Resolving the clinico-radiological paradox in multiple sclerosis

Understanding the clinico-radiological paradox is important in the search for more sensitive and specific surrogates of relapses and disability progression (such that they can be used to inform treatment choices in individual people with multiple sclerosis) and to gain a better understanding of the pathophysiological basis of disability in multiple sclerosis (to identify and assess key therapeutic targets). In this brief review, we will consider themes and issues underlying the clinico-radiological paradox and recent advances in its resolution

Opportunities for improving irrigation efficiency with quantitative models, soil water sensors and wireless technology

Increasingly serious shortages of water make it imperative to improve the efficiency of irrigation in agriculture, horticulture and in the maintenance of urban landscapes. The main aim of the current review is to identify ways of meeting this objective. After reviewing current irrigation practices, discussion is centred on the sensitivity of crops to water deficit, the finding that growth of many crops is unaffected by considerable lowering of soil water content and, on this basis, the creation of improved means of irrigation scheduling. Subsequently, attention is focused on irrigation problems associated with spatial variability in soil water and the often slow infiltration of water into soil, especially the subsoil. As monitoring of soil water is important for estimating irrigation requirements, the attributes of the two main types of soil water sensors and their most appropriate uses are described. Attention is also drawn to the contribution of wireless technology to the transmission of sensor outputs. Rapid progress is being made in transmitting sensor data, obtained from different depths down the soil profile across irrigated areas, to a PC that processes the data and on this basis automatically commands irrigation equipment to deliver amounts of water, according to need, across the field. To help interpret sensor outputs, and for many other reasons, principles of water processes in the soil–plant system are incorporated into simulation models that are calibrated and tested in field experiments. Finally, it is emphasized that the relative importance of the factors discussed in this review to any particular situation varies enormously

1000 Norms Project: Protocol of a cross-sectional study cataloging human variation

Background Clinical decision-making regarding diagnosis and management largely depends on comparison with healthy or ‘normal’ values. Physiotherapists and researchers therefore need access to robust patient-centred outcome measures and appropriate reference values. However there is a lack of high-quality reference data for many clinical measures. The aim of the 1000 Norms Project is to generate a freely accessible database of musculoskeletal and neurological reference values representative of the healthy population across the lifespan. Methods/design In 2012 the 1000 Norms Project Consortium defined the concept of ‘normal’, established a sampling strategy and selected measures based on clinical significance, psychometric properties and the need for reference data. Musculoskeletal and neurological items tapping the constructs of dexterity, balance, ambulation, joint range of motion, strength and power, endurance and motor planning will be collected in this cross-sectional study. Standardised questionnaires will evaluate quality of life, physical activity, and musculoskeletal health. Saliva DNA will be analysed for the ACTN3 genotype (‘gene for speed’). A volunteer cohort of 1000 participants aged 3 to 100 years will be recruited according to a set of self-reported health criteria. Descriptive statistics will be generated, creating tables of mean values and standard deviations stratified for age and gender. Quantile regression equations will be used to generate age charts and age-specific centile values. Discussion This project will be a powerful resource to assist physiotherapists and clinicians across all areas of healthcare to diagnose pathology, track disease progression and evaluate treatment response. This reference dataset will also contribute to the development of robust patient-centred clinical trial outcome measures

The effects of beta-human chorionic gonadotrophin on the in vitro growth of bladder cancer cell lines

The effects of human chorionic gonadotrophin (hCG) and its subunits on in vitro bladder cancer cell growth have been assessed using the a tetrazolium salt reduction assay (MTT). Intact hCG, alpha-hCG and beta-core hCG all had no effect on cell growth, while beta-hCG increased MTT reduction in all four bladder cancer lines tested. The magnitude of beta-hCG stimulation was maximal in the T24 line, which does not itself produce beta-hCG and appeared to be correspondingly lower in beta-hCG-secreting lines. The addition of antibodies to beta-hCG inhibited MTT reduction among high secretors but failed to inhibit MTT reduction in non-beta-hCG producers. These results are consistent with the poor prognosis associated with beta-hCG expression by bladder tumours in vivo and suggest an autocrine/paracrine stimulation of tumour growth by endogenously produced beta-hCG

Computing environments for reproducibility: Capturing the 'Whole Tale'

The act of sharing scientific knowledge is rapidly evolving away from traditional articles and presentations to the delivery of executable objects that integrate the data and computational details (e.g., scripts and workflows) upon which the findings rely. This envisioned coupling of data and process is essential to advancing science but faces technical and institutional barriers. The Whole Tale project aims to address these barriers by connecting computational, data-intensive research efforts with the larger research process—transforming the knowledge discovery and dissemination process into one where data products are united with research articles to create “living publications” or tales. The Whole Tale focuses on the full spectrum of science, empowering users in the long tail of science, and power users with demands for access to big data and compute resources. We report here on the design, architecture, and implementation of the Whole Tale environment

Measurement of cortisol in saliva: a comparison of measurement error within and between international academic-research laboratories

Objective: Hundreds of scientific publications are produced annually that involve the measurement of cortisol in saliva. Intra- and inter-laboratory variation in salivary cortisol results has the potential to contribute to cross- study inconsistencies in findings, and the perception that salivary cortisol results are unreliable. This study rigor- ously estimates sources of measurement variability in the assay of salivary cortisol within and between established international academic-based laboratories that specialize in saliva analyses. One hundred young adults (Mean age: 23.10 years; 62 females) donated 2 mL of whole saliva by passive drool. Each sample was split into multiple- 100 µL aliquots and immediately frozen. One aliquot of each of the 100 participants’ saliva was transported to academic laboratories (N = 9) in the United States, Canada, UK, and Germany and assayed for cortisol by the same commercially available immunoassay. Results: 1.76% of the variance in salivary cortisol levels was attributable to differences between duplicate assays of the same sample within laboratories, 7.93% of the variance was associated with differences between laboratories, and 90.31% to differences between samples. In established-qualified laboratories, measurement error of salivary cortisol is minimal, and inter-laboratory differences in measurement are unlikely to have a major influence on the determined values

Switching treatments in clinically stable relapsing remitting multiple sclerosis patients planning for pregnancy

Background: The decision to have children can be complex, particularly for people with multiple sclerosis (MS). A key concern is the use of disease modifying drugs (DMDs) during pregnancy, and how continuing, stopping or switching them may affect the mother and child. In people with active MS, stopping medications puts the mother at risk of relapse and disease rebound. Objectives: Review evidence on the effect of different switching strategies in people with stable relapsing remitting MS (RRMS). Methods: We searched MEDLINE, EMBASE, EMCARE, CINAHL, SCOPUS, Cochrane Library up to March 2020. Only papers in English were included and no other limits were applied. Seven articles were included: four cohorts, two case reports and one randomized controlled trial (RCT). Results: Two strategies were found: de-escalating, which was associated with an increased risk of relapses, and switching between first line injectables, with no change in relapse rate observed. Conclusion: Evidence on the effect of switching strategy on disease course in stable RRMS patients planning for pregnancy is scarce, but when switching, current evidence suggests the risk of relapses mirrors known medication efficacy