Stocks of soil organic carbon represent a large component of the carbon cycle that may participate in climate change feedbacks, particularly on decadal and centennial timescales. For Earth system ...models (ESMs), the ability to accurately represent the global distribution of existing soil carbon stocks is a prerequisite for accurately predicting future carbon-climate feedbacks. We compared soil carbon simulations from 11 model centers to empirical data from the Harmonized World Soil Database (HWSD) and the Northern Circumpolar Soil Carbon Database (NCSCD). Model estimates of global soil carbon stocks ranged from 510 to 3040 Pg C, compared to an estimate of 1260 Pg C (with a 95% confidence interval of 890-1660 Pg C) from the HWSD. Model simulations for the high northern latitudes fell between 60 and 820 Pg C, compared to 500 Pg C (with a 95% confidence interval of 380-620 Pg C) for the NCSCD and 290 Pg C for the HWSD. Global soil carbon varied 5.9 fold across models in response to a 2.6-fold variation in global net primary productivity (NPP) and a 3.6-fold variation in global soil carbon turnover times. Model-data agreement was moderate at the biome level (R super(2) values ranged from 0.38 to 0.97 with a mean of 0.75); however, the spatial distribution of soil carbon simulated by the ESMs at the 1 degree scale was not well correlated with the HWSD (Pearson correlation coefficients less than 0.4 and root mean square errors from 9.4 to 20.8 kg C m super(-2)). In northern latitudes where the two data sets overlapped, agreement between the HWSD and the NCSCD was poor (Pearson correlation coefficient 0.33), indicating uncertainty in empirical estimates of soil carbon. We found that a reduced complexity model dependent on NPP and soil temperature explained much of the 1 degree spatial variation in soil carbon within most ESMs (R super(2) values between 0.62 and 0.93 for 9 of 11 model centers). However, the same reduced complexity model only explained 10% of the spatial variation in HWSD soil carbon when driven by observations of NPP and temperature, implying that other drivers or processes may be more important in explaining observed soil carbon distributions. The reduced complexity model also showed that differences in simulated soil carbon across ESMs were driven by differences in simulated NPP and the parameterization of soil heterotrophic respiration (inter-model R super(2) = 0.93), not by structural differences between the models. Overall, our results suggest that despite fair global-scale agreement with observational data and moderate agreement at the biome scale, most ESMs cannot reproduce grid-scale variation in soil carbon and may be missing key processes. Future work should focus on improving the simulation of driving variables for soil carbon stocks and modifying model structures to include additional processes.
The Ni(IMes)2-catalyzed transformation of fluoroarenes into arylboronic acid pinacol esters via C–F bond activation and transmetalation with bis(pinacolato)diboron (B2pin2) is reported. Various ...partially fluorinated arenes with different degrees of fluorination were converted into their corresponding boronate esters.
The majority of the Earth's terrestrial carbon is stored in the soil. If anthropogenic warming stimulates the loss of this carbon to the atmosphere, it could drive further planetary warming. Despite ...evidence that warming enhances carbon fluxes to and from the soil, the net global balance between these responses remains uncertain. Here we present a comprehensive analysis of warming-induced changes in soil carbon stocks by assembling data from 49 field experiments located across North America, Europe and Asia. We find that the effects of warming are contingent on the size of the initial soil carbon stock, with considerable losses occurring in high-latitude areas. By extrapolating this empirical relationship to the global scale, we provide estimates of soil carbon sensitivity to warming that may help to constrain Earth system model projections. Our empirical relationship suggests that global soil carbon stocks in the upper soil horizons will fall by 30 ± 30 petagrams of carbon to 203 ± 161 petagrams of carbon under one degree of warming, depending on the rate at which the effects of warming are realized. Under the conservative assumption that the response of soil carbon to warming occurs within a year, a business-as-usual climate scenario would drive the loss of 55 ± 50 petagrams of carbon from the upper soil horizons by 2050. This value is around 12-17 per cent of the expected anthropogenic emissions over this period. Despite the considerable uncertainty in our estimates, the direction of the global soil carbon response is consistent across all scenarios. This provides strong empirical support for the idea that rising temperatures will stimulate the net loss of soil carbon to the atmosphere, driving a positive land carbon-climate feedback that could accelerate climate change.
Climate change jeopardizes human health, global biodiversity, and sustainability of the biosphere. To make reliable predictions about climate change, scientists use Earth system models (ESMs) that ...integrate physical, chemical, and biological processes occurring on land, the oceans, and the atmosphere. Although critical for catalyzing coupled biogeochemical processes, microorganisms have traditionally been left out of ESMs. Here, we generate a "top 10" list of priorities, opportunities, and challenges for the explicit integration of microorganisms into ESMs. We discuss the need for coarse-graining microbial information into functionally relevant categories, as well as the capacity for microorganisms to rapidly evolve in response to climate-change drivers. Microbiologists are uniquely positioned to collect novel and valuable information necessary for next-generation ESMs, but this requires data harmonization and transdisciplinary collaboration to effectively guide adaptation strategies and mitigation policy.
N‐heterocyclic carbenes (NHCs) and cyclic (alkyl)(amino)carbenes (CAACs) are of great interest, as their electronic and steric properties provide a unique class of ligands and organocatalysts. ...Herein, substitution reactions involving novel carbonyl complexes of rhodium and nickel were studied to provide a deeper understanding of the fundamental electronic factors characterizing CAACmethyl, which were compared with the large array of data available for NHC and sterically more demanding CAAC ligands.
All CAACed up: Substitution reactions involving novel carbonyl complexes of rhodium and nickel were studied to provide a deeper understanding of the fundamental electronic factors characterizing the cyclic (alkyl)(amino)carbine ligand CAACmethyl, namely, the percentage buried volume (%Vbur), the Tolman electronic parameter (TEP), and π‐backbonding (see figure).
To evaluate the maximum-tolerated dose (MTD), safety, and efficacy of elotuzumab in combination with bortezomib in patients with relapsed or relapsed and refractory multiple myeloma (MM).
Elotuzumab ...(2.5, 5.0, 10, or 20 mg/kg intravenously IV) and bortezomib (1.3 mg/m(2) IV) were administered on days 1 and 11 and days 1, 4, 8, and 11, respectively, in 21-day cycles by using a 3 + 3 dose-escalation design. Patients with stable disease or better after four cycles could continue treatment until disease progression or unexpected toxicity. Responses were assessed during each cycle by using European Group for Blood and Marrow Transplantation (EBMT) criteria.
Twenty-eight patients with a median of two prior therapies were enrolled; three patients each received 2.5, 5.0, and 10 mg/kg of elotuzumab and 19 received 20 mg/kg (six during dose escalation and 13 during an expansion phase). No dose-limiting toxicities were observed during cycle 1 of the dose-escalation phase, and the MTD was not reached up to the maximum planned dose of 20 mg/kg. The most frequent grade 3 to 4 adverse events (AEs) were lymphopenia (25%) and fatigue (14%). Two elotuzumab-related serious AEs of chest pain and gastroenteritis occurred in one patient. An objective response (a partial response or better) was observed in 13 (48%) of 27 evaluable patients and in two (67%) of three patients refractory to bortezomib. Median time to progression was 9.46 months.
The combination of elotuzumab and bortezomib was generally well-tolerated and showed encouraging activity in patients with relapsed/refractory MM.
The two halves of the brain are believed to play different roles in emotional processing, but the specific contribution of each hemisphere continues to be debated. The right-hemisphere hypothesis ...suggests that the right cerebrum is dominant for processing all emotions regardless of affective valence, whereas the valence specific hypothesis posits that the left hemisphere is specialized for processing positive affect while the right hemisphere is specialized for negative affect. Here, healthy participants viewed two split visual-field facial affect perception tasks during functional magnetic resonance imaging, one presenting chimeric happy faces (i.e. half happy/half neutral) and the other presenting identical sad chimera (i.e. half sad/half neutral), each masked immediately by a neutral face. Results suggest that the posterior right hemisphere is generically activated during non-conscious emotional face perception regardless of affective valence, although greater activation is produced by negative facial cues. The posterior left hemisphere was generally less activated by emotional faces, but also appeared to recruit bilateral anterior brain regions in a valence-specific manner. Findings suggest simultaneous operation of aspects of both hypotheses, suggesting that these two rival theories may not actually be in opposition, but may instead reflect different facets of a complex distributed emotion processing system.
Background Among populations with established chronic kidney disease (CKD), metabolic acidosis is associated with more rapid progression of kidney disease. The association of serum bicarbonate ...concentrations with early declines in kidney function is less clear. Study Design Retrospective cohort study. Setting & Participants 5,810 participants in the Multi-Ethnic Study of Atherosclerosis (MESA) with a baseline estimated glomerular filtration rate (eGFR) > 60 mL/min/1.73 m2 using the CKD-EPI (CKD Epidemiology Collaboration) creatinine−cystatin C equation. Predictors Serum bicarbonate concentrations. Outcomes Rapid kidney function decline (eGFR decline > 5% per year) and incident reduced eGFR (eGFR < 60 mL/min/1.73 m2 with minimum rate of eGFR loss of 1 mL/min/1.73 m2 per year). Results Average bicarbonate concentration was 23.2 ± 1.8 mEq/L. 1,730 (33%) participants had rapid kidney function decline, and 487 had incident reduced eGFR during follow-up. Each 1-SD lower baseline bicarbonate concentration was associated with 12% higher adjusted odds of rapid kidney function decline (95% CI, 6%-20%) and higher risk of incident reduced eGFR (adjusted incidence rate ratio, 1.11; 95% CI, 1.03-1.20) in models adjusting for demographics, baseline eGFR, albuminuria, and CKD risk factors. The OR for the associations of bicarbonate level < 21 mEq/L relative to 23-24 mEq/L was 1.35 (95% CI, 1.05-1.73) for rapid kidney function decline, and the incidence rate ratio was 1.16 (95% CI, 0.83-1.62) for incident reduced eGFR. Limitations Cause of metabolic acidosis cannot be determined in this study. Conclusions Lower serum bicarbonate concentrations are associated independently with rapid kidney function decline independent of eGFR or albuminuria in community-living persons with baseline eGFR > 60 mL/min/1.73 m2 . If confirmed, our findings suggest that metabolic acidosis may indicate either early kidney disease that is not captured by eGFR or albuminuria or may have a causal role in the development of eGFR < 60 mL/min/1.73 m2.
There has been growing interest in the mechanical behaviour of skin due to the rapid development of microneedle devices for drug delivery applications into skin. However, most in vitro ...experimentation studies that are used to evaluate microneedle performance do not consider the biomechanical properties of skin or that of the subcutaneous layers. In this study, a representative experimental model of skin was developed which was comprised of subcutaneous and muscle mimics. Neonatal porcine skin from the abdominal and back regions was used, with gelatine gels of differing water content (67, 80, 88 and 96%) to represent the subcutaneous tissue, and a type of ballistic gelatine, Perma-Gel®, as a muscle mimic. Dynamic nanoindentation was used to characterize the mechanical properties of each of these layers. A custom-developed impact test rig was used to apply dense polymethylmethacrylate (PMMA) microneedles to the skin models in a controlled and repeatable way with quantification of the insertion force and velocity. Image analysis methods were used to measure penetration depth and area of the breach caused by microneedle penetration following staining and optical imaging. The nanoindentation tests demonstrated that the tissue mimics matched expected values for subcutaneous and muscle tissue, and that the compliance of the subcutaneous mimics increased linearly with water content. The abdominal skin was thinner and less stiff as compared to back skin. The maximum force decreased with gel water content in the abdominal skin but not in the back skin. Overall, larger and deeper perforations were found in the skin models with increasing water content. These data demonstrate the importance of subcutaneous tissue on microneedle performance and the need for representative skin models in microneedle technology development.
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The efficacy of repetitive transcranial magnetic stimulation (rTMS) for depression may vary depending on the subregion stimulated within the dorsolateral prefrontal cortex (DLPFC). Clinical TMS ...typically uses scalp-based landmarks for DLPFC targeting, rather than individualized MRI guidance.
In rTMS patients, determine the brain systems targeted by multiple DLPFC stimulation rules by computing several surrogate measures: underlying brain targets labeled with connectivity-based atlases, subgenual cingulate anticorrelation strength, and functionally connected networks.
Forty-nine patients in a randomized controlled trial of rTMS therapy for treatment resistant major depression underwent structural and functional MRI. DLPFC rules were applied virtually using MR-image guidance. Underlying cortical regions were labeled, and connectivity with the subgenual cingulate and whole-brain computed.
Scalp-targeting rules applied post hoc to these MRIs that adjusted for head size, including Beam F3, were comparably precise, successful in directly targeting classical DLPFC and frontal networks, and anticorrelated with the subgenual cingulate. In contrast, all rules involving fixed distances introduced variability in regions and networks targeted. The 5 cm rule targeted a transitional DLPFC region with a different connectivity profile from the adjusted rules. Seed-based connectivity analyses identified multiple regions, such as posterior cingulate and inferior parietal lobe, that warrant further study in order to understand their potential contribution to clinical response.
EEG-based rules consistently targeted DLPFC brain regions with resting-state fMRI features known to be associated with depression response. These results provide a bridge from lab to clinic by enabling clinicians to relate scalp-targeting rules to functionally connected brain systems.
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•Rules for dorsolateral prefrontal cortex targeting (DLPFC) were virtually traced.•Cortical locations and networks were compared to connectivity-based atlases.•Fixed distance rules were more variable in regions and networks targeted.•EEG-based targets consistently targeted DLPFC regions.•EEG-based targets had fMRI features associated with depression response.
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