Effect of pulsed methylprednisolone on pain, in patients with HTLV-1-associated myelopathy

HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is an immune mediated myelopathy caused by the human T-lymphotropic virus type 1 (HTLV-1). The efficacy of treatments used for patients with HAM/TSP is uncertain. The aim of this study is to document the efficacy of pulsed methylprednisolone in patients with HAM/TSP. Data from an open cohort of 26 patients with HAM/TSP was retrospectively analysed. 1g IV methylprednisolone was infused on three consecutive days. The outcomes were pain, gait, urinary frequency and nocturia, a range of inflammatory markers and HTLV-1 proviral load. Treatment was well tolerated in all but one patient. Significant improvements in pain were: observed immediately, unrelated to duration of disease and maintained for three months. Improvement in gait was only seen on Day 3 of treatment. Baseline cytokine concentrations did not correlate to baseline pain or gait impairment but a decrease in tumour necrosis factor-alpha (TNF-α) concentration after pulsed methylprednisolone was associated with improvements in both. Until compared with placebo, treatment with pulsed methylprednisolone should be offered to patients with HAM/TSP for the treatment of pain present despite regular analgesia

The potential of portable luminescence readers in geomorphological investigations : a review

The development of functional portable optically stimulated luminescence (OSL) readers over the last decade has provided practitioners with the capability to acquire luminescence signals from geological materials relatively rapidly, which allows for expedient preliminary chronostratigraphic insight when working with complex depositional systems of late Quaternary age. Typically, when using the portable OSL reader, infrared (IR) or blue post-IR OSL signals are acquired from bulk unprocessed materials, in contrast to regular luminescence dating which is usually based on measurements on pure quartz or feldspar mineral separates, or on select silt-sized polymineralic portions. To demonstrate the utility of portable OSL measurements, this paper outlines the basic features of portable OSL readers and their constraints. Afterwards, case studies in which the instrument has been used to elucidate cryptostratigraphic variations in sedimentary sequences for geomorphological applications are reviewed. The studies can generally be grouped into three main categories. The first includes studies where the variation of portable OSL reader luminescence signal intensities with depth are plotted to generate profiles that contextualise sediment stratigraphy. In the second group, portable OSL reader luminescence signal intensities are used to interpret sediment processes that shed light on depositional histories. In the last category, luminescence signals from the portable OSL reader are calibrated to approximate numerical burial ages of depositional units. The paper concludes with a discussion of possible future directions.PostprintPeer reviewe

Thermodynamic entropy of a many body energy eigenstate

It is argued that a typical many body energy eigenstate has a well defined thermodynamic entropy and that individual eigenstates possess thermodynamic characteristics analogous to those of generic isolated systems. We examine large systems with eigenstate energies equivalent to finite temperatures. When quasi-static evolution of a system is adiabatic (in the quantum mechanical sense), two coupled subsystems can transfer heat from one subsystem to another yet remain in an energy eigenstate. To explicitly construct the entropy from the wave function, degrees of freedom are divided into two unequal parts. It is argued that the entanglement entropy between these two subsystems is the thermodynamic entropy per degree of freedom for the smaller subsystem. This is done by tracing over the larger subsystem to obtain a density matrix, and calculating the diagonal and off-diagonal contributions to the entanglement entropy.Comment: 18 page

Three-phase optimal power flow for networked microgrids based on semidefinite programming convex relaxation

Many autonomous microgrids have extensive penetration of distributed generation (DG). Optimal power flow (OPF) is necessary for the optimal dispatch of networked microgrids (NMGs). Existing convex relaxation methods for three-phase OPF are limited to radial networks. In light of this, we develop a semidefinite programming (SDP) convex relaxation model which can cope with meshed networks and also includes a model of three-phase DG and under-load voltage regulators with different connection types. The SDP model solves the OPF problem of multi-phase meshed network effectively, with satisfactory accuracy, as validated by real 6-bus, 9-bus, and 30-bus NMGs, and the IEEE 123-bus test cases. In the SDP model, the convex symmetric component of the three-phase DG model is demonstrated to be more accurate than a three-phase DG modelled as three single-phase DG units in three-phase unbalanced OPF. The proposed method also has higher accuracy than the existing convex relaxation methods. The resultant optimal control variables obtained from the convex relaxation optimization can be used for both final optimal dispatch strategy and initial value of the non-convex OPF to obtain the globally optimal solution efficiently

The foundations of statistical mechanics from entanglement: Individual states vs. averages

We consider an alternative approach to the foundations of statistical mechanics, in which subjective randomness, ensemble-averaging or time-averaging are not required. Instead, the universe (i.e. the system together with a sufficiently large environment) is in a quantum pure state subject to a global constraint, and thermalisation results from entanglement between system and environment. We formulate and prove a "General Canonical Principle", which states that the system will be thermalised for almost all pure states of the universe, and provide rigorous quantitative bounds using Levy's Lemma.Comment: 12 pages, v3 title changed, v2 minor change

Publication Recommendations to Report Laboratory Data of Neonates - a Modified Delphi Approach

Background: Clinical and analytical information on laboratory data of neonates in scientific publications is sparse and incomplete. Furthermore, interpreting neonatal laboratory data can be complex due to their time-dependent and developmental physiology, and paucity of well-established age-appropriate reference ranges for neonates. This study aims to develop publication recommendations to report laboratory data of neonates to enhance the quality of these data in research and clinical care. Methods: A modified Delphi approach was used to develop recommendations in cooperation with the International Neonatal Consortium. A Core Group, including different stakeholders, was responsible for developing the recommendations, in collaboration with a Reflection Group, responsible for providing additional input. Results: The recommendations were classified into three categories: ‘Clinical Characteristics’, ‘Bio-analytical Information’ and ‘Data-analytical Information’. These were each divided into ‘Core Data’ (always to be reported) and ‘Supplemental Considerations’ (to be reported when considered relevant to the study). Conclusion: Our recommendations provide guidance on standardization of neonatal laboratory data in publications. This will enhance the comparison, replication, and application of study results in research initiatives and clinical practice. Furthermore, these recommendations also serve as foundational work to develop reference ranges for neonatal laboratory values by standardizing the quality of information needed for such efforts. Impact: Standardized reporting of neonatal laboratory data in scientific publications will enhance the comparison, replication, and application of study results in research initiatives and clinical practice, as well as improve reporting to regulatory agencies. To integrate multistakeholder perspectives, a modified Delphi approach was used to develop publication recommendations which strengthens the applicability of the recommendations. Implementation of standardization will likely improve the overall quality of neonatal clinical research and neonatal healthcare. In addition, these recommendations are foundational to develop reference ranges for neonatal laboratory values by standardizing the quality of information needed for such efforts.</p

Interleukin-7 deficiency in rheumatoid arthritis: consequences for therapy-induced lymphopenia

We previously demonstrated prolonged, profound CD4+ T-lymphopenia in rheumatoid arthritis (RA) patients following lymphocyte-depleting therapy. Poor reconstitution could result either from reduced de novo T-cell production through the thymus or from poor peripheral expansion of residual T-cells. Interleukin-7 (IL-7) is known to stimulate the thymus to produce new T-cells and to allow circulating mature T-cells to expand, thereby playing a critical role in T-cell homeostasis. In the present study we demonstrated reduced levels of circulating IL-7 in a cross-section of RA patients. IL-7 production by bone marrow stromal cell cultures was also compromised in RA. To investigate whether such an IL-7 deficiency could account for the prolonged lymphopenia observed in RA following therapeutic lymphodepletion, we compared RA patients and patients with solid cancers treated with high-dose chemotherapy and autologous progenitor cell rescue. Chemotherapy rendered all patients similarly lymphopenic, but this was sustained in RA patients at 12 months, as compared with the reconstitution that occurred in cancer patients by 3–4 months. Both cohorts produced naïve T-cells containing T-cell receptor excision circles. The main distinguishing feature between the groups was a failure to expand peripheral T-cells in RA, particularly memory cells during the first 3 months after treatment. Most importantly, there was no increase in serum IL-7 levels in RA, as compared with a fourfold rise in non-RA control individuals at the time of lymphopenia. Our data therefore suggest that RA patients are relatively IL-7 deficient and that this deficiency is likely to be an important contributing factor to poor early T-cell reconstitution in RA following therapeutic lymphodepletion. Furthermore, in RA patients with stable, well controlled disease, IL-7 levels were positively correlated with the T-cell receptor excision circle content of CD4+ T-cells, demonstrating a direct effect of IL-7 on thymic activity in this cohort

Nitrogen uptake and internal recycling in Zostera marina exposed to oyster farming: eelgrass potential as a natural biofilter

Oyster farming in estuaries and coastal lagoons frequently overlaps with the distribution of seagrass meadows, yet there are few studies on how this aquaculture practice affects seagrass physiology. We compared in situ nitrogen uptake and the productivity of Zostera marina shoots growing near off-bottom longlines and at a site not affected by oyster farming in San Quintin Bay, a coastal lagoon in Baja California, Mexico. We used benthic chambers to measure leaf NH4 (+) uptake capacities by pulse labeling with (NH4)-N-15 (+) and plant photosynthesis and respiration. The internal N-15 resorption/recycling was measured in shoots 2 weeks after incubations. The natural isotopic composition of eelgrass tissues and vegetative descriptors were also examined. Plants growing at the oyster farming site showed a higher leaf NH4 (+) uptake rate (33.1 mmol NH4 (+) m(-2) day(-1)) relative to those not exposed to oyster cultures (25.6 mmol NH4 (+) m(-2) day(-1)). We calculated that an eelgrass meadow of 15-16 ha (which represents only about 3-4 % of the subtidal eelgrass meadow cover in the western arm of the lagoon) can potentially incorporate the total amount of NH4 (+) excreted by oysters (similar to 5.2 x 10(6) mmol NH4 (+) day(-1)). This highlights the potential of eelgrass to act as a natural biofilter for the NH4 (+) produced by oyster farming. Shoots exposed to oysters were more efficient in re-utilizing the internal N-15 into the growth of new leaf tissues or to translocate it to belowground tissues. Photosynthetic rates were greater in shoots exposed to oysters, which is consistent with higher NH4 (+) uptake and less negative delta C-13 values. Vegetative production (shoot size, leaf growth) was also higher in these shoots. Aboveground/belowground biomass ratio was lower in eelgrass beds not directly influenced by oyster farms, likely related to the higher investment in belowground biomass to incorporate sedimentary nutrients

RAGE deficiency predisposes mice to virus-induced paucigranulocytic asthma

© 2017, eLife Sciences Publications Ltd. All rights reserved. Asthma is a chronic inflammatory disease. Although many patients with asthma develop type-2 dominated eosinophilic inflammation, a number of individuals develop paucigranulocytic asthma, which occurs in the absence of eosinophilia or neutrophilia. The aetiology of paucigranulocytic asthma is unknown. However, both respiratory syncytial virus (RSV) infection and mutations in the receptor for advanced glycation endproducts (RAGE) are risk factors for asthma development. Here, we show that RAGE deficiency impairs anti-viral immunity during an early-life infection with pneumonia virus of mice (PVM; a murine analogue of RSV). The elevated viral load was associated with the release of high mobility group box-1 (HMGB1) which triggered airway smooth muscle remodelling in early-life. Re-infection with PVM in later-life induced many of the cardinal features of asthma in the absence of eosinophilic or neutrophilic inflammation. Anti-HMGB1 mitigated both early-life viral disease and asthma-like features, highlighting HMGB1 as a possible novel therapeutic target