Micromagnetic simulations of interacting dipoles on a fcc lattice: Application to nanoparticle assemblies

Micromagnetic simulations are used to examine the effects of cubic and axial anisotropy, magnetostatic interactions and temperature on M-H loops for a collection of magnetic dipoles on fcc and sc lattices. We employ a simple model of interacting dipoles that represent single-domain particles in an attempt to explain recent experimental data on ordered arrays of magnetoferritin nanoparticles that demonstrate the crucial role of interactions between particles in a fcc lattice. Significant agreement between the simulation and experimental results is achieved, and the impact of intra-particle degrees of freedom and surface effects on thermal fluctuations are investigated.Comment: 10 pages, 9 figure

Serum Neurofilament Light Association With Progression in Natalizumab-Treated Patients With Relapsing-Remitting Multiple Sclerosis

OBJECTIVE: The objective of this study was to investigate the potential of serum neurofilament light (NfL) to reflect or predict progression mostly independent of acute inflammatory disease activity in patients with relapsing remitting multiple sclerosis (RRMS) treated with natalizumab. METHODS: Patients were selected from a prospective observational cohort study initiated in 2006 at the VU University Medical Center Amsterdam, The Netherlands, including patients with RRMS treated with natalizumab. Selection criteria included an age of 18 years or older and a minimum follow-up of 3 years from natalizumab initiation. Clinical and MRI assessments were performedon a yearly basis, and serum NfL was measured at 5 time-points during the follow-up, including on the day of natalizumab initiation (baseline), 3 months, 1 year and 2 years after natalizumab initiation, and on last follow-up visit. Using general linear regression models, we compared the longitudinal dynamics of NfL between patients with and without confirmed EDSS progression between year 1 visit and last follow-up, and between individuals with and without EDSS+ progression, a composite endpoint including the EDSS, 9 hole peg test and timed 25 foot-walk. RESULTS: Eighty-nine natalizumab-treated patients with RRMS were included. Median follow-up time was 5.2 years (IQR 4.3-6.7, range 3.0-11.0) after natalizumab initiation, mean age at time of natalizumab initiation was 36.9 (SD: 8.5), and median disease duration was 7.4 years (IQR 3.8-12.1). Between year 1 and the last follow-up, 28/89 (31.5%) individuals showed confirmed EDSS progression. Data for the EDSS+ endpoint was available for 73 out of the 89 patients and 35/73 (47.9%) showed confirmed EDSS+ progression.We observed a significant reduction in NfL levels 3 months after natalizumab initiation, which reached its nadir of close to 50% of baseline levels 1 year after treatment initiation. We found no difference in the longitudinal dynamics of NfL in progressors versus non-progressors. NfL levels at baseline and 1 year after natalizumab initiation did not predict progression at last follow-up. DISCUSSION: In our cohort of natalizumab-treated patients with RRMS, NfL fails to capture or predict progression that occurs largely independently of clinical or radiological signs of acute focal inflammatory disease activity. Additional biomarkers may thus be needed to monitor progression in these patients. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that serum NfL levels are not associated with disease progression in natalizumab-treated patients with RRMS

Smartphone-derived keystroke dynamics are sensitive to relevant changes in multiple sclerosis

BACKGROUND: To investigate smartphone keystroke dynamics (KD), derived from regular typing, on sensitivity to relevant change in disease activity, fatigue, and clinical disability in multiple sclerosis (MS). METHODS: Preplanned interim analysis of a cohort study with 102 MS patients assessed at baseline and 3-month follow-up for gadolinium-enhancing lesions on MRI, relapses, fatigue and clinical disability outcomes. Keyboard interactions were unobtrusively collected during typing using the Neurokeys App. From these interactions 15 keystroke features were derived and aggregated using 16 summary and time series statistics. Responsiveness of KD to clinical anchor-based change was assessed by calculating the area under the receiver operating characteristic curve (AUC). The optimal cut-point was used to determine the minimal clinically important difference (MCID) and compared to the smallest real change (SRC). Commonly used clinical measures were analyzed for comparison. RESULTS: 94 patients completed the follow-up. The five best performing keystroke features had AUC-values ranging from 0.72 to 0.78 for change in gadolinium-enhancing lesions, 0.67-0.70 for the Checklist Individual Strength Fatigue subscale, 0.66-0.79 for the Expanded Disability Status Scale, 0.69-0.73 for the Ambulation Functional System, and 0.72-0.75 for Arm function in MS Questionnaire. The MCID of these features exceeded the SRC on group level. KD had higher AUC-values than comparative clinical measures for the study outcomes, aside from ambulatory function. CONCLUSIONS: KD demonstrated good responsiveness to changes in disease activity, fatigue, and clinical disability in MS, and detected important change beyond measurement error on group level. Responsiveness of KD was better than commonly used clinical measures

Serum contactin-1 as a biomarker of long-term disease progression in natalizumab-treated multiple sclerosis.

BACKGROUND: Natalizumab treatment provides a model for non-inflammation-induced disease progression in multiple sclerosis (MS). OBJECTIVE: To study serum contactin-1 (sCNTN1) as a novel biomarker for disease progression in natalizumab-treated relapsing-remitting MS (RRMS) patients. METHODS: Eighty-nine natalizumab-treated RRMS patients with minimum follow-up of 3 years were included. sCNTN1 was analyzed at baseline (before natalizumab initiation), 3, 12, 24 months (M) and last follow-up (median 5.2 years) and compared to 222 healthy controls (HC) and 15 primary progressive MS patients (PPMS). Results were compared between patients with progressive, stable, or improved disability according to EDSS-plus criteria. RESULTS: Median sCNTN1 levels (ng/mL,) in RRMS (baseline: 10.7, 3M: 9.7, 12M: 10.4, 24M: 10.8; last follow-up: 9.7) were significantly lower compared to HC (12.5; p ⩽ 0.001). It was observed that 48% of patients showed progression during follow-up, 11% improved, and 40% remained stable. sCNTN1 levels were significantly lower in progressors both at baseline and at 12M compared to non-progressors. A 1 ng/mL decrease in baseline sCNTN1 was consistent with an odds ratio of 1.23 (95% confidence interval 1.04-1.45) (p = 0.017) for progression during follow-up. CONCLUSION: Lower baseline sCNTN1 concentrations were associated with long-term disability progression during natalizumab treatment, making it a possible blood-based prognostic biomarker for RRMS

On subsequential spaces

AbstractSimple generators for the coreflective category of subsequential spaces, one of them countable, are constructed. Every such must have subsequential order ω1. Subsequentialness is a local property and a countable property, both in a strong sense. A T2-subsequential space may be pseudocompact without being sequential, in contrast to T2-subsequential compact (countably compact, sequentially compact) spaces all being sequential. A compact subsequential space need not be sequential

Supporting Nature-Based Solutions via Nature-Based Thinking across European and Latin American cities

Nature-Based Solutions concepts and practices are being used worldwide as part of attempts to address societal challenges but have also been criticised for not dealing with deeper transformations needed to face urgent issues including biodiversity loss, climate change and inclusion. In this paper, we explore how an inclusive, integrated and long-sighted approach, emphasising a more radical integration of nature within cities, might support the transformations needed to endure major contemporary challenges. Addressing important emerging critiques of Nature-Based Solutions, we consider the potential of a more incisive form of Nature-Based Thinking (NBT) in cities, based on more holistic perspectives. The paper draws on a reflective and iterative research process that engaged both the research and practice communities through a symposium and a series of futures workshops that together explored the potential of NBT to develop future nature-cities relations in Europe and Latin America. The results of the reflective process suggest that notions of nature with people-not for people- new organisational structures, and the intention and capacity to apply long-term perspectives, are needed when planning for NBS interventions aimed at sustainable urban development. This includes developing a cultural-structural change based on new and inclusive understandings of human-nature relations, and novel governance paradigms that allow cross-sectoral coordination and engagement of local stakeholders beyond formal organisational structures