Pilot study of the safety and effect of adalimumab on pain, physical function, and musculoskeletal disease in mucopolysaccharidosis types I and II.

Mucopolysaccharidosis I and II are lysosomal storage disorders that, despite treatment with hematopoietic cell transplantation (HCT) and/or enzyme replacement therapy (ERT), continue to cause significant skeletal abnormalities leading to pain, stiffness, physical dysfunction, and short stature. Tumor necrosis factor - alpha (TNF-α) is elevated in individuals with MPS I and II and associated with pain and physical dysfunction. Therefore, we evaluated the safety and effects of the TNF-α inhibitor adalimumab in patients with MPS I and II in a 32-week, randomized, double blind, placebo-controlled, crossover study of adalimumab at a dose of 20 mg (weight 15-<30 kg) or 40 mg (weight ≥ 30 kg) administered subcutaneously every other week or saline placebo for 16 weeks. Participants were evaluated at baseline, week 16, and week 32 with the Children's Health Questionnaire - Parent Form 50 (CHQ-PF50), the Pediatric Pain Questionnaire (PPQ), range-of-motion (ROM) measurements, anthropometry, six-minute walk test (6MWT), hand dynamometer, and laboratory evaluations for safety. The primary outcome was safety and primary efficacy outcome was bodily pain (BP) measured by the CHQ-PF50. Two subjects, one with MPS I and one with MPS II, completed the study. Adalimumab was well tolerated and there were no serious adverse events. Standardized BP scores for age and gender were higher (i.e. less pain) at the end of the treatment versus placebo phase for both subjects. Subject #1 became unblinded during treatment due to skin erythema. Behavior measured by both CHQ-PF50 and parental report improved during treatment compared to placebo in both subjects. ROM improved by > 5° in seven of eight joints in Subject #1 and five of eight joints in Subject #2 (range 7.0° to 52.8°). There was no change in the PPQ, 6MWT, or hand dynamometer. Data from this small pilot study suggest that treatment with adalimumab is safe, tolerable, and may improve ROM, physical function, and possibly pain, in children with MPS I or II. However, additional clinical trials are needed before this therapy should be recommended as part of clinical care

Landscape of MS patient cohorts and registries: recommendations for maximizing impact

BACKGROUND: There is a growing number of cohorts and registries collecting phenotypic and genotypic data from groups of multiple sclerosis patients. Improved awareness and better coordination of these efforts is needed. OBJECTIVE: The purpose of this report is to provide a global landscape of the major longitudinal MS patient data collection efforts and share recommendations for increasing their impact. METHODS: A workshop that included over 50 MS research and clinical experts from both academia and industry was convened to evaluate how current and future MS cohorts could be better used to provide answers to urgent questions about progressive MS. RESULTS: The landscape analysis revealed a significant number of largely uncoordinated parallel studies. Strategic oversight and direction is needed to streamline and leverage existing and future efforts. A number of recommendations for enhancing these efforts were developed. CONCLUSIONS: Better coordination, increased leverage of evolving technology, cohort designs that focus on the most important unanswered questions, improved access, and more sustained funding will be needed to close the gaps in our understanding of progressive MS and accelerate the development of effective therapies

Spin Gap in the Single Spin-1/2 Chain Cuprate Sr1.9_{1.9}Ca0.1_{0.1}CuO3_3

We report $^{63}$Cu nuclear magnetic resonance and muon spin rotation measurements on the S=1/2 antiferromagnetic Heisenberg spin chain compound Sr$_{1.9}$Ca$_{0.1}$CuO$_3$. An exponentially decreasing spin-lattice relaxation rate 1/T$_1$ indicates the opening of a spin gap. This behavior is very similar to what has been observed for the cognate zigzag spin chain compound Sr$_{0.9}$Ca$_{0.1}$CuO$_2$, and confirms that the occurrence of a spin gap upon Ca doping is independent of the interchain exchange coupling $J'$. Our results therefore generally prove the appearance of a spin gap in an antiferromagnetic Heisenberg spin chain induced by a local bond disorder of the intrachain exchange coupling $J$. A low temperature upturn of 1/T$_1$ evidences growing magnetic correlations. However, zero field muon spin rotation measurements down to 1.5 K confirm the absence of magnetic order in this compound which is most likely suppressed by the opening of the spin gap.Comment: 5 pages, 4 figure

Exclusion of fish and invertebrates from benthic patches of artificial aquatic environments across water conductivity levels using high-frequency (10 Hz) pulses and adjustable electrical settings

Citation: Utz, R. M., Cooper, S. D., Gido, K. B., & Stewart, J. R. (2017). Exclusion of fish and invertebrates from benthic patches of artificial aquatic environments across water conductivity levels using high-frequency (10 Hz) pulses and adjustable electrical settings. Freshwater Science, 36(1), 151-161. doi:10.1086/690599Livestock fence chargers are often used to generate pulsed electrical fields in freshwater environments to exclude fish and invertebrates from benthic patches so that their ecological function can be investigated. Such devices appear to be effective, but the precise characteristics of the electrical fields they generate and specific settings needed to exclude organisms across water conductivity levels have not been described. We present an electrical engineering and experimental framework to predict and evaluate the effectiveness of a modified device at different combinations of electrical settings and water conductivities. We avoided toxic materials and considered safety issues. We conducted laboratory experiments to identify the electrical fields with a 10-Hz pulse frequency needed to exclude adult Fathead Minnows (Pimephales promelas) and crayfish (Procambarus clarkii) from electrical exclosures across a range of water conductivities (13-800 S/cm). Fish and crayfish in waters of low conductivity (550 S/cm) were excluded from exclosures at >= 200 V of electric potential. In water of higher conductivity (>= 250 S/cm), similar settings caused consumer immobilization. Electrical pulse durations of 150 1.ts were more effective than 50-gs pulse durations at excluding organisms. Further refinement toward standardized methods requires analogous experimentation in the field, but our findings emphasize the importance of comprehensively considering electrical fields (voltage, pulse frequency and duration), water conductivity, and electrode configuration a priori when using these devices to optimize designs

The Concept of Ecologically Oriented Progress and Natural Resource Preservation

The most important issue of scientific and technological progress is considering the environment challenges of industrial development. It means that the progress must be ecologically oriented and environmentally friendly. The most adequate concept for the approach to the issue of "man - society – nature" relations is the ontology of the noosphere - the idea of a common space for human beings and nature. It presents an ideal example of an optimistic attitude towards the coordination between accelerating the scientific and technological development and natural resource saving. However, to maintain the balance between human needs and environmental processes determined by this concept, it is essential to include the lean production training into technological development of society

Crossover between Equilibrium and Shear-controlled Dynamics in Sheared Liquids

We present a numerical simulation study of a simple monatomic Lennard-Jones liquid under shear flow, as a function of both temperature and shear rate. By investigating different observables we find that i) It exists a line in the (temperature-shear) plane that sharply marks the boarder between an ``equilibrium'' and a ``shear-controlled'' region for both the dynamic and the thermodynamic quantities; and ii) Along this line the structural relaxation time, is proportional to the inverse shear rate, i.e. to the typical time-scale introduced by the shear flow. Above the line the liquid dynamics is unaffected by the shear flow, while below it both temperature and shear rate control the particle motion.Comment: 14 pages, 5 figure