Cholinesterase inhibitor to prevent falls in Parkinson's disease (CHIEF-PD) trial:a phase 3 randomised, double-blind placebo-controlled trial of rivastigmine to prevent falls in Parkinson's disease

Abstract Background Falls are a common complication of Parkinson’s disease. There is a need for new therapeutic options to target this debilitating aspect of the disease. Cholinergic deficit has been shown to contribute to both gait and cognitive dysfunction seen in the condition. Potential benefits of using cholinesterase inhibitors were shown during a single centre phase 2 trial. The aim of this trial is to evaluate the effectiveness of a cholinesterase inhibitor on fall rate in people with idiopathic Parkinson’s disease. Methods This is a multi-centre, double-blind, randomised placebo-controlled trial in 600 people with idiopathic Parkinson’s disease (Hoehn and Yahr stages 1 to 4) with a history of a fall in the past year. Participants will be randomised to two groups, receiving either transdermal rivastigmine or identical placebo for 12 months. The primary outcome is the fall rate over 12 months follow-up. Secondary outcome measures, collected at baseline and 12 months either face-to-face or via remote video/telephone assessments, include gait and balance measures, neuropsychiatric indices, Parkinson’s motor and non-motor symptoms, quality of life and cost-effectiveness. Discussion This trial will establish whether cholinesterase inhibitor therapy is effective in preventing falls in Parkinson’s disease. If cost-effective, it will alter current management guidelines by offering a new therapeutic option in this high-risk population. Trial registration REC reference: 19/SW/0043. EudraCT: 2018–003219-23. ISCRTN: 41639809 (registered 16/04/2019). ClinicalTrials.gov Identifier: NCT04226248 Protocol at time of publication Version 7.0, 20th January 2021

Morphodynamics of a width-variable gravel bed stream: new insights on pool-riffle formation from physical experiments

Field observations, experiments, and numerical simulations suggest that pool-riffles along gravel bed mountain streams develop due to downstream variations of channel width. Where channels narrow, pools are observed, and at locations of widening, riffles occur. Based on previous work, we hypothesize that the bed profile is coupled to downstream width variations through momentum fluxes imparted to the channel surface, which scale with downstream changes of flow velocity. We address this hypothesis with flume experiments understood through scaling theory. Our experiments produce pool-riffle like structures across average Shields stresses t* that are a factor 1.5–2 above the threshold mobility condition of the experimental grain size distribution. Local topographic responses are coupled to channel width changes, which drive flows to accelerate or decelerate on average, for narrowing and widening, respectively. We develop theory which explains the topography-width-velocity coupling as a ratio of two reinforcing timescales. The first timescale captures the time necessary to do work to the channel bed. The second timescale characterizes the relative time magnitude of momentum transfer from the flowing fluid to the channel bed surface. Riffle-like structures develop where the work and momentum timescales are relatively large, and pools form where the two timescales are relatively small. We show that this result helps to explain local channel bed slopes along pool-riffles for five data sets representing experimental, numerical, and natural cases, which span 2 orders of magnitude of reach-averaged slope. Additional model testing is warranted.Peer ReviewedPostprint (published version

Pilot testing the feasibility of a game intervention aimed at improving help seeking and coping among sexual and gender minority youth: protocol for a randomized controlled trial

Background: Sexual and gender minority youth (SGMY; e.g., lesbian, gay, bisexual, and transgender youth) experience myriad substance use and mental health disparities compared with their cisgender (non-transgender) heterosexual peers. Despite much research showing these disparities are driven by experiences of bullying and cyberbullying victimization, few interventions have aimed to improve the health of bullied SGMY. One possible way to improve the health of bullied SGMY is via an online-accessible game intervention. Nevertheless, little research has examined the feasibility of using an online-accessible game intervention with SGMY. Objectives: To describe the protocol for a randomized controlled trial (RCT) pilot testing the feasibility and limited-efficacy of a game-based intervention for increasing help-seeking-related knowledge, intentions, self-efficacy, and behaviors, productive coping skills use, and coping flexibility, and reducing health risk factors and behaviors among SGMY. Methods: We enrolled 240 SGMY aged 14-18 years residing in the United States into a two-arm prospective RCT. The intervention is a theory-based, community-informed, computer-based, role playing game with three primary components: (1) encouraging help-seeking behaviors; (2) encouraging use of productive coping; and (3) raising awareness of online resources. SGMY randomized to both the intervention and control conditions will receive a list of SGMY-inclusive resources covering a variety of health-related topics. Control condition participants received only the list of resources. Notably, all study procedures are conducted online. We conveniently sampled SGMY using online website advertisements. Study assessments occur at enrollment, 1 month after enrollment, and 2 months after enrollment. The primary outcomes of this feasibility study include implementation procedures, game demand, and game acceptability. Secondary outcomes include help-seeking intentions, self-efficacy, and behaviors; productive coping strategies and coping flexibility; and knowledge and use of online resources. Tertiary outcomes include bullying and cyberbullying victimization; loneliness; mental health issues; substance use; and internalized sexual and gender minority stigma. Results: From April through July 2018, 240 participants were enrolled and randomized. Half of the enrolled participants (n=120) were randomized into the intervention condition, and half (n=120) into the control condition. At baseline, 52% of participants identified as gay or lesbian, 27% as bisexual, 24% as queer, and 12% as another non-heterosexual identity. Nearly half (47%) of participants were a gender minority, 37% were cisgender boys, and 16% were cisgender girls. There were no differences in demographic characteristics between intervention and control condition participants. Data collection is anticipated to end in November 2018. Conclusions: Online-accessible game interventions overcome common impediments of face-to-face interventions and present a unique opportunity to reach SGMY and improve their health. This trial will provide data on feasibility and limited-efficacy that can inform future online studies and a larger RCT aimed at improving health equity for SGMY. Trial Registration: ClinicalTrials.gov NCT03501264; https://clinicaltrials.gov/ct2/show/NCT03501264 (Archived by WebCite at http://www.webcitation.org/72HpafarW

The Holy Grail: A road map for unlocking the climate record stored within Mars' polar layered deposits

In its polar layered deposits (PLD), Mars possesses a record of its recent climate, analogous to terrestrial ice sheets containing climate records on Earth. Each PLD is greater than 2 ​km thick and contains thousands of layers, each containing information on the climatic and atmospheric state during its deposition, creating a climate archive. With detailed measurements of layer composition, it may be possible to extract age, accumulation rates, atmospheric conditions, and surface activity at the time of deposition, among other important parameters; gaining the information would allow us to “read” the climate record. Because Mars has fewer complicating factors than Earth (e.g. oceans, biology, and human-modified climate), the planet offers a unique opportunity to study the history of a terrestrial planet’s climate, which in turn can teach us about our own planet and the thousands of terrestrial exoplanets waiting to be discovered. During a two-part workshop, the Keck Institute for Space Studies (KISS) hosted 38 Mars scientists and engineers who focused on determining the measurements needed to extract the climate record contained in the PLD. The group converged on four fundamental questions that must be answered with the goal of interpreting the climate record and finding its history based on the climate drivers. The group then proposed numerous measurements in order to answer these questions and detailed a sequence of missions and architecture to complete the measurements. In all, several missions are required, including an orbiter that can characterize the present climate and volatile reservoirs; a static reconnaissance lander capable of characterizing near surface atmospheric processes, annual accumulation, surface properties, and layer formation mechanism in the upper 50 ​cm of the PLD; a network of SmallSat landers focused on meteorology for ground truth of the low-altitude orbiter data; and finally, a second landed platform to access ~500 ​m of layers to measure layer variability through time. This mission architecture, with two landers, would meet the science goals and is designed to save costs compared to a single very capable landed mission. The rationale for this plan is presented below. In this paper we discuss numerous aspects, including our motivation, background of polar science, the climate science that drives polar layer formation, modeling of the atmosphere and climate to create hypotheses for what the layers mean, and terrestrial analogs to climatological studies. Finally, we present a list of measurements and missions required to answer the four major questions and read the climate record. 1. What are present and past fluxes of volatiles, dust, and other materials into and out of the polar regions? 2. How do orbital forcing and exchange with other reservoirs affect those fluxes? 3. What chemical and physical processes form and modify layers? 4. What is the timespan, completeness, and temporal resolution of the climate history recorded in the PLD

The Holy Grail: A road map for unlocking the climate record stored within Mars' polar layered deposits

In its polar layered deposits (PLD), Mars possesses a record of its recent climate, analogous to terrestrial ice sheets containing climate records on Earth. Each PLD is greater than 2 ​km thick and contains thousands of layers, each containing information on the climatic and atmospheric state during its deposition, creating a climate archive. With detailed measurements of layer composition, it may be possible to extract age, accumulation rates, atmospheric conditions, and surface activity at the time of deposition, among other important parameters; gaining the information would allow us to “read” the climate record. Because Mars has fewer complicating factors than Earth (e.g. oceans, biology, and human-modified climate), the planet offers a unique opportunity to study the history of a terrestrial planet’s climate, which in turn can teach us about our own planet and the thousands of terrestrial exoplanets waiting to be discovered. During a two-part workshop, the Keck Institute for Space Studies (KISS) hosted 38 Mars scientists and engineers who focused on determining the measurements needed to extract the climate record contained in the PLD. The group converged on four fundamental questions that must be answered with the goal of interpreting the climate record and finding its history based on the climate drivers. The group then proposed numerous measurements in order to answer these questions and detailed a sequence of missions and architecture to complete the measurements. In all, several missions are required, including an orbiter that can characterize the present climate and volatile reservoirs; a static reconnaissance lander capable of characterizing near surface atmospheric processes, annual accumulation, surface properties, and layer formation mechanism in the upper 50 ​cm of the PLD; a network of SmallSat landers focused on meteorology for ground truth of the low-altitude orbiter data; and finally, a second landed platform to access ~500 ​m of layers to measure layer variability through time. This mission architecture, with two landers, would meet the science goals and is designed to save costs compared to a single very capable landed mission. The rationale for this plan is presented below. In this paper we discuss numerous aspects, including our motivation, background of polar science, the climate science that drives polar layer formation, modeling of the atmosphere and climate to create hypotheses for what the layers mean, and terrestrial analogs to climatological studies. Finally, we present a list of measurements and missions required to answer the four major questions and read the climate record. 1. What are present and past fluxes of volatiles, dust, and other materials into and out of the polar regions? 2. How do orbital forcing and exchange with other reservoirs affect those fluxes? 3. What chemical and physical processes form and modify layers? 4. What is the timespan, completeness, and temporal resolution of the climate history recorded in the PLD

What’s retinoic acid got to do with it? Retinoic acid regulation of the neural crest in craniofacial and ocular development

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/151310/1/dvg23308.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/151310/2/dvg23308_am.pd

Climate drives the geography of marine consumption by changing predator communities

Este artículo contiene 7 páginas, 3 figuras, 1 tabla.The global distribution of primary production and consumption by humans (fisheries) is well-documented, but we have no map linking the central ecological process of consumption within food webs to temperature and other ecological drivers. Using standardized assays that span 105° of latitude on four continents, we show that rates of bait consumption by generalist predators in shallow marine ecosystems are tightly linked to both temperature and the composition of consumer assemblages. Unexpectedly, rates of consumption peaked at midlatitudes (25 to 35°) in both Northern and Southern Hemispheres across both seagrass and unvegetated sediment habitats. This pattern contrasts with terrestrial systems, where biotic interactions reportedly weaken away from the equator, but it parallels an emerging pattern of a subtropical peak in marine biodiversity. The higher consumption at midlatitudes was closely related to the type of consumers present, which explained rates of consumption better than consumer density, biomass, species diversity, or habitat. Indeed, the apparent effect of temperature on consumption was mostly driven by temperature-associated turnover in consumer community composition. Our findings reinforce the key influence of climate warming on altered species composition and highlight its implications for the functioning of Earth’s ecosystems.We acknowledge funding from the Smithsonian Institution and the Tula Foundation.Peer reviewe

Assessing the potential of acoustic telemetry to underpin the regional management of basking sharks (Cetorhinus maximus)

Acoustic telemetry can provide valuable space-use data for a range of marine species. Yet the deployment of species-specific arrays over vast areas to gather data on highly migratory vertebrates poses formidable challenges, often rendering it impractical. To address this issue, we pioneered the use of acoustic telemetry on basking sharks (Cetorhinus maximus) to test the feasibility of using broadscale, multi-project acoustic receiver arrays to track the movements of this species of high conservation concern through the coastal waters of Ireland, Northern Ireland, and Scotland. Throughout 2021 and 2022, we tagged 35 basking sharks with acoustic transmitters off the west coast of Ireland; 27 of these were detected by 96 receiver stations throughout the study area (n = 9 arrays) with up to 216 detections of an individual shark (mean = 84, s.d. 65). On average, sharks spent ~ 1 day at each acoustic array, with discrete residency periods of up to nine days. Twenty-one sharks were detected at multiple arrays with evidence of inter-annual site fidelity, with the same individuals returning to the same locations in Ireland and Scotland over 2 years. Eight pairs of sharks were detected within 24 h of each other at consecutive arrays, suggesting some level of social coordination and synchronised movement. These findings demonstrate how multi-project acoustic telemetry can support international, cost-effective monitoring of basking sharks and other highly mobile species. Decision support tools such as these can consolidate cross-border management strategies, but to achieve this goal, collaborative efforts across jurisdictions are necessary to establish the required infrastructure and secure ongoing support

Unlocking the Climate Record Stored within Mars’ Polar Layered Deposits

In the icy beds of its polar layered deposits (PLD), Mars likely possesses a record of its recent climate history, analogous to terrestrial ice sheets that contain records of Earth's past climate. Both northern and southern PLDs store information on the climatic and atmospheric state during the deposition of each layer (WPs: Becerra et al.; Smith et al). Reading the climate record stored in these layers requires detailed measurements of layer composition, thickness, isotope variability, and near-surface atmospheric measurements. We identify four fundamental questions that must be answered in order to interpret this climate record and decipher the recent climatic history of Mars: 1. Fluxes: What are the present and past fluxes of volatiles, dust, and other materials into and out of the polar regions? 2. Forcings: How do orbital/axial forcing and exchange with other reservoirs affect those fluxes? 3. Layer Processes: What chemical and physical processes form and modify layers? 4. Record: What is the timespan, completeness, and temporal resolution of the climate history recorded in the PLD? In a peer reviewed report (1), we detailed a sequence of missions, instruments, and architecture needed to answer these questions. Here, we present the science drivers and a mission concept for a polar lander that would enable a future reading of the past few million years of the Martian climate record. The mission addresses as-yet-unachieved science goals of the current Decadal Survey and of MEPAG for obtaining a record of Mars climate and has parallel goals to the NEXSAG and ICE-SAG reports