Tree-ring records can provide valuable information to advance our understanding of contemporary terrestrial carbon cycling and to reconstruct key metrics in the decades preceding monitoring data. The ...growing use of tree rings in carbon-cycle research is being facilitated by increasing recognition of reciprocal benefits among research communities. Yet, basic questions persist regarding what tree rings represent at the ecosystem level, how to optimally integrate them with other data streams, and what related challenges need to be overcome. It is also apparent that considerable unexplored potential exists for tree rings to refine assessments of terrestrial carbon cycling across a range of temporal and spatial domains. Here, we summarize recent advances and highlight promising paths of investigation with respect to (1) growth phenology, (2) forest productivity trends and variability, (3) CO₂ fertilization and water-use efficiency, (4) forest disturbances, and (5) comparisons between observational and computational forest productivity estimates. We encourage the integration of tree-ring data: with eddy-covariance measurements to investigate carbon allocation patterns and water-use efficiency; with remotely sensed observations to distinguish the timing of cambial growth and leaf phenology; and with forest inventories to develop continuous, annually-resolved and long-term carbon budgets. In addition, we note the potential of tree-ring records and derivatives thereof to help evaluate the performance of earth system models regarding the simulated magnitude and dynamics of forest carbon uptake, and inform these models about growth responses to (non-)climatic drivers. Such efforts are expected to improve our understanding of forest carbon cycling and place current developments into a long-term perspective.
The UK Medical Research Council’s widely used guidance for developing and evaluating complex interventions has been replaced by a new framework, commissioned jointly by the Medical Research Council ...and the National Institute for Health Research, which takes account of recent developments in theory and methods and the need to maximise the efficiency, use, and impact of research.
As global temperatures increase, the potential for longer growing seasons to enhance the terrestrial carbon sink has been proposed as a mechanism to reduce the rate of further warming. At the Niwot ...Ridge AmeriFlux site, a subalpine forest in the Colorado Rocky Mountains, we used a 9-year record (1999-2007) of continuous eddy flux observations to show that longer growing season length (GSL) actually resulted in less annual CO₂ uptake. Years with a longer GSL were correlated with a shallower snow pack, as measured using snow water equivalent (SWE). Furthermore, years with a lower SWE correlated with an earlier start of spring. For three years, 2005, 2006, and 2007, we used observations of stable hydrogen isotopes (δD) of snow vs. rain, and extracted xylem water from the three dominant tree species, lodgepole pine, Engelmann spruce, and subalpine fir, to show that the trees relied heavily on snow melt water even late into the growing season. By mid-August, 57% to 68% of xylem water reflected the isotopic signature of snow melt. By coupling the isotopic water measurements with an ecosystem model, SIPNET, we found that annual forest carbon uptake was highly dependent on snow water, which decreases in abundance during years with longer growing seasons. Once again, for the 3 years 2005, 2006, and 2007, annual gross primary productivity, which was derived as an optimized parameter from the SIPNET model was estimated to be 67% 77%, and 71% dependent on snow melt water, respectively. Past studies have shown that the mean winter snow pack in mountain ecosystems of the Western US has been declining for decades and is correlated with positive winter temperature anomalies. Since climate change models predict continuation of winter warming and reduced snow in mountains of the Western US, the strength of the forest carbon sink is likely to decline further.
The mitochondrial protein MAVS (also known as IPS-1, VISA, and CARDIF) interacts with RIG-I-like receptors (RLRs) to induce type I interferon (IFN-I). NLRX1 is a mitochondrial nucleotide-binding, ...leucine-rich repeats (NLR)-containing protein that attenuates MAVS-RLR signaling. Using Nlrx1−/− cells, we confirmed that NLRX1 attenuated IFN-I production, but additionally promoted autophagy during viral infection. This dual function of NLRX1 paralleled the previously described functions of the autophagy-related proteins Atg5-Atg12, but NLRX1 did not associate with Atg5-Atg12. High-throughput quantitative mass spectrometry and endogenous protein-protein interaction revealed an NLRX1-interacting partner, mitochondrial Tu translation elongation factor (TUFM). TUFM interacted with Atg5-Atg12 and Atg16L1 and has similar functions as NLRX1 by inhibiting RLR-induced IFN-I but promoting autophagy. In the absence of NLRX1, increased IFN-I and decreased autophagy provide an advantage for host defense against vesicular stomatitis virus. This study establishes a link between an NLR protein and the viral-induced autophagic machinery via an intermediary partner, TUFM.
► NLRX1 suppresses VSV-mediated type 1 IFN production but enhances autophagy ► TUFM works with NLRX1 to inhibit RLR-induced type 1 IFN signaling ► TUFM enhances autophagy and interacts with Atg5-Atg12 and Atg16L1 ► NLRX1-mediated autophagy and IFN-I inhibition enhance VSV replication
Earth's future carbon balance and regional carbon exchange dynamics are inextricably linked to plant photosynthesis. Spectral vegetation indices are widely used as proxies for vegetation greenness ...and to estimate state variables such as vegetation cover and leaf area index. However, the capacity of green leaves to take up carbon can change throughout the season. We quantify photosynthetic capacity as the maximum rate of RuBP carboxylation (Vcmax) and regeneration (Jmax). Vcmax and Jmax vary within-season due to interactions between ontogenetic processes and meteorological variables. Remote sensing-based estimation of Vcmax and Jmax using leaf reflectance spectra is promising, but temporal variation in relationships between these key determinants of photosynthetic capacity, leaf reflectance spectra, and the models that link these variables has not been evaluated. To address this issue, we studied hybrid poplar (Populus spp.) during a 7-week mid-summer period to quantify seasonally-dynamic relationships between Vcmax, Jmax, and leaf spectra. We compared in situ estimates of Vcmax and Jmax from gas exchange measurements to estimates of Vcmax and Jmax derived from partial least squares regression (PLSR) and fresh-leaf reflectance spectroscopy. PLSR models were robust despite dynamic temporal variation in Vcmax and Jmax throughout the study period. Within-population variation in plant stress modestly reduced PLSR model predictive capacity. Hyperspectral vegetation indices were well-correlated to Vcmax and Jmax, including the widely-used Normalized Difference Vegetation Index. Our results show that hyperspectral estimation of plant physiological traits using PLSR may be robust to temporal variation. Additionally, hyperspectral vegetation indices may be sufficient to detect temporal changes in photosynthetic capacity in contexts similar to those studied here. Overall, our results highlight the potential for hyperspectral remote sensing to estimate determinants of photosynthetic capacity during periods with dynamic temporal variations related to seasonality and plant stress, thereby improving estimates of plant productivity and characterization of the associated carbon budget.
The Medical Research Council published the second edition of its framework in 2006 on developing and evaluating complex interventions. Since then, there have been considerable developments in the ...field of complex intervention research. The objective of this project was to update the framework in the light of these developments. The framework aims to help research teams prioritise research questions and design, and conduct research with an appropriate choice of methods, rather than to provide detailed guidance on the use of specific methods.
There were four stages to the update: (1) gap analysis to identify developments in the methods and practice since the previous framework was published; (2) an expert workshop of 36 participants to discuss the topics identified in the gap analysis; (3) an open consultation process to seek comments on a first draft of the new framework; and (4) findings from the previous stages were used to redraft the framework, and final expert review was obtained. The process was overseen by a Scientific Advisory Group representing the range of relevant National Institute for Health Research and Medical Research Council research investments.
Key changes to the previous framework include (1) an updated definition of complex interventions, highlighting the dynamic relationship between the intervention and its context; (2) an emphasis on the use of diverse research perspectives: efficacy, effectiveness, theory-based and systems perspectives; (3) a focus on the usefulness of evidence as the basis for determining research perspective and questions; (4) an increased focus on interventions developed outside research teams, for example changes in policy or health services delivery; and (5) the identification of six 'core elements' that should guide all phases of complex intervention research: consider context; develop, refine and test programme theory; engage stakeholders; identify key uncertainties; refine the intervention; and economic considerations. We divide the research process into four phases: development, feasibility, evaluation and implementation. For each phase we provide a concise summary of recent developments, key points to address and signposts to further reading. We also present case studies to illustrate the points being made throughout.
The framework aims to help research teams prioritise research questions and design and conduct research with an appropriate choice of methods, rather than to provide detailed guidance on the use of specific methods. In many of the areas of innovation that we highlight, such as the use of systems approaches, there are still only a few practical examples. We refer to more specific and detailed guidance where available and note where promising approaches require further development.
This new framework incorporates developments in complex intervention research published since the previous edition was written in 2006. As well as taking account of established practice and recent refinements, we draw attention to new approaches and place greater emphasis on economic considerations in complex intervention research. We have introduced a new emphasis on the importance of context and the value of understanding interventions as 'events in systems' that produce effects through interactions with features of the contexts in which they are implemented. The framework adopts a pluralist approach, encouraging researchers and research funders to adopt diverse research perspectives and to select research questions and methods pragmatically, with the aim of providing evidence that is useful to decision-makers.
We call for further work to develop relevant methods and provide examples in practice. The use of this framework should be monitored and the move should be made to a more fluid resource in the future, for example a web-based format that can be frequently updated to incorporate new material and links to emerging resources.
This project was jointly funded by the Medical Research Council (MRC) and the National Institute for Health Research (Department of Health and Social Care 73514).
The proportion of births via cesarean section (CS) varies worldwide and in many countries exceeds WHO-recommended rates. Long-term health outcomes for children born by CS are poorly understood, but ...limited data suggest that CS is associated with increased infection-related hospitalisation. We investigated the relationship between mode of birth and childhood infection-related hospitalisation in high-income countries with varying CS rates.
We conducted a multicountry population-based cohort study of all recorded singleton live births from January 1, 1996 to December 31, 2015 using record-linked birth and hospitalisation data from Denmark, Scotland, England, and Australia (New South Wales and Western Australia). Birth years within the date range varied by site, but data were available from at least 2001 to 2010 for each site. Mode of birth was categorised as vaginal or CS (emergency/elective). Infection-related hospitalisations (overall and by clinical type) occurring after the birth-related discharge date were identified in children until 5 years of age by primary/secondary International Classification of Diseases, 10th Revision (ICD-10) diagnosis codes. Analysis used Cox regression models, adjusting for maternal factors, birth parameters, and socioeconomic status, with results pooled using meta-analysis. In total, 7,174,787 live recorded births were included. Of these, 1,681,966 (23%, range by jurisdiction 17%-29%) were by CS, of which 727,755 (43%, range 38%-57%) were elective. A total of 1,502,537 offspring (21%) had at least 1 infection-related hospitalisation. Compared to vaginally born children, risk of infection was greater among CS-born children (hazard ratio (HR) from random effects model, HR 1.10, 95% confidence interval (CI) 1.09-1.12, p < 0.001). The risk was higher following both elective (HR 1.13, 95% CI 1.12-1.13, p < 0.001) and emergency CS (HR 1.09, 95% CI 1.06-1.12, p < 0.001). Increased risks persisted to 5 years and were highest for respiratory, gastrointestinal, and viral infections. Findings were comparable in prespecified subanalyses of children born to mothers at low obstetric risk and unchanged in sensitivity analyses. Limitations include site-specific and longitudinal variations in clinical practice and in the definition and availability of some data. Data on postnatal factors were not available.
In this study, we observed a consistent association between birth by CS and infection-related hospitalisation in early childhood. Notwithstanding the limitations of observational data, the associations may reflect differences in early microbial exposure by mode of birth, which should be investigated by mechanistic studies. If our findings are confirmed, they could inform efforts to reduce elective CS rates that are not clinically indicated.
Platinum-based chemotherapy is the standard of care for platinum-sensitive ovarian cancer, but complications from repeated platinum therapy occur. We assessed the activity of two all-oral nonplatinum ...alternatives, olaparib or olaparib/cediranib, versus platinum-based chemotherapy.
NRG-GY004 is an open-label, randomized, phase III trial conducted in the United States and Canada. Eligible patients had high-grade serous or endometrioid platinum-sensitive ovarian cancer. Patients were randomly assigned 1:1:1 to platinum-based chemotherapy, olaparib, or olaparib/cediranib. The primary end point was progression-free survival (PFS) in the intention-to-treat population. Secondary end points included activity within germline
-mutated or wild-type subgroups and patient-reported outcomes (PROs).
Between February 04, 2016, and November 13, 2017, 565 eligible patients were randomly assigned. Median PFS was 10.3 (95% CI, 8.7 to 11.2), 8.2 (95% CI, 6.6 to 8.7), and 10.4 (95% CI, 8.5 to 12.5) months with chemotherapy, olaparib, and olaparib/cediranib, respectively. Olaparib/cediranib did not improve PFS versus chemotherapy (hazard ratio HR 0.86; 95% CI, 0.66 to 1.10;
= .077). In women with germline
mutation, the PFS HR versus chemotherapy was 0.55 (95% CI, 0.32 to 0.94) for olaparib/cediranib and 0.63 (95% CI, 0.37 to 1.07) for olaparib. In women without a germline
mutation, the PFS HR versus chemotherapy was 0.97 (95% CI, 0.73 to 1.30) for olaparib/cediranib and 1.41 (95% CI, 1.07 to 1.86) for olaparib. Hematologic adverse events occurred more commonly with chemotherapy; however, nonhematologic adverse events were higher with olaparib/cediranib. In 489 patients evaluable for PROs, patients receiving olaparib/cediranib scored on average 1.1 points worse on the NFOSI-DRS-P subscale (97.5% CI, -2.0 to -0.2,
= .0063) versus chemotherapy; no difference between olaparib and chemotherapy was observed.
Combination olaparib/cediranib did not improve PFS compared with chemotherapy and resulted in reduced PROs. Notably, in patients with a germline
mutation, both olaparib and olaparib/cediranib had significant clinical activity.
Summary
Atmospheric carbon dioxide concentration (CO2) is increasing, which increases leaf‐scale photosynthesis and intrinsic water‐use efficiency. These direct responses have the potential to ...increase plant growth, vegetation biomass, and soil organic matter; transferring carbon from the atmosphere into terrestrial ecosystems (a carbon sink). A substantial global terrestrial carbon sink would slow the rate of CO2 increase and thus climate change. However, ecosystem CO2 responses are complex or confounded by concurrent changes in multiple agents of global change and evidence for a CO2‐driven terrestrial carbon sink can appear contradictory. Here we synthesize theory and broad, multidisciplinary evidence for the effects of increasing CO2 (iCO2) on the global terrestrial carbon sink. Evidence suggests a substantial increase in global photosynthesis since pre‐industrial times. Established theory, supported by experiments, indicates that iCO2 is likely responsible for about half of the increase. Global carbon budgeting, atmospheric data, and forest inventories indicate a historical carbon sink, and these apparent iCO2 responses are high in comparison to experiments and predictions from theory. Plant mortality and soil carbon iCO2 responses are highly uncertain. In conclusion, a range of evidence supports a positive terrestrial carbon sink in response to iCO2, albeit with uncertain magnitude and strong suggestion of a role for additional agents of global change.
See also the Commentary on this article by Way et al., 229: 2383–2385.
Amid a worldwide increase in tree mortality, mountain pine beetles (Dendroctonus ponderosae Hopkins) have led to the death of billions of trees from Mexico to Alaska since 2000. This is predicted to ...have important carbon, water and energy balance feedbacks on the Earth system. Counter to current projections, we show that on a decadal scale, tree mortality causes no increase in ecosystem respiration from scales of several square metres up to an 84 km² valley. Rather, we found comparable declines in both gross primary productivity and respiration suggesting little change in net flux, with a transitory recovery of respiration 6–7 years after mortality associated with increased incorporation of leaf litter C into soil organic matter, followed by further decline in years 8–10. The mechanism of the impact of tree mortality caused by these biotic disturbances is consistent with reduced input rather than increased output of carbon.
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