Primary progressive multiple sclerosis presenting under the age of 18 years: fact or fiction?

Previous cohort studies on pediatric multiple sclerosis (MS) have reported very low frequencies for a primary progressive MS (PPMS) course ranging from 0 to 7%. We identified six patients presenting prior to the age of 18 years and fulfilling the 2017 McDonald Criteria for primary progressive multiple sclerosis (PPMS). Presentation with progressive neurological symptoms and signs in young people should prompt evaluation for genetic causes such as leukodystrophies, hereditary spastic paraparesis and mitochondrial diseases given the rarity of primary progressive course in pediatric MS. In the absence of an alternative diagnosis, with new therapeutic options becoming available for PPMS, this diagnosis should then be considered

Landmarks and ant search strategies after interrupted tandem runs

© 2014. Published by The Company of Biologists Ltd. During a tandem run, a single leading ant recruits a single follower to an important resource such as a new nest. To examine this process, we used a motorized gantry, which has not previously been used in ant studies, to track tandem running ants accurately in a large arena and we compared their performance in the presence of different types of landmark. We interrupted tandem runs by taking away the leader and moved a large distant landmark behind the new nest just at the time of this separation. Our aim was to determine what information followers might have obtained from the incomplete tandem run they had followed, and how they behaved after the tandem run had been interrupted. Our results show that former followers search by using composite random strategies with elements of sub-diffusive and diffusive movements. Furthermore, when we provided more landmarks former followers searched for longer. However, when all landmarks were removed completely from the arena, the ants' search duration lasted up to four times longer. Hence, their search strategy changes in the presence or absence of landmarks. Even after extensive search of this kind, former followers headed back to their old nest but did not return along the path of the tandem run they had followed. The combination of the position to which the large distant landmark behind the new nest was moved and the presence or absence of additional landmarks influenced the orientation of the former followers' paths back to the old nest. We also found that these ants exhibit behavioural lateralization in which they possibly use their right eye more than their left eye to recognize landmarks for navigation. Our results suggest that former follower ants learn landmarks during tandem running and use this information to make strategic decisions

Medicines adherence: Involving patients in decisions about prescribed medicines and supporting adherence

It is thought that between a third and a half of all medicines1 There are many causes of non-adherence but they fall into two overlapping categories: intentional and unintentional. Unintentional non-adherence occurs when the patient wants to follow the agreed treatment but is prevented from doing so by barriers that are beyond their control. Examples include poor recall or difficulties in understanding the instructions, problems with using the treatment, inability to pay for the treatment, or simply forgetting to take it. prescribed for long-term conditions are not taken as recommended. If the prescription is appropriate, then this may represent a loss to patients, the healthcare system and society. The costs are both personal and economic. Adherence presumes an agreement between prescriber and patient about the prescriber’s recommendations. Adherence to medicines is defined as the extent to which the patient’s action matches the agreed recommendations. Non-adherence may limit the benefits of medicines, resulting in lack of improvement, or deterioration, in health. The economic costs are not limited to wasted medicines but also include the knock-on costs arising from increased demands for healthcare if health deteriorates. Non-adherence should not be seen as the patient’s problem. It represents a fundamental limitation in the delivery of healthcare, often because of a failure to fully agree the prescription in the first place or to identify and provide the support that patients need later on. Addressing non-adherence is not about getting patients to take more medicines per se. Rather, it starts with an exploration of patients’ perspectives of medicines and the reasons why they may not want or are unable to use them. Healthcare professionals have a duty to help patients make informed decisions about treatment and use appropriately prescribed medicines to best effec

Chiral dynamics of kaon-nucleon interactions, revisited

The anti-kaon nucleon system close to threshold is analyzed in view of the new accurate DEAR kaonic hydrogen data. The calculations are performed using chiral SU(3) effective field theory in combination with non-perturbative schemes based on coupled channels. Several variants of such approaches are compared with experimental data and the differences in the results are discussed. Coulomb and isospin breaking effects turn out to be important and are both taken into account. The pole structure of the Lambda(1405) resonance close to the anti-kaon nucleon threshold is critically examined.Comment: 30 pages, 14 figures, 11 table

Evaluating the Quality of Research into a Single Prognostic Biomarker: A Systematic Review and Meta-analysis of 83 Studies of C-Reactive Protein in Stable Coronary Artery Disease

Background Systematic evaluations of the quality of research on a single prognostic biomarker are rare. We sought to evaluate the quality of prognostic research evidence for the association of C-reactive protein (CRP) with fatal and nonfatal events among patients with stable coronary disease. Methods and Findings We searched MEDLINE (1966 to 2009) and EMBASE (1980 to 2009) and selected prospective studies of patients with stable coronary disease, reporting a relative risk for the association of CRP with death and nonfatal cardiovascular events. We included 83 studies, reporting 61,684 patients and 6,485 outcome events. No study reported a prespecified statistical analysis protocol; only two studies reported the time elapsed (in months or years) between initial presentation of symptomatic coronary disease and inclusion in the study. Studies reported a median of seven items (of 17) from the REMARK reporting guidelines, with no evidence of change over time. The pooled relative risk for the top versus bottom third of CRP distribution was 1.97 (95% confidence interval [CI] 1.78–2.17), with substantial heterogeneity (I2 = 79.5). Only 13 studies adjusted for conventional risk factors (age, sex, smoking, obesity, diabetes, and low-density lipoprotein [LDL] cholesterol) and these had a relative risk of 1.65 (95% CI 1.39–1.96), I2 = 33.7. Studies reported ten different ways of comparing CRP values, with weaker relative risks for those based on continuous measures. Adjusting for publication bias (for which there was strong evidence, Egger's p<0.001) using a validated method reduced the relative risk to 1.19 (95% CI 1.13–1.25). Only two studies reported a measure of discrimination (c-statistic). In 20 studies the detection rate for subsequent events could be calculated and was 31% for a 10% false positive rate, and the calculated pooled c-statistic was 0.61 (0.57–0.66). Conclusion Multiple types of reporting bias, and publication bias, make the magnitude of any independent association between CRP and prognosis among patients with stable coronary disease sufficiently uncertain that no clinical practice recommendations can be made. Publication of prespecified statistical analytic protocols and prospective registration of studies, among other measures, might help improve the quality of prognostic biomarker research

Colloidal stability of tannins: astringency, wine tasting and beyond

Tannin-tannin and tannin-protein interactions in water-ethanol solvent mixtures are studied in the context of red wine tasting. While tannin self-aggregation is relevant for visual aspect of wine tasting (limpidity and related colloidal phenomena), tannin affinities for salivary proline-rich proteins is fundamental for a wide spectrum of organoleptic properties related to astringency. Tannin-tannin interactions are analyzed in water-ethanol wine-like solvents and the precipitation map is constructed for a typical grape tannin. The interaction between tannins and human salivary proline-rich proteins (PRP) are investigated in the framework of the shell model for micellization, known for describing tannin-induced aggregation of beta-casein. Tannin-assisted micellization and compaction of proteins observed by SAXS are described quantitatively and discussed in the case of astringency

Prognosis research strategy (PROGRESS) 1: a framework for researching clinical outcomes.

The PROGRESS series (www.progress-partnership.org) sets out a framework of four interlinked prognosis research themes and provides examples from several disease fields to show why evidence from prognosis research is crucial to inform all points in the translation of biomedical and health related research into better patient outcomes. Recommendations are made in each of the four papers to improve current research standards What is prognosis research? Prognosis research seeks to understand and improve future outcomes in people with a given disease or health condition. However, there is increasing evidence that prognosis research standards need to be improved Why is prognosis research important? More people now live with disease and conditions that impair health than at any other time in history; prognosis research provides crucial evidence for translating findings from the laboratory to humans, and from clinical research to clinical practice This first article introduces the framework of four interlinked prognosis research themes and then focuses on the first of the themes - fundamental prognosis research, studies that aim to describe and explain future outcomes in relation to current diagnostic and treatment practices, often in relation to quality of care Fundamental prognosis research provides evidence informing healthcare and public health policy, the design and interpretation of randomised trials, and the impact of diagnostic tests on future outcome. It can inform new definitions of disease, may identify unanticipated benefits or harms of interventions, and clarify where new interventions are required to improve prognosis