients undergoing IOL at 41 weeks with an unfavorable cervix had a successful rate of 51.32 %. Younger maternal age, lower weight, and lower BMI were associated with successful IOL.”
“The purpose of this study was to review occupational reproductive abnormalities and occupational bladder cancer in Korea and to discuss their toxicological implications. Reproductive dysfunction as a result of 2-bromopropane poisoning was first reported in Korean workers.
Moreover, the challenge dose of MA (1 mg/kg) increased
seizure threshold in all groups of rats, shortened duration of ADs in controls and prenatally saline-exposed animals, shortened duration of SADs in prenatally saline-exposed rats and totally eliminated WDS in all groups. Thus, the present study demonstrates that both chronic prenatal MA exposure and a single dose of MA in adulthood decrease focally BGJ398 concentration induced epileptiform activity in adult male rats. (C) 2011 Elsevier Inc. All rights reserved.”
“We characterized the genetic variability of gene expression in terms of trans and cis variability for each yeast transcript. Genes that are highly regulated by nucleosomes showed a high degree of trans variability. From the expression profiles of mutants for various chromatin modifiers, we found that transvariable genes are distinctly regulated at the chromatin level. The effect of chromatin regulators was highly significant, even GSI-IX clinical trial when compared with that of transcription factors. The DNA-binding activities of transcription factors had a low influence on trans variability. In the case of the basal transcription factor TBP and TBP- associated factor TAF1, expression variability was coupled with the histone acetyltransferase activities of TAF1 and other
factors, rather than with the binding of TBP to DNA. Additionally, we found that the correlation of TATA-box presence and expression variability could be explained in terms of chromatin regulation. The lack of activating histone modifications may subject TATA- containing promoters to chromatin regulation processes. Our results propose that epigenetic regulation has a central role in the variation and evolution of gene expression.”
promazine and chlorpromazine elicited cutaneous anesthesia, no study of spinal anesthesia with chlorpromazine and promazine has been reported. Selleckchem Small molecule library This study was to examine whether chlorpromazine and promazine produce spinal anesthesia. Using a rat model via intrathecal injection, we tested spinal blockades of motor function and nociception by promazine, chlorpromazine or bupivacaine, and so were dose-response studies and durations. We demonstrated that chlorpromazine and promazine elicited dose-dependent spinal blockades in motor function and nociception. On the 50% effective dose (ED50) basis, the rank of potency of these drugs was bupivacaine > promazine > chlorpromazine (P < 0.05 for the differences). On an equipotent basis (25% effective dose [ED25]. ED50, and ED75), the block duration caused by chlorpromazine or promazine was longer than that caused by the long-lasting local anesthetic bupivacaine (P<0.01 for the differences). Chlorpromazine and promazine, as well as bupivacaine, showed longer duration of sensory block than that of motor block.
(Hypertension. 2011;58:1066-1072.). Online Data Supplement”
“Species have traditionally been defined as cortisol-dominant or corticosterone-dominant, depending on the glucocorticoid that is reported. To assess the degree of covariance versus independence between cortisol and corticosterone, 245 serum samples belonging to 219 individuals from 18 cortisol-dominant, non-domesticated species (6 mammalian orders) were compared by mass spectrometry. In these samples, which were elevated above baseline, concentration ranges were overlapping for cortisol and corticosterone
although cortisol was dominant in every Bromosporine in vivo sample except one of 17 bighorn sheep with a corticosterone-biased cortisol-to-corticosterone ratio of 0.17. As expected, cortisol and corticosterone were strongly associated among species (r(2) = 0.8; species with high absolute cortisol tend to have high absolute corticosterone concentrations), with wide variation in the species-average cortisol-to-corticosterone ratio (range 7.5-49) and an even wider ratio range DZNeP ic50 across individuals (0.2-341). However, only 9 out of 13 species with >7 individuals showed a positive association between cortisol and corticosterone among
individuals, and repeated measures of the cortisol-to-corticosterone ratio within individuals were weakly associated (CV range 3-136%). We conclude that corticosterone, although at lower concentrations, has the potential to signal independently of cortisol, and should be included in integrated endocrine models of stress responses. (C) 2012 Elsevier Inc. All rights reserved.”
are widely distributed over all the continents. As they are well adapted to urban areas they can often cause accidents to humans by injecting venom produced in the glands located inside their maxillipeds, The STI571 cost fine morphology of the centipede venom glands is practically unknown. This present study is the first comparative report on the histology, histochemistry and ultrastructure of the venom glands of the centipede species responsible for the majority of accidents to humans in Brazil: Scolopendra viridicornis, Cryptops iheringi and Otostigmus pradoi. In all species the glands are basically composed of columnar secretory cells radially disposed side by side, individually opening through pores in a central chitinous duct. Each secretory cell is covered by striated muscular fibres. The secretion has the form of small PAS positive granules and large hyaline secretory bromophenol blue positive vacuoles, indicating the presence of neutral polysaccharides and protein. The secretion is conducted through the secretory cell necks to the pores, which open into the central chitinous duct. The results indicate a great similarity both in morphology and primary chemical composition of the venom among the studied species, except for the size of the glands, which is proportional to the body dimensions of each species. (C) 2008 Elsevier Ltd.
\n\nMethods. We retrospectively identified NSCLC patients who underwent EGFR mutation testing and pretreatment FDG-PET and CT scans. The maximum standard uptake value (SUVmax) of the primary tumor and any metastases was measured and normalized to the SUV of blood in the pulmonary artery. We compared normalized
SUVmax values between EGFR-mutant and wild-type patients and modeled radiographic and clinical predictors of EGFR mutation status. Receiver operator characteristic (ROC) curves NSC23766 mw were used to identify potential SUV cutoffs predictive of genotype.\n\nResults. We included 100 patients (24 EGFR-mutant and 76 wild-type). There was a trend for higher normalized SUVmax in the primary tumors among patients with EGFR-wild-type versus mutant (median, 3.4; range, 0.6-12.8; versus median, 2.9; range, 0.4-5.0; p = .09). Normalized SUVmax of nodal and distant metastases, and CT characteristics were not associated with genotype. On multivariate analysis, low normalized SUVmax of the primary tumor was predictive for EGFR mutation (odds ratio, 0.72; 95% confidence interval, 0.53-0.98; p = .034). ROC curve analyses yielded an area under the curve of 0.62, and identified a potential cutoff of >= 5.0 to distinguish wild-type from mutant tumors.\n\nConclusions. In this retrospective study, high FDG avidity (normalized SUVmax >= 5) correlated with EGFR-wild-type genotype. Although genotyping
remains the gold standard, further work to validate FDG-PET as a surrogate AZD8931 cost for tumor genotype may provide useful information in patients without available tumor tissue. The Oncologist 2011; 16: 319-326″
“Leaf and petiole explants of monocotyledonous pothos (Epipremnum aureum) ‘Jade’ were cultured on Murashige and Skoog basal medium supplemented with N-(2-chloro-4-pyridl)-N’-phenylurea (CPPU) or N-phenyl-N’-1,2,3-thiadiazol-5-ylurea (TDZ) with alpha-naphthalene acetic acid (NAA). Somatic embryos
appeared directly from explants after 4-8 weeks of culture; 9.1 mu M TDZ with 1.1 mu M NAA induced 61.1 % leaf discs and 94.4 % of petiole segments Ricolinostat solubility dmso to produce plantlets through embryo conversion. Using this established regeneration method and an enhanced green fluorescent protein (GFP) gene (egfp) as a reporter marker, an Agrobacterium-mediated transformation procedure was developed. Leaf discs and petiole segments were inoculated with Agrobacterium tumefaciens strain EHA105 harboring a binary vector pLC902 that contains novel bi-directional duplex promoters driving the egfp gene and hygromycin phosphotransferase gene (hpt), respectively. The explants were co-cultivated with strain EHA105 for 3, 5, and 7 days, respectively prior to selective culture with 25 mg l(-1) hygromycin. A 5-day co-cultivation led to 100 % of leaf discs to show transient GFP expression and 23.8 % of the discs to produce stable GFP-expressing somatic embryos. A 7-day co-cultivation of petiole explants resulted in the corresponding responses at 100 and 14.3 %, respectively.
However, changes in hedge quality and floral diversity were not linked directly to a 60% increase in the Transmembrane Transporters inhibitor proportion of land use categories classified as ‘intensive’ adjacent to the sites over the 70 years. Recommendations are made for future hedgerow management based
on conservation objectives for specific groups of hedge plant species. (C) 2013 Elsevier Ltd. All rights reserved.”
“Professional military training makes tough demands on soldiers’ perceptual and motor skills, as well as on their physical fitness and cognitive capabilities in the course of preparation for stressful operational environments. In this pilot study we attempted to identify difference in pattern of neural responses between extensively trained, professional mission-ready soldiers and novice soldiers during audiovisual simulation of mission conditions. We performed fMRI scanning on a few volunteers during presentation of semantically relevant video-clips of real combat from Afghanistan to evaluate influence of military training on mental responses of soldiers. We showed that for professional mission-ready soldiers a week before their deployment to Afghanistan, video-clips with deadly ambush combat induce greater overall brain activation
compared to novice soldiers. this website Mission-ready soldiers showed greater activation in premotor/prefrontal cortex, posterior parietal cortex, and posterior temporal cortex. These results imply that fMRI technique could be used as challenging step forward in the multidimensional evaluation of military training influence on neural responses and operational capabilities of professional soldiers. This is extremely important not only for potential failure prevention and mere Cl-amidine cell line success
of the mission, but even more for the survival and the well-being of the servicemen and servicewomen.”
“There is an increasing recognition of autoimmune limbic encephalopathy with the hope for earlier diagnosis and expedited and improved treatment. Although antibody testing remains the definitive clinical diagnostic feature, the presentation of a rapid dementia, behavioral changes, and seizures leads to investigation using cerebral imaging, electroencephalography, and cerebrospinal fluid to confirm the diagnosis and also to exclude similar disorders. The electroencephalographer may be asked to comment on the types of electroencephalography abnormality and provide input toward the diagnosis of limbic encephalopathy. This article reviews the literature on limbic paraneoplastic and nonparaneoplastic encephalopathies, providing descriptions and examples of the electroencephalography findings. Typically, there are patterns of slow theta and delta activity and different patterns of temporal and frontal epileptic activity.”
“1. Research in the field of poultry meat quality has become more varied during the last 50 years.
Belostoma employs extra-oral digestion, which allows for ingestion of larger prey than itself, including small vertebrates such as amphibians and fish. Therefore, prey immobilization during digestion is essential, and we show here that Belostoma saliva and B. anurum saliva purified LPC have paralytic activity in zebrafish. This is the first evidence that lysophospholipids might play an important role in prey immobilization, CA3 Stem Cells & Wnt inhibitor in addition to contributing to blood feeding, and might
have been an evolutionary acquisition that occurred long before the appearance of hematophagy in this animal group.”
“The multikinase inhibitor sorafenib has demonstrated an overall survival benefit in phase III hepatocellular carcinoma (HCC) trials and has become the new standard
of care for advanced stages of this disease. However, selleck chemicals llc in clinical practice, the vast majority of patients obtain disease stabilization and occasionally tumor shrinkage. Furthermore, the appropriate timing of sorafenib therapy initiation, in order to maximize its clinical activity, remains under debate. We report a case of 4-year sorafenib treatment in a patient with an advanced hepatitis C virus (HCV)-related HCC with extensive infiltration of the inferior vena cava. Sorafenib treatment induced a rapid complete biochemical response and a long-term favorable outcome. Additionally, no major toxicities or detrimental effects on quality of life were observed. Thus, it is likely that a subgroup of human HCC may be highly sensitive to sorafenib; R406 new molecular determinants are required to select those patients who may benefit from this therapy. Furthermore, a prompt initiation of treatment when the hepatic function is not compromised is a prerequisite for maximizing the clinical activity of sorafenib.”
“The 7-hydroxy-4-methylquinolin-2-(1H)-one 1 on treatment with phthalic anhydride produced 2-[(4 ''-methyl-2'-oxo-1',2'-dihydroquinolin-7'-yl)-oxy-carbonyl]-benzoic acid 2. The compound 2 on treatment with 8-amino-4-phenylquinazolin-2-(1H)-one 3 produced 4-methyl-2-oxo-1,2-dihydroquinolin-7-yl-2′-[(4
''-phenyl-3 '',4 ''-dihydroquinazolin-2 ''-(1 '' H)-one-8 ''-yl)-amino-carbonyl]-benzoate 4. Further treatment of compound 1 with 4-oxo-2-phenylquinazolin-3-(4H)-carboxamide 5 synthesized 4-methyl-2-oxo-1,2-dihydroquinolin-7-yl-2′-[(2 ''-phenylquinazolin-4 ''-(3 '' H)-one-3 ''-yl)-carbonyl-amino-carbonyl]-benzoate 6. On treatment with 4-(4′-oxo-2′-phenylquinazolin-3′(4′H)-yl) benzenesulfonamide 7, compound 1 yielded 4-methyl-2-oxo-1,2-dihydroquinolin-7-yl-2′-[(N-4 ''-(2 ''-phenyl-4'''-oxoquinazolin-3'''-(4'''H)-yl)-phenyl-sulfonyl]-amino-carbonyl-benzoate 8. Compound 1 also yielded 4-methyl-2-oxo-1,2-dihydroquinolin-7-yl-2′-[(4 ''-oxo-2 ''-phenyl-quinazolin-3 ''(4 '' H)-yl)-amino-carbonyl]-benzoate 10 on treatment with 3-amino-2-phenylquinazolin-4(3H)-one 9.
1). In female patients older than 4.5 months of age, there was also a trend toward smaller ICV in patients with the combined form than in those with sagittal synostosis alone (p < 0.1), and the ICV of patients with the combined form was significantly
smaller than the volume in controls in the same age group (p < 0.05). Brain tissue volume was significantly smaller in both patient groups than in controls (p < 0.05). Ventricular volume was significantly increased (compared with controls) only in the patients with isolated sagittal synostosis who were younger than 4.5 months of age (p < 0.05). Overall CSF space, however, was significantly larger in both patient groups in patients younger than 4.5 months of age (p < 0.05).\n\nConclusions. These findings raise concerns about intracranial and brain volume reduction in patients with sagittal and combined learn more metopic and sagittal synostoses and the possibility that this volume reduction may be associated with brain dysfunction. Because the ICV reduction is greater JPH203 in combined metopic and sagittal synostosis in patients older than 4.5 months
of age than in sagittal synostosis in this age group, the potential for brain dysfunction may be particularly true for these younger infants. (DOI: 10.3171/2011.6.FOCUS11100)”
“This study reports on controlling the formation of nanoimpurities on suspended graphene to investigate the inelastic scattering of electrons using a two-phonon Raman process. Results were analyzed by transmission electron microscopy (TEM) and scanning Raman spectroscopy in the same region of suspended graphene. The findings revealed that the area with a higher concentration of impurities shown in the TEM image corresponds directly to the area with a lower integrated intensity and a wider full width at half maximum in the Raman mapping of the 2D band and vice versa. The same trend is also apparent in the 2D and D+D bands.
In conclusion, the results are explained by an increase in the electronic scattering rate due to impurities, which affects two-phonon Raman scattering. Combining the TEM image MDV3100 cost and Raman mapping image effectively demonstrates how electron behavior is affected by the distribution of impurities in graphene systems. Copyright (c) 2012 John Wiley & Sons, Ltd.”
“Multiple sclerosis (MS) is a chronic disease in which disability progresses over time. Progressive forms of MS have a poor prognosis, are associated with greater levels of disability and, unfortunately, are unresponsive to current treatments. Here, we have reviewed the management of 100 patients with MS. The majority of these patients had progressive disease, Expanded Disability Status Scale ‘scores >6, and extensive medical complications. A significant number of patients in this cohort were also treated with MS disease-modifying agents that lack efficacy in patients with progressive disease.