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Here, we investigate Mid- to Late-Holocene vegetation changes in low-lying coastal areas in Tonga and how changing sea levels and recurrent volcanic eruptions have influenced vegetation dynamics on four islands of the Tongan archipelago (South Pacific). To investigate past vegetation and environmental change at Ngofe Marsh (‘Uta Vava’u), we examined palynomorphs (pollen and spores), charcoal (fire), and sediment characteristics (volcanic activity) from a 6.7-m-long sediment core. Radiocarbon dating indicated the sediments were deposited over the last 7700 years. We integrated the Ngofe Marsh data with similar previously published data from Avai’o’vuna Swamp on Pangaimotu Island, Lotofoa Swamp on Foa Island, and Finemui Swamp on Ha’afeva Island. Plant taxa were categorized as littoral, mangrove, rainforest, successional/ disturbance, and wetland groups, and linear models were used to examine relationships between vegetation, relative sea level change, and volcanic eruptions (tephra). We found that relative sea level change has impacted vegetation on three of the four islands investigated. Volcanic eruptions were not identified as a driver of vegetation change. Rainforest decline does not appear to be driven by sea level changes or volcanic eruptions. From all sites analyzed, vegetation at Finemui Swamp was most sensitive to changes in relative sea level. While vegetation on low-lying Pacific islands is sensitive to changing sea levels, island characteristics, such as area and elevation, are also likely to be important factors that mediate specific island responses to drivers of change.

The purpose of the current study was to use intravascular ultrasound (IVUS) to clarify anatomical and morphological lesion characteristics of uncrossable lesions.Uncrossable lesions are not always severely calcified. The prevalence of uncrossable lesions that are nonseverely calcified as well as other mechanisms for uncrossability has not been well clarified.A total of 252 de novo uncrossable lesions in native coronary arteries that underwent either rotational or orbital atherectomy due to inability of any balloon to cross the lesion and 38 lesions with severe calcium in which IVUS crossed preatherectomy were included. Severe calcium is defined as maximum arc of calcium ≥270°.Severe calcification was absent in 16% of uncrossable lesions, 83% of which had a significant vessel bend. Compared with crossable lesions with severe calcium, uncrossable lesions with severe calcium more often had a bend in the vessel (71% vs. 21%, p 0.001) and a longer length of continuous severe calcium (median length of calcium ≥270° 3.8 mm vs. 1.9 mm, p = 0.001). Other than severe calcium (especially long continuous calcium) or a bend in the vessel, anatomical factors associated with uncrossabilty were aorto-ostial lesion location and small vessels.Uncrossable lesions are not always severely calcified. The interaction of lesion morphology (continuous long and large arcs of calcium) and vessel geometry (bend in the vessel or ostial lesion location) affect lesion crossability.

Norovirus is the leading cause of sporadic and epidemic acute gastroenteritis (AGE) in children and adults around the world. We investigated the molecular diversity of noroviruses in a paediatric population in Senegal between 2007-2010 prior to rotavirus vaccine implementation. Stool samples were collected from 599 children under 5 years of age consulting for AGE in a hospital in Dakar. Specimens were screened for noroviruses using the Allplex™ GI-Virus Assay. Positive samples were genotyped after sequencing of conventional RT-PCR products. Noroviruses were detected in 79 (13.2%) of the children, with GII.4 (64%) and GII.6 (10%) as the most frequently identified genotypes. Our study describes the distribution of genotypes between 2007 and 2010 and should be a baseline for comparison with more contemporary studies. This could help decision makers on possible choices of norovirus vaccines in the event of future introduction. This article is protected by copyright. All rights reserved.

NEW FINDINGS What is the central question of this study? To what extent do hypoxia-induced changes in the peripheral and central respiratory chemoreflex modulate anterior and posterior cerebral oxygen delivery, with corresponding implications for susceptibility to acute mountain sickness? What is the main finding and its importance? We provide evidence for site-specific regulation of cerebral blood flow in hypoxia that preserves oxygen delivery in the posterior but not the anterior cerebral circulation, with minimal contribution from the central respiratory chemoreflex. External carotid artery vasodilatation might prove to be an alternative haemodynamic risk factor that predisposes to acute mountain sickness. ABSTRACT The aim of the present study was to determine the extent to which hypoxia-induced changes in the peripheral and central respiratory chemoreflex modulate anterior and posterior cerebral blood flow (CBF) and oxygen delivery (CDO2 ), with corresponding implications for the pathophysiology of the neurological syndrome, acute mountain sickness (AMS). Eight healthy men were randomly assigned single blind to 7 h of passive exposure to both normoxia (21% O2 ) and hypoxia (12% O2 ). The peripheral and central respiratory chemoreflex, internal carotid artery, external carotid artery (ECA) and vertebral artery blood flow (duplex ultrasound) and AMS scores (questionnaires) were measured throughout. A reduction in internal carotid artery CDO2 was observed during hypoxia despite a compensatory elevation in perfusion. In contrast, vertebral artery and ECA CDO2 were preserved, and the former was attributable to a more marked increase in perfusion. Hypoxia was associated with progressive activation of the peripheral respiratory chemoreflex (P 0.05). Symptom severity in participants who developed clinical AMS was positively related to ECA blood flow (Lake Louise score, r = 0.546-0.709, P = 0.004-0.043; Environmental Symptoms Questionnaires-Cerebral symptoms score, r = 0.587-0.771, P = 0.001-0.027, n = 4). Collectively, these findings highlight the site-specific regulation of CBF in hypoxia that maintains CDO2 selectively in the posterior but not the anterior cerebral circulation, with minimal contribution from the central respiratory chemoreflex. Furthermore, ECA vasodilatation might represent a hitherto unexplored haemodynamic risk factor implicated in the pathophysiology of AMS.

NEW FINDINGS What is the central question of this study? How does recurrent contact incurred across a season of professional rugby union impact molecular, cerebrovascular and cognitive function? What is the main findings and its importance? A single season of professional rugby union increases systemic oxidative-nitrosative stress (OXNOS) confirmed by a free radical-mediated suppression in nitric oxide bioavailability. Forwards encountered a higher frequency of contact events compared to backs, exhibiting elevated OXNOS and lower cerebrovascular function and cognition. Collectively, these findings provide mechanistic insight into the possible cause of reduced cognition in rugby union subsequent to impairment in the redox regulation of cerebrovascular function. ABSTRACT Contact events in rugby union remain a public health concern. We determined the molecular, cerebrovascular and cognitive consequences of contact events during a season of professional rugby. Twenty-one male players aged 25 (mean) ± 4 (SD) years were recruited from a professional rugby team comprising forwards (n = 13) and backs (n = 8). Data were collected across the season. Pre- and post-season, venous blood was assayed for the ascorbate free radical (A•- , electron paramagnetic resonance spectroscopy) and nitric oxide (NO, reductive ozone-based chemiluminescence) to quantify oxidative-nitrosative stress (OXNOS). Middle cerebral artery velocity (MCAv, Doppler ultrasound) was measured to assess cerebrovascular reactivity (CVR), and cognition was assessed using the Montreal Cognitive Assessment (MoCA). Notational analysis determined contact events over the season. Forwards incurred more collisions (Mean difference [MD ] 7.49; 95% CI, 2.58-12.40; P = 0.005), tackles (MD 3.49; 95% CI, 0.42-6.56; P = 0.028) and jackals (MD 2.21; 95% CI, 0.18-4.24; P = 0.034). Forwards suffered five concussions while backs suffered one concussion. An increase in systemic OXNOS, confirmed by elevated A•- (F2,19 = 10.589, P = 0.004) and corresponding suppression of NO bioavailability (F2,19 = 11.492, P = 0.003) was apparent in forwards and backs across the season. This was accompanied by a reduction in cerebral oxygen delivery ( cDO2 , F2,19 = 9.440, P = 0.006) and cognition (F2,19 = 4.813, P = 0.041). Forwards exhibited a greater decline in the cerebrovascular reactivity range to changes in PETCO2 ( CVRCO2RANG compared to backs (MD 1.378; 95% CI, 0.74-2.02; P

The fields of human genetics and genomics have generated considerable knowledge about the mechanistic basis of many diseases. Genomic approaches to diagnosis, prognostication, prevention and treatment - genomic-driven precision medicine (GDPM) - may help optimize medical practice. Here, we provide a comprehensive review of GDPM of complex diseases across major medical specialties. We focus on technological readiness: how rapidly a test can be implemented into health care. Although these areas of medicine are diverse, key similarities exist across almost all areas. Many medical areas have, within their standards of care, at least one GDPM test for a genetic variant of strong effect that aids the identification/diagnosis of a more homogeneous subset within a larger disease group or identifies a subset with different therapeutic requirements. However, for almost all complex diseases, the majority of patients do not carry established single-gene mutations with large effects. Thus, research is underway that seeks to determine the polygenic basis of many complex diseases. Nevertheless, most complex diseases are caused by the interplay of genetic, behavioural and environmental risk factors, which will likely necessitate models for prediction and diagnosis that incorporate genetic and non-genetic data. Funding Agencies|SciLifeLab; Swedish Research Council (Vetenskapsradet)Swedish Research Council [D0886501]; US National Institute of Mental HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Mental Health (NIMH) [MH077139, MH1095320]; European UnionEuropean Commission [610307, 733161, 825843]; Swedish Cancer SocietySwedish Cancer Society; Swedish Research CouncilSwedish Research CouncilEuropean Commission [2018-02837, 2014-03352, 2009-1039, 2018-03307]; Knut and Alice Wallenberg FoundationKnut & Alice Wallenberg Foundation; Karolinska Institutet, Karolinska University HospitalKarolinska Institutet; Radiumhemmets Forskningsfonder; European Research CouncilEuropean Research Council (ERC)European Commission [CoG-2015_681742_NASCENT]; Swedish Heart-Lung FoundationSwedish Heart-Lung Foundation [20160872]; Swedish Foundation for Strategic Research (IRC Center); Novo Nordisk FoundationNovo Nordisk FoundationNovocure Limited; ALF; Strategic Research Area Epidemiology at Karolinska Institutet; Swedish Rheumatism Association; Vth 80-year Foundation; Swedish Society of Medicine; Clinical Research Support (Avtal om Lakarutbildning och Forskning); Swedish government; county councils; ALF-agreement; Swedish Foundation for Strategic ResearchSwedish Foundation for Strategic Research [15-0067]; IMI2 Joint Undertaking [115974]; European Federation of Pharmaceutical Industries and Associations with JDRF; H2020 Program ERA PerMed JTC 2018 Call (VR) [2018-05619]

IntroductionThe learning health system (LHS) aligns science, informatics, incentives, stakeholders, and culture for continuous improvement and innovation. The Agency for Healthcare Research and Quality and the Patient-Centered Outcomes Research Institute designed a K12 initiative to grow the number of LHS scientists. We describe approaches developed by 11 funded centers of excellence (COEs) to promote partnerships between scholars and health system leaders and to provide mentored research training.MethodsSince 2018, the COEs have enlisted faculty, secured institutional resources, partnered with health systems, developed and implemented curricula, recruited scholars, and provided mentored training. Program directors for each COE provided descriptive data on program context, scholar characteristics, stakeholder engagement, scholar experiences with health system partnerships, roles following program completion, and key training challenges.ResultsTo date, the 11 COEs have partnered with health systems to train 110 scholars. Nine (82%) programs partner with a Veterans Affairs health system and 9 (82%) partner with safety net providers. Clinically trained scholars (n=87; 79%) include 70 physicians and 17 scholars in other clinical disciplines. Non-clinicians (n=29; 26%) represent diverse fields, dominated by population health sciences. Stakeholder engagement helps scholars understand health system and patient/family needs and priorities, enabling opportunities to conduct embedded research, improve outcomes, and grow skills in translating research methods and findings into practice. Challenges include supporting scholars through roadblocks that threaten to derail projects during their limited program time, ranging from delays in access to data to COVID-19-related impediments and shifts in organizational priorities.ConclusionsFour years into this novel training program, there is evidence of scholars' accomplishments, both in traditional academic terms and in terms of moving along career trajectories that hold the potential to lead and accelerate transformational health system change. Future LHS training efforts should focus on sustainability, including organizational support for scholar activities.

No abstract available.

International audience; Two new dumbbell-shaped molecules based on two solubilizing and structuring triazatruxene (TAT) units linked by a central chromophore were synthesized and studied. The central chromophore was an electro-deficient fluorene-malononitrile (FM) unit, that can be functionalized symmetrically on two different positions, giving rise to two positional isomers, called TAT-pFM and TAT-mFM, when the TATs are connected to the 2,7-and 3,6positions, respectively. The two isomers exhibited different electronic conjugation pathways that drastically affect their absorption properties and energy levels. Moreover, while TAT-pFM was organized in a stable 3D mesomorphic structure from room-temperature to the melting, TAT-mFM remained crystalline and decomposed before melting. Finally, despite a lower hole mobility, the TAT-mFM exhibited the highest Power Conversion Efficiency (PCE) of about 2% in organic solar cells. This higher PCE was attributed essentially to the pronounced internal charge transfer band contribution to the charge photogeneration observed in TAT-mFM solar cells.