39 research outputs found
Transient disruption of M1 during response planning impairs subsequent offline consolidation
Transcranial magnetic stimulation (TMS) was used to probe the involvement of the left primary motor cortex (M1) in the consolidation of a sequencing skill. In particular we asked: (1) if M1 is involved in consolidation of planning processes prior to response execution (2) whether movement preparation and movement execution can undergo consolidation independently and (3) whether sequence consolidation can occur in a stimulus specific manner. TMS was applied to left M1 while subjects prepared left hand sequential finger responses for three different movement sequences, presented in an interleaved fashion. Subjects also trained on three control sequences, where no TMS was applied. Disruption of subsequent consolidation was observed, but only for sequences where subjects had been exposed to TMS during training. Further, reduced consolidation was only observed for movement preparation, not movement execution. We conclude that left M1 is causally involved in the consolidation of effective response planning for left hand movements prior to response execution, and mediates consolidation in a sequence specific manner. These results provide important new insights into the role of M1 in sequential memory consolidation and sequence response planning
Trajectories of Self-Reported Opioid Use Among Patients With HIV Engaged in Care: Results From a National Cohort Study.
BACKGROUND: No prior studies have characterized long-term patterns of opioid use regardless of source or reason for use among patients with HIV (PWH). We sought to identify trajectories of self-reported opioid use and their correlates among a national sample of PWH engaged in care. SETTING: Veterans Aging Cohort Study, a prospective cohort including PWH receiving care at 8 US Veterans Health Administration (VA) sites. METHODS: Between 2002 and 2018, we assessed past year opioid use frequency based on self-reported "prescription painkillers" and/or heroin use at baseline and follow-up. We used group-based trajectory models to identify opioid use trajectories and multinomial logistic regression to determine baseline factors independently associated with escalating opioid use compared to stable, infrequent use. RESULTS: Among 3702 PWH, we identified 4 opioid use trajectories: (1) no lifetime use (25%); (2) stable, infrequent use (58%); (3) escalating use (7%); and (4) de-escalating use (11%). In bivariate analysis, anxiety; pain interference; prescribed opioids, benzodiazepines and gabapentinoids; and marijuana use were associated with escalating opioid group membership compared to stable, infrequent use. In multivariable analysis, illness severity, pain interference, receipt of prescribed benzodiazepine medications, and marijuana use were associated with escalating opioid group membership compared to stable, infrequent use. CONCLUSION: Among PWH engaged in VA care, 1 in 15 reported escalating opioid use. Future research is needed to understand the impact of psychoactive medications and marijuana use on opioid use and whether enhanced uptake of evidence-based treatment of pain and psychiatric symptoms can prevent escalating use among PWH
Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK.
BACKGROUND: A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials. METHODS: This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5 × 1010 viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1 - relative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674. FINDINGS: Between April 23 and Nov 4, 2020, 23 848 participants were enrolled and 11 636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0-75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4-97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; pinteraction=0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8-80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74 341 person-months of safety follow-up (median 3·4 months, IQR 1·3-4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation. INTERPRETATION: ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials. FUNDING: UK Research and Innovation, National Institutes for Health Research (NIHR), Coalition for Epidemic Preparedness Innovations, Bill & Melinda Gates Foundation, Lemann Foundation, Rede D'Or, Brava and Telles Foundation, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midland's NIHR Clinical Research Network, and AstraZeneca
Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK
Background
A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials.
Methods
This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5 × 1010 viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1 - relative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674.
Findings
Between April 23 and Nov 4, 2020, 23 848 participants were enrolled and 11 636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0–75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4–97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; pinteraction=0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8–80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74 341 person-months of safety follow-up (median 3·4 months, IQR 1·3–4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation.
Interpretation
ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials
BradfordetalSTARCODE
The code file used to analyze the two associated data sets is named ‘BradfordetalSTARCODE.txt’ and contains all R (the statistical freeware package) code used for data analysis in the accepted manuscript. Analytical steps are explained ahead of each section of code within the code file. Full data and description of the variables and their units for the field and lab-incubated soils are in the associated csv and associated readme.txt file
Data from: Cross-biome patterns in soil microbial respiration predictable from evolutionary theory on thermal adaptation
Climate warming may stimulate microbial metabolism of soil carbon, causing a carbon cycle-climate feedback whereby carbon is redistributed from soil to atmospheric CO2. The magnitude of this feedback is uncertain, in part because warming-induced shifts in microbial physiology and/or community composition could retard or accelerate soil carbon losses. Here, we measure microbial respiration rates for soils collected from 22 sites in each of three years, at locations spanning boreal to tropical climates. Respiration was measured in the laboratory with standard temperatures, moisture and excess carbon substrate, to allow physiological and community effects to be detected independent from the influence of these abiotic controls. Patterns in respiration for soils collected across the climate gradient are consistent with evolutionary theory on physiological responses that compensate for positive effects of temperature on metabolism. Respiration rates per unit microbial biomass were as much as 2.6-times higher for soils sampled from sites with a mean annual temperature (MAT) of -2.0 versus 21.7ºC. Subsequent 100-day incubations suggested differences in the plasticity of the thermal response among microbial communities, with communities sampled from sites with higher MAT having a more plastic response. Our findings are consistent with adaptive metabolic responses to contrasting thermal regimes that are also observed in plants and animals. These results may help build confidence in soil carbon-climate feedback projections by improving understanding of microbial processes represented in biogeochemical models
BradfordetalSTARIncData
The data file is named ‘BradfordetalSTARIncData.csv’. A full description of the original purpose of these data, as well as the methods used to collect them, are described in the accepted manuscript. Data are organized across 31 columns, and 234 rows of data, with a single header row with the column title. The code file used to analyze these data is named ‘BradfordetalSTARCODE.txt’ and contains all R (the statistical freeware package) code used for data analysis in the accepted manuscript. Analytical steps are explained ahead of each section of code within the code file. Full description of the variables and their units for these field collected and then lab-incubated soils are in the associated readme.txt fil
BradfordetalSTARObsData
The data file is named ‘BradfordetalSTARObsData.csv’. A full description of the original purpose of these data, as well as the methods used to collect them, are described in the accepted manuscript. Data are organized across 30 columns, and 792 rows of data, with a single header row with the column title. The code file used to analyze these data is named ‘BradfordetalSTARCODE.txt’ and contains all R (the statistical freeware package) code used for data analysis in the accepted manuscript. Analytical steps are explained ahead of each section of code within the code file. Full description of the variables and their units for these field collected soils are in the associated readme.txt fil
Predicting the Responsiveness of Soil Biodiversity to Deforestation: A Cross-Biome Study
The consequences of deforestation for aboveground biodiversity have been a scientific and political concern for decades. In contrast, despite being a dominant component of biodiversity that is essential to the functioning of ecosystems, the responses of belowground biodiversity to forest removal have received less attention. Single-site studies suggest that soil microbes can be highly responsive to forest removal, but responses are highly variable, with negligible effects in some regions. Using high throughput sequencing, we characterize the effects of deforestation on microbial communities across multiple biomes and explore what determines the vulnerability of microbial communities to this vegetative change. We reveal consistent directional trends in the microbial community response, yet the magnitude of this vegetation effect varied between sites, and was explained strongly by soil texture. In sandy sites, the difference in vegetation type caused shifts in a suite of edaphic characteristics, driving substantial differences in microbial community composition. In contrast, fine-textured soil buffered microbes against these effects and there were minimal differences between communities in forest and grassland soil. These microbial community changes were associated with distinct changes in the microbial catabolic profile, placing community changes in an ecosystem functioning context. The universal nature of these patterns allows us to predict where deforestation will have the strongest effects on soil biodiversity, and how these effects could be mitigated
Growing the urban forest: tree performance in response to biotic and abiotic land management
Forests are vital components of the urban landscape because they provide ecosystem services such as carbon sequestration, storm-water mitigation, and air-quality improvement. To enhance these services, cities are investing in programs to create urban forests. A major unknown, however, is whether planted trees will grow into the mature, closed-canopied forest on which ecosystem service provision depends. We assessed the influence of biotic and abiotic land management on planted tree performance as part of urban forest restoration in New York City, U.S.A. Biotic treatments were designed to improve tree growth, with the expectation that higher tree species composition (six vs. two) and greater stand complexity (with shrubs vs. without) would facilitate tree performance. Similarly, the abiotic treatment (compost amendment vs. without) was expected to increase tree performance by improving soil conditions. Growth and survival was measured for approximately 1,300 native saplings across three growing seasons. The biotic and abiotic treatments significantly improved tree performance, where shrub presence increased tree height for five of the six tree species, and compost increased basal area and stem volume of all species. Species-specific responses, however, highlighted the difficulty of achieving rapid growth with limited mortality. Pioneer species had the highest growth in stem volume over 3 years (up to 3,500%), but also the highestmortality (up to 40%). Mid-successional species had lower mortality (\u3c16%), but also the slowest growth in volume (approximately 500% in volume). Our results suggest that there will be trade-offs between optimizing tree growth versus survival when implementing urban tree planting initiatives