Advancing trial design in progressive multiple sclerosis

The failure of a majority of clinical trials in progressive multiple sclerosis (MS) has highlighted the need to reconsider how these trials are designed and conducted, and many areas deserve focus. Basic scientists are reconceptualising the pathophysiology of progressive MS into three broad areas: systemic inflammation, compartmentalized inflammation and non-inflammatory neurodegeneration, with the latter two becoming predominant as the disease progresses. This framework will guide the choice of experimental therapies. Previous clinical trials have highlighted how participant selection can have a significant impact on study outcome. Phase 2 biomarkers which are biologically stable, dynamically changing over time, and easy to assess in multi-centre studies are greatly needed. Shortcomings inherent in the Expanded Disability Status Scale are prompting the development and validation of better clinical measures. The standard two-arm, fixed-duration trial paradigm has been challenged with new, innovative approaches that can test more therapies efficiently. International collaboratives such as the Progressive MS Alliance will support increased dialogue with regulators, industry and other funding agencies. Better engagement with people living with progressive MS will transform them from simply being the recipient of MS therapies to partners in the search for new treatments. Focused, targeted action will drive further development of effective therapies for progressive MS

Why pair? Evidence of aggregative mating in a socially monogamous marine fish (Siganus doliatus, Siganidae)

© 2015 The Authors. Many species live in stable pairs, usually to breed and raise offspring together, but this cannot be assumed. Establishing whether pairing is based on mating, or an alternative cooperative advantage, can be difficult, especially where species show no obvious sexual dimorphism and where the act of reproduction itself is difficult to observe. In the tropical marine fishes known as rabbitfish (Siganidae), half of extant species live in socially monogamous, territorial pairs. It has been assumed that partnerships are for mating, but the reproductive mode of pairing rabbitfish is currently unconfirmed. Using passive acoustic telemetry to track movements of fishes belonging to one such species (Siganus doliatus), we provide the first evidence that paired adult fish undertake highly synchronized migrations with multiple conspecifics on a monthly cycle. All tagged individuals migrated along the same route in three consecutive months and were absent from home territories for 2–3 days just after the new moon. The timing and directionality of migrations suggest that S. doliatus may form spawning aggregations, offering the potential for exposure to multiple reproductive partners. The finding raises fundamental questions about the basis of pairing, mate choice and partnership longevity in this family

Progressive multiple sclerosis: Prospects for disease therapy, repair, and restoration of function

Multiple sclerosis is a major cause of neurological disability, which accrues predominantly during progressive forms of the disease. Although development of multifocal inflammatory lesions is the underlying pathological process in relapsing-remitting multiple sclerosis, the gradual accumulation of disability that characterises progressive multiple sclerosis seems to result more from diffuse immune mechanisms and neurodegeneration. As a result, the 14 anti-inflammatory drugs that have regulatory approval for treatment of relapsing-remitting multiple sclerosis have little or no efficacy in progressive multiple sclerosis without inflammatory lesion activity. Effective therapies for progressive multiple sclerosis that prevent worsening, reverse damage, and restore function are a major unmet need. In this Series paper we summarise the current status of therapy for progressive multiple sclerosis and outline prospects for the future

Sediments and herbivory as sensitive indicators of coral reef degradation

© 2016 by the author(s). Around the world, the decreasing health of coral reef ecosystems has highlighted the need to better understand the processes of reef degradation. The development of more sensitive tools, which complement traditional methods of monitoring coral reefs, may reveal earlier signs of degradation and provide an opportunity for pre-emptive responses. We identify new, sensitive metrics of ecosystem processes and benthic composition that allow us to quantify subtle, yet destabilizing, changes in the ecosystem state of an inshore coral reef on the Great Barrier Reef. Following severe climatic disturbances over the period 2011-2012, the herbivorous reef fish community of the reef did not change in terms of biomass or functional groups present. However, fish-based ecosystem processes showed marked changes, with grazing by herbivorous fishes declining by over 90%. On the benthos, algal turf lengths in the epilithic algal matrix increased more than 50% while benthic sediment loads increased 37-fold. The profound changes in processes, despite no visible change in ecosystem state, i.e., no shift to macroalgal dominance, suggest that although the reef has not undergone a visible regime-shift, the ecosystem is highly unstable, and may sit on an ecological knife-edge. Sensitive, process-based metrics of ecosystem state, such as grazing or browsing rates thus appear to be effective in detecting subtle signs of degradation and may be critical in identifying ecosystems at risk for the future

Predicting range-shift success potential for tropical marine fishes using external morphology

© 2016 The Author(s) Published by the Royal Society. All rights reserved. With global change accelerating the rate of species' range shifts, predicting which are most likely to establish viable populations in their new habitats is key tounderstanding howbiological systemswill respond. Annually, in Australia, tropical fish larvae from the Great Barrier Reef (GBR) are transported south via the East Australian Current (EAC), settling into temperate coastal habitats for the summer period, before experiencing near-100% mortality in winter. However, within 10 years, predicted winter ocean temperatures for the southeast coast of Australia will remain high enough for more of these so-called 'tropical vagrants' to survive over winter. We used a method of morphological niche analysis, previously shownto be an effective predictor of invasion success by fishes, to project which vagrants have the greatest likelihood of undergoing successful range shifts under these newclimatic conditions. We find that species from the family of butterflyfishes (Chaetodontidae), and the moorish idol, Zanclus cornutus, are most likely to be able to exploit new niches within the ecosystem once physiological barriers to overwintering by tropical vagrant species are removed. Overall, the position of vagrants within the morphospace was strongly skewed, suggesting that impending competitive pressures may impact disproportionately on particular parts of the native community

Landscape of MS patient cohorts and registries: recommendations for maximizing impact

BACKGROUND: There is a growing number of cohorts and registries collecting phenotypic and genotypic data from groups of multiple sclerosis patients. Improved awareness and better coordination of these efforts is needed. OBJECTIVE: The purpose of this report is to provide a global landscape of the major longitudinal MS patient data collection efforts and share recommendations for increasing their impact. METHODS: A workshop that included over 50 MS research and clinical experts from both academia and industry was convened to evaluate how current and future MS cohorts could be better used to provide answers to urgent questions about progressive MS. RESULTS: The landscape analysis revealed a significant number of largely uncoordinated parallel studies. Strategic oversight and direction is needed to streamline and leverage existing and future efforts. A number of recommendations for enhancing these efforts were developed. CONCLUSIONS: Better coordination, increased leverage of evolving technology, cohort designs that focus on the most important unanswered questions, improved access, and more sustained funding will be needed to close the gaps in our understanding of progressive MS and accelerate the development of effective therapies

Facial Expressions of Emotion: Are Angry Faces Detected More Efficiently?

The rapid detection of facial expressions of anger or threat has obvious adaptive value. In this study, we examined the efficiency of facial processing by means of a visual search task. Participants searched displays of schematic faces and were required to determine whether the faces displayed were all the same or whether one was different. Four main results were found: (1) When displays contained the same faces, people were slower in detecting the absence of a discrepant face when the faces displayed angry (or sad/angry) rather than happy expressions. (2) When displays contained a discrepant face people were faster in detecting this when the discrepant face displayed an angry rather than a happy expression. (3) Neither of these patterns for same and different displays was apparent when face displays were inverted, or when just the mouth was presented in isolation. (4) The search slopes for angry targets were significantly lower than for happy targets. These results suggest that detection of angry facial expressions is fast and efficient, although does not 'pop-out, in the traditional sense

Women's views on screening for Type 2 diabetes after gestational diabetes: a systematic review, qualitative synthesis and recommendations for increasing uptake.

AIM: Many women do not attend recommended glucose testing following a pregnancy affected by gestational diabetes (GDM). We aimed to synthesize the literature regarding the views and experiences of women with a history of GDM on postpartum glucose testing, focusing on barriers and facilitators to attendance. METHODS: We systematically identified qualitative studies that examine women's experiences following GDM relating to glucose testing (diabetes screening) or experience of interventions to promote uptake of testing. We conducted a thematic synthesis to develop descriptive and then analytical themes, then developed recommendations to increase uptake based on the findings. We evaluated the quality of each study and the confidence that we had in the recommendations using published checklists. RESULTS: We included 16 articles after screening 23 160 citations and 129 full texts. We identified four themes of influences relating to the healthcare system and personal factors that affected both ability and motivation to attend: relationship with health care, logistics of appointments and tests, family-related practicalities and concern about diabetes. We developed 10 recommendations addressing diabetes risk information and education, and changes to healthcare systems to promote increased attendance at screening in this population, most with high or moderate confidence. CONCLUSIONS: We have identified a need to improve women's understanding about Type 2 diabetes and GDM, and to adjust healthcare provision during and after pregnancy to decrease barriers and increase motivation for testing. Encouraging higher uptake by incorporating these recommendations into practice will enable earlier management of diabetes and improve long-term outcomes.R.D. is funded by a PhD studentship from the National Institute for Health Research (NIHR) School for Primary Care Research (SPCR; SPCR-S-S102). This paper presents independent research funded by the NIHR SPCR. The views expressed are those of the author(s) and not necessarily those of the NIHR, the NHS or the Department of Health. R.W. is funded by an NIHR Academic Clinical Fellowship. S.G. is supported by the Medical Research Council (MC_UU_12015/4). S.G. is an NIHR Senior Investigator. The University of Cambridge has received salary support in respect of S.G. from the NHS in the East of England through the Clinical Academic Reserve. J.U-S. is funded by a Cancer Research UK Cancer Prevention Fellowship (C55650/A21464)

Building governance and energy efficiency: Mapping the interdisciplinary challenge

Improving the energy efficiency of multi-owned properties (MoPs)—commonly known as apartment or condominium buildings—is central to the achievement of European energy targets. However, little work to date has focused on how to facilitate retrofit in this context. Drawing on interdisciplinary Social Sciences and Humanities expertise in academia, policy and practice, this chapter posits that decision-making processes within MoPs might provide a key to the retrofit challenge. Existing theories or models of decision-making, applied in the MoP context, might help to explain how collective retrofit decisions are taken—or overlooked. Insights from case studies and practitioners are also key. Theories of change might then be employed to develop strategies to facilitate positive retrofit decisions. The chapter maps the issues and sets an agenda for further interdisciplinary research in this novel area

Vocation, Belongingness, and Balance: A Qualitative Study of Veterinary Student Well-Being

An elevated risk for suicide among veterinarians has stimulated research into the mental health of the veterinary profession, and more recently attention has turned to the veterinary student population. This qualitative study sought to explore UK veterinary students' perceptions and experiences of university life, and to consider how these may affect well-being. Semi-structured interviews were conducted with 18 students from a single UK school who were purposively selected to include perspectives from male, female, graduate-entry, standard-entry (straight from high school), and widening participation students across all 5 years of the program. Three main themes were identified: a deep-rooted vocation, navigating belongingness, and finding balance. Participants described a long-standing goal of becoming a veterinarian, with a determination reflected by often circuitous routes to veterinary school and little or no consideration of alternatives. Although some had been motivated by a love of animals, others were intrinsically interested in the scientific and problem-solving challenges of veterinary medicine. Most expressed strong feelings of empathy with animal owners. The issue of belongingness was central to participants' experiences, with accounts reflecting their efforts to negotiate a sense of belongingness both in student and professional communities. Participants also frequently expressed a degree of acceptance of poor balance between work and relaxation, with indications of a belief that this imbalance could be rectified later. This study helps highlight future avenues for research and supports initiatives aiming to nurture a sense of collegiality among veterinary students as they progress through training and into the profession