A plain language summary on assessing the long-term effectiveness of cladribine tablets in people living with relapsing multiple sclerosis: The CLASSIC-MS study

Cladribina; Multiple sclerosis; RelapsesCladribina; Esclerosi múltiple; RecaigudesCladribina; Esclerosis múltiple; RecaídasWhat is this summary about? Previous studies have shown that people living with multiple sclerosis (MS) treated with cladribine tablets have fewer relapses (where new symptoms occur or existing symptoms get worse for 24 hours or more) and delayed disability progression (slowing down of the disease getting worse). The CLASSIC-MS study looked at the long-term effectiveness of treatment with cladribine tablets in people living with MS who had taken part in the original CLARITY and CLARITY Extension clinical studies. What were the results? Results showed that people treated with cladribine tablets maintained their mobility (the ability to move freely) for longer and experienced other positive effects long after their treatment ended, including being less likely to need further treatment for their MS. What do the results mean? The results obtained from CLASSIC-MS show that the benefits of taking cladribine tablets carry on even when patients stop taking the treatment

Breath air measurement using wide-band frequency tuning IR laser photo-acoustic spectroscopy

The results of measuring of biomarkers in breath air of patients with broncho-pulmonary diseases using wide-band frequency tuning IR laser photo-acoustic spectroscopy and the methods of data mining are presented. We will discuss experimental equipment and various methods of intellectual analysis of the experimental spectra in context of above task

Protective Allele for Multiple Sclerosis HLA-DRB1*01:01 Provides Kinetic Discrimination of Myelin and Exogenous Antigenic Peptides.

Risk of the development of multiple sclerosis (MS) is known to be increased in individuals bearing distinct class II human leukocyte antigen (HLA) variants, whereas some of them may have a protective effect. Here we analyzed distribution of a highly polymorphous HLA-DRB1 locus in more than one thousand relapsing-remitting MS patients and healthy individuals of Russian ethnicity. Carriage of HLA-DRB1*15 and HLA-DRB1*03 alleles was associated with MS risk, whereas carriage of HLA-DRB1*01 and HLA-DRB1*11 was found to be protective. Analysis of genotypes revealed the compensatory effect of risk and resistance alleles in trans. We have identified previously unknown MBP153−161 peptide located at the C-terminus of MBP protein and MBP90−98 peptide that bound to recombinant HLA-DRB1*01:01 protein with affinity comparable to that of classical antigenic peptide 306-318 from the hemagglutinin (HA) of the influenza virus demonstrating the ability of HLA-DRB1*01:01 to present newly identified MBP153−161 and MBP90−98 peptides. Measurements of kinetic parameters of MBP and HA peptides binding to HLA-DRB1*01:01 catalyzed by HLA-DM revealed a significantly lower rate of CLIP exchange for MBP153−161 and MBP90−98 peptides as opposed to HA peptide. Analysis of the binding of chimeric MBP-HA peptides demonstrated that the observed difference between MBP153−161, MBP90−98, and HA peptide epitopes is caused by the lack of anchor residues in the C-terminal part of the MBP peptides resulting in a moderate occupation of P6/7 and P9 pockets of HLA-DRB1*01:01 by MBP153−161 and MBP90−98 peptides in contrast to HA308−316 peptide. This leads to the P1 and P4 docking failure and rapid peptide dissociation and release of empty HLA-DM–HLA-DR complex. We would like to propose that protective properties of the HLA-DRB1*01 allele could be directly linked to the ability of HLA-DRB1*01:01 to kinetically discriminate between antigenic exogenous peptides and endogenous MBP derived peptides

Creation of Supply Chain Management Aimed At Improving the Quality and Accessibility of Municipal Services

Abstract— Supply chain management of regulation are mainly used in the field of municipal services management. Coordination between local governments and other organizations that control the provision of municipal services is poorly developed on the territory of municipal entities. The solution to this problem becomes particularly relevant in the context of creating the supply chain system for the management.  It is quite obvious that a review of approaches and methods in organizing the provision of municipal services is necessary under supply chain strategy. First of all, we implemented the effective supply chain for allocation of resources in the context of the transition to medium-term budget planning, and also to the integration of supply chain mechanism for organizing the provision of municipal services in the existing territorial development management system. This article provides an insight into supply chain management practices in a municipal context. It highlights the status, challenges and way forward for the implementation of supply chain management in a municipal environment

TT-SDF2PC: Registration of Point Cloud and Compressed SDF Directly in the Memory-Efficient Tensor Train Domain

This paper addresses the following research question: ``can one compress a detailed 3D representation and use it directly for point cloud registration?''. Map compression of the scene can be achieved by the tensor train (TT) decomposition of the signed distance function (SDF) representation. It regulates the amount of data reduced by the so-called TT-ranks. Using this representation we have proposed an algorithm, the TT-SDF2PC, that is capable of directly registering a PC to the compressed SDF by making use of efficient calculations of its derivatives in the TT domain, saving computations and memory. We compare TT-SDF2PC with SOTA local and global registration methods in a synthetic dataset and a real dataset and show on par performance while requiring significantly less resources

Alemtuzumab outcomes by age: Post hoc analysis from the randomized CARE-MS studies over 8 years

Alemtuzumab; Efficacy; SafetyAlemtuzumab; Eficacia; SeguridadAlemtuzumab; Eficàcia; SeguretatBackground Alemtuzumab significantly improved clinical and MRI outcomes vs. subcutaneous interferon beta-1a (SC IFNB-1a) in the CARE-MS trials (NCT00530348, NCT00548405), with sustained efficacy in 2 consecutive extensions (NCT00930553, NCT02255656 [TOPAZ]). Methods Post hoc analysis of 8-year alemtuzumab efficacy and safety in pooled CARE-MS patients (N=811) stratified by baseline age (≥18 to ≤25, >25 to ≤35, >35 to ≤45, >45 to ≤55 years). Results Compared with SC IFNB-1a over 2 years across age cohorts, alemtuzumab lowered annualized relapse rates (ARR; 0.22–0.24 vs. 0.38–0.51), improved or stabilized disability (freedom from 6-month confirmed disability worsening [CDW]: 85%–92% vs. 62%–88%; achievement of 6-month confirmed disability improvement [CDI]: 20%–31% vs. 13%–25%), increased proportions free of MRI disease activity (70%–86% vs. 42%–63% per year), and slowed brain volume loss (BVL; –0.45% to –0.87% vs. –0.50% to –1.39%). Through Year 2, the treatment effect with alemtuzumab did not significantly differ among age groups for ARR (p-interaction=0.6325), 6-month CDW-free (p-interaction=0.4959), 6-month CDI (p-interaction=0.9268), MRI disease activity-free (p-interaction=0.6512), and BVL (p-interaction=0.4970). Alemtuzumab remained effective on outcomes through Year 8 across age groups. Age-related increases in malignancies (≤45 years: 0.9%–2.2% vs. >45 years: 8.1%) and deaths (0%–1.7% vs. 7.0%) were observed. Serious infections also increased from the youngest (5.1%) to oldest (12.8%) age cohorts. Conclusions Alemtuzumab had greater efficacy than SC IFNB-1a over 2 years across comparable age groups, with no significant differences between alemtuzumab-treated age groups. Efficacy on relapse, disability, and MRI outcomes continued through Year 8 across age groups. Age-related increases in serious infections, malignancies, and deaths were observed.The study was supported by Sanofi and Bayer HealthCare Pharmaceuticals

Impact of Aeolian Dry Deposition of Reactive Iron Minerals on Sulfur Cycling in Sediments of the Gulf of Aqaba

The Gulf of Aqaba is an oligotrophic marine system with oxygen-rich water column and organic carbon-poor sediments (≤0.6% at sites that are not influenced by anthropogenic impact). Aeolian dust deposition from the Arabian, Sinai, and Sahara Deserts is an important source of sediment, especially at the deep-water sites of the Gulf, which are less affected by sediment transport from the Arava Desert during seasonal flash floods. Microbial sulfate reduction in sediments is inferred from the presence of pyrite (although at relatively low concentrations), the presence of sulfide oxidation intermediates, and by the sulfur isotopic composition of sulfate and solid-phase sulfides. Saharan dust is characterized by high amounts of iron minerals such as hematite and goethite. We demonstrated, that the resulting high sedimentary content of reactive iron(III) (hydr)oxides, originating from this aeolian dry deposition of desert dust, leads to fast re-oxidation of hydrogen sulfide produced during microbial sulfate reduction and limits preservation of reduced sulfur in the form of pyrite. We conclude that at these sites the sedimentary sulfur cycle may be defined as cryptic

Subcutaneous interferon β-1a in pediatric patients with multiple sclerosis: Regional differences in clinical features, disease management, and treatment outcomes in an international retrospective study

AbstractBackgroundTo further understand management of pediatric patients with multiple sclerosis (MS), we examined disease features, clinical practice patterns, and response to treatment in the United States (US) and seven other countries ('rest of World'; ROW).MethodsAnonymized data, recorded as part of routine clinical practice, were obtained from medical records (1997–2009) of study participants (who received subcutaneous interferon β-1a before age 18years) from the US and ROW. Samples were stratified by age (preadolescents [<12years] and adolescents [12–17years]).ResultsUS adolescents had a higher mean body mass index versus ROW adolescents (BMI; 27.2 versus 22.5kg/m2), started disease-modifying therapy (DMT) earlier after the first relapse, were more likely to have received a DMT before initiating subcutaneous interferon β-1a, had a higher relapse rate, and were more likely to switch from subcutaneous interferon β-1a to another DMT before the end of the observation period.ConclusionsThis retrospective analysis of a multinational sample of pediatric MS patients who received subcutaneous interferon β-1a found that those from the US had higher BMI, relapsed more frequently, and were managed differently, compared with ROW patients. Future prospective studies are needed to confirm these observations and ascertain their clinical significance

Higher satisfaction and adherence with glatiramer acetate 40 mg/mL TIW vs 20 mg/mL QD in RRMS.

Abstract Background Patients who perceive their medication to be ineffective or inconvenient are less likely to be adherent to treatment, with potentially significant consequences on long-term clinical outcomes. Many patients with multiple sclerosis (MS) are nonadherent to treatment despite demonstrated efficacy of disease-modifying therapies (DMTs). While glatiramer acetate (GA; Copaxone®, Teva Pharmaceuticals) both 20 mg/mL once daily (GA20) and 40 mg/mL three times weekly (GA40) have demonstrated efficacy in relapsing-remitting MS (RRMS), GA40 has a superior tolerability profile in addition to a more convenient dosing schedule. These characteristics may give rise to greater treatment satisfaction and higher rates of adherence with potentially beneficial effects on clinical outcomes and health-related costs. Methods CONFIDENCE was a Phase 4, interventional, open-label, randomized, 2-arm, parallel-group, global study with a duration of 6 months. Patients (N = 861) were randomly assigned 1:1 to receive GA20 (n = 430) or GA40 (n = 431) during the core phase. The primary endpoint was patient-reported medication satisfaction using the Medication Satisfaction Questionnaire (MSQ). Secondary endpoints included self-reported convenience perception using the Treatment Satisfaction Questionnaire for Medication-9 convenience component, symptomatic changes (Modified Fatigue Impact Scale, MFIS), and Mental Health Inventory (MHI). Treatment adherence was measured by Multiple Sclerosis Treatment Adherence Questionnaire. Results from the core phase were included. Results During the core phase, 857 patients received treatments. Patients on GA40 were statistically significantly more satisfied with their medication than those on GA20 (LSM difference in MSQ, 0.3; 95% CI, 0.2, 0.5; p Conclusions Higher levels of satisfaction, perception of convenience, and adherence were reported by patients on GA40 than those on GA20. Clinical trial registration number This trial was registered with ClinicalTrials.gov (NCT02499900)

Subcutaneous Interferon Beta-1a inPediatric Multiple Sclerosis: A Retrospective Study

To expand current knowledge, we examined the safety and tolerability of subcutaneous interferon b-1a in patients with pediatriconset multiple sclerosis. Records from 307 patients who had received at least 1 injection of subcutaneous interferon b-1a for demyelinating events when aged younger than 18 years were reviewed. Overall, 168 (54.7%) patients had at least 1 prespecified medical event related to or under close monitoring with subcutaneous interferon b-1a or specific to pediatric patients, 184 (59.9%) had nonserious medical events related to treatment or of unknown causality, and 12 (3.9%) had serious medical events irrespective of causality. The most common laboratory abnormalities were increased alanine (74/195; 37.9%) and aspartate aminotransferase levels (59/194; 30.4%). Annualized relapse rates were 1.79 before treatment and 0.47 during treatment. In conclusion, adult doses of subcutaneous interferon b-1a (44 and 22 mg, 3 times weekly) were well tolerated in pediatric patients and were associated with reduced relapse rates