Abstract Although amyloid imaging with PiB-PET (C-11Pittsburgh Compound-B positron emission tomography), and now with F-18-labeled tracers, has produced remarkably consistent qualitative findings ...across a large number of centers, there has been considerable variability in the exact numbers reported as quantitative outcome measures of tracer retention. In some cases this is as trivial as the choice of units, in some cases it is scanner dependent, and of course, different tracers yield different numbers. Our working group was formed to standardize quantitative amyloid imaging measures by scaling the outcome of each particular analysis method or tracer to a 0 to 100 scale, anchored by young controls (≤45 years) and typical Alzheimer's disease patients. The units of this scale have been named “Centiloids.” Basically, we describe a “standard” method of analyzing PiB PET data and then a method for scaling any “nonstandard” method of PiB PET analysis (or any other tracer) to the Centiloid scale.
Full text
Available for:
FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
In the human hematopoietic system, aging is associated with decreased bone marrow cellularity, decreased adaptive immune system function, and increased incidence of anemia and other hematological ...disorders and malignancies. Recent studies in mice suggest that changes within the hematopoietic stem cell (HSC) population during aging contribute significantly to the manifestation of these age-associated hematopoietic pathologies. Though the mouse HSC population has been shown to change both quantitatively and functionally with age, changes in the human HSC and progenitor cell populations during aging have been incompletely characterized. To elucidate the properties of an aged human hematopoietic system that may predispose to age-associated hematopoietic dysfunction, we evaluated immunophenotypic HSC and other hematopoietic progenitor populations from healthy, hematologically normal young and elderly human bone marrow samples. We found that aged immunophenotypic human HSC increase in frequency, are less quiescent, and exhibit myeloid-biased differentiation potential compared with young HSC. Gene expression profiling revealed that aged immunophenotypic human HSC transcriptionally up-regulate genes associated with cell cycle, myeloid lineage specification, and myeloid malignancies. These age-associated alterations in the frequency, developmental potential, and gene expression profile of human HSC are similar to those changes observed in mouse HSC, suggesting that hematopoietic aging is an evolutionarily conserved process.
The late Permian mass extinction event was the largest biotic crisis of the Phanerozoic and has the longest recovery interval of any extinction event. It has been hypothesised that subsequent carbon ...isotope perturbations during the Early Triassic are associated with biotic crises that impeded benthic recovery. We test this hypothesis by undertaking the highest-resolution study yet made of the rock and fossil records of the entire Werfen Formation, Italy. Here, we show that elevated extinction rates were recorded not only in the Dienerian, as previously recognised, but also around the Smithian/Spathian boundary. Functional richness increases across the Smithian/Spathian boundary associated with elevated origination rates in the lower Spathian. The taxonomic and functional composition of benthic faunas only recorded two significant changes: (1) reduced heterogeneity in the Dienerian, and (2) and a faunal turnover across the Smithian/Spathian boundary. The elevated extinctions and compositional shifts in the Dienerian and across the Smithian/Spathian boundary are associated with a negative and positive isotope excursion, respectively, which supports the hypothesis that subsequent biotic crises are associated with carbon isotope shifts. The Spathian fauna represents a more advanced ecological state, not recognised in the previous members of the Werfen Formation, with increased habitat differentiation, a shift in the dominant modes of life, appearance of stenohaline taxa and the occupation of the erect and infaunal tiers. In addition to subsequent biotic crises delaying the recovery, therefore, persistent environmental stress limited the ecological complexity of benthic recovery prior to the Spathian.
Full text
Available for:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Human milk is a complex fluid comprised of myriad substances, with one of the most abundant substances being a group of complex carbohydrates referred to as human milk oligosaccharides (HMOs). There ...has been some evidence that HMO profiles differ in populations, but few studies have rigorously explored this variability.
We tested the hypothesis that HMO profiles differ in diverse populations of healthy women. Next, we examined relations between HMO and maternal anthropometric and reproductive indexes and indirectly examined whether differences were likely related to genetic or environmental variations.
In this cross-sectional, observational study, milk was collected from a total of 410 healthy, breastfeeding women in 11 international cohorts and analyzed for HMOs by using high-performance liquid chromatography.
There was an effect of the cohort (
< 0.05) on concentrations of almost all HMOs. For instance, the mean 3-fucosyllactose concentration was >4 times higher in milk collected in Sweden than in milk collected in rural Gambia (mean ± SEM: 473 ± 55 compared with 103 ± 16 nmol/mL, respectively;
< 0.05), and disialyllacto-
-tetraose (DSLNT) concentrations ranged from 216 ± 14 nmol/mL (in Sweden) to 870 ± 68 nmol/mL (in rural Gambia) (
< 0.05). Maternal age, time postpartum, weight, and body mass index were all correlated with several HMOs, and multiple differences in HMOs e.g., lacto-
-neotetrose and DSLNT were shown between ethnically similar (and likely genetically similar) populations who were living in different locations, which suggests that the environment may play a role in regulating the synthesis of HMOs.
The results of this study support our hypothesis that normal HMO concentrations and profiles vary geographically, even in healthy women. Targeted genomic analyses are required to determine whether these differences are due at least in part to genetic variation. A careful examination of sociocultural, behavioral, and environmental factors is needed to determine their roles in this regard. This study was registered at clinicaltrials.gov as NCT02670278.
Full text
Available for:
CMK, GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
We describe and evaluate version 2.1 of the Community Ice Sheet Model (CISM).
CISM is a parallel, 3-D thermomechanical model, written mainly in Fortran,
that solves equations for the momentum balance ...and the thickness and
temperature evolution of ice sheets. CISM's velocity solver incorporates a
hierarchy of Stokes flow approximations, including shallow-shelf,
depth-integrated higher order, and 3-D higher order. CISM also includes a
suite of test cases, links to third-party solver libraries, and
parameterizations of physical processes such as basal sliding, iceberg
calving, and sub-ice-shelf melting. The model has been verified for standard
test problems, including the Ice Sheet Model Intercomparison Project for
Higher-Order Models (ISMIP-HOM) experiments, and has participated in the
initMIP-Greenland initialization experiment. In
multimillennial simulations with modern climate forcing on a 4 km grid, CISM
reaches a steady state that is broadly consistent with observed flow patterns
of the Greenland ice sheet. CISM has been integrated into version 2.0 of the
Community Earth System Model, where it is being used for Greenland
simulations under past, present, and future climates. The code is open-source
with extensive documentation and remains under active development.
Full text
Available for:
IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Accurately simulating gross primary productivity (GPP) in terrestrial ecosystem models is critical because errors in simulated GPP propagate through the model to introduce additional errors in ...simulated biomass and other fluxes. We evaluated simulated, daily average GPP from 26 models against estimated GPP at 39 eddy covariance flux tower sites across the United States and Canada. None of the models in this study match estimated GPP within observed uncertainty. On average, models overestimate GPP in winter, spring, and fall, and underestimate GPP in summer. Models overpredicted GPP under dry conditions and for temperatures below 0°C. Improvements in simulated soil moisture and ecosystem response to drought or humidity stress will improve simulated GPP under dry conditions. Adding a low‐temperature response to shut down GPP for temperatures below 0°C will reduce the positive bias in winter, spring, and fall and improve simulated phenology. The negative bias in summer and poor overall performance resulted from mismatches between simulated and observed light use efficiency (LUE). Improving simulated GPP requires better leaf‐to‐canopy scaling and better values of model parameters that control the maximum potential GPP, such asεmax (LUE), Vcmax (unstressed Rubisco catalytic capacity) or Jmax (the maximum electron transport rate).
Key Points
Gross primary productivity (GPP) from 26 models tested at 39 flux tower sites
Simulated light use efficiency controls model performance
Models overpredict GPP under dry conditions
The evidence base for many aspects of the management of foot ulcers in people with diabetes is weak, and good-quality research, especially relating to studies of direct relevance to routine clinical ...care, is needed. In this paper, we summarise the core details required in the planning and reporting of intervention studies in the prevention and management of diabetic foot ulcers, including studies that focus on off-loading, stimulation of wound healing, peripheral artery disease, and infection. We highlight aspects of trial design, conduct, and reporting that should be taken into account to minimise bias and improve quality. We also provide a 21-point checklist for researchers and for readers who assess the quality of published work.
SignificanceAgricultural methane emissions must be decreased by 11 to 30% of the 2010 level by 2030 and by 24 to 47% by 2050 to meet the 1.5 °C target. We identified three strategies to decrease ...product-based methane emissions while increasing animal productivity and five strategies to decrease absolute methane emissions without reducing animal productivity. Globally, 100% adoption of the most effective product-based and absolute methane emission mitigation strategy can meet the 1.5 °C target by 2030 but not 2050, because mitigation effects are offset by projected increases in methane. On a regional level, Europe but not Africa may be able to meet their contribution to the 1.5 °C target, highlighting the different challenges faced by high- and middle- and low-income countries.
Neonatal gastrointestinal (GI) bacterial community structure may be related to bacterial communities of the mother, including those of her milk. However, very little is known about the diversity in ...and relationships among complex bacterial communities in mother-infant dyads.
Our primary objective was to assess whether microbiomes of milk are associated with those of oral and fecal samples of healthy lactating women and their infants.
Samples were collected 9 times from day 2 to 6 mo postpartum from 21 healthy lactating women and their infants. Milk was collected via complete breast expression, oral samples via swabs, and fecal samples from tissue (mothers) and diapers (infants). Microbiomes were characterized using high-throughput sequencing of the 16S ribosomal RNA (rRNA) gene. Alpha and beta diversity indices were used to compare microbiomes across time and sample types. Membership and composition of microbiomes were analyzed using nonmetric multidimensional scaling and canonical correlation analysis (CCA). The contribution of various bacterial communities of the mother-infant dyad to both milk and infant fecal bacterial communities were estimated using SourceTracker2.
Bacterial community structures were relatively unique to each sample type. The most abundant genus in milk and maternal and infant oral samples was Streptococcus (47.1% ± 2.3%, 53.9% ± 1.3%, and 69.1% ± 1.8%, respectively), whereas Bacteroides were predominant in maternal and infant fecal microbiomes (22.9% ± 1.3% and 21.4% ± 2.4%, respectively). The milk microbiome was more similar to the infant oral microbiome than the infant fecal microbiome. However, CCA suggested strong associations between the complex microbial communities of milk and those of all other sample types collected.
These findings suggest complex microbial interactions between breastfeeding mothers and their infants and support the hypothesis that variation in the milk microbiome may influence the infant GI microbiome.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
PDF
