Free-flowing rivers (FFRs) support diverse, complex and dynamic ecosystems globally, providing important societal and economic services. Infrastructure development threatens the ecosystem processes, ...biodiversity and services that these rivers support. Here we assess the connectivity status of 12 million kilometres of rivers globally and identify those that remain free-flowing in their entire length. Only 37 per cent of rivers longer than 1,000 kilometres remain free-flowing over their entire length and 23 per cent flow uninterrupted to the ocean. Very long FFRs are largely restricted to remote regions of the Arctic and of the Amazon and Congo basins. In densely populated areas only few very long rivers remain free-flowing, such as the Irrawaddy and Salween. Dams and reservoirs and their up- and downstream propagation of fragmentation and flow regulation are the leading contributors to the loss of river connectivity. By applying a new method to quantify riverine connectivity and map FFRs, we provide a foundation for concerted global and national strategies to maintain or restore them.
Exposure to endocrine disruptors (EDs), including some phthalates, phytoestrogens and phenols can be quantified using biomarkers of exposure. However, reliability in the use of these biomarkers ...requires an understanding of the timeframe of exposure represented by one measurement. Data on the temporal variability of ED biomarkers are sparse, especially among children.
To evaluate intraindividual temporal variability in 19 individual urinary biomarkers (eight phthalate metabolites from six phthalate diesters, six phytoestrogens (two lignans and four isoflavones) and five phenols) among New York City children.
Healthy Hispanic and Black children (
N=35; 6–10 years old) donated several urine samples over 6 months. To assess temporal variability we used three statistical methods: intraclass correlation coefficient (ICC), Spearman correlation coefficients (SCC) between concentrations measured at different timepoints, and surrogate category analysis to determine how well the tertile categories based on a single measurement represented a 6-month average concentration.
Surrogate category analysis indicated that a single sample provides reliable ranking for all analytes; at least three of four surrogate samples predicted the 6-month mean concentration. Of the 19 analytes, the ICC was >0.2 for 18 analytes and >0.3 for 10 analytes. Correlations among sample concentrations throughout the 6-month period were observed for all analytes; 14 analyte concentrations were correlated at 16 weeks.
The reasonable degree of temporal reliability and the wide range of concentrations of phthalate metabolites, phytoestrogens and phenols suggest that these biomarkers are appropriate for use in epidemiologic studies of environmental exposures in relation to health outcomes in children.
Protecting the world's freshwater resources requires diagnosing threats over a broad range of scales, from global to local. Here we present the first worldwide synthesis to jointly consider human and ...biodiversity perspectives on water security using a spatial framework that quantifies multiple stressors and accounts for downstream impacts. We find that nearly 80% of the world's population is exposed to high levels of threat to water security. Massive investment in water technology enables rich nations to offset high stressor levels without remedying their underlying causes, whereas less wealthy nations remain vulnerable. A similar lack of precautionary investment jeopardizes biodiversity, with habitats associated with 65% of continental discharge classified as moderately to highly threatened. The cumulative threat framework offers a tool for prioritizing policy and management responses to this crisis, and underscores the necessity of limiting threats at their source instead of through costly remediation of symptoms in order to assure global water security for both humans and freshwater biodiversity.
Although neoadjuvant chemoradiotherapy achieves low local recurrence rates in clinical stages II to III rectal cancer, it delays administration of optimal chemotherapy. We evaluated preoperative ...infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX)/bevacizumab with selective rather than consistent use of chemoradiotherapy.
Thirty-two patients with clinical stages II to III rectal cancer participated in this single-center phase II trial. All were candidates for low anterior resection with total mesorectal excision (TME). Patients were to receive six cycles of FOLFOX, with bevacizumab included for cycles 1 to 4. Patients with stable/progressive disease were to have radiation before TME, whereas responders were to have immediate TME. Postoperative radiation was planned if R0 resection was not achieved. Postoperative FOLFOX × 6 was recommended, but adjuvant regimens were left to clinician discretion. The primary outcome was R0 resection rate.
Between April 2007 and December 2008, 32 (100%) of 32 study participants had R0 resections. Two did not complete preoperative chemotherapy secondary to cardiovascular toxicity. Both had preoperative chemoradiotherapy and then R0 resections. Of 30 patients completing preoperative chemotherapy, all had tumor regression and TME without preoperative chemoradiotherapy. The pathologic complete response rate to chemotherapy alone was 8 of 32 (25%; 95% CI, 11% to 43%). The 4-year local recurrence rate was 0% (95% CI, 0% to 11%); the 4-year disease-free survival was 84% (95% CI, 67% to 94%).
For selected patients with clinical stages II to III rectal cancer, neoadjuvant chemotherapy and selective radiation does not seem to compromise outcomes. Preoperative Radiation or Selective Preoperative Radiation and Evaluation Before Chemotherapy and TME (PROSPECT), a randomized phase III trial to validate this experience, is now open in the US cooperative group network.
Loss of muscle mass and strength after disuse followed by impaired muscle recovery commonly occurs with aging. Metformin (MET) and leucine (LEU) individually have shown positive effects in skeletal ...muscle during atrophy conditions but have not been evaluated in combination nor tested as a remedy to enhance muscle recovery following disuse atrophy in aging. The purpose of this study was to determine if a dual treatment of metformin and leucine (MET + LEU) would prevent disuse‐induced atrophy and/or promote muscle recovery in aged mice and if these muscle responses correspond to changes in satellite cells and collagen remodeling. Aged mice (22–24 months) underwent 14 days of hindlimb unloading (HU) followed by 7 or 14 days of reloading (7 or 14 days RL). MET, LEU, or MET + LEU was administered via drinking water and were compared to Vehicle (standard drinking water) and ambulatory baseline. We observed that during HU, MET + LEU resolved whole body grip strength and soleus muscle specific force decrements caused by HU. Gastrocnemius satellite cell abundance was increased with MET + LEU treatment but did not alter muscle size during disuse or recovery conditions. Moreover, MET + LEU treatment alleviated gastrocnemius collagen accumulation caused by HU and increased collagen turnover during 7 and 14 days RL driven by a decrease in collagen IV content. Transcriptional pathway analysis revealed that MET + LEU altered muscle hallmark pathways related to inflammation and myogenesis during HU. Together, the dual treatment of MET and LEU was able to increase muscle function, satellite cell content, and reduce collagen accumulation, thus improving muscle quality during disuse and recovery in aging.
Particle precipitation is a loss mechanism from the radiation belts whereby particles trapped by the Earth's magnetic field are scattered into the loss cone due to wave‐particle interactions. ...Energetic electron precipitation creates ozone destroying chemicals which can affect the temperatures of the polar regions, therefore it is crucial to accurately quantify this impact on the Earth's atmosphere. We use bounce‐averaged pitch angle diffusion coefficients for whistler mode chorus waves, plasmaspheric hiss and atmospheric collisions to calculate magnetic local time (MLT) dependent electron precipitation inside the field of view of the Polar Orbiting Environmental Satellites (POES) T0 detector, between 26–30 March 2013. These diffusion coefficients are used in the BAS Radiation Belt Model (BAS‐RBM) and this paper is a first step toward testing the loss in this model via comparison with real world data. We find the best agreement between the calculated and measured T0 precipitation at L* > 5 on the dawnside for the >30 keV electron channel, consistent with precipitation driven by lower band chorus. Additional diffusion is required to explain the flux at higher energies and on the dusk side. The POES T0 detector underestimates electron precipitation as its field of view does not measure the entire loss cone. We demonstrate the potential for utilizing diffusion coefficients to reconstruct precipitating flux over the entire loss cone. Our results show that the total precipitation can exceed that measured by the POES >30 keV electron channel by a factor that typically varies from 1 to 10 for L* = 6, 6.5, and 7.
Key Points
The simulated and measured precipitation are well correlated on the dawnside at L* > 5 for >30 keV electrons
Additional diffusion is required at higher energies, >100 keV, and on the duskside
The total precipitating flux typically exceeds that measured by Polar Orbiting Environmental Satellites by a factor between 1 and 10
Understanding potential trajectories in health and drivers of health is crucial to guiding long-term investments and policy implementation. Past work on forecasting has provided an incomplete ...landscape of future health scenarios, highlighting a need for a more robust modelling platform from which policy options and potential health trajectories can be assessed. This study provides a novel approach to modelling life expectancy, all-cause mortality and cause of death forecasts —and alternative future scenarios—for 250 causes of death from 2016 to 2040 in 195 countries and territories.
We modelled 250 causes and cause groups organised by the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) hierarchical cause structure, using GBD 2016 estimates from 1990–2016, to generate predictions for 2017–40. Our modelling framework used data from the GBD 2016 study to systematically account for the relationships between risk factors and health outcomes for 79 independent drivers of health. We developed a three-component model of cause-specific mortality: a component due to changes in risk factors and select interventions; the underlying mortality rate for each cause that is a function of income per capita, educational attainment, and total fertility rate under 25 years and time; and an autoregressive integrated moving average model for unexplained changes correlated with time. We assessed the performance by fitting models with data from 1990–2006 and using these to forecast for 2007–16. Our final model used for generating forecasts and alternative scenarios was fitted to data from 1990–2016. We used this model for 195 countries and territories to generate a reference scenario or forecast through 2040 for each measure by location. Additionally, we generated better health and worse health scenarios based on the 85th and 15th percentiles, respectively, of annualised rates of change across location-years for all the GBD risk factors, income per person, educational attainment, select intervention coverage, and total fertility rate under 25 years in the past. We used the model to generate all-cause age-sex specific mortality, life expectancy, and years of life lost (YLLs) for 250 causes. Scenarios for fertility were also generated and used in a cohort component model to generate population scenarios. For each reference forecast, better health, and worse health scenarios, we generated estimates of mortality and YLLs attributable to each risk factor in the future.
Globally, most independent drivers of health were forecast to improve by 2040, but 36 were forecast to worsen. As shown by the better health scenarios, greater progress might be possible, yet for some drivers such as high body-mass index (BMI), their toll will rise in the absence of intervention. We forecasted global life expectancy to increase by 4·4 years (95% UI 2·2 to 6·4) for men and 4·4 years (2·1 to 6·4) for women by 2040, but based on better and worse health scenarios, trajectories could range from a gain of 7·8 years (5·9 to 9·8) to a non-significant loss of 0·4 years (–2·8 to 2·2) for men, and an increase of 7·2 years (5·3 to 9·1) to essentially no change (0·1 years –2·7 to 2·5) for women. In 2040, Japan, Singapore, Spain, and Switzerland had a forecasted life expectancy exceeding 85 years for both sexes, and 59 countries including China were projected to surpass a life expectancy of 80 years by 2040. At the same time, Central African Republic, Lesotho, Somalia, and Zimbabwe had projected life expectancies below 65 years in 2040, indicating global disparities in survival are likely to persist if current trends hold. Forecasted YLLs showed a rising toll from several non-communicable diseases (NCDs), partly driven by population growth and ageing. Differences between the reference forecast and alternative scenarios were most striking for HIV/AIDS, for which a potential increase of 120·2% (95% UI 67·2–190·3) in YLLs (nearly 118 million) was projected globally from 2016–40 under the worse health scenario. Compared with 2016, NCDs were forecast to account for a greater proportion of YLLs in all GBD regions by 2040 (67·3% of YLLs 95% UI 61·9–72·3 globally); nonetheless, in many lower-income countries, communicable, maternal, neonatal, and nutritional (CMNN) diseases still accounted for a large share of YLLs in 2040 (eg, 53·5% of YLLs 95% UI 48·3–58·5 in Sub-Saharan Africa). There were large gaps for many health risks between the reference forecast and better health scenario for attributable YLLs. In most countries, metabolic risks amenable to health care (eg, high blood pressure and high plasma fasting glucose) and risks best targeted by population-level or intersectoral interventions (eg, tobacco, high BMI, and ambient particulate matter pollution) had some of the largest differences between reference and better health scenarios. The main exception was sub-Saharan Africa, where many risks associated with poverty and lower levels of development (eg, unsafe water and sanitation, household air pollution, and child malnutrition) were projected to still account for substantive disparities between reference and better health scenarios in 2040.
With the present study, we provide a robust, flexible forecasting platform from which reference forecasts and alternative health scenarios can be explored in relation to a wide range of independent drivers of health. Our reference forecast points to overall improvements through 2040 in most countries, yet the range found across better and worse health scenarios renders a precarious vision of the future—a world with accelerating progress from technical innovation but with the potential for worsening health outcomes in the absence of deliberate policy action. For some causes of YLLs, large differences between the reference forecast and alternative scenarios reflect the opportunity to accelerate gains if countries move their trajectories toward better health scenarios—or alarming challenges if countries fall behind their reference forecasts. Generally, decision makers should plan for the likely continued shift toward NCDs and target resources toward the modifiable risks that drive substantial premature mortality. If such modifiable risks are prioritised today, there is opportunity to reduce avoidable mortality in the future. However, CMNN causes and related risks will remain the predominant health priority among lower-income countries. Based on our 2040 worse health scenario, there is a real risk of HIV mortality rebounding if countries lose momentum against the HIV epidemic, jeopardising decades of progress against the disease. Continued technical innovation and increased health spending, including development assistance for health targeted to the world's poorest people, are likely to remain vital components to charting a future where all populations can live full, healthy lives.
Bill & Melinda Gates Foundation.
As students of the Civil War have long known, emancipation was not merely a product of Lincoln's proclamation or of Confederate defeat in April 1865. It was a process that required more than legal or ...military action. With enslaved people fully engaged as actors, emancipation necessitated a fundamental reordering of a way of life whose implications stretched well beyond the former slave states. Slavery did not die quietly or quickly, nor did freedom fulfill every dream of the enslaved or their allies. The process unfolded unevenly.
In this sweeping reappraisal of slavery's end during the Civil War era, Joseph P. Reidy employs the lenses of time, space, and individuals' sense of personal and social belonging to understand how participants and witnesses coped with drastic change, its erratic pace, and its unforeseeable consequences. Emancipation disrupted everyday habits, causing sensations of disorientation that sometimes intensified the experience of reality and sometimes muddled it. While these illusions of emancipation often mixed disappointment with hope, through periods of even intense frustration they sustained the promise that the struggle for freedom would result in victory.
A series of titania and doped titania materials were prepared from sol-gel methods using a titanium isopropoxide precursor. Powder XRD and SEM were used to follow the anatase to rutile transformation ...(ART) phase change. Powder XRD was used to estimate the relative amounts of each phase and the average particle size at a series of temperatures. Doping with Si, Zr, Al and tertiary mixtures of these produced an elevated ART temperature whilst Co, Mn and V had the opposite effect. The most likely explanation for the elevation in the ART temperature is the presence of dopant strain fields, which limit mass transport in the system. Lowering of the ART temperature is probably related to creation of defect sites, which provide low energy mass transport routes. In the majority of samples, the mechanism for phase change was related to attaining a critical particle size. This was measured at around 450 Angstrom, independent of the dopant used. Results are discussed in terms of previous work. 26 refs.
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