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Purpose. The Center for International Rehabilitation (CIR) developed a wheelchair provision strategy that combines central fabrication with regional distribution and local service provision by trained practitioners. A field study was initiated in Kabul, Afghanistan to evaluate this plan. Method. The CIR-Whirlwind Wheelchair (study wheelchair) is an adult size, manual wheelchair designed to be adjustable to accommodate the individual user and durable to withstand rugged terrain. Manufactured in India, the study wheelchairs, with seat cushions, were packaged as kits and shipped to Afghanistan. Local practitioners in Kabul were trained on user assessment, fitting and training, and wheelchair assembly, maintenance and repair. One hundred subjects with previous experience of independently propelling a manual wheelchair participated in the study. This 4-month study entailed three subject visits for initial wheelchair fitting and training and then follow-up at 3 and 10 weeks. Subject training included wheelchair use and maintenance, and wheelchair skill activities. Results. The study wheelchair was rated favorably by the subjects in all of five categories. Adjustments made to the wheelchairs during the study were typical for maintaining or improving the fit or function of a manual wheelchair. With the exception of brake handles, the need to repair or replace components on the wheelchairs was minimal. The subjects' proficiency at wheelchair skill activities increased throughout the study. Conclusions. Data collected indicates that the study wheelchair performed very well. The data also served to identify those aspects of the wheelchair that may require additional development and testing prior to further production. To gain additional information on long term wheelchair use and performance, the CIR plans to extend this study by interviewing the same subjects at nine and fifteen months from the date they originally received the study wheelchair. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The aim of this study was to assess the experiences and outcomes of patients receiving intratympanic gentamicin treatment for Ménière's disease in Norfolk, UK. DESIGN: This study was based on a retrospective questionnaire survey and a review of patients' medical records. SETTING: Two district hospitals. PARTICIPANTS: All 29 patients treated between 1999 and 2001, with a minimum follow up of two years post-treatment, were included in the study. Twenty-three patients completed the questionnaires (79 per cent response rate). MAIN OUTCOME MEASURES: Glasgow benefit inventory (GBI) and vertigo symptom scale (VSS) scores, plus change in hearing thresholds. RESULTS: The mean GBI total score was +36, indicating substantial improvement in patients' overall quality of life following gentamicin treatment. The VSS scores demonstrated low levels of vertigo or unsteadiness in treated patients. Three patients suffered deterioration in their hearing thresholds following a single injection of gentamicin. However, 96 per cent of responders stated that they would be willing to have such treatment again, if necessary. CONCLUSION: Intratympanic gentamicin treatment ought to be offered to Ménière's patients suffering from disabling vertigo, with the proviso that they be made aware of the possibility of hearing deterioration. [ABSTRACT FROM AUTHOR]

In the semi-arid grasslands of the southwest United States, annual precipitation is divided between warm-season (July-September) convective precipitation and cool-season (December-March) frontal storms. While evidence suggests shifts in precipitation seasonal distribution, there is a poor understanding of the ecosystem carbon flux responses to cool-season precipitation and the potential legacy effects on subsequent warm-season carbon fluxes. Results from a two-year experiment with three cool-season precipitation treatments (dry, received 5th percentile cool-season total precipitation; normal, 50th; wet, 95th) and constant warm-season precipitation illustrate the direct and legacy effects on carbon fluxes, but in opposing ways. In wet cool-season plots, gross primary productivity (GPP) and ecosystem respiration (ER) were 103% and 127% higher than in normal cool-season plots. In dry cool-season plots, GPP and ER were 47% and 85% lower compared to normal cool-season plots. Unexpectedly, we found a positive legacy effect of the dry cool-season treatment on warm-season carbon flux, resulting in a significant increase in both GPP and ER in the subsequent warm season, compared to normal cool-season plots. Our results reveal positive legacy effects of cool-season drought on warm-season carbon fluxes and highlight the importance of the relatively under-studied cool-growing season and its direct/indirect impact on the ecosystem carbon budget., (© 2024 John Wiley & Sons Ltd.)

Some plants exhibit dynamic hydraulic regulation, in which the strictness of hydraulic regulation (i.e. iso/anisohydry) changes in response to environmental conditions. However, the environmental controls over iso/anisohydry and the implications of flexible hydraulic regulation for plant productivity remain unknown. In Juniperus osteosperma, a drought-resistant dryland conifer, we collected a 5-month growing season time series of in situ, high temporal-resolution plant water potential ( Ψ ) and stand gross primary productivity (GPP). We quantified the stringency of hydraulic regulation associated with environmental covariates and evaluated how predawn water potential contributes to empirically predicting carbon uptake. Juniperus osteosperma showed less stringent hydraulic regulation (more anisohydric) after monsoon precipitation pulses, when soil moisture and atmospheric demand were high, and corresponded with GPP pulses. Predawn water potential matched the timing of GPP fluxes and improved estimates of GPP more strongly than soil and/or atmospheric moisture, notably resolving GPP underestimation before vegetation green-up. Flexible hydraulic regulation appears to allow J. osteosperma to prolong soil water extraction and, therefore, the period of high carbon uptake following monsoon precipitation pulses. Water potential and its dynamic regulation may account for why process-based and empirical models commonly underestimate the magnitude and temporal variability of dryland GPP., (© 2024 The Authors. New Phytologist © 2024 New Phytologist Foundation.)

Extended growing season lengths under climatic warming suggest increased time for plant growth. However, research has focused on climatic impacts to the timing or duration of distinct phenological events. Comparatively little is known about impacts to the relative time allocation to distinct phenological events, for example, the proportion of time dedicated to leaf growth versus senescence. We use multiple satellite and ground-based observations to show that, despite recent climate change during 2001 to 2020, the ratio of time allocated to vegetation green-up over senescence has remained stable [1.27 (± 0.92)] across more than 83% of northern ecosystems. This stability is independent of changes in growing season lengths and is caused by widespread positive relationships among vegetation phenological events; longer vegetation green-up results in longer vegetation senescence. These empirical observations were also partly reproduced by 13 dynamic global vegetation models. Our work demonstrates an intrinsic biotic control to vegetation phenology that could explain the timing of vegetation senescence under climate change.

During extensive periods without rain, known as dry-downs, decreasing soil moisture (SM) induces plant water stress at the point when it limits evapotranspiration, defining a critical SM threshold (θ crit ). Better quantification of θ crit is needed for improving future projections of climate and water resources, food production, and ecosystem vulnerability. Here, we combine systematic satellite observations of the diurnal amplitude of land surface temperature (dLST) and SM during dry-downs, corroborated by in-situ data from flux towers, to generate the observation-based global map of θ crit . We find an average global θ crit of 0.19 m 3 /m 3 , varying from 0.12 m 3 /m 3 in arid ecosystems to 0.26 m 3 /m 3 in humid ecosystems. θ crit simulated by Earth System Models is overestimated in dry areas and underestimated in wet areas. The global observed pattern of θ crit reflects plant adaptation to soil available water and atmospheric demand. Using explainable machine learning, we show that aridity index, leaf area and soil texture are the most influential drivers. Moreover, we show that the annual fraction of days with water stress, when SM stays below θ crit , has increased in the past four decades. Our results have important implications for understanding the inception of water stress in models and identifying SM tipping points., (© 2024. The Author(s).)

A novel salt-tolerant cation-exchange membrane, prepared with a multimodal ligand, 2-mercaptopyridine-3-carboxylic acid (MMC-MPCA), was examined for its purification properties in a bind-and-elute mode from the high conductivity supernatant of a Pichia pastoris fermentation producing and secreting a single-chain variable fragment (scFv). If successful, this approach would eliminate the need for a buffer exchange prior to product capture by ion-exchange. Two fed-batch fermentations of Pichia pastoris resulted in fermentation supernatants reaching an scFv titer of 395.0 mg/L and 555.7 mg/L, both with a purity of approximately 83 %. The MMC-MPCA membrane performance was characterized in terms of pH, residence time (RT), scFv load, and scFv concentration to identify the resulting dynamic binding capacity (DBC), yield, and purity achieved under optimal conditions. The MMC-MPCA membrane exhibited the highest DBC of 39.06 mg/mL at pH 5.5, with a residence time of 1 min, while reducing the pH below 5.0 resulted in a significant decrease of the DBC to around 2.5 mg/mL. With almost no diffusional limitations, reducing the RT from 2 to 0.2 min did not negatively impact the DBC of the MMC-MPCA membrane, resulting in a significant improvement in productivity of up to 180 mg/mL/min at 0.2 min RT. Membrane fouling was observed when reusing the membranes at 0.2 and 0.5 min RT, likely due to the enhanced adsorption of impurities on the membrane. Changing the amount of scFv loaded onto the membrane column did not show any changes in yield, instead a 10-20 % loss of scFv was observed, which suggested that some of the produced scFv were fragmented or had aggregated. When performing the purification under the optimized conditions, the resulting purity of the product improved from 83 % to approximately 92-95 %., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Adeno-associated viruses (AAVs) have acquired a central role in modern medicine as delivery agents for gene therapies targeting rare diseases. While new AAVs with improved tissue targeting, potency, and safety are being introduced, their biomanufacturing technology is lagging. In particular, the AAV purification pipeline hinges on protein ligands for the affinity-based capture step. While featuring excellent AAV binding capacity and selectivity, these ligands require strong acid (pH <3) elution conditions, which can compromise the product's activity and stability. Additionally, their high cost and limited lifetime has a significant impact on the price tag of AAV-based therapies. Seeking to introduce a more robust and affordable affinity technology, this study introduces a cohort of peptide ligands that (i) mimic the biorecognition activity of the AAV receptor (AAVR) and anti-AAV antibody A20, (ii) enable product elution under near-physiological conditions (pH 6.0), and (iii) grant extended reusability by withstanding multiple regenerations. A20-mimetic CYIHFSGYTNYNPSLKSC and AAVR-mimetic CVIDGSQSTDDDKIC demonstrated excellent capture of serotypes belonging to distinct clones/clades - namely, AAV1, AAV2, AAV5, AAV6, AAV8, and AAV9. This corroborates the in silico models documenting their ability to target regions of the viral capsid that are conserved across all serotypes. CVIDGSQSTDDDKIC-Toyopearl resin features binding capacity (≈10 14 vp mL -1 ) and product yields (≈60%-80%) on par with commercial adsorbents, and purifies AAV2 from HEK293 and Sf9 cell lysates with high recovery (up to 78%), reduction of host cell proteins (up to 700-fold), and high transduction activity (up to 65%)., (© 2023 The Authors. Biotechnology Journal published by Wiley-VCH GmbH.)

The importance of adequate sleep for good health cannot be overstated. Excessive light exposure at night disrupts sleep, therefore, it is important to find more healthy drinks that can promote sleep under sleep-disturbed conditions. The present study investigated the use of A. sinensis (Lour.) Spreng leaf tea, a natural product, to reduce the adverse effects of nighttime light on sleep. Here, Aquilaria sinensis leaf tea at 1.0 and 1.5 g/L significantly increased sleep time in zebrafish larvae (5-7 dpf) with light-induced sleep disturbance. Transcriptome sequencing and qRT-PCR analysis revealed a decrease in the immune-related genes, such as nfkbiab , tnfrsf1a , nfkbiaa , il1b , traf3 , and cd40 in the 1.5 g/L Aquilaria sinensis leaf tea treatment group. In addition, a gene associated with sleep, bhlhe41 , showed a significant decrease. Moreover, Aquilaria sinensis leaf tea suppressed the increase in neutrophils of Tg(mpo:GFP) zebrafish under sleep-disturbed conditions, indicating its ability to improve the immune response. Widely targeted metabolic profiling of the Aquilaria sinensis tea using ultra-performance liquid chromatography coupled with electrospray tandem mass spectrometry (UPLC-ESI-MS/MS) revealed flavonoids as the predominant component. Network pharmacological and molecular docking analyses suggested that the flavonoids quercetin and eupatilin in Aquilaria sinensis leaf tea improved the sleep of zebrafish by interacting with il1b and cd40 genes under light exposure at night. Therefore, the results of the study provide evidence supporting the notion that Aquilaria sinensis leaf tea has a positive impact on sleep patterns in zebrafish subjected to disrupted sleep due to nighttime light exposure. This suggests that the utilization of Aquilaria sinensis leaf tea as a potential therapeutic intervention for sleep disturbances induced by light may yield advantageous outcomes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Tan, Wang, Smith, Sun, Long, Mao, Huang, Huang and Zhong.)

To investigate the presence of hop stunt viroid (HSVd) in mulberry ( Morus alba ) plants in China, HSVd was detected by reverse transcription (RT)-PCR using dsRNAs extracted from symptomatic or asymptomatic mulberry leaf samples collected from a mulberry field located in Zhenjiang, China, as a template and the primer pairs for HSVd detection. The primer pairs were designed based on the conserved sequence of 25 HSVd variants deposited in the GenBank database. Four out of a total of 53 samples were HSVd-positive, confirming that HSVd is present in mulberry plants in China. The consensus full-length nucleotide (nt) sequence of two HSVd variants determined by sequencing the HSVd variants in these four HSVd-positive samples consisted of 296 nt and shared the highest nt identity of 96.8% with that from plum in Turkey but relatively low identity with those from mulberry in Iran (87.3 to 90.8%). Phylogenetic analysis showed that these HSVd variants clustered together with those of the HSVd-hop group. Analysis of the infectivity and pathogenicity to hosts by the constructed Agrobacterium -mediated dimeric head-to-tail HSVd cDNA infectious clones demonstrated that one of the HSVd variants identified in this study infects the natural host, mulberry plants, and also infects experimental plants, cucumber, and tomato. It probably induces stunting symptoms in HSVd-infected tomatoes but does not induce symptoms on mulberry leaves or in cucumbers. Although HSVd infecting mulberry has been found in Iran, Italy, and Lebanon, this is the first study to report this viroid in naturally infected mulberry plants in China., Competing Interests: The author(s) declare no conflict of interest.

Drylands of the southwestern United States are rapidly warming, and rainfall is becoming less frequent and more intense, with major yet poorly understood implications for ecosystem structure and function. Thermography-based estimates of plant temperature can be integrated with air temperature to infer changes in plant physiology and response to climate change. However, very few studies have evaluated plant temperature dynamics at high spatiotemporal resolution in rainfall pulse-driven dryland ecosystems. We address this gap by incorporating high-frequency thermal imaging into a field-based precipitation manipulation experiment in a semi-arid grassland to investigate the impacts of rainfall temporal repackaging. All other factors held constant, we found that fewer/larger precipitation events led to cooler plant temperatures (1.4°C) compared to that of many/smaller precipitation events. Perennials, in particular, were 2.5°C cooler than annuals under the fewest/largest treatment. We show these patterns were driven by: increased and consistent soil moisture availability in the deeper soil layers in the fewest/largest treatment; and deeper roots of perennials providing access to deeper plant available water. Our findings highlight the potential for high spatiotemporal resolution thermography to quantify the differential sensitivity of plant functional groups to soil water availability. Detecting these sensitivities is vital to understanding the ecohydrological implications of hydroclimate change., (© 2023 The Authors New Phytologist © 2023 New Phytologist Foundation.)

Monitoring and estimating drought impact on plant physiological processes over large regions remains a major challenge for remote sensing and land surface modeling, with important implications for understanding plant mortality mechanisms and predicting the climate change impact on terrestrial carbon and water cycles. The Orbiting Carbon Observatory 3 (OCO-3), with its unique diurnal observing capability, offers a new opportunity to track drought stress on plant physiology. Using radiative transfer and machine learning modeling, we derive a metric of afternoon photosynthetic depression from OCO-3 solar-induced chlorophyll fluorescence (SIF) as an indicator of plant physiological drought stress. This unique diurnal signal enables a spatially explicit mapping of plants' physiological response to drought. Using OCO-3 observations, we detect a widespread increasing drought stress during the 2020 southwest US drought. Although the physiological drought stress is largely related to the vapor pressure deficit (VPD), our results suggest that plants' sensitivity to VPD increases as the drought intensifies and VPD sensitivity develops differently for shrublands and grasslands. Our findings highlight the potential of using diurnal satellite SIF observations to advance the mechanistic understanding of drought impact on terrestrial ecosystems and to improve land surface modeling., (© 2023 John Wiley & Sons Ltd.)

The whole genome sequence of mulberry crinivirus (MuCV), a novel member of the genus Crinivirus (family Closteroviridae) identified in mulberry (Morus alba L), was determined. The virus possesses a bipartite genome. RNA1 contains 8571 nucleotides (nt) with four open reading frames (ORFs). ORF1a encodes a putative polyprotein with papain-like protease, methyltransferase, and RNA helicase domains. ORF1b putatively encodes an RNA-dependent RNA polymerase (RdRp), which is probably expressed via a + 1 ribosomal frameshift. RNA2 consists of 8082 nt, containing eight ORFs that are similar in size and position to orthologous genes of other criniviruses. Phylogenetic analysis based on RdRp amino acid sequences of criniviruses placed MuCV in group 1., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Premise: First-year seedlings (FYS) of tree species may be a critical demographic bottleneck in semi-arid, seasonally dry ecosystems such as savannas. Given the highly variable water availability and potentially strong FYS-grass competition for water, FYS water-use strategies may play a crucial role in FYS establishment in savannas and, ultimately, in tree-grass competition and coexistence., Methods: We examined drought responses in FYS of two tree species that are dominant on opposite ends of an aridity gradient in Serengeti, Acacia (=Vachellia) tortilis and A. robusta. In a glasshouse experiment, gas exchange and whole-plant hydraulic conductance (K plant ) were measured as soil water potential (Ψ soil ) declined. Trajectory of the Ψ leaf /Ψ soil relationship during drought elucidated the degree of iso/anisohydry., Results: Both species were strongly anisohydric "water-spenders," allowing rapid wet-season C gain after pulses of moisture availability. Despite being equally vulnerable to declines in K plant under severe drought, they differed in their rates of water use. Acacia tortilis, which occurs in the more arid regions, initially had greater K max , transpiration (E), and photosynthesis (A net ) than A. robusta., Conclusions: This work demonstrates an important mechanism of FYS establishment in savannas: Rather than investing in drought tolerance, savanna FYS maximize gas exchange during wet periods at the expense of desiccation during dry seasons. FYS establishment appears dependent on high C uptake during the pulses of water availability that characterize habitats dominated by these species. This study increases our understanding of species-scale plant ecophysiology and ecosystem-scale patterns of tree-grass coexistence., (© 2022 The Authors. American Journal of Botany published by Wiley Periodicals LLC on behalf of Botanical Society of America.)

Earth's ecosystems are increasingly threatened by "hot drought," which occurs when hot air temperatures coincide with precipitation deficits, intensifying the hydrological, physiological, and ecological effects of drought by enhancing evaporative losses of soil moisture (SM) and increasing plant stress due to higher vapor pressure deficit (VPD). Drought-induced reductions in gross primary production (GPP) exert a major influence on the terrestrial carbon sink, but the extent to which hotter and atmospherically drier conditions will amplify the effects of precipitation deficits on Earth's carbon cycle remains largely unknown. During summer and autumn 2020, the U.S. Southwest experienced one of the most intense hot droughts on record, with record-low precipitation and record-high air temperature and VPD across the region. Here, we use this natural experiment to evaluate the effects of hot drought on GPP and further decompose those negative GPP anomalies into their constituent meteorological and hydrological drivers. We found a 122 Tg C (>25%) reduction in GPP below the 2015-2019 mean, by far the lowest regional GPP over the Soil Moisture Active Passive satellite record. Roughly half of the estimated GPP loss was attributable to low SM (likely a combination of record-low precipitation and warming-enhanced evaporative depletion), but record-breaking VPD amplified the reduction of GPP, contributing roughly 40% of the GPP anomaly. Both air temperature and VPD are very likely to continue increasing over the next century, likely leading to more frequent and intense hot droughts and substantially enhancing drought-induced GPP reductions., (© 2022 The Authors. Global Change Biology published by John Wiley & Sons Ltd. This article has been contributed to by US Government employees and their work is in the public domain in the USA.)

Mulberry crinkle leaf virus (MCLV) is a novel geminivirus identified from mulberry. The pathogenicity and natural vector transmission of MCLV remain unknown. Here, infectious clones consisting of the complete tandem dimeric genome of MCLV in a binary vector were constructed and agroinoculated into young mulberry plants. The results showed that the infectious clones of MCLV were systemically infectious in mulberry, but the infected mulberry plants did not show any virus infection-like symptoms. The natural transmission vectors of MCLV were also identified from possible vector insects occurring on the MCLV-infected mulberry plants. The vector ability of Tautoneura mori was identified through an inoculation assay. Three of 21 (14.3%) plants inoculated with T . mori collected from MCLV-infected mulberry plants grown naturally were found to be MCLV-positive 50 days postinoculation. These MCLV-positive mulberry plants did not show any virus infection-like symptoms. Collectively, these results suggest that MCLV is infectious to mulberry plants but, by itself, does not induce infection symptoms. The leafhopper T . mori was experimentally determined to be a transmission vector of MCLV for the first time.

Paper mulberry vein banding virus (PMVBV), a member of the genus Badnavirus in the family Caulimoviridae, infects paper mulberry (Broussonetia papyrifera), a dicotyledonous plant. Putative promoter regions in the PMVBV genome were tested using recombinant plant expression vectors, revealing that the promoter activity of three genome fragments was about 1.5-fold higher than that of the 35S promoter of cauliflower mosaic virus in Nicotiana benthamiana. In transformed transgenic Arabidopsis thaliana plants, these promoter constructs showed constitutive expression. Based on the activity and gene expression patterns of these three promoter constructs, a fragment of 384 bp (named PmVP) was deduced to contain the full-length promoter of the PMVBV genome. The results suggest that the PMVBV-derived promoter can be used for the constitutive expression of transgenes in dicotyledonous plants., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Our study suggests that the global CO 2 fertilization effect (CFE) on vegetation photosynthesis has declined during the past four decades. The Comments suggest that the temporal inconsistency in AVHRR data and the attribution method undermine the results’ robustness. Here, we provide additional evidence that these arguments did not affect our finding and that the global decline in CFE is robust.

Despite the growing interest in predicting global and regional trends in vegetation productivity in response to a changing climate, changes in water constraint on vegetation productivity (i.e., water limitations on vegetation growth) remain poorly understood. Here we conduct a comprehensive evaluation of changes in water constraint on vegetation growth in the extratropical Northern Hemisphere between 1982 and 2015. We document a significant increase in vegetation water constraint over this period. Remarkably divergent trends were found with vegetation water deficit areas significantly expanding, and water surplus areas significantly shrinking. The increase in water constraints associated with water deficit was also consistent with a decreasing response time to water scarcity, suggesting a stronger susceptibility of vegetation to drought. We also observed shortened water surplus period for water surplus areas, suggesting a shortened exposure to water surplus associated with humid conditions. These observed changes were found to be attributable to trends in temperature, solar radiation, precipitation, and atmospheric CO 2 . Our findings highlight the need for a more explicit consideration of the influence of water constraints on regional and global vegetation under a warming climate.

The influence of aquaporin (AQP) activity on plant water movement remains unclear, especially in plants subject to unfavorable conditions. We applied a multitiered approach at a range of plant scales to (i) characterize the resistances controlling water transport under drought, flooding, and flooding plus salinity conditions; (ii) quantify the respective effects of AQP activity and xylem structure on root (Kroot), stem (Kstem), and leaf (Kleaf) conductances; and (iii) evaluate the impact of AQP-regulated transport capacity on gas exchange. We found that drought, flooding, and flooding plus salinity reduced Kroot and root AQP activity in Pinus taeda, whereas Kroot of the flood-tolerant Taxodium distichum did not decline under flooding. The extent of the AQP control of transport efficiency varied among organs and species, ranging from 35-55% in Kroot to 10-30% in Kstem and Kleaf. In response to treatments, AQP-mediated inhibition of Kroot rather than changes in xylem acclimation controlled the fluctuations in Kroot. The reduction in stomatal conductance and its sensitivity to vapor pressure deficit were direct responses to decreased whole-plant conductance triggered by lower Kroot and larger resistance belowground. Our results provide new mechanistic and functional insights on plant hydraulics that are essential to quantifying the influences of future stress on ecosystem function., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Atmospheric carbon dioxide concentration ([CO 2 ]) 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 [CO 2 ] increase and thus climate change. However, ecosystem CO 2 responses are complex or confounded by concurrent changes in multiple agents of global change and evidence for a [CO 2 ]-driven terrestrial carbon sink can appear contradictory. Here we synthesize theory and broad, multidisciplinary evidence for the effects of increasing [CO 2 ] (iCO 2 ) 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 iCO 2 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 iCO 2 responses are high in comparison to experiments and predictions from theory. Plant mortality and soil carbon iCO 2 responses are highly uncertain. In conclusion, a range of evidence supports a positive terrestrial carbon sink in response to iCO 2 , albeit with uncertain magnitude and strong suggestion of a role for additional agents of global change., (© 2020 The Authors New Phytologist Foundation © 2020 New Phytologist.)

Background: Adverse drug/device reactions (ADRs) can result in severe patient harm. We define very serious ADRs as being associated with severe toxicity, as measured on the Common Toxicity Criteria Adverse Events (CTCAE)) scale, following use of drugs or devices with large sales, large financial settlements, and large numbers of injured persons. We report on impacts on patients, clinicians, and manufacturers following very serious ADR reporting., Methods: We reviewed clinician identified very serious ADRs published between 1997 and 2019. Drugs and devices associated with reports of very serious ADRs were identified. Included drugs or devices had market removal discussed at Food and Drug Advisory (FDA) Advisory Committee meetings, were published by clinicians, had sales > $1 billion, were associated with CTCAE Grade 4 or 5 toxicity effects, and had either >$1 billion in settlements or >1,000 injured patients. Data sources included journals, Congressional transcripts, and news reports. We reviewed data on: 1) timing of ADR reports, Boxed warnings, and product withdrawals, and 2) patient, clinician, and manufacturer impacts. Binomial analysis was used to compare sales pre- and post-FDA Advisory Committee meetings., Findings: Twenty very serious ADRs involved fifteen drugs and one device. Legal settlements totaled $38.4 billion for 753,900 injured persons. Eleven of 18 clinicians (61%) reported harms, including verbal threats from manufacturer (five) and loss of a faculty position (one). Annual sales decreased 94% from $29.1 billion pre-FDA meeting to $4.9 billion afterwards ( p <0.0018). Manufacturers of four drugs paid $1.7 billion total in criminal fines for failing to inform the FDA and physicians about very serious ADRs. Following FDA approval, the median time to ADR reporting was 7.5 years (Interquartile range 3,13 years). Twelve drugs received Box warnings and one drug received a warning (median, 7.5 years following ADR reporting (IQR 5,11 years). Six drugs and 1 device were withdrawn from marketing (median, 5 years after ADR reporting (IQR 4,6 years))., Interpretation: Because very serious ADRs impacts are so large, policy makers should consider developing independently funded pharmacovigilance centers of excellence to assist with clinician investigations., Funding: This work received support from the National Cancer Institute (1R01 CA102713 (CLB), https://www.nih.gov/about-nih/what-we-do/nih-almanac/national-cancer-institute-nci; and two Pilot Project grants from the American Cancer Society's Institutional Grant Award to the University of South Carolina (IRG-13-043-01) https://www.cancer.org/ (SH; BS)., Competing Interests: Dr. Sartor reports grants and personal fees from AAA, personal fees from ASTELLAS, grants and personal fees from ASTRAZENECA, grants and personal fees from BAYER, personal fees from BLUE EARTH DIAGNOSTICS, INC., personal fees from EMD SERONO, grants and personal fees from ENDOCYTE, personal fees from PFIZER, grants and personal fees from PROGENICS, grants and personal fees from SANOFI, grants from INVITAE, grants and personal fees from MERCK, grants and personal fees from NOVARTIS, grants and personal fees from JANSSEN, personal fees from CONSTELLATION, personal fees from DENDREON, personal fees from BRISTOL-MYERS SQUIBB, grants from INNOCRIN, grants from SOTIO, other from NRG, other from NCI, personal fees from BRAVARIN NORDIC, personal fees from CLOVIS, personal fees from MYRIAD, personal fees from NORIA THERAPEUTICS, INC., personal fees from NOXOPHARM, personal fees from POINT BIOPHARMA, personal fees from TENEBIO, personal fees from THERAGNOSTICS, personal fees from TELIX, personal fees from CLARITY PHARMACUEITCALS, personal fees from Celegne, personal fees from FUSION, personal fees from ISOTOPEN TECHNOLOGIEN MEUNCHEN, during the conduct of the study. All other authors report no conflict., (© 2020 The Author(s).)

The enhanced vegetation productivity driven by increased concentrations of carbon dioxide (CO 2 ) [i.e., the CO 2 fertilization effect (CFE)] sustains an important negative feedback on climate warming, but the temporal dynamics of CFE remain unclear. Using multiple long-term satellite- and ground-based datasets, we showed that global CFE has declined across most terrestrial regions of the globe from 1982 to 2015, correlating well with changing nutrient concentrations and availability of soil water. Current carbon cycle models also demonstrate a declining CFE trend, albeit one substantially weaker than that from the global observations. This declining trend in the forcing of terrestrial carbon sinks by increasing amounts of atmospheric CO 2 implies a weakening negative feedback on the climatic system and increased societal dependence on future strategies to mitigate climate warming., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Variability in climate exerts a strong influence on vegetation productivity (gross primary productivity; GPP), and therefore has a large impact on the land carbon sink. However, no direct observations of global GPP exist, and estimates rely on models that are constrained by observations at various spatial and temporal scales. Here, we assess the consistency in GPP from global products which extend for more than three decades; two observation-based approaches, the upscaling of FLUXNET site observations (FLUXCOM) and a remote sensing derived light use efficiency model (RS-LUE), and from a suite of terrestrial biosphere models (TRENDYv6). At local scales, we find high correlations in annual GPP among the products, with exceptions in tropical and high northern latitudes. On longer time scales, the products agree on the direction of trends over 58% of the land, with large increases across northern latitudes driven by warming trends. Further, tropical regions exhibit the largest interannual variability in GPP, with both rainforests and savannas contributing substantially. Variability in savanna GPP is likely predominantly driven by water availability, although temperature could play a role via soil moisture-atmosphere feedbacks. There is, however, no consensus on the magnitude and driver of variability of tropical forests, which suggest uncertainties in process representations and underlying observations remain. These results emphasize the need for more direct long-term observations of GPP along with an extension of in situ networks in underrepresented regions (e.g., tropical forests). Such capabilities would support efforts to better validate relevant processes in models, to more accurately estimate GPP., (©2020. The Authors.)

The response of terrestrial carbon uptake to increasing atmospheric [CO 2 ], that is the CO 2 fertilization effect (CFE), remains a key area of uncertainty in carbon cycle science. Here we provide a perspective on how satellite observations could be better used to understand and constrain CFE. We then highlight data assimilation (DA) as an effective way to reconcile different satellite datasets and systematically constrain carbon uptake trends in Earth System Models. As a proof-of-concept, we show that joint DA of multiple independent satellite datasets reduced model ensemble error by better constraining unobservable processes and variables, including those directly impacted by CFE. DA of multiple satellite datasets offers a powerful technique that could improve understanding of CFE and enable more accurate forecasts of terrestrial carbon uptake., (© 2019 The Authors. New Phytologist © 2019 New Phytologist Trust.)

Forests play a major role in the global carbon cycle. Previous studies on the capacity of forests to sequester atmospheric CO 2 have mostly focused on carbon uptake, but the roles of carbon turnover time and its spatiotemporal changes remain poorly understood. Here, we used long-term inventory data (1955 to 2018) from 695 mature forest plots to quantify temporal trends in living vegetation carbon turnover time across tropical, temperate, and cold climate zones, and compared plot data to 8 Earth system models (ESMs). Long-term plots consistently showed decreases in living vegetation carbon turnover time, likely driven by increased tree mortality across all major climate zones. Changes in living vegetation carbon turnover time were negatively correlated with CO 2 enrichment in both forest plot data and ESM simulations. However, plot-based correlations between living vegetation carbon turnover time and climate drivers such as precipitation and temperature diverged from those of ESM simulations. Our analyses suggest that forest carbon sinks are likely to be constrained by a decrease in living vegetation carbon turnover time, and accurate projections of forest carbon sink dynamics will require an improved representation of tree mortality processes and their sensitivity to climate in ESMs., Competing Interests: The authors declare no competing interest., (Copyright © 2019 the Author(s). Published by PNAS.)

Earth's hydroclimatic variability is increasing, with changes in the frequency of extreme events that may negatively affect forest ecosystems. We examined possible consequences of changing precipitation variability using tree rings in the conterminous United States. While many growth records showed either little evidence of precipitation limitation or linear relationships to precipitation, growth of some species (particularly those in semiarid regions) responded asymmetrically to precipitation such that tree growth reductions during dry years were greater than, and not compensated by, increases during wet years. The U.S. Southwest, in particular, showed a large increase in precipitation variability, coupled with asymmetric responses of growth to precipitation. Simulations suggested roughly a twofold increase in the probability of large negative growth anomalies across the Southwest resulting solely from 20th century increases in variability of cool-season precipitation. Models project continued increases in precipitation variability, portending future growth reductions across semiarid forests of the western United States., (Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).)

Atmospheric vapor pressure deficit (VPD) is a critical variable in determining plant photosynthesis. Synthesis of four global climate datasets reveals a sharp increase of VPD after the late 1990s. In response, the vegetation greening trend indicated by a satellite-derived vegetation index (GIMMS3g), which was evident before the late 1990s, was subsequently stalled or reversed. Terrestrial gross primary production derived from two satellite-based models (revised EC-LUE and MODIS) exhibits persistent and widespread decreases after the late 1990s due to increased VPD, which offset the positive CO 2 fertilization effect. Six Earth system models have consistently projected continuous increases of VPD throughout the current century. Our results highlight that the impacts of VPD on vegetation growth should be adequately considered to assess ecosystem responses to future climate conditions.

Premise of the Study: Deciduous tree species remove some nutrients from their leaves during fall leaf senescence through retranslocation. Retranslocation impacts the timeline of leaf fall, amount of active chlorophyll, and overall leaf nitrogen content as fall color change occurs. Our objective was to identify interspecific differences in the timing of abscission layer formation, leaf color change, and the level of chlorophyll degradation of young trees during fall senescence., Methods: Leaf relative chlorophyll content for three tree species was measured during fall 2015 by a greenness meter. These measurements were calibrated for each species through spectrophotometric determination of leaf chlorophyll concentration. Abscission layer formation was tracked using light microscopy of sampled leaves. Excised leaves were photographed on a flat white surface to track species leaf color through time., Key Results: All three species had different chlorophyll declination rates throughout the fall season. The maple species started with less chlorophyll and began abscission layer formation earlier. The other two species had a similar starting chlorophyll level and onset timing of abscission layer formation. Visible leaf color change was not associated with a threshold in either chlorophyll degradation or abscission layer formation across species., Conclusions: Maple species degraded less chlorophyll on average, in the fall, than did the oak and beech species. The rate of chlorophyll degradation in coordination with abscission layer formation varied by species. Color change was not a good predictor of level of chlorophyll degradation in leaves across species., (© 2019 Botanical Society of America.)

Historical and future trends in net primary productivity (NPP) and its sensitivity to global change are largely unknown because of the lack of long-term, high-resolution data. Here we test whether annually resolved tree-ring stable carbon (δ 13 C) and oxygen (δ 18 O) isotopes can be used as proxies for reconstructing past NPP. Stable isotope chronologies from four sites within three distinct hydroclimatic environments in the eastern United States (US) were compared in time and space against satellite-derived NPP products, including the long-term Global Inventory Modeling and Mapping Studies (GIMMS3g) NPP (1982-2011), the newest high-resolution Landsat NPP (1986-2015), and the Moderate Resolution Imaging Spectroradiometer (MODIS, 2001-2015) NPP. We show that tree-ring isotopes, in particular δ 18 O, correlate strongly with satellite NPP estimates at both local and large geographical scales in the eastern US. These findings represent an important breakthrough for estimating interannual variability and long-term changes in terrestrial productivity at the biome scale.

Voluntary sustainability standards (VSS) are stakeholder-derived principles with measurable and enforceable criteria to promote sustainable production outcomes. While institutional commitments to use VSS to meet sustainable procurement policies have grown rapidly over the past decade, we still have relatively little understanding of the ( i ) direct environmental benefits of large-scale VSS adoption; ( ii ) potential perverse indirect impacts of adoption; and ( iii ) implementation pathways. Here, we illustrate and address these knowledge gaps using an ecosystem service modeling and scenario analysis of Bonsucro, the leading VSS for sugarcane. We find that global compliance with the Bonsucro environmental standards would reduce current sugarcane production area (-24%), net tonnage (-11%), irrigation water use (-65%), nutrient loading (-34%), and greenhouse gas emissions from cultivation (-51%). Under a scenario of doubled global sugarcane production, Bonsucro adoption would further limit water use and greenhouse gas emissions by preventing sugarcane expansion into water-stressed and high-carbon stock ecosystems. This outcome was achieved via expansion largely on existing agricultural lands. However, displacement of other crops could drive detrimental impacts from indirect land use. We find that over half of the potential direct environmental benefits of Bonsucro standards under the doubling scenario could be achieved by targeting adoption in just 10% of global sugarcane production areas. However, designing policy that generates the most environmentally beneficial Bonsucro adoption pathway requires a better understanding of the economic and social costs of VSS adoption. Finally, we suggest research directions to advance sustainable consumption and production., Competing Interests: The authors declare no conflict of interest., (Copyright © 2019 the Author(s). Published by PNAS.)

Climate change is shifting the phenological cycles of plants 1 , thereby altering the functioning of ecosystems, which in turn induces feedbacks to the climate system 2 . In northern (north of 30° N) ecosystems, warmer springs lead generally to an earlier onset of the growing season 3,4 and increased ecosystem productivity early in the season 5 . In situ 6 and regional 7-9 studies also provide evidence for lagged effects of spring warmth on plant productivity during the subsequent summer and autumn. However, our current understanding of these lagged effects, including their direction (beneficial or adverse) and geographic distribution, is still very limited. Here we analyse satellite, field-based and modelled data for the period 1982-2011 and show that there are widespread and contrasting lagged productivity responses to spring warmth across northern ecosystems. On the basis of the observational data, we find that roughly 15 per cent of the total study area of about 41 million square kilometres exhibits adverse lagged effects and that roughly 5 per cent of the total study area exhibits beneficial lagged effects. By contrast, current-generation terrestrial carbon-cycle models predict much lower areal fractions of adverse lagged effects (ranging from 1 to 14 per cent) and much higher areal fractions of beneficial lagged effects (ranging from 9 to 54 per cent). We find that elevation and seasonal precipitation patterns largely dictate the geographic pattern and direction of the lagged effects. Inadequate consideration in current models of the effects of the seasonal build-up of water stress on seasonal vegetation growth may therefore be able to explain the differences that we found between our observation-constrained estimates and the model-constrained estimates of lagged effects associated with spring warming. Overall, our results suggest that for many northern ecosystems the benefits of warmer springs on growing-season ecosystem productivity are effectively compensated for by the accumulation of seasonal water deficits, despite the fact that northern ecosystems are thought to be largely temperature- and radiation-limited 10 .

Global-scale studies suggest that dryland ecosystems dominate an increasing trend in the magnitude and interannual variability of the land CO 2 sink. However, such analyses are poorly constrained by measured CO 2 exchange in drylands. Here we address this observation gap with eddy covariance data from 25 sites in the water-limited Southwest region of North America with observed ranges in annual precipitation of 100-1000 mm, annual temperatures of 2-25°C, and records of 3-10 years (150 site-years in total). Annual fluxes were integrated using site-specific ecohydrologic years to group precipitation with resulting ecosystem exchanges. We found a wide range of carbon sink/source function, with mean annual net ecosystem production (NEP) varying from -350 to +330 gCm -2 across sites with diverse vegetation types, contrasting with the more constant sink typically measured in mesic ecosystems. In this region, only forest-dominated sites were consistent carbon sinks. Interannual variability of NEP, gross ecosystem production (GEP), and ecosystem respiration (R eco ) was larger than for mesic regions, and half the sites switched between functioning as C sinks/C sources in wet/dry years. The sites demonstrated coherent responses of GEP and NEP to anomalies in annual evapotranspiration (ET), used here as a proxy for annually available water after hydrologic losses. Notably, GEP and R eco were negatively related to temperature, both interannually within site and spatially across sites, in contrast to positive temperature effects commonly reported for mesic ecosystems. Models based on MODIS satellite observations matched the cross-site spatial pattern in mean annual GEP but consistently underestimated mean annual ET by ~50%. Importantly, the MODIS-based models captured only 20-30% of interannual variation magnitude. These results suggest the contribution of this dryland region to variability of regional to global CO 2 exchange may be up to 3-5 times larger than current estimates., (Published 2017. This article is a U.S. Government work and is in the public domain in the USA.)

Purpose: The purpose of the study is to describe medical record retrieval for a study validating claims-based algorithms used to identify seven adverse events of special interest (AESI) in a Medicare population., Methods: We analyzed 2010-2011 Medicare claims of women with postmenopausal osteoporosis and men ≥65 years of age in the Medicare 5% national sample. The final cohorts included beneficiaries covered continuously for 12+ months by Medicare parts A, B, and D and not enrolled in Medicare Advantage before starting follow-up. We identified beneficiaries using each AESI algorithm and randomly selected 400 women and 100 men with each AESI for medical record retrieval. The Centers for Medicare and Medicaid Services provided beneficiary contact information, and we requested medical records directly from providers, without patient contact., Results: We selected 3331 beneficiaries (women: 2272; men: 559) for whom we requested 3625 medical records. Overall, we received 1738 [47.9% (95%CI 46.3%, 49.6%)] of the requested medical records. We observed small differences in the characteristics of the total population with AESIs compared with those randomly selected for retrieval; however, no differences were seen between those selected and those retrieved. We retrieved 54.7% of records requested from hospitals compared with 26.3% of records requested from physician offices (p < 0.001). Retrieval did not differ by sex or vital status of the beneficiaries., Conclusions: Our national medical record validation study of claims-based algorithms produced a modest retrieval rate. The medical record procedures outlined in this paper could have led to the improved retrieval from our previous medical record retrieval study. Copyright © 2016 John Wiley & Sons, Ltd., (Copyright © 2016 John Wiley & Sons, Ltd.)

Stability in population dynamics is an emergent property of the interaction between direct and delayed density dependence, the strengths of which vary with environmental covariates. Analysis of variation across populations in the strength of direct and delayed density dependence can reveal variation in stability properties of populations at the species level. We examined the stability properties of 22 elk/red deer populations in a two-stage analysis. First, we estimated direct and delayed density dependence applying an AR(2) model in a Bayesian hierarchical framework. Second, we plotted the coefficients of direct and delayed density dependence in the Royama parameter plane. We then used a hierarchical approach to test the significance of environmental covariates of direct and delayed density dependence. Three populations exhibited highly stable and convergent dynamics with strong direct, and weak delayed, density dependence. The remaining 19 populations exhibited more complex dynamics characterized by multi-annual fluctuations. Most (15 of 19) of these exhibited a combination of weak to moderate direct and delayed density dependence. Best-fit models included environmental covariates in 17 populations (77% of the total). Of these, interannual variation in growing-season primary productivity and interannual variation in winter temperature were the most common, performing as the best-fit covariate in six and five populations, respectively. Interannual variation in growing-season primary productivity was associated with the weakest combination of direct and delayed density dependence, while interannual variation in winter temperature was associated with the strongest combination of direct and delayed density dependence. These results accord with a classic theoretical prediction that environmental variability should weaken population stability. They furthermore suggest that two forms of environmental variability, one related to forage resources and the other related to abiotic conditions, both reduce stability, but in opposing fashion: one through weakened direct density dependence and the other through strengthened delayed density dependence. Importantly, however, no single abiotic or biotic environmental factor emerged as generally predictive of the strengths of direct or delayed density dependence, nor of the stability properties emerging from their interaction. Our results emphasize the challenges inherent to ascribing primacy to drivers of such parameters at the species level and distribution scale., (© 2016 by the Ecological Society of America.)

Stress-testing (forced degradation) studies have been conducted on pemetrexed disodium heptahydrate (1) (LY231514·2Na·7H 2 O) drug substance in order to identify its likely degradation products and establish its degradation pathways. Solid samples of the drug substance were stressed under various conditions of heat, humidity, and light, and solutions of the drug substance were stressed under various conditions of heat, light, oxidation, and over a wide pH range (1-13). The stressed samples were analyzed using a gradient elution reversed-phase HPLC method. The 7 major degradation products detected in the stress-testing studies were isolated, and the structures were elucidated via spectroscopic characterization. The structures of the degradation products and their proposed mechanisms of formation indicate that 1 degrades via 2 main pathways: oxidation and hydrolysis. Of the 7 identified degradation products, 6 are proposed to result from oxidation and 1 from hydrolysis., (Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.)

Objectives: To estimate the effects of medical home support on the use of clinical services and Medicaid expenditures., Data Source: Medicaid claims., Study Design: A difference-in-differences model where changes in utilization and expenditures of the intervention group are compared to changes in the nonintervention group., Extraction Methods: Using Medicaid claims from October 2010 through September 2013, service use and expenditures are measured for 12 months before and 21 months after implementation. Changes for four health status groups are examined separately., Principal Findings: The introduction of community-based support was associated with a small reduction in use and no statistically significant overall effect on expenditures. However, among those with chronic and/or mental health conditions, there were modest, statistically significant increases in use of and expenditures for a range of ambulatory and inpatient health care services, while service use for those without these conditions declined. Emergency department use increased for all groups., Conclusions: Community-based support for medical home practices is associated with a shift in the service mix provided to higher cost, more vulnerable subgroups in Medicaid. Such systems are unlikely to be associated with significant overall cost savings, at least in the short term, but may have other benefits., (© Health Research and Educational Trust.)

The terrestrial biosphere is currently a strong carbon (C) sink but may switch to a source in the 21st century as climate-driven losses exceed CO2-driven C gains, thereby accelerating global warming. Although it has long been recognized that tropical climate plays a critical role in regulating interannual climate variability, the causal link between changes in temperature and precipitation and terrestrial processes remains uncertain. Here, we combine atmospheric mass balance, remote sensing-modeled datasets of vegetation C uptake, and climate datasets to characterize the temporal variability of the terrestrial C sink and determine the dominant climate drivers of this variability. We show that the interannual variability of global land C sink has grown by 50-100% over the past 50 y. We further find that interannual land C sink variability is most strongly linked to tropical nighttime warming, likely through respiration. This apparent sensitivity of respiration to nighttime temperatures, which are projected to increase faster than global average temperatures, suggests that C stored in tropical forests may be vulnerable to future warming.

Validation of claims-based algorithms to identify serious hypersensitivity reactions and osteonecrosis of the jaw has not been performed in large osteoporosis populations. The objective of this project is to estimate the positive predictive value of the claims-based algorithms in older women with osteoporosis enrolled in Medicare. Using the 2006-2008 Medicare 5% sample data, we identified potential hypersensitivity and osteonecrosis of the jaw cases based on ICD-9 diagnosis codes. Potential hypersensitivity cases had a 995.0, 995.2, or 995.3 diagnosis code on emergency department or inpatient claims. Potential osteonecrosis of the jaw cases had ≥1 inpatient or outpatient physician claim with a 522.7, 526.4, 526.5, or 733.45 diagnosis code or ≥2 claims of any type with a 526.9 diagnosis code. All retrieved records were redacted and reviewed by experts to determine case status: confirmed, not confirmed, or insufficient information. We calculated the positive predictive value as the number of confirmed cases divided by the total number of retrieved records with sufficient information. We requested 412 potential hypersensitivity and 304 potential osteonecrosis of the jaw records and received 174 (42%) and 84 (28%) records respectively. Of 84 potential osteonecrosis of the jaw cases, 6 were confirmed, resulting in a positive predictive value (95% CI) of 7.1% (2.7, 14.9). Of 174 retrieved potential hypersensitivity records, 95 were confirmed. After exclusion of 25 records with insufficient information for case determination, the overall positive predictive value (95% CI) for hypersensitivity reactions was 76.0% (67.5, 83.2). In a random sample of Medicare data, a claim-based algorithm to identify serious hypersensitivity reactions performed well. An algorithm for osteonecrosis of the jaw did not, partly due to the inclusion of diagnosis codes that are not specific for osteoporosis of the jaw.

Although tropical forests account for only a fraction of the planet's terrestrial surface, they exchange more carbon dioxide with the atmosphere than any other biome on Earth, and thus play a disproportionate role in the global climate. In the next 20 years, the tropics will experience unprecedented warming, yet there is exceedingly high uncertainty about their potential responses to this imminent climatic change. Here, we prioritize research approaches given both funding and logistical constraints in order to resolve major uncertainties about how tropical forests function and also to improve predictive capacity of earth system models. We investigate overall model uncertainty of tropical latitudes and explore the scientific benefits and inevitable trade-offs inherent in large-scale manipulative field experiments. With a Coupled Model Intercomparison Project Phase 5 analysis, we found that model variability in projected net ecosystem production was nearly 3 times greater in the tropics than for any other latitude. Through a review of the most current literature, we concluded that manipulative warming experiments are vital to accurately predict future tropical forest carbon balance, and we further recommend the establishment of a network of comparable studies spanning gradients of precipitation, edaphic qualities, plant types, and/or land use change. We provide arguments for long-term, single-factor warming experiments that incorporate warming of the most biogeochemically active ecosystem components (i.e. leaves, roots, soil microbes). Hypothesis testing of underlying mechanisms should be a priority, along with improving model parameterization and constraints. No single tropical forest is representative of all tropical forests; therefore logistical feasibility should be the most important consideration for locating large-scale manipulative experiments. Above all, we advocate for multi-faceted research programs, and we offer arguments for what we consider the most powerful and urgent way forward in order to improve our understanding of tropical forest responses to climate change., (© 2015 John Wiley & Sons Ltd.)

The south-central Rocky Mountains, USA, are characterised by a dry, continental mesoclimate with typical convective cloud formation during the afternoon. Little is known about the specific influence of such predictable cloud patterns on the microclimate and ecophysiology of associated species. During the summer of 2012, days with afternoon clouds were most common (50% of all days) compared with completely clear (24%) or cloudy days (6.5%). In two representative alpine species, Caltha leptosepala DC. and Arnica parryi A. Gray, fully overcast days reduced mean daily photosynthesis (A) by nearly 50% relative to fully clear days. Mean afternoon A was significantly lower on fully cloudy days relative to days with afternoon clouds only or no clouds in both species. Notably, A did not differ during afternoon cloud days relative to clear afternoons. Afternoon clouds significantly reduced transpiration (E) in C. leptosepala relative to clear days, and both species showed mean reductions in plant water stress (i.e. higher Ψ), though this difference was not significant. Water use efficiency (WUE) (A/E) decreased from morning to afternoon, especially on cloudy days, and the presence of clouds had a positive effect on the light reactions of photosynthesis based on fluorescence measurements (Fv'/Fm'), in both species. Cloudy days were characterised by higher Fv/Fm than afternoon clouds and clear days during both the morning and the afternoon (especially for A. parryi) and recovery to near pre-dawn values for cloudy and afternoon cloud day types, but not clear days. Overall, similar ecophysiological advantages of this typical afternoon cloud pattern was apparent in both species, although their spatial microsite differences related to winter snow accumulation may also play an important role.