Search for eccentric black hole coalescences during the third observing run of LIGO and Virgo

Despite the growing number of confident binary black hole coalescences observed through gravitational waves so far, the astrophysical origin of these binaries remains uncertain. Orbital eccentricity is one of the clearest tracers of binary formation channels. Identifying binary eccentricity, however, remains challenging due to the limited availability of gravitational waveforms that include effects of eccentricity. Here, we present observational results for a waveform-independent search sensitive to eccentric black hole coalescences, covering the third observing run (O3) of the LIGO and Virgo detectors. We identified no new high-significance candidates beyond those that were already identified with searches focusing on quasi-circular binaries. We determine the sensitivity of our search to high-mass (total mass M>70 M⊙) binaries covering eccentricities up to 0.3 at 15 Hz orbital frequency, and use this to compare model predictions to search results. Assuming all detections are indeed quasi-circular, for our fiducial population model, we place an upper limit for the merger rate density of high-mass binaries with eccentricities 0<e≤0.3 at 0.33 Gpc−3 yr−1 at 90\% confidence level

Ultralight vector dark matter search using data from the KAGRA O3GK run

Among the various candidates for dark matter (DM), ultralight vector DM can be probed by laser interferometric gravitational wave detectors through the measurement of oscillating length changes in the arm cavities. In this context, KAGRA has a unique feature due to differing compositions of its mirrors, enhancing the signal of vector DM in the length change in the auxiliary channels. Here we present the result of a search for U(1)B−L gauge boson DM using the KAGRA data from auxiliary length channels during the first joint observation run together with GEO600. By applying our search pipeline, which takes into account the stochastic nature of ultralight DM, upper bounds on the coupling strength between the U(1)B−L gauge boson and ordinary matter are obtained for a range of DM masses. While our constraints are less stringent than those derived from previous experiments, this study demonstrates the applicability of our method to the lower-mass vector DM search, which is made difficult in this measurement by the short observation time compared to the auto-correlation time scale of DM

The hedgehog pathway suppresses neuropathogenesis in CD4 T cell-driven inflammation

International audienceThe concerted actions of the CNS and the immune system are essential to coordinating the outcome of neuroinflammatory responses. Yet, the precise mechanisms involved in this crosstalk and their contribution to the pathophysiology of neuroinflammatory diseases largely elude us. Here, we show that the CNS-endogenous hedgehog pathway, a signal triggered as part of the host response during the inflammatory phase of multiple sclerosis and experimental autoimmune encephalomyelitis, attenuates the pathogenicity of human and mouse effector CD4 T cells by regulating their production of inflammatory cytokines. Using a murine genetic model, in which the hedgehog signalling is compromised in CD4 T cells, we show that the hedgehog pathway acts on CD4 T cells to suppress the pathogenic hallmarks of autoimmune neuroinflammation, including demyelination and axonal damage, and thus mitigates the development of experimental autoimmune encephalomyelitis. Impairment of hedgehog signalling in CD4 T cells exacerbates brain-brainstem-cerebellum inflammation and leads to the development of atypical disease. Moreover, we present evidence that hedgehog signalling regulates the pathogenic profile of CD4 T cells by limiting their production of the inflammatory cytokines granulocyte-macrophage colony-stimulating factor and interferon-?? and by antagonizing their inflammatory program at the transcriptome level. Likewise, hedgehog signalling attenuates the inflammatory phenotype of human CD4 memory T cells. From a therapeutic point of view, our study underlines the potential of harnessing the hedgehog pathway to counteract ongoing excessive CNS inflammation, as systemic administration of a hedgehog agonist after disease onset effectively halts disease progression and significantly reduces neuroinflammation and the underlying neuropathology. We thus unveil a previously unrecognized role for the hedgehog pathway in regulating pathogenic inflammation within the CNS and propose to exploit its ability to modulate this neuroimmune network as a strategy to limit the progression of ongoing neuroinflammation

Implementation strategies in the Exploration and Preparation phases of a colorectal cancer screening intervention in community health centers

Abstract Background Adoption of colorectal cancer (CRC) screening has lagged in community health center (CHC) populations in the USA. To address this implementation gap, we developed a multilevel intervention to improve screening in CHCs in our region. We used the Exploration, Preparation, Implementation, Sustainment (EPIS) framework to guide this effort. Here, we describe the use of implementation strategies outlined in the Expert Recommendations for Implementing Change (ERIC) compilation in both the Exploration and Preparation phases of this project. During these two EPIS phases, we aimed to answer three primary questions: (1) What factors in the inner and outer contexts may support or hinder colorectal cancer screening in North Carolina CHCs?; (2) What evidence-based practices (EBPs) best fit the needs of North Carolina CHCs?; and (3) How can we best integrate the selected EBPs into North Carolina CHC systems? Methods During the Exploration phase, we conducted local needs assessments, built a coalition, and conducted local consensus discussions. In the Preparation phase, we formed workgroups corresponding to the intervention’s core functional components. Workgroups used cyclical small tests of change and process mapping to identify implementation barriers and facilitators and to adapt intervention components to fit inner and outer contexts. Results Exploration activities yielded a coalition of stakeholders, including two rural CHCs, who identified barriers and facilitators and reached consensus on two EBPs: mailed FIT and navigation to colonoscopy. Stakeholders further agreed that the delivery of those two EBPs should be centralized to an outreach center. During Preparation, workgroups developed and refined protocols for the following centrally-delivered intervention components: a registry to identify and track eligible patients, a centralized system for mailing at-home stool tests, and a process to navigate patients to colonoscopy after an abnormal stool test. Conclusions This description may be useful both to implementation scientists, who can draw lessons from applied implementation studies such as this to refine their implementation strategy typologies and frameworks, as well as to implementation practitioners seeking exemplars for operationalizing strategies in early phases of implementation in healthcare

Reshaping the path of mild cognitive impairment by refining exercise prescription : a study protocol of a randomized controlled trial to understand the “what,” “for whom,” and “how” of exercise to promote cognitive function

Background Targeted exercise training is a promising strategy for promoting cognitive function and preventing dementia in older age. Despite the utility of exercise as an intervention, variation still exists in exercise-induced cognitive gains and questions remain regarding the type of training (i.e., what), as well as moderators (i.e., for whom) and mechanisms (i.e., how) of benefit. Both aerobic training (AT) and resistance training (RT) enhance cognitive function in older adults without cognitive impairment; however, the vast majority of trials have focused exclusively on AT. Thus, more research is needed on RT, as well as on the combination of AT and RT, in older adults with mild cognitive impairment (MCI), a prodromal stage of dementia. Therefore, we aim to conduct a 6-month, 2 × 2 factorial randomized controlled trial in older adults with MCI to assess the individual effects of AT and RT, and the combined effect of AT and RT on cognitive function and to determine the possible underlying biological mechanisms. Methods Two hundred and sixteen community-dwelling adults, aged 65 to 85 years, with MCI from metropolitan Vancouver will be recruited to participate in this study. Randomization will be stratified by biological sex and participants will be randomly allocated to one of the four experimental groups: (1) 4×/week balance and tone (BAT; i.e., active control); (2) combined 2×/week AT + 2×/week RT; (3) 2×/week AT + 2×/week BAT; or (4) 2×/week RT + 2×/week BAT. The primary outcome is cognitive function as measured by the Alzheimer’s Disease Assessment Scale-Cognitive-Plus. Secondary outcomes include cognitive function, health-related quality of life, physical function, actigraphy measures, questionnaires, and falls. Outcomes will be measured at baseline, 6 months (i.e., trial completion), and 18 months (i.e., 12-month follow-up). Discussion Establishing the efficacy of different types and combinations of exercise training to minimize cognitive decline will advance our ability to prescribe exercise as “medicine” to treat MCI and delay the onset and progression of dementia. This trial is extremely timely as cognitive impairment and dementia pose a growing threat to global public health. Trial registration ClinicalTrials.gov NCT02737878 . Registered on April 14, 2016.Arts, Faculty ofPsychology, Department ofReviewedFacultyResearche

Additional file 1 of Implementation strategies in the Exploration and Preparation phases of a colorectal cancer screening intervention in community health centers

Additional file 1. Adherence to reporting guidelines. Description of project adherence to reporting guidelines as outlined in Proctor, E.K., Powell, B.J. & McMillen, J.C. Implementation strategies: recommendations for specifying and reporting. Implementation Sci 8, 139 (2013)