International Guillain-Barré Syndrome Outcome Study (IGOS): protocol of a prospective observational cohort study on clinical and biological predictors of disease course and outcome in Guillain-Barré syndrome

Guillain-Barré syndrome (GBS) is an acute polyradiculoneuropathy with a highly variable clinical presentation, course, and outcome. The factors that determine the clinical variation of GBS are poorly understood which complicates the care and treatment of individual patients. The protocol of the ongoing International GBS Outcome Study (IGOS), a prospective, observational, multi-centre cohort study that aims to identify the clinical and biological determinants and predictors of disease onset, subtype, course and outcome of GBS is presented here. Patients fulfilling the diagnostic criteria for GBS, regardless of age, disease severity, variant forms, or treatment, can participate if included within two weeks after onset of weakness. Information about demography, preceding infections, clinical features, diagnostic findings, treatment, course and outcome is collected. In addition, cerebrospinal fluid and serial blood samples for serum and DNA is collected at standard time points. The original aim was to include at least 1000 patients with a follow-up of 1-3 years. Data are collected via a web-based data entry system and stored anonymously. IGOS started in May 2012 and by January 2017 included more than 1400 participants from 143 active centres in 19 countries across 5 continents. The IGOS data/biobank is available for research projects conducted by expertise groups focusing on specific topics including epidemiology, diagnostic criteria, clinimetrics, electrophysiology, antecedent events, antibodies, genetics, prognostic modelling, treatment effects and long-term outcome of GBS. The IGOS will help to standardize the international collection of data and biosamples for future research of GBS. ClinicalTrials.gov Identifier: NCT01582763

A more active lifestyle in persons with a recent spinal cord injury benefits physical fitness and health

Study design:A prospective cohort study. Objectives:To study the longitudinal relationship between objectively measured everyday physical activity level, and physical fitness and lipid profile in persons with a recent spinal cord injury (SCI).Setting:A rehabilitation centre in the Netherlands and the participant's home environment. Methods:Data of 30 persons with a recent SCI were collected at the start of active rehabilitation, 3 months later, at discharge from inpatient rehabilitation, and 1 year after discharge. Physical activity level (duration of dynamic activities as % of 24 h) was measured with an accelerometry-based activity monitor. Regarding physical fitness, peak oxygen uptake (VO2peak) and peak power output (POpeak) were determined with a maximal wheelchair exercise test, and upper extremity muscle strength was measured with a handheld dynamometer. Fasting blood samples were taken to determine the lipid profile. Results:An increase in physical activity level was significantly related to an increase in VO2peak and POpeak, and an increase in physical activity level favourably affected the lipid profile. A nonsignificant relation was found with muscle strength. Conclusion:Everyday physical activity seems to have an important role in the fitness and health of persons with a recent SCI. An increase in physical activity level was associated with an increase in physical fitness and with a lower risk of cardiovascular disease.Spinal Cord advance online publication, 6 December 2011; doi:10.1038/sc.2011.152

Secondary cities as catalysts for nutritious diets in low- and middle-income countries

The world is facing a malnutrition crisis in the midst of rising rates of urbanization; more than half of the world's population lives in urban areas, a number that is expected to reach two-thirds by 2050, consuming 80% of the world's food. Instead of the development of existing cities into 'mega-cities, ' urbanization is creating a patchwork of smaller urban areas. In 2018, close to half of the world's urban residents lived in settlements or towns with less than 500, 000 inhabitants. These settlements are classified as secondary cities and are, in terms of population, the fastest growing urban areas. Poor diets among city inhabitants are the consequence of a combination of forces. These include changes in types of occupation, particularly for women; food-environment factors; shifts in norms and attitudes regarding food; globalization of food supply chains; lack of infrastructure; post-harvest food loss and waste, etc. Secondary cities offer entry points for food system transformation. Secondary cities are characterized by strong urban-rural linkages and the opportunity for localized food production and consumption. These cities could also play a key role in enhancing resilience to food security shocks. This chapter discusses the challenge of the growing triple burden of malnutrition in urban contexts and argues for the important role of secondary cities in transforming urban food systems. Through three case studies of secondary cities in LMICs, these cities are shown as emerging players in nutrition-centered food system interventions. © The Author(s) 2023

Characterization of potential biomarkers of reactogenicity of licensed antiviral vaccines: randomized controlled clinical trials conducted by the BIOVACSAFE consortium

Funding text The authors are grateful for the vital contributions of the participating study volunteers, clinicians, nurses, and laboratory technicians at the Surrey study site. The work by Roberto Leone, laboratory technician at Humanitas Clinical and Research Center, is gratefully acknowledged. Finally, they thank Ellen Oe (GSK) for scientific writing assistance. The research leading to these results has received support from the Innovative Medicines Initiative Joint Undertaking under grant agreement n°115308, resources of which are composed of financial contribution from the European Union’s Seventh Framework Programme (FP7/2007–2013) and EFPIA companies’ in-kind contribution. The contribution of the European Commission to the Advanced Immunization Technologies (ADITEC) project (grant agreement n° 280873) is also gratefully acknowledged. Publisher Copyright: © 2019, The Author(s).Biomarkers predictive of inflammatory events post-vaccination could accelerate vaccine development. Within the BIOVACSAFE framework, we conducted three identically designed, placebo-controlled inpatient/outpatient clinical studies (NCT01765413/NCT01771354/NCT01771367). Six antiviral vaccination strategies were evaluated to generate training data-sets of pre-/post-vaccination vital signs, blood changes and whole-blood gene transcripts, and to identify putative biomarkers of early inflammation/reactogenicity that could guide the design of subsequent focused confirmatory studies. Healthy adults (N = 123; 20–21/group) received one immunization at Day (D)0. Alum-adjuvanted hepatitis B vaccine elicited vital signs and inflammatory (CRP/innate cells) responses that were similar between primed/naive vaccinees, and low-level gene responses. MF59-adjuvanted trivalent influenza vaccine (ATIV) induced distinct physiological (temperature/heart rate/reactogenicity) response-patterns not seen with non-adjuvanted TIV or with the other vaccines. ATIV also elicited robust early (D1) activation of IFN-related genes (associated with serum IP-10 levels) and innate-cell-related genes, and changes in monocyte/neutrophil/lymphocyte counts, while TIV elicited similar but lower responses. Due to viral replication kinetics, innate gene activation by live yellow-fever or varicella-zoster virus (YFV/VZV) vaccines was more suspended, with early IFN-associated responses in naïve YFV-vaccine recipients but not in primed VZV-vaccine recipients. Inflammatory responses (physiological/serum markers, innate-signaling transcripts) are therefore a function of the vaccine type/composition and presence/absence of immune memory. The data reported here have guided the design of confirmatory Phase IV trials using ATIV to provide tools to identify inflammatory or reactogenicity biomarkers.Peer reviewe

On-line Excited-State Laser Spectroscopy of Trapped Short-Lived Ra+^+ Ions

As an important step towards an atomic parity violation experiment in one single trapped Ra$^+$ ion, laser spectroscopy experiments were performed with on-line produced short-lived $^{212,213,214}$Ra$^+$ ions. The isotope shift of the 6\,^2D$_{3/2}$\,-\,7\,^2P$_{1/2}$ and 6\,^2D$_{3/2}$\,-\,7\,^2P$_{3/2}$ transitions and the hyperfine structure constant of the 7\,^2S$_{1/2}$ and 6\,^2D$_{3/2}$ states in $^{213}$Ra$^+$ were measured. These values provide a benchmark for the required atomic theory. A lower limit of $232(4)$ ms for the lifetime of the metastable 6\,^2D$_{5/2}$ state was measured by optical shelving.Comment: 4.2 pages, 6 figures, 2 tables

First Test of Lorentz Invariance in the Weak Decay of Polarized Nuclei

A new test of Lorentz invariance in the weak interactions has been made by searching for variations in the decay rate of spin-polarized 20Na nuclei. This test is unique to Gamow-Teller transitions, as was shown in the framework of a recently developed theory that assumes a Lorentz symmetry breaking background field of tensor nature. The nuclear spins were polarized in the up and down direction, putting a limit on the amplitude of sidereal variations of the form |(\Gamma_{up} - \Gamma_{down})| / (\Gamma_{up} + \Gamma_{down}) < 3 * 10^{-3}. This measurement shows a possible route toward a more detailed testing of Lorentz symmetry in weak interactions.Comment: 11 pages, 6 figure

Diffusive and ballistic current spin-polarization in magnetron-sputtered L1o-ordered epitaxial FePt

We report on the structural, magnetic, and electron transport properties of a L1o-ordered epitaxial iron-platinum alloy layer fabricated by magnetron-sputtering on a MgO(001) substrate. The film studied displayed a long range chemical order parameter of S~0.90, and hence has a very strong perpendicular magnetic anisotropy. In the diffusive electron transport regime, for temperatures ranging from 2 K to 258 K, we found hysteresis in the magnetoresistance mainly due to electron scattering from magnetic domain walls. At 2 K, we observed an overall domain wall magnetoresistance of about 0.5 %. By evaluating the spin current asymmetry alpha = sigma_up / sigma_down, we were able to estimate the diffusive spin current polarization. At all temperatures ranging from 2 K to 258 K, we found a diffusive spin current polarization of > 80%. To study the ballistic transport regime, we have performed point-contact Andreev-reflection measurements at 4.2 K. We obtained a value for the ballistic current spin polarization of ~42% (which compares very well with that of a polycrystalline thin film of elemental Fe). We attribute the discrepancy to a difference in the characteristic scattering times for oppositely spin-polarized electrons, such scattering times influencing the diffusive but not the ballistic current spin polarization.Comment: 22 pages, 13 figure

Clinical and self-reported markers of reproductive function in female survivors of childhood Hodgkin lymphoma

Purpose: To evaluate the impact of treatment for Hodgkin lymphoma (HL) on clinical reproductive markers and pregnancy outcomes.Methods: This study was embedded within the DCOG LATER-VEVO study; a Dutch, multicenter, retrospective cohort study between 2004 and 2014. Serum anti-Müllerian hormone (AMH), follicle stimulating hormone (FSH), inhibin B, antral follicle count (AFC), and self-reported (first) pregnancy outcomes were evaluated in female childhood HL survivors and controls.Results: 84 HL survivors and 798 controls were included, aged 29.6 and 32.7 years old at time of assessment. Median age at HL diagnosis was 13.4 years. Cyclophosphamide equivalent dose (CED-score) exceeded 6000 mg/m2 in 56 women and 14 survivors received pelvic irradiation.All clinical markers were significantly deteriorated in survivors (odds-ratio for low AMH (&lt; p10) 10.1 [95% CI 4.9; 20.6]; low AFC (&lt; p10) 4.6 [95% CI 2.1; 9.9]; elevated FSH (&gt; 10 IU/l) 15.3 [95% CI 5.7; 41.1], low Inhibin B (&lt; 20 ng/l) 3.6 [95% CI 1.7; 7.7], p &lt; 0.001). Pregnancy outcomes were comparable between survivors and controls (± 80% live birth, ± 20% miscarriage). However, survivors were significantly younger at first pregnancy (27.0 years vs 29.0 years, P = 0.04). Adjusted odds-ratio for time to pregnancy &gt; 12 months was 2.5 [95% CI 1.1; 5.6] in survivors, p = 0.031. Adverse outcomes were specifically present after treatment with procarbazine and higher CED-score.Conclusion: HL survivors appear to have an impaired ovarian reserve. However, chance to achieve pregnancy seems reassuring at a young age. Additional follow-up studies are needed to assess fertile life span and reproductive potential of HL survivors, in particular for current HL treatments that are hypothesized to be less gonadotoxic.</p