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Background: Postpartum depression (PPD) occurs after delivery, with severity and onset varying by individual. Women with low social support may be at higher risk for PPD. This study examined the association between social support and self-reported postpartum depression symptoms (PDS) among Illinois postpartum women., Methods: Using 2016-2020 data from the Illinois Pregnancy Risk Assessment Monitoring System (PRAMS) (n = 5886), instrumental support (physical, hands-on support) and partner emotional support were each categorized as high/low and were combined in a composite measure (high = high on both types, moderate = high on one type, and low = low on both types). PDS were self-reported. Crude and adjusted odds ratios (aOR) and 95% confidence intervals (CI) were calculated using logistic regression., Results: Overall, 9.6% (95% CI = 8.8-10.4) of Illinois postpartum women experienced PDS. Of Illinois postpartum women, 63.5% (95% CI = 62.1-64.9) had high composite support, 29.3% (95% CI = 28.0-30.6) had moderate composite support, and 7.1% (95% CI = 6.4-7.9) had low composite support. After adjustment for maternal characteristics, instrumental support, partner emotional support, and a composite measure of support were each significantly associated with PDS. Compared to women with high composite support, women with low composite support had six times the odds of PDS (aOR = 6.1, 95% CI = 4.5-8.2), and women with moderate composite support had nearly three times the odds of PDS (aOR = 2.7, 95% CI = 2.2-3.4)., Conclusion: PDS was associated with instrumental support, partner emotional support, and a composite measure of support in Illinois postpartum women. This suggests the importance of addressing social support for postpartum individuals., (© 2024 The Author(s). Birth published by Wiley Periodicals LLC. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

Purpose: Within a multi-state Collaborative Improvement and Innovation Network addressing the social determinants of health during 2017-2020, the Illinois Department of Public Health led an exploratory project to understand how the availability of child care affects maternal health care utilization. The project assessed whether lack of child care was a barrier to perinatal health care utilization and gathered information on health facility practices, resources, and policies related to child care DESCRIPTION: TWe surveyed (1) birthing hospitals (n = 98), (2) federally qualified health centers (FQHCs) (n = 40), and (3) a convenience sample of postpartum persons (n = 60)., Assessment: Each group reported that child care concerns negatively affect health care utilization (66% of birthing hospitals, 50% of FQHCs, and 32% of postpartum persons). Among postpartum persons, the most common reported reason for missing a visit due to child care issues was "not feeling comfortable leaving my child(ren) in the care of others" (22%). The most common child care resource reported by facilities was "staff watching children" (53% of birthing hospitals, 75% of FQHCs); however, most did not have formal child care policies or dedicated space for children. Fewer than half of FQHCs (43%) discussed child care at the first prenatal visit., Conclusion: The project prompted the Illinois Title V program to add a child care-related strategy to their 2021-2025 Action Plan, providing opportunity for further examination of practices and policies that could be implemented to reduce child care barriers to perinatal care. Systematically addressing child care in health care settings may improve health care utilization among birthing/postpartum persons., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Climate change will impact gross primary productivity (GPP), net primary productivity (NPP), and carbon storage in wooded ecosystems. The extent of change will be influenced by thermal acclimation of photosynthesis-the ability of plants to adjust net photosynthetic rates in response to growth temperatures-yet regional differences in acclimation effects among wooded ecosystems is currently unknown. We examined the effects of changing climate on 17 Australian wooded ecosystems with and without the effects of thermal acclimation of C3 photosynthesis. Ecosystems were drawn from five ecoregions (tropical savanna, tropical forest, Mediterranean woodlands, temperate woodlands, and temperate forests) that span Australia's climatic range. We used the CABLE-POP land surface model adapted with thermal acclimation functions and forced with HadGEM2-ES climate projections from RCP8.5. For each site and ecoregion we examined (a) effects of climate change on GPP, NPP, and live tree carbon storage; and (b) impacts of thermal acclimation of photosynthesis on simulated changes. Between the end of the historical (1976-2005) and projected (2070-2099) periods simulated annual carbon uptake increased in the majority of ecosystems by 26.1%-63.3% for GPP and 15%-61.5% for NPP. Thermal acclimation of photosynthesis further increased GPP and NPP in tropical savannas by 27.2% and 22.4% and by 11% and 10.1% in tropical forests with positive effects concentrated in the wet season (tropical savannas) and the warmer months (tropical forests). We predicted minimal effects of thermal acclimation of photosynthesis on GPP, NPP, and carbon storage in Mediterranean woodlands, temperate woodlands, and temperate forests. Overall, positive effects were strongly enhanced by increasing CO 2 concentrations under RCP8.5. We conclude that the direct effects of climate change will enhance carbon uptake and storage in Australian wooded ecosystems (likely due to CO 2 enrichment) and that benefits of thermal acclimation of photosynthesis will be restricted to tropical ecoregions., (© 2023 The Authors. Global Change Biology published by John Wiley & Sons Ltd.)

Gross primary productivity (GPP) is the key determinant of land carbon uptake, but its representation in terrestrial biosphere models (TBMs) does not reflect our latest physiological understanding. We implemented three empirically well supported but often omitted mechanisms into the TBM CABLE-POP: photosynthetic temperature acclimation, explicit mesophyll conductance, and photosynthetic optimization through redistribution of leaf nitrogen. We used the RCP8.5 climate scenario to conduct factorial model simulations characterizing the individual and combined effects of the three mechanisms on projections of GPP. Simulated global GPP increased more strongly (up to 20% by 2070-2099) in more comprehensive representations of photosynthesis compared to the model lacking the three mechanisms. The experiments revealed non-additive interactions among the mechanisms as combined effects were stronger than the sum of the individual effects. The modeled responses are explained by changes in the photosynthetic sensitivity to temperature and CO 2 caused by the added mechanisms. Our results suggest that current TBMs underestimate GPP responses to future CO 2 and climate conditions.

Thermophilic cyanobacteria have been extensively studied in Yellowstone National Park (YNP) hot springs, particularly during decades of work on the thick laminated mats of Octopus and Mushroom springs. However, focused studies of cyanobacteria outside these two hot springs have been lacking, especially regarding how physical and chemical parameters along with community morphology influence the genomic makeup of these organisms. Here, we used a metagenomic approach to examine cyanobacteria existing at the upper temperature limit of photosynthesis. We examined 15 alkaline hot spring samples across six geographic areas of YNP, all with various physical and chemical parameters and community morphology. We recovered 22 metagenome-assembled genomes (MAGs) belonging to thermophilic cyanobacteria, notably an uncultured Synechococcus -like taxon recovered from a setting at the upper temperature limit of photosynthesis, 73°C, in addition to thermophilic Gloeomargarita . Furthermore, we found that three distinct groups of Synechococcus -like MAGs recovered from different temperature ranges vary in their genomic makeup. MAGs from the uncultured very-high-temperature (up to 73°C) Synechococcus -like taxon lack key nitrogen metabolism genes and have genes implicated in cellular stress responses that diverge from other Synechococcus -like MAGs. Across all parameters measured, temperature was the primary determinant of taxonomic makeup of recovered cyanobacterial MAGs. However, total Fe, community morphology, and biogeography played an additional role in the distribution and abundance of upper-temperature-limit-adapted Synechococcus -like MAGs. These findings expand our understanding of cyanobacterial diversity in YNP and provide a basis for interrogation of understudied thermophilic cyanobacteria. IMPORTANCE Oxygenic photosynthesis arose early in microbial evolution-approximately 2.5 to 3.5 billion years ago-and entirely reshaped the biological makeup of Earth. However, despite the span of time in which photosynthesis has been refined, it is strictly limited to temperatures below 73°C, a barrier that many other biological processes have been able to overcome. Furthermore, photosynthesis at temperatures above 56°C is limited to circumneutral and alkaline pH. Hot springs in Yellowstone National Park (YNP), which have a large diversity in temperatures, pH, and geochemistry, provide a natural laboratory to study thermophilic microbial mats and the cyanobacteria within. While cyanobacteria in YNP microbial mats have been studied for decades, a vast majority of the work has focused on two springs within the same geyser basin, both containing similar community morphologies. Thus, the drivers of cyanobacterial adaptations to the upper limits of photosynthesis across a variety of environmental parameters have been understudied. Our findings provide new insights into the influence of these parameters on both taxonomic diversity and genomic content of cyanobacteria across a range of hot spring samples.

Objectives: The Illinois Department of Public Health (IDPH) assessed whether increases in the SARS-CoV-2 test positivity rate among pregnant people at labor and delivery (L&D) could signal increases in SARS-CoV-2 prevalence in the general Illinois population earlier than current state metrics., Materials and Methods: Twenty-six birthing hospitals universally testing for SARS-CoV-2 at L&D voluntarily submitted data from June 21, 2020 through January 23, 2021, to IDPH. Hospitals reported the daily number of people who delivered, SARS-CoV-2 tests, and test results as well as symptom status. We compared the test positivity rate at L&D with the test positivity rate of the general population and the number of hospital admissions for COVID-19-like illness by quantifying correlations in trends and identifying a lead time., Results: Of 26 633 reported pregnant people who delivered, 96.8% (n = 25 772) were tested for SARS-CoV-2. The overall test positivity rate was 2.4% (n = 615); 77.7% (n = 478) were asymptomatic. In Chicago, the only region with a sufficient sample size for analysis, the test positivity rate at L&D (peak of 5% on December 7, 2020) was lower and more stable than the test positivity rate of the general population (peak of 14% on November 13, 2020) and lagged hospital admissions for COVID-19-like illness (peak of 118 on November 15, 2020) and the test positivity rate of the general population by about 10 days (Pearson correlation = 0.73 and 0.75, respectively)., Practice Implications: Trends in the test positivity rate at L&D did not provide an earlier signal of increases in Illinois's SARS-CoV-2 prevalence than current state metrics did. Nonetheless, the role of universal testing protocols in identifying asymptomatic infection is important for clinical decision making and patient education about infection prevention and control.

Tropical forests are some of the most biodiverse ecosystems in the world, yet their functioning is threatened by anthropogenic disturbances and climate change. Global actions to conserve tropical forests could be enhanced by having local knowledge on the forests' functional diversity and functional redundancy as proxies for their capacity to respond to global environmental change. Here we create estimates of plant functional diversity and redundancy across the tropics by combining a dataset of 16 morphological, chemical and photosynthetic plant traits sampled from 2,461 individual trees from 74 sites distributed across four continents together with local climate data for the past half century. Our findings suggest a strong link between climate and functional diversity and redundancy with the three trait groups responding similarly across the tropics and climate gradient. We show that drier tropical forests are overall less functionally diverse than wetter forests and that functional redundancy declines with increasing soil water and vapour pressure deficits. Areas with high functional diversity and high functional redundancy tend to better maintain ecosystem functioning, such as aboveground biomass, after extreme weather events. Our predictions suggest that the lower functional diversity and lower functional redundancy of drier tropical forests, in comparison with wetter forests, may leave them more at risk of shifting towards alternative states in face of further declines in water availability across tropical regions., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Alkaline hot springs in Yellowstone National Park (YNP) provide a framework to study the relationship between photoautotrophs and temperature. Previous work has focused on studying how cyanobacteria (oxygenic phototrophs) vary with temperature, sulfide, and pH, but many questions remain regarding the ecophysiology of anoxygenic photosynthesis due to the taxonomic and metabolic diversity of these taxa. To this end, we examined the distribution of genes involved in phototrophy, carbon fixation, and nitrogen fixation in eight alkaline (pH 7.3-9.4) hot spring sites near the upper temperature limit of photosynthesis (71ºC) in YNP using metagenome sequencing. Based on genes encoding key reaction center proteins, geographic isolation plays a larger role than temperature in selecting for distinct phototrophic Chloroflexi, while genes typically associated with autotrophy in anoxygenic phototrophs, did not have distinct distributions with temperature. Additionally, we recovered Calvin cycle gene variants associated with Chloroflexi, an alternative carbon fixation pathway in anoxygenic photoautotrophs. Lastly, we recovered several abundant nitrogen fixation gene sequences associated with Roseiflexus, providing further evidence that genes involved in nitrogen fixation in Chloroflexi are more common than previously assumed. Together, our results add to the body of work on the distribution and functional potential of phototrophic bacteria in Yellowstone National Park hot springs and support the hypothesis that a combination of abiotic and biotic factors impact the distribution of phototrophic bacteria in hot springs. Future studies of isolates and metagenome assembled genomes (MAGs) from these data and others will further our understanding of the ecology and evolution of hot spring anoxygenic phototrophs. IMPORTANCE Photosynthetic bacteria in hot springs are of great importance to both microbial evolution and ecology. While a large body of work has focused on oxygenic photosynthesis in cyanobacteria in Mushroom and Octopus Springs in Yellowstone National Park, many questions remain regarding the metabolic potential and ecology of hot spring anoxygenic phototrophs. Anoxygenic phototrophs are metabolically and taxonomically diverse, and further investigations into their physiology will lead to a deeper understanding of microbial evolution and ecology of these taxa. Here, we have quantified the distribution of key genes involved in carbon and nitrogen metabolism in both oxygenic and anoxygenic phototrophs. Our results suggest that temperature >68ºC selects for distinct groups of cyanobacteria and that carbon fixation pathways associated with these taxa are likely subject to the same selective pressure. Additionally, our data suggest that phototrophic Chloroflexi genes and carbon fixation genes are largely influenced by local conditions as evidenced by our gene variant analysis. Lastly, we recovered several genes associated with potentially novel phototrophic Chloroflexi. Together, our results add to the body of work on hot springs in Yellowstone National Park and set the stage for future work on metagenome assembled genomes.

In 2020, the Australian and New Zealand flux research and monitoring network, OzFlux, celebrated its 20 th anniversary by reflecting on the lessons learned through two decades of ecosystem studies on global change biology. OzFlux is a network not only for ecosystem researchers, but also for those 'next users' of the knowledge, information and data that such networks provide. Here, we focus on eight lessons across topics of climate change and variability, disturbance and resilience, drought and heat stress and synergies with remote sensing and modelling. In distilling the key lessons learned, we also identify where further research is needed to fill knowledge gaps and improve the utility and relevance of the outputs from OzFlux. Extreme climate variability across Australia and New Zealand (droughts and flooding rains) provides a natural laboratory for a global understanding of ecosystems in this time of accelerating climate change. As evidence of worsening global fire risk emerges, the natural ability of these ecosystems to recover from disturbances, such as fire and cyclones, provides lessons on adaptation and resilience to disturbance. Drought and heatwaves are common occurrences across large parts of the region and can tip an ecosystem's carbon budget from a net CO 2 sink to a net CO 2 source. Despite such responses to stress, ecosystems at OzFlux sites show their resilience to climate variability by rapidly pivoting back to a strong carbon sink upon the return of favourable conditions. Located in under-represented areas, OzFlux data have the potential for reducing uncertainties in global remote sensing products, and these data provide several opportunities to develop new theories and improve our ecosystem models. The accumulated impacts of these lessons over the last 20 years highlights the value of long-term flux observations for natural and managed systems. A future vision for OzFlux includes ongoing and newly developed synergies with ecophysiologists, ecologists, geologists, remote sensors and modellers., (© 2022 The Authors. Global Change Biology published by John Wiley & Sons Ltd.)

Gross primary productivity (GPP) of wooded ecosystems (forests and savannas) is central to the global carbon cycle, comprising 67%-75% of total global terrestrial GPP. Climate change may alter this flux by increasing the frequency of temperatures beyond the thermal optimum of GPP (T opt ). We examined the relationship between GPP and air temperature (Ta) in 17 wooded ecosystems dominated by a single plant functional type (broadleaf evergreen trees) occurring over a broad climatic gradient encompassing five ecoregions across Australia ranging from tropical in the north to Mediterranean and temperate in the south. We applied a novel boundary-line analysis to eddy covariance flux observations to (a) derive ecosystem GPP-Ta relationships and T opt (including seasonal analyses for five tropical savannas); (b) quantitatively and qualitatively assess GPP-Ta relationships within and among ecoregions; (c) examine the relationship between T opt and mean daytime air temperature (MDTa) across all ecosystems; and (d) examine how down-welling short-wave radiation (Fsd) and vapour pressure deficit (VPD) influence the GPP-Ta relationship. GPP-Ta relationships were convex parabolas with narrow curves in tropical forests, tropical savannas (wet season), and temperate forests, and wider curves in temperate woodlands, Mediterranean woodlands, and tropical savannas (dry season). Ecosystem T opt ranged from 15℃ (temperate forest) to 32℃ (tropical savanna-wet and dry seasons). The shape of GPP-Ta curves was largely determined by daytime Ta range, MDTa, and maximum GPP with the upslope influenced by Fsd and the downslope influenced by VPD. Across all ecosystems, there was a strong positive linear relationship between T opt and MDTa (Adjusted R 2 : 0.81; Slope: 1.08) with T opt exceeding MDTa by >1℃ at all but two sites. We conclude that ecosystem GPP has adjusted to local MDTa within Australian broadleaf evergreen forests and that GPP is buffered against small Ta increases in the majority of these ecosystems., (© 2021 John Wiley & Sons Ltd.)

Biosimilars are biologic drug products that are highly similar to reference products in analytic features, pharmacokinetics and pharmacodynamics, immunogenicity, safety, and efficacy. Biosimilar epoetin received Food and Drug Administration (FDA) approval in 2018. The manufacturer received an FDA nonapproval letter in 2017, despite receiving a favorable review by FDA's Oncologic Drugs Advisory Committee (ODAC) and an FDA nonapproval letter in 2015 for an earlier formulation. We discuss the 2018 FDA approval, the 2017 FDA ODAC Committee review, and the FDA complete response letters in 2015 and 2017; review concepts of litigation, naming, labeling, substitution, interchangeability, and pharmacovigilance; review European and U.S. oncology experiences with biosimilar epoetin; and review the safety of erythropoiesis-stimulating agents. In 2020, policy statements from AETNA, United Health Care, and Humana indicated that new epoetin oncology starts must be for biosimilar epoetin unless medical need for other epoetins is documented. Empirical studies report that as of 2012, reference epoetin use decreased from 40%-60% of all patients with cancer with chemotherapy-induced anemia to <5% of such patients because of safety concerns. Between 2018 and 2020, biosimilar epoetin use varied, increasing to 81% among one private insurer's patients covered by Medicare whose cancer care is administered with Oncology Analytics and to 41% with the same private insurer's patients with cancer covered by commercial health insurance and administered by the private insurer, to 0% in several Veterans Administration Hospitals, increasing to 100% in one large county hospital in California, and with yet-to-be-reported data from most oncology settings. We conclude that biosimilar epoetin appears to have overcome some barriers since 2015, although current uptake in the U.S. is variable. Pricing and safety considerations for all erythropoiesis-stimulating agents are primary determinants of biosimilar epoetin oncology uptake. IMPLICATIONS FOR PRACTICE: Few oncologists understand substitution and interchangeability of biosimilars with reference drugs. Epoetin biosimilar is new to the market, and physician and patient understanding is limited. The development of epoetin biosimilar is not familiar to oncologists., (© 2021 AlphaMed Press.)

Aim: Serological assays for the detection of anti-SARS coronavirus-2 (SARS-CoV-2) antibodies are essential to the response to the global pandemic. A ligand binding-based serological assay was validated for the semiquantitative detection of IgG, IgM, IgA and neutralizing antibodies (nAb) against SARS-CoV-2 in serum. Results: The assay demonstrated high levels of diagnostic specificity and sensitivity (85-99% for all analytes). Serum IgG, IgM, IgA and nAb correlated positively (R 2  = 0.937, R 2  = 0.839, R 2  = 0.939 and R 2  = 0.501, p < 0.001, respectively) with those measured in dried blood spot samples collected using the hemaPEN ® microsampling device (Trajan Scientific and Medical, Victoria, Australia). In vitro SARS-CoV-2 pseudotype neutralization correlated positively with the solid phase nAb signals in convalescent donors (R 2  = 0.458, p < 0.05). Conclusion: The assay is applicable in efficacy studies, infection monitoring and postmarketing surveillance following vaccine rollout.

Progressive multifocal leukoencephalopathy (PML) is a serious and usually fatal CNS infection caused by the John Cunningham virus. CD4 + and CD8 + T-cell lymphopenia, resulting from HIV infection, chemotherapy, or immunosuppressive therapy, are primary risk factors for PML. Following its introduction in 1997, the immunomodulatory anti-CD20 monoclonal antibody, rituximab, has received regulatory approval worldwide for treatment of non-Hodgkin lymphoma, rheumatoid arthritis, chronic lymphocytic leukaemia, granulomatosis with polyangiitis, microscopic polyangiitis, and pemphigus vulagris. Rituximab leads to prolonged B-lymphocyte depletion, potentially allowing John Cunningham viral infection to occur. Six unexpected cases of PML infection developing in rituximab-treated patients were first reported in 2002. We review 20 years of information on clinical findings, pathology, epidemiology, proposed pathogenesis, and risk-management issues associated with PML infection developing after rituximab treatment. Since the first case series report of 52 cases of rituximab-associated PML among patients with non-Hodgkin lymphoma or chronic lymphocytic leukaemia in 2009, updated and diligent pharmacovigilance efforts have provided reassurance that this fatal toxicity is a rare clinical event with concurring causal factors. International harmonisation of safety warnings around rituximab-associated PML should be considered, with these notifications listing rituximab-associated PML under a section titled warnings and precautions as is the case in most countries, rather than a boxed warning as is the case in the USA., Competing Interests: Declaration of interests JOA reports being a member of and on the board of directors for Cardiff Oncology and consulting for Samus Therapeutics Ascentage. JRB reports grants and personal fees from Biogen and Genentech–Roche; and personal fees from Bristol Myers Squibb, Celgene, Dr Reddy, Excision Bio, Inhibikase, Merck, Amgen, Serono, Genzyme, Morphic, Encycle, Genzyme, Millennium–Takeda, and Mapi, outside of the submitted work. All other authors declare no competing interests., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Tropical forests store 40-50 per cent of terrestrial vegetation carbon 1 . However, spatial variations in aboveground live tree biomass carbon (AGC) stocks remain poorly understood, in particular in tropical montane forests 2 . Owing to climatic and soil changes with increasing elevation 3 , AGC stocks are lower in tropical montane forests compared with lowland forests 2 . Here we assemble and analyse a dataset of structurally intact old-growth forests (AfriMont) spanning 44 montane sites in 12 African countries. We find that montane sites in the AfriMont plot network have a mean AGC stock of 149.4 megagrams of carbon per hectare (95% confidence interval 137.1-164.2), which is comparable to lowland forests in the African Tropical Rainforest Observation Network 4 and about 70 per cent and 32 per cent higher than averages from plot networks in montane 2,5,6 and lowland 7 forests in the Neotropics, respectively. Notably, our results are two-thirds higher than the Intergovernmental Panel on Climate Change default values for these forests in Africa 8 . We find that the low stem density and high abundance of large trees of African lowland forests 4 is mirrored in the montane forests sampled. This carbon store is endangered: we estimate that 0.8 million hectares of old-growth African montane forest have been lost since 2000. We provide country-specific montane forest AGC stock estimates modelled from our plot network to help to guide forest conservation and reforestation interventions. Our findings highlight the need for conserving these biodiverse 9,10 and carbon-rich ecosystems., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

The responses of tropical forests to environmental change are critical uncertainties in predicting the future impacts of climate change. The positive phase of the 2015-2016 El Niño Southern Oscillation resulted in unprecedented heat and low precipitation in the tropics with substantial impacts on the global carbon cycle. The role of African tropical forests is uncertain as their responses to short-term drought and temperature anomalies have yet to be determined using on-the-ground measurements. African tropical forests may be particularly sensitive because they exist in relatively dry conditions compared with Amazonian or Asian forests, or they may be more resistant because of an abundance of drought-adapted species. Here, we report responses of structurally intact old-growth lowland tropical forests inventoried within the African Tropical Rainforest Observatory Network (AfriTRON). We use 100 long-term inventory plots from six countries each measured at least twice prior to and once following the 2015-2016 El Niño event. These plots experienced the highest temperatures and driest conditions on record. The record temperature did not significantly reduce carbon gains from tree growth or significantly increase carbon losses from tree mortality, but the record drought did significantly decrease net carbon uptake. Overall, the long-term biomass increase of these forests was reduced due to the El Niño event, but these plots remained a live biomass carbon sink (0.51 ± 0.40 Mg C ha -1 y -1 ) despite extreme environmental conditions. Our analyses, while limited to African tropical forests, suggest they may be more resistant to climatic extremes than Amazonian and Asian forests., Competing Interests: The authors declare no competing interest., (Copyright © 2021 the Author(s). Published by PNAS.)

Background: A two-phase study (clinical and genomic-based) was conducted to evaluate the effect of timing of chronic obstructive pulmonary disease (COPD) diagnosis on lung cancer outcomes., Methods: The prognostic influence of COPD was investigated in a clinical cohort of 1,986 patients who received surgery for stage I lung cancer; 823 (41.4%) of them also had COPD, including 549 (27.6%) incidental COPD (diagnosed within 6-months of lung cancer diagnosis) and 274 (13.8%) prior COPD (>6 months before lung cancer diagnosis). The genomic variations were analyzed from another cohort of 1,549 patients for association with 384 lung cancer-related single nucleotide polymorphisms (SNPs)., Results: Older age (≥70 years), smokers, and respiratory symptoms were independent predictors of incidental COPD in lung cancer (all P<0.05). Similar to prior COPD, incidental COPD increased postoperative complications and worsened quality-of-life related to dyspnea (both P<0.05). Multivariate Cox regression analysis showed lung cancer survival decreased significantly in incidental COPD (HR, 1.30; 95% CI, 1.02-1.66), but not in prior COPD (HR, 1.15; 95% CI, 0.87-1.52). Among prior COPD, median survival showed a trend for being better in those with fewer exacerbations (0-1 vs. ≥2 exacerbation/year; 6.1 vs. 4.1 years; P=0.10). The SNP-based analysis identified ADCY2:rs52827085 was significantly associated with risk of incidental COPD (OR, 1.76; 95% CI, 1.30-2.38) and NRXN1:rs1356888 associated with prior COPD complicated with lung cancer (OR, 1.73; 95% CI, 1.29-2.33)., Conclusions: Different long-term survival and genomic variants were observed between lung cancer patients with incidental and with prior COPD, suggesting timing of COPD diagnosis should be considered in lung cancer clinical management and mechanistic research., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/tlcr-20-1017). The authors have no conflicts of interest to declare., (2021 Translational Lung Cancer Research. All rights reserved.)

Objective: This paper will discuss the process of mapping opioid use disorder (OUD) treatment resources for pregnant women and discuss the intersection between treatment resources and rates of neonatal abstinence syndrome (NAS)., Design: A resource manual was developed through a systematic process with stakeholders across Illinois. Resources were mapped by county and overlaid with county rates of NAS, using hospital discharge data., Results: Across Illinois, 89 treatment resources were identified for pregnant women insured by Medicaid. Resources were concentrated in 36% of Illinois' counties. Counties with limited treatment resources generally had high rates of NAS. Sixty-six percent of NAS cases among rural Illinois residents had no OUD treatment resources in their county. Rural counties had less access to medication-assisted treatment (MAT), the standard of care for treatment of OUD, compared with other counties across the state., Conclusions: Efforts to increase OUD treatment options for pregnant women insured by Medicaid should concentrate on geographic areas with limited access and high need., (© 2020 Wiley Periodicals LLC.)

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).)

Photosynthetic bacteria are abundant in alkaline, terrestrial hot springs and there is a long history of research on phototrophs in Yellowstone National Park (YNP). Hot springs provide a framework to examine the ecophysiology of phototrophs in situ because they provide natural gradients of geochemistry, pH and temperature. Phototrophs within the Cyanobacteria and Chloroflexi groups are frequently observed in alkaline hot springs. Decades of research has determined that temperature constrains Cyanobacteria in alkaline hot springs, but factors that constrain the distribution of phototrophic Chloroflexi remain unresolved. Using a combination of 16S rRNA gene sequencing and photoassimilation microcosms, we tested the hypothesis that temperature would constrain the activity and composition of phototrophic Cyanobacteria and Chloroflexi. We expected diversity and rates of photoassimilation to decrease with increasing temperature. We report 16S rRNA amplicon sequencing along with carbon isotope signatures and photoassimilation from 45 to 72°C in two alkaline hot springs. We find that Roseiflexus, Chloroflexus (Chloroflexi) and Leptococcus (Cyanobacteria) operational taxonomic units (OTUs) have distinct distributions with temperature. This distribution suggests that, like phototrophic Cyanobacteria, temperature selects for specific phototrophic Chloroflexi taxa. The richness of phototrophic Cyanobacteria decreased with increasing temperature along with a decrease in oxygenic photosynthesis, whereas Chloroflexi richness and rates of anoxygenic photosynthesis did not decrease with increasing temperature, even at temperatures approaching the upper limit of photosynthesis (~72-73°C). Our carbon isotopic data suggest an increasing prevalence of the 3-hydroxypropionate pathway with decreasing temperature coincident with photoautotrophic Chloroflexi. Together these results indicate temperature plays a role in defining the niche space of phototrophic Chloroflexi (as has been observed for Cyanobacteria), but other factors such as morphology, geochemistry, or metabolic diversity of Chloroflexi, in addition to temperature, could determine the niche space of this highly versatile group., (© 2020 The Authors. Environmental Microbiology Reports published by Society for Applied Microbiology and John Wiley & Sons Ltd.)

Introduction: Pulmonary fibrosis includes several lung disorders characterized by progressive fibrosis, of which idiopathic pulmonary fibrosis (IPF) is a particularly severe form with a median survival time of 3-5 years after diagnosis. Although numerous compounds have shown efficacy in attenuating pulmonary fibrosis using animal models, only a few compounds have shown their beneficial effects for IPF in clinical trials. Thus, there is an ongoing need to improve the preclinical development process to better identify, characterize and select clinically useful targets., Areas Covered: In this review, we extensively describe current models of pulmonary fibrosis, focusing on rodent models, ex vivo models, and in vitro models., Expert Opinion: Based upon our current understanding, improving the identification and characterization of clinically relevant molecules or pathways responsible for progressive fibrotic diseases and use of the robust preclinical model system to test these will be required to improve the drug development pipeline for pulmonary fibrosis. Combination of appropriate preclinical models with ex vivo (precision-cut lung slices) or in vitro models will benefit high-throughput drug discovery and validation of drug effects.

The sensitivity of tropical forest carbon to climate is a key uncertainty in predicting global climate change. Although short-term drying and warming are known to affect forests, it is unknown if such effects translate into long-term responses. Here, we analyze 590 permanent plots measured across the tropics to derive the equilibrium climate controls on forest carbon. Maximum temperature is the most important predictor of aboveground biomass (-9.1 megagrams of carbon per hectare per degree Celsius), primarily by reducing woody productivity, and has a greater impact per °C in the hottest forests (>32.2°C). Our results nevertheless reveal greater thermal resilience than observations of short-term variation imply. To realize the long-term climate adaptation potential of tropical forests requires both protecting them and stabilizing Earth's climate., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Importance: Reducing neonatal mortality is a national health care priority. Understanding the association between neonatal mortality and antenatal transfer of pregnant women to a level III perinatal hospital for delivery of infants who are very preterm (VPT) may help identify opportunities for improvement., Objective: To assess whether antenatal transfer to a level III hospital is associated with neonatal mortality in infants who are VPT., Design, Setting, and Participants: This population-based cross-sectional study included infants who were born VPT to Illinois residents in Illinois perinatal-network hospitals between January 1, 2015, and December 31, 2016, and followed up for 28 days after birth. Data analysis was conducted from June 2017 to September 2018., Exposures: Delivery of an infant who was VPT at a (1) level III hospital after maternal presentation at that hospital (reference group), (2) a level III hospital after antenatal (in utero) transfer from another hospital, or (3) a non-level III hospital., Main Outcomes and Measures: Neonatal mortality., Results: The study included 4817 infants who were VPT (gestational age, 22-31 completed weeks) and were born to Illinois residents in 2015 and 2016. Of those, 3302 infants (68.5%) were born at a level III hospital after maternal presentation at that hospital, 677 (14.1%) were born at a level III hospital after antenatal transfer, and 838 (17.4%) were born at a non-level III hospital. Neonatal mortality for all infants who were VPT included in this study was 573 of 4817 infants (11.9%). The neonatal mortality was 10.7% for the reference group (362 of 3302 infants), 9.8% for the antenatal transfer group (66 of 677 infants), and 17.3% for the non-level III birth group (145 of 838 infants). When adjusted for significant social and medical characteristics, infants born VPT at a level III hospital after antenatal transfer from another facility had a similar risk of neonatal mortality as infants born at a level III hospital (odds ratio, 0.79 [95% CI, 0.56-1.13]) after maternal presentation at the same hospital. Infants born at a non-level III hospital had an increased risk of neonatal mortality compared with infants born at a level III hospital after maternal presentation to the same hospital (odds ratio, 1.52 [95% CI, 1.14-2.02])., Conclusions and Relevance: The risk of neonatal mortality was similar for infants who were VPT, whether women initially presented at a level III hospital or were transferred to a level III hospital before delivery. This suggests that the increased risk of mortality associated with delivery at a non-level III hospital may be mitigated by optimizing opportunities for early maternal transfer to a level III hospital.

Structurally intact tropical forests sequestered about half of the global terrestrial carbon uptake over the 1990s and early 2000s, removing about 15 per cent of anthropogenic carbon dioxide emissions 1-3 . Climate-driven vegetation models typically predict that this tropical forest 'carbon sink' will continue for decades 4,5 . Here we assess trends in the carbon sink using 244 structurally intact African tropical forests spanning 11 countries, compare them with 321 published plots from Amazonia and investigate the underlying drivers of the trends. The carbon sink in live aboveground biomass in intact African tropical forests has been stable for the three decades to 2015, at 0.66 tonnes of carbon per hectare per year (95 per cent confidence interval 0.53-0.79), in contrast to the long-term decline in Amazonian forests 6 . Therefore the carbon sink responses of Earth's two largest expanses of tropical forest have diverged. The difference is largely driven by carbon losses from tree mortality, with no detectable multi-decadal trend in Africa and a long-term increase in Amazonia. Both continents show increasing tree growth, consistent with the expected net effect of rising atmospheric carbon dioxide and air temperature 7-9 . Despite the past stability of the African carbon sink, our most intensively monitored plots suggest a post-2010 increase in carbon losses, delayed compared to Amazonia, indicating asynchronous carbon sink saturation on the two continents. A statistical model including carbon dioxide, temperature, drought and forest dynamics accounts for the observed trends and indicates a long-term future decline in the African sink, whereas the Amazonian sink continues to weaken rapidly. Overall, the uptake of carbon into Earth's intact tropical forests peaked in the 1990s. Given that the global terrestrial carbon sink is increasing in size, independent observations indicating greater recent carbon uptake into the Northern Hemisphere landmass 10 reinforce our conclusion that the intact tropical forest carbon sink has already peaked. This saturation and ongoing decline of the tropical forest carbon sink has consequences for policies intended to stabilize Earth's climate.

Extant anoxygenic phototrophs are taxonomically, physiologically, and metabolically diverse and include examples from all seven bacterial phyla with characterized phototrophic members. pH, temperature, and sulfide are known to constrain phototrophs, but how these factors dictate the distribution and activity of specific taxa of anoxygenic phototrophs has not been reported. Here, we hypothesized that within the known limits of pH, temperature, and sulfide, the distribution, abundance, and activity of specific anoxygenic phototrophic taxa would vary due to key differences in the physiology of these organisms. To test this hypothesis, we examined the distribution, abundance, and potential activity of anoxygenic phototrophs in filaments, microbial mats, and sediments across geochemical gradients in geothermal features of Yellowstone National Park, which ranged in pH from 2.2 to 9.4 and in temperature from 31.5°C to 71.0°C. Indeed, our data indicate putative aerobic anoxygenic phototrophs within the Proteobacteria are more abundant at lower pH and lower temperature, while phototrophic Chloroflexi are prevalent in circumneutral to alkaline springs. In contrast to previous studies, our data suggest sulfide is not a key determinant of anoxygenic phototrophic taxa. Finally, our data underscore a role for photoheterotrophy (or photomixotrophy) across geochemical gradients in terrestrial geothermal ecosystems. IMPORTANCE There is a long and rich history of literature on phototrophs in terrestrial geothermal springs. These studies have revealed sulfide, pH, and temperature are the main constraints on phototrophy. However, the taxonomic and physiological diversity of anoxygenic phototrophs suggests that, within these constraints, specific geochemical parameters determine the distribution and activity of individual anoxygenic phototrophic taxa. Here, we report the recovery of sequences affiliated with characterized anoxygenic phototrophs in sites that range in pH from 2 to 9 and in temperature from 31°C to 71°C. Transcript abundance indicates anoxygenic phototrophs are active across this temperature and pH range. Our data suggest sulfide is not a key determinant of anoxygenic phototrophic taxa and underscore a role for photoheterotrophy in terrestrial geothermal ecosystems. These data provide the framework for high-resolution sequencing and in situ activity approaches to characterize the physiology of specific anoxygenic phototrophic taxa across a broad range of temperatures and pH., (Copyright © 2019 Hamilton et al.)

Introduction : Ciprofloxacin, levofloxacin, and moxifloxacin belong to the fluoroquinolone class of antibiotics and are amongst the most commonly prescribed antibiotics. In 2018 and 2019, Food and Drug Administration (FDA) and the European Medicine Agency (EMA) requested that manufacturers harmonize FQ safety information related to neuropsychiatric, aortic dissection, and long-term disability. The authors hypothesize that FDA and EMA epidemiologists support a strong association between these drugs and the three toxicities. Areas covered : Studies of FQ-associated neuropsychiatric toxicity, long-term disability, and aortic ruptures/dissections. Clinical sources include FDA Advisory Committee documents, a 2014 Citizen Petition filed with the FDA requesting safety information additions to FQ labels for neuropsychiatric toxicities (partially granted in 2018), an under-review Citizen Petition under review by the FDA requesting a FQ Risk Evaluation and Mitigation Strategy, and safety notifications from the EMA. Expert opinion : FDA and the EMA report state that neuropsychiatric toxicity, long-term disability, and aortic dissections//aneurysms occur with all FQs. Disability and neuropsychiatric toxicity can occur after one dose or several months after FQs. United States' and European' regulators warn physicians not to prescribe FQs for uncomplicated acute urinary tract infection, sinusitis, or bronchitis, unless other possible choices are tried first, as risks outweigh benefits in these settings.

Cyanidin and chlorogenic acid are polyphenols from plant origin that are present in many common fruits, particularly in berries. To corroborate the protective or detrimental effects of both compounds from a neuro-inflammatory perspective, in vitro experiments were carried out in human astrocytes (U-373). Astrocytes were pre-treated with a range of concentrations of either cyanidin, chlorogenic acid or a combined treatment for a period of 30 min, before exposure to Escherichia coli lipopolysaccharide (LPS) challenge for 23.5 h, after which cytotoxicity (propidium iodide exclusion assay), cytoprotective effects (XTT assay) and effects on functional capacity (secretion of pro-inflammatory cytokines IL-6 and MCP-1) were evaluated. No treatment resulted in cytotoxicity, but high dose (20 µg/mL) LPS significantly reduced mitochondrial reductive capacity (p < 0.001). This effect was prevented in a dose-dependent manner by both cyanidin and chlorogenic acid, as well as by the combination treatment. However, in the absence of LPS, IL-6 secretion was significantly increased in response to 2 µM of either cyanidin or chlorogenic acid (both p < 0.0001), as well as the combination treatment (p < 0.01). MCP-1 secretion followed a similar trend, but did not reach statistical significance. Although we acknowledge the requirement for in vivo investigations to validate our interpretations, current data highlight the potential risk for antioxidant toxicity that is linked to high dose supplementation with single compound antioxidants. Research focused at elucidating synergistic effects between different antioxidants is required to minimise risk of adverse effects.

Introduction: Mental health and substance use are growing public health concerns, but established surveillance methods do not measure the burden of these conditions among women of reproductive age. We developed a standardized indicator from administrative data to identify inpatient hospitalizations related to mental health or substance use (MHSU) among women of reproductive age, as well as co-occurrence of mental health and substance use conditions among those hospitalizations., Materials and Methods: We used inpatient hospital discharge data from 2012-2014 for women aged 15-44 residing in Illinois and Wisconsin. We identified MHSU-related hospitalizations through the principal International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) diagnosis and first-listed ICD-9-CM external cause of injury code (E code). We classified hospitalizations as related to 1 of 3 mutually exclusive categories: a mental disorder, a substance use disorder, or an acute MHSU-related event. We defined co-occurrence as the presence of both mental health and substance use codes in any available diagnosis or E-code field., Results: Of 1 173 758 hospitalizations of women of reproductive age, 150 318 (12.8%) were related to a mental disorder, a substance use disorder, or an acute MHSU-related event, for a rate of 135.6 hospitalizations per 10 000 women. Of MHSU-related hospitalizations, 115 163 (76.6%) were for a principal mental disorder, 22 466 (14.9%) were for a principal substance use disorder, and 12 709 (8.5%) were for an acute MHSU-related event; 42.4% had co-occurring mental health codes and substance use codes on the discharge record., Practice Implications: MHSU-related disorders and events are common causes of hospitalization for women of reproductive age, and nearly half of these hospitalizations involved co-occurring mental health and substance use diagnoses or events. This new indicator may improve public health surveillance by establishing a systematic and comprehensive method to measure the burden of MHSU-related hospitalizations among women of reproductive age.

The link between obesity-induced systemic inflammation and decreased insulin signalling is well-known. It is also known that peripherally produced inflammatory cytokines can cross the blood-brain barrier, resulting in the release of neurotoxins that can ultimately lead to the demise of central nervous system integrity. A high-mesembrine Sceletium tortuosum extract was recently shown to possess cytoprotective and mild anti-inflammatory properties in monocytes and to target specific p450 enzymes to reduce adrenal glucocorticoid synthesis. This is significant since the aetiology of both obesity and diabetes is linked to inflammation and excess glucocorticoid production. Given the interlinked nature of glucocorticoid action and inflammation, central immunomodulatory effects of two Sceletium tortuosum extracts prepared by different extraction methods were investigated. Human astrocytes were pre-treated for 30 min, before exposure to Escherichia coli lipopolysaccharide for 23.5 h (in the presence of treatment). Cytotoxicity, mitotoxicity and cytokine responses (basally and in response to inflammatory stimulus) were assessed. In addition, total polyphenol content, antioxidant capacity and selected neural enzyme inhibition capacity were assessed for both extracts. The high-mesembrine Sceletium extract exerted cytoprotective and anti-inflammatory effects. In contrast, the high delta7-mesembrenone extract, rich in polyphenols, exhibited potent antioxidant effect, although with relatively higher risk of adverse effects with overdose. We conclude that both Sceletium tortuosum extracts may be employed as either a preventative supplement or complimentary treatment in the context of obesity and diabetes; however, current data also highlights the impact that extraction methods can have on plant product mechanism of action.

Ethnopharmacological Relevance: Sceletium tortuosum, among other Sceletium species, was traditionally used by the Khoisan people of Southern Africa for relief of pain-related ailments. However, the commercial availability of this supplement has greatly expanded due to anecdotal claims of its mood-elevating and anxiolytic properties. Unrelated research has elucidated a significant link between cytokines and the mediation of depression. Therefore, the effect of Sceletium supplementation on immune cell functionality is of interest, since the efficacy of potential depression treatments could, at least in part, rely on downregulation of pro-inflammatory signalling., Aim of the Study: The current study evaluated the immunomodulatory effects of a Sceletium extract, both basally and in the context of acute endotoxin stimulation., Materials and Methods: Primary human monocytes were supplemented with either a 0.01mg/ml or 1mg/ml Sceletium extract dose, with or without E. coli LPS stimulation in vitro, for 24h. Mitochondrial viability, as an indirect measure of cytotoxicity, and cytokine release in response to the treatment intervention were assessed., Results: Sceletium extract treatment was associated with increased mitochondrial viability, as well as up-regulated IL-10 release under basal conditions. LPS exposure significantly decreased mitochondrial viability, but this was prevented completely under Sceletium-treated conditions. The acute inflammatory response to LPS stimulation was not negatively affected. Sceletium treatment conferred most significant effects at a dose of 0.01mg/ml., Conclusions: Sceletium exerts significant cytoprotective effects in the setting of endotoxin stimulation. Cytokine assessment indicated that Sceletium possesses mild anti-inflammatory properties, but does not hinder the mounting of an adequate immune response to acute immune challenge. These findings indicate that Sceletium may be beneficial for the attenuation of cytokine-induced depression, as well as in systemic low-grade inflammation., (Copyright © 2017 Elsevier B.V. All rights reserved.)

If fieldable riboswitch-based biological sensors are to fulfill their potential, it is necessary to increase their signal output. Here we report a novel modular amplification system using a riboswitch to initiate signaling between a sensing strain and a reporter strain of E. coli. A quorum sensing signaling molecule biologically wires the sensing and reporter strains together. The amplification circuit increased the amount of fluorescence generated on ligand binding compared to when the riboswitch controlled fluorescence expression directly. This had the corollary effect of increasing the sensitivity of the system, and allowed riboswitch-based reporting in E. coli strains that did not produce a detectable output when the riboswitch directly controlled reporter expression. The amplification circuit also reduced the time required to detect a signal output. The modularity of this amplification system coupled with the achievable increases in output can advance the development of riboswitches and biological sensors.

An MRI of the brain and spine of an 11-year-old male revealed the following abnormality which is consistent with his chronic condition.

The frequency of severe droughts is increasing in many regions around the world as a result of climate change(1-3). Droughts alter the structure and function of forests(4,5). Site- and region-specific studies suggest that large trees, which play keystone roles in forests(6) and can be disproportionately important to ecosystem carbon storage(7) and hydrology(8), exhibit greater sensitivity to drought than small trees(4,5,9,10). Here, we synthesize data on tree growth and mortality collected during 40 drought events in forests worldwide to see whether this size-dependent sensitivity to drought holds more widely. We find that droughts consistently had a more detrimental impact on the growth and mortality rates of larger trees. Moreover, drought-related mortality increased with tree size in 65% of the droughts examined, especially when community-wide mortality was high or when bark beetles were present. The more pronounced drought sensitivity of larger trees could be underpinned by greater inherent vulnerability to hydraulic stress(11-14), the higher radiation and evaporative demand experienced by exposed crowns(4,15), and the tendency for bark beetles to preferentially attack larger trees(16). We suggest that future droughts will have a more detrimental impact on the growth and mortality of larger trees, potentially exacerbating feedbacks to climate change.

Concussive and subconcussive head injury is a global phenomenon that affects millions of people each year. Concussive injury has been extensively studied in sport, which has led to a greater understanding of the biomechanical forces involved and guidelines aimed at preventing athletes from playing while concussed. Subconcussive forces by definition do not meet the threshold for concussion but nonetheless may have significant long term consequences due to the repetitive pattern of injury to the head. Quantifying these impact forces using a forensic head model provides the groundwork for future studies by establishing a range or threshold of subconcussive impact forces that could be correlated with clinical assessments. The use of a forensic head model has distinct advantages in terms of ethics and safety., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Global change is impacting forests worldwide, threatening biodiversity and ecosystem services including climate regulation. Understanding how forests respond is critical to forest conservation and climate protection. This review describes an international network of 59 long-term forest dynamics research sites (CTFS-ForestGEO) useful for characterizing forest responses to global change. Within very large plots (median size 25 ha), all stems ≥ 1 cm diameter are identified to species, mapped, and regularly recensused according to standardized protocols. CTFS-ForestGEO spans 25 °S-61 °N latitude, is generally representative of the range of bioclimatic, edaphic, and topographic conditions experienced by forests worldwide, and is the only forest monitoring network that applies a standardized protocol to each of the world's major forest biomes. Supplementary standardized measurements at subsets of the sites provide additional information on plants, animals, and ecosystem and environmental variables. CTFS-ForestGEO sites are experiencing multifaceted anthropogenic global change pressures including warming (average 0.61 °C), changes in precipitation (up to ± 30% change), atmospheric deposition of nitrogen and sulfur compounds (up to 3.8 g N m(-2) yr(-1) and 3.1 g S m(-2) yr(-1)), and forest fragmentation in the surrounding landscape (up to 88% reduced tree cover within 5 km). The broad suite of measurements made at CTFS-ForestGEO sites makes it possible to investigate the complex ways in which global change is impacting forest dynamics. Ongoing research across the CTFS-ForestGEO network is yielding insights into how and why the forests are changing, and continued monitoring will provide vital contributions to understanding worldwide forest diversity and dynamics in an era of global change., (© 2014 John Wiley & Sons Ltd.)

Background: In stark contrast to the J or U- shaped relationship between age and low birth weight rates (< 2500g) seen among non-Latino White and Mexican American mothers, low birth weight rates among US-born Blacks are lowest in their teens and rise with increasing age (ie, weathering). The age-related pattern of low birth weight rates among foreign-born Black mothers is unknown., Objective: To determine the relationship between age and low birth weight rates among foreign-born Black mothers., Design: Stratified analyses were performed on the 2003-2004 National Center for Health Statistics vital record datasets of foreign-born Black mothers. Maternal age was categorized into six subgroups. Potential confounding variables examined included marital status, parity, and prenatal care usage., Results: Foreign-born Black mothers (N = 143,235) demonstrated a J/U-shaped age-related pattern of low birth weight rates with the lowest rates observed among those in their twenties and early thirties. The subgroups of 15-19 and 35-39 year old mothers had low birth weight rates of 12.0% and 11.4% compared to 9.1% for 25-29 year old mothers; RR = 1.31 (1.22-1.42) and 1.25 (1.20-1.31), respectively. The J/U-shaped age-related pattern persisted independent of marital status, parity and prenatal care usage., Conclusions: Foreign-born black mothers do not exhibit a weathering pattern of rising low birth weight rates with advancing age regardless of traditional individual-level risk factors. Further research into the age-related pattern of birth outcome among impoverished foreign-born Black mothers is warranted.

To determine whether maternal nativity (US-born versus foreign-born) is associated with the first year mortality rates of term births. Stratified and multivariable binomial regression analyses were performed on the 2003-2004 National Center for Health Statistics linked live birth-infant death cohort files. Only term (37-42 weeks) infants with non-Latina White, African-American, and Mexican-American mothers were studied. The infant mortality rate (<365 days, IMR) of births to US-born non-Latina White mothers (n = 3,684,569) exceeded that of births to foreign-born White mothers (n = 226,621): 2.4/1,000 versus 1.3/1,000, respectively; relative risk (RR) = 1.8 [95 % confidence interval (CI) 1.6-2.0]. The IMR of births to US-born African-American mothers (n = 787,452) exceeded that of births to foreign-born African-American mothers (n = 118,246): 4.1/1,000 versus 2.2/1,000, respectively; RR = 1.8 (1.6-2.1). The IMR of births to US-born Mexican-American mothers (n = 338,337) exceeded that of births to Mexican-born mothers (n = 719,837): 2.4/1,000 versus 1.8/1,000, respectively; RR = 1.3 (1.2-1.4). These disparities were not limited to a singular cause of death and were widest among deaths due to Sudden Infant Death Syndrome. In multivariable binomial regression models, the adjusted RR of infant mortality for non-LBW, term births to US-born (compared to foreign-born) for White, African-American, and Mexican-American mothers equaled 1.5 (1.3-1.7), 1.7 (1.5-2.1) and 1.6 (1.4-1.8), respectively. The IMR of term births to White, African-American, and Mexican-American mothers exceeds that of their counterparts with foreign-born mothers independent of traditional individual level risk factors.

This study extends mediation analysis techniques to explore whether and to what extent differential access to a medical home explains the black/white disparity in unmet healthcare needs among children with special healthcare needs (CSHCN). Data were obtained from the 2007 National Survey of Children's Health, with analyses limited to non-Hispanic white and black CSHCN (n = 14,677). The counterfactual approach to mediation analysis was used to estimate odds ratios for the natural direct and indirect effects of race on unmet healthcare needs. Overall, 43.0 % of white CSHCN and 60.4 % of black CSHCN did not have a medical home. Additionally, 8.8 % of white CSHCN and 15.3 % of black CSHCN had unmet healthcare needs. The natural indirect effect indicates that the odds of unmet needs among black CSHCN are elevated by approximately 20 % as a result of their current level of access to the medical home rather than access at a level equal to white CSHCN (OR(NIE) = 1.2, 95 % CI = 1.1, 1.3). The natural direct effect indicates that even if black CSHCN had the same level of access to a medical home as white CSHCN, blacks would still have 60 % higher odds of unmet healthcare needs than whites (OR(NDE) = 1.6, 95 % CI = 1.1, 2.4). The racial disparity in unmet healthcare needs among CSHCN is only partially explained by disparities in having a medical home. Ensuring all CSHCN have equal access to a medical home may reduce the racial disparity in unmet needs, but will not completely eliminate it.

The purpose of this study is to examine the association of child mental health conditions and parent mental health status. This study used data from the 2007 National Survey of Children's Health on 80,982 children ages 2-17. The presence of a child mental health condition was defined as a parent-reported diagnosis of at least one of seven child mental health conditions. Parent mental health was assessed via a 5-point scale. Logistic regression was used to assess the association of child mental health conditions and parent mental health status, while examining socioeconomic, parent, family, and community factors as potential effect modifiers and confounders of the association. 11.1% of children had a mental health condition (95% CI = 10.5-11.6). The prevalence of child mental health conditions increased as parent mental health status worsened. Race/ethnicity was the only significant effect modifier of the child-parent mental health association. After adjustment for confounders, the stratum-specific adjusted odds ratios (95% CI) of child mental health conditions related to a one-level decline in parent mental health were: 1.44 (1.35-1.55) for non-Hispanic whites, 1.24 (1.06-1.46) for non-Hispanic blacks, 1.04 (0.81-1.32) for Hispanics from non-immigrant families, 1.21 (0.96-1.93) for Hispanics from immigrant families, and 1.43 (1.21-1.70) for non-Hispanic other race children. The effect of parent mental health status on child mental health conditions was significant only among non-Hispanic children. Parent-focused interventions to prevent or improve child mental health conditions may be best targeted to the sub-populations for whom parent and child mental health are most strongly associated.

Planar cell polarity (PCP) describes the polarized orientation of cells within the plane of a tissue. Unlike epithelial PCP, the mechanisms underlying PCP signaling in migrating cells remain undefined. Here, the establishment of PCP must be coordinated with dynamic changes in cell adhesion and extracellular matrix (ECM) organization. During gastrulation, the membrane type-1 matrix metalloproteinase (MT1-MMP or MMP14) is required for PCP and convergence and extension cell movements. We report that the PCP protein Vang-like 2 (VANGL2) regulates the endocytosis and cell-surface availability of MMP14 in manner that is dependent on focal adhesion kinase. We demonstrate that zebrafish trilobite/vangl2 mutant embryos exhibit increased Mmp14 activity and decreased ECM. Furthermore, in vivo knockdown of Mmp14 partially rescues the Vangl2 loss-of-function convergence and extension phenotype. This study identifies a mechanism linking VANGL2 with MMP14 trafficking and suggests that establishment of PCP in migrating gastrula cells requires regulated proteolytic degradation or remodeling of the ECM. Our findings implicate matrix metalloproteinases as downstream effectors of PCP and suggest a broadly applicable mechanism whereby VANGL2 affects diverse morphogenetic processes.

Objective: To evaluate the efficacy of ondansetron for the treatment of schizophrenia., Data Sources: Searches of MEDLINE (1950-March 2010) and Google Scholar were performed. Key search terms included ondansetron, Zofran, serotonin antagonists, 5-HT(3) serotonin receptor, and schizophrenia., Study Selection and Data Extraction: All articles published in English identified from the data sources were evaluated. All studies and case reports evaluating ondansetron for the treatment of schizophrenia were reviewed., Data Synthesis: Six clinical trials, including 3 double-blind, randomized trials, and 2 case reports pertinent to ondansetron use in schizophrenia, were identified. Ondansetron daily doses ranged from 4 to 16 mg, with doses administered once or twice daily. Ondansetron was used as monotherapy in 3 trials and as an adjunct to therapy with clozapine, haloperidol, or risperidone, respectively, in 3 trials. Studies were of varying durations, ranging from a single-dose study with a 3-hour follow-up to three 12-week studies. Most studies evaluated ondansetron's efficacy in treating schizophrenia as measured with changes in Positive and Negative Syndrome Scale (PANSS), Brief Psychiatric Rating Scale, and Clinical Global Impression scale scores. In the 2 largest trials, with a combined patient population of 151, treatment with adjunctive ondansetron resulted in statistically significant improvement in negative symptoms as assessed with PANSS. In all studies, ondansetron was well tolerated, with no severe adverse reactions reported., Conclusions: Ondansetron may be effective as an adjunct to antipsychotics for the treatment of schizophrenia, specifically negative symptoms, as assessed with PANSS. Due to the variation in concurrent therapies and dosing regimens, it is difficult to establish an optimal dose from the reviewed trials. Further large, randomized, double-blind, active-controlled studies would be helpful in determining the role of ondansetron in the treatment of schizophrenia.