33 research outputs found

    Chronic alendronate therapy impairs epithelial morphology and homeostasis in the human oral mucosa

    Get PDF
    Alendronate (ALN) is a nitrogen containing bisphosphonate (BP) widely used for the chronic treatment of osteoporotic patients, especially women over 60 years old. The diffusion of BPs in clinical practice has brought attention to one of their most serious side-effects, osteonecrosis of the jaw (ONJ) [1]. Several theories have been proposed to explain its pathogenesis, but the effect of BPs on the oral mucosa is still matter of debate despite its extensive involvement and injury in ONJ. This study aimed at evaluating from a morphological point of view the effects of ALN therapy on the oral epithelium of clinically healthy keratinized oral mucosa. Six women over 60 years old undergoing chronic therapy (2-7 years) with oral ALN after diagnosis of osteoporosis were recruited and compared to a gender and age matched group (n=6). Smoking habit, past history of head and neck cancer treatment, and concomitant assumption of steroidal and antiangiogenic drugs were excluding criteria. Proliferation, apoptosis, intercellular adhesion, and terminal differentiation were investigated by immunofluorescence and transmission electron microscopy (TEM). A significant decrease in keratinocyte proliferation was detected in the oral epithelium of patients undergoing ALN therapy compared to the control group (237.62 BrdU/mm2 ± 92.22 vs 104.16 BrdU/mm2 ± 66.20; p = 0.0002), without any sign of apoptosis induction by light microscopy and TEM. The presence of well established adherens and tight junctions was accompanied by profound alterations in desmosomal ultrastructure and molecular composition in the uppermost layers of the oral epithelium of the ALN group. Proceeding from the lower spinous to the granular layer, TEM analysis showed a progressive reduction in desmosomal thickness paralleled by a lower immunostaining for desmoglein 1 and desmoglein 3 in the suprabasal keratinocytes. In the upper epithelial layers, intermediate filaments gradually aggregated forming electron-dense bundles detached from the desmosomal plaque and a significant decrease in keratin 10 expression was observed. Taken together the reported results suggested a profound impairment in structure and function of the clinically healthy oral epithelium related to chronic ALN assumption. For the first time our results show that epithelial homeostasis in human oral mucosa is profoundly affected by nitrogen containing BPs, confirming previous in vitro studies [2-4] and strongly supporting the need of further investigation on the molecular mechanisms involved in ONJ pathogenesis

    Bacterial Communities in the Embryo of Maize Landraces:Relation with Susceptibility to Fusarium Ear Rot

    Get PDF
    Locally adapted maize accessions (landraces) represent an untapped resource of nutritional and resistance traits for breeding, including the shaping of distinct microbiota. Our study focused on five different maize landraces and a reference commercial hybrid, showing different susceptibility to fusarium ear rot, and whether this trait could be related to particular compositions of the bacterial microbiota in the embryo, using different approaches. Our cultivation-independent approach utilized the metabarcoding of a portion of the 16S rRNA gene to study bacterial populations in these samples. Multivariate statistical analyses indicated that the microbiota of the embryos of the accessions grouped in two different clusters: one comprising three landraces and the hybrid, one including the remaining two landraces, which showed a lower susceptibility to fusarium ear rot in field. The main discriminant between these clusters was the frequency of Firmicutes, higher in the second cluster, and this abundance was confirmed by quantification through digital PCR. The cultivation-dependent approach allowed the isolation of 70 bacterial strains, mostly Firmicutes. In vivo assays allowed the identification of five candidate biocontrol strains against fusarium ear rot. Our data revealed novel insights into the role of the maize embryo microbiota and set the stage for further studies aimed at integrating this knowledge into plant breeding programs

    Closing the yield gap while ensuring water sustainability

    Get PDF
    Water is a major factor limiting crop production in many regions around the world. Irrigation can greatly enhance crop yields, but the local availability and timing of freshwater resources constrains the ability of humanity to increase food production. Innovations in irrigation infrastructure have allowed humanity to utilize previously inaccessible water resources, enhancing water withdrawals for agriculture while increasing pressure on environmental flows and other human uses. While substantial additional water will be required to support future food production, it is not clear whether and where freshwater availability is sufficient to sustainably close the yield gap in cultivated lands. The extent to which irrigation can be expanded within presently rainfed cropland without depleting environmental flows remains poorly understood. Here we perform a spatially explicit biophysical assessment of global consumptive water use for crop production under current and maximum attainable yield scenarios assuming current cropping practices. We then compare these present and anticipated water consumptions to local water availability to examine potential changes in water scarcity. We find that global water consumption for irrigation could sustainably increase by 48% (408 km 3 H 2 O yr -1 ) - expanding irrigation to 26% of currently rainfed cultivated lands (2.67 × 10 6 km 2 ) and producing 37% (3.38 × 10 15 kcal yr -1 ) more calories, enough to feed an additional 2.8 billion people. If current unsustainable blue water consumption (336 km 3 yr -1 ) and production (1.19 × 10 15 kcal yr -1 ) practices were eliminated, a sustainable irrigation expansion and intensification would still enable a 24% increase in calorie (2.19 × 10 15 kcal yr -1 ) production. Collectively, these results show that the sustainable expansion and intensification of irrigation in selected croplands could contribute substantially to achieving food security and environmental goals in tandem in the coming decades

    The AXIOM software layers

    Get PDF
    AXIOM project aims at developing a heterogeneous computing board (SMP-FPGA).The Software Layers developed at the AXIOM project are explained.OmpSs provides an easy way to execute heterogeneous codes in multiple cores. People and objects will soon share the same digital network for information exchange in a world named as the age of the cyber-physical systems. The general expectation is that people and systems will interact in real-time. This poses pressure onto systems design to support increasing demands on computational power, while keeping a low power envelop. Additionally, modular scaling and easy programmability are also important to ensure these systems to become widespread. The whole set of expectations impose scientific and technological challenges that need to be properly addressed.The AXIOM project (Agile, eXtensible, fast I/O Module) will research new hardware/software architectures for cyber-physical systems to meet such expectations. The technical approach aims at solving fundamental problems to enable easy programmability of heterogeneous multi-core multi-board systems. AXIOM proposes the use of the task-based OmpSs programming model, leveraging low-level communication interfaces provided by the hardware. Modular scalability will be possible thanks to a fast interconnect embedded into each module. To this aim, an innovative ARM and FPGA-based board will be designed, with enhanced capabilities for interfacing with the physical world. Its effectiveness will be demonstrated with key scenarios such as Smart Video-Surveillance and Smart Living/Home (domotics).Peer ReviewedPostprint (author's final draft

    Burden of disease scenarios for 204 countries and territories, 2022–2050: a forecasting analysis for the Global Burden of Disease Study 2021

    Get PDF
    Background: Future trends in disease burden and drivers of health are of great interest to policy makers and the public at large. This information can be used for policy and long-term health investment, planning, and prioritisation. We have expanded and improved upon previous forecasts produced as part of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) and provide a reference forecast (the most likely future), and alternative scenarios assessing disease burden trajectories if selected sets of risk factors were eliminated from current levels by 2050. Methods: Using forecasts of major drivers of health such as the Socio-demographic Index (SDI; a composite measure of lag-distributed income per capita, mean years of education, and total fertility under 25 years of age) and the full set of risk factor exposures captured by GBD, we provide cause-specific forecasts of mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) by age and sex from 2022 to 2050 for 204 countries and territories, 21 GBD regions, seven super-regions, and the world. All analyses were done at the cause-specific level so that only risk factors deemed causal by the GBD comparative risk assessment influenced future trajectories of mortality for each disease. Cause-specific mortality was modelled using mixed-effects models with SDI and time as the main covariates, and the combined impact of causal risk factors as an offset in the model. At the all-cause mortality level, we captured unexplained variation by modelling residuals with an autoregressive integrated moving average model with drift attenuation. These all-cause forecasts constrained the cause-specific forecasts at successively deeper levels of the GBD cause hierarchy using cascading mortality models, thus ensuring a robust estimate of cause-specific mortality. For non-fatal measures (eg, low back pain), incidence and prevalence were forecasted from mixed-effects models with SDI as the main covariate, and YLDs were computed from the resulting prevalence forecasts and average disability weights from GBD. Alternative future scenarios were constructed by replacing appropriate reference trajectories for risk factors with hypothetical trajectories of gradual elimination of risk factor exposure from current levels to 2050. The scenarios were constructed from various sets of risk factors: environmental risks (Safer Environment scenario), risks associated with communicable, maternal, neonatal, and nutritional diseases (CMNNs; Improved Childhood Nutrition and Vaccination scenario), risks associated with major non-communicable diseases (NCDs; Improved Behavioural and Metabolic Risks scenario), and the combined effects of these three scenarios. Using the Shared Socioeconomic Pathways climate scenarios SSP2-4.5 as reference and SSP1-1.9 as an optimistic alternative in the Safer Environment scenario, we accounted for climate change impact on health by using the most recent Intergovernmental Panel on Climate Change temperature forecasts and published trajectories of ambient air pollution for the same two scenarios. Life expectancy and healthy life expectancy were computed using standard methods. The forecasting framework includes computing the age-sex-specific future population for each location and separately for each scenario. 95% uncertainty intervals (UIs) for each individual future estimate were derived from the 2·5th and 97·5th percentiles of distributions generated from propagating 500 draws through the multistage computational pipeline. Findings: In the reference scenario forecast, global and super-regional life expectancy increased from 2022 to 2050, but improvement was at a slower pace than in the three decades preceding the COVID-19 pandemic (beginning in 2020). Gains in future life expectancy were forecasted to be greatest in super-regions with comparatively low life expectancies (such as sub-Saharan Africa) compared with super-regions with higher life expectancies (such as the high-income super-region), leading to a trend towards convergence in life expectancy across locations between now and 2050. At the super-region level, forecasted healthy life expectancy patterns were similar to those of life expectancies. Forecasts for the reference scenario found that health will improve in the coming decades, with all-cause age-standardised DALY rates decreasing in every GBD super-region. The total DALY burden measured in counts, however, will increase in every super-region, largely a function of population ageing and growth. We also forecasted that both DALY counts and age-standardised DALY rates will continue to shift from CMNNs to NCDs, with the most pronounced shifts occurring in sub-Saharan Africa (60·1% [95% UI 56·8–63·1] of DALYs were from CMNNs in 2022 compared with 35·8% [31·0–45·0] in 2050) and south Asia (31·7% [29·2–34·1] to 15·5% [13·7–17·5]). This shift is reflected in the leading global causes of DALYs, with the top four causes in 2050 being ischaemic heart disease, stroke, diabetes, and chronic obstructive pulmonary disease, compared with 2022, with ischaemic heart disease, neonatal disorders, stroke, and lower respiratory infections at the top. The global proportion of DALYs due to YLDs likewise increased from 33·8% (27·4–40·3) to 41·1% (33·9–48·1) from 2022 to 2050, demonstrating an important shift in overall disease burden towards morbidity and away from premature death. The largest shift of this kind was forecasted for sub-Saharan Africa, from 20·1% (15·6–25·3) of DALYs due to YLDs in 2022 to 35·6% (26·5–43·0) in 2050. In the assessment of alternative future scenarios, the combined effects of the scenarios (Safer Environment, Improved Childhood Nutrition and Vaccination, and Improved Behavioural and Metabolic Risks scenarios) demonstrated an important decrease in the global burden of DALYs in 2050 of 15·4% (13·5–17·5) compared with the reference scenario, with decreases across super-regions ranging from 10·4% (9·7–11·3) in the high-income super-region to 23·9% (20·7–27·3) in north Africa and the Middle East. The Safer Environment scenario had its largest decrease in sub-Saharan Africa (5·2% [3·5–6·8]), the Improved Behavioural and Metabolic Risks scenario in north Africa and the Middle East (23·2% [20·2–26·5]), and the Improved Nutrition and Vaccination scenario in sub-Saharan Africa (2·0% [–0·6 to 3·6]). Interpretation: Globally, life expectancy and age-standardised disease burden were forecasted to improve between 2022 and 2050, with the majority of the burden continuing to shift from CMNNs to NCDs. That said, continued progress on reducing the CMNN disease burden will be dependent on maintaining investment in and policy emphasis on CMNN disease prevention and treatment. Mostly due to growth and ageing of populations, the number of deaths and DALYs due to all causes combined will generally increase. By constructing alternative future scenarios wherein certain risk exposures are eliminated by 2050, we have shown that opportunities exist to substantially improve health outcomes in the future through concerted efforts to prevent exposure to well established risk factors and to expand access to key health interventions

    Global burden and strength of evidence for 88 risk factors in 204 countries and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

    Get PDF
    Background: Understanding the health consequences associated with exposure to risk factors is necessary to inform public health policy and practice. To systematically quantify the contributions of risk factor exposures to specific health outcomes, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 aims to provide comprehensive estimates of exposure levels, relative health risks, and attributable burden of disease for 88 risk factors in 204 countries and territories and 811 subnational locations, from 1990 to 2021. Methods: The GBD 2021 risk factor analysis used data from 54 561 total distinct sources to produce epidemiological estimates for 88 risk factors and their associated health outcomes for a total of 631 risk–outcome pairs. Pairs were included on the basis of data-driven determination of a risk–outcome association. Age-sex-location-year-specific estimates were generated at global, regional, and national levels. Our approach followed the comparative risk assessment framework predicated on a causal web of hierarchically organised, potentially combinative, modifiable risks. Relative risks (RRs) of a given outcome occurring as a function of risk factor exposure were estimated separately for each risk–outcome pair, and summary exposure values (SEVs), representing risk-weighted exposure prevalence, and theoretical minimum risk exposure levels (TMRELs) were estimated for each risk factor. These estimates were used to calculate the population attributable fraction (PAF; ie, the proportional change in health risk that would occur if exposure to a risk factor were reduced to the TMREL). The product of PAFs and disease burden associated with a given outcome, measured in disability-adjusted life-years (DALYs), yielded measures of attributable burden (ie, the proportion of total disease burden attributable to a particular risk factor or combination of risk factors). Adjustments for mediation were applied to account for relationships involving risk factors that act indirectly on outcomes via intermediate risks. Attributable burden estimates were stratified by Socio-demographic Index (SDI) quintile and presented as counts, age-standardised rates, and rankings. To complement estimates of RR and attributable burden, newly developed burden of proof risk function (BPRF) methods were applied to yield supplementary, conservative interpretations of risk–outcome associations based on the consistency of underlying evidence, accounting for unexplained heterogeneity between input data from different studies. Estimates reported represent the mean value across 500 draws from the estimate's distribution, with 95% uncertainty intervals (UIs) calculated as the 2·5th and 97·5th percentile values across the draws. Findings: Among the specific risk factors analysed for this study, particulate matter air pollution was the leading contributor to the global disease burden in 2021, contributing 8·0% (95% UI 6·7–9·4) of total DALYs, followed by high systolic blood pressure (SBP; 7·8% [6·4–9·2]), smoking (5·7% [4·7–6·8]), low birthweight and short gestation (5·6% [4·8–6·3]), and high fasting plasma glucose (FPG; 5·4% [4·8–6·0]). For younger demographics (ie, those aged 0–4 years and 5–14 years), risks such as low birthweight and short gestation and unsafe water, sanitation, and handwashing (WaSH) were among the leading risk factors, while for older age groups, metabolic risks such as high SBP, high body-mass index (BMI), high FPG, and high LDL cholesterol had a greater impact. From 2000 to 2021, there was an observable shift in global health challenges, marked by a decline in the number of all-age DALYs broadly attributable to behavioural risks (decrease of 20·7% [13·9–27·7]) and environmental and occupational risks (decrease of 22·0% [15·5–28·8]), coupled with a 49·4% (42·3–56·9) increase in DALYs attributable to metabolic risks, all reflecting ageing populations and changing lifestyles on a global scale. Age-standardised global DALY rates attributable to high BMI and high FPG rose considerably (15·7% [9·9–21·7] for high BMI and 7·9% [3·3–12·9] for high FPG) over this period, with exposure to these risks increasing annually at rates of 1·8% (1·6–1·9) for high BMI and 1·3% (1·1–1·5) for high FPG. By contrast, the global risk-attributable burden and exposure to many other risk factors declined, notably for risks such as child growth failure and unsafe water source, with age-standardised attributable DALYs decreasing by 71·5% (64·4–78·8) for child growth failure and 66·3% (60·2–72·0) for unsafe water source. We separated risk factors into three groups according to trajectory over time: those with a decreasing attributable burden, due largely to declining risk exposure (eg, diet high in trans-fat and household air pollution) but also to proportionally smaller child and youth populations (eg, child and maternal malnutrition); those for which the burden increased moderately in spite of declining risk exposure, due largely to population ageing (eg, smoking); and those for which the burden increased considerably due to both increasing risk exposure and population ageing (eg, ambient particulate matter air pollution, high BMI, high FPG, and high SBP). Interpretation: Substantial progress has been made in reducing the global disease burden attributable to a range of risk factors, particularly those related to maternal and child health, WaSH, and household air pollution. Maintaining efforts to minimise the impact of these risk factors, especially in low SDI locations, is necessary to sustain progress. Successes in moderating the smoking-related burden by reducing risk exposure highlight the need to advance policies that reduce exposure to other leading risk factors such as ambient particulate matter air pollution and high SBP. Troubling increases in high FPG, high BMI, and other risk factors related to obesity and metabolic syndrome indicate an urgent need to identify and implement interventions

    The green and blue crop water requirement WATNEEDS model and its global gridded outputs

    Get PDF
    Accurately assessing green and blue water requirements from croplands is fundamental to promote sustainable water management. In the last decade, global hydrological models have provided important insights into global patterns of water requirements for crop production. As important as these models are, they do not provide monthly crop-specific and year-specific data of green and blue water requirements. Gridded crop-specific products are therefore needed to better understand the spatial and temporal evolution of water demand. Here, we present a global gridded database of monthly crop-specific green (rain-fed) and blue (irrigated) water requirements for 23 main crops and 3 crop groups obtained using our WATNEEDS model. For the time periods in which our dataset matched, these estimates are validated against existing global products and satellite based datasets of evapotranspiration. The data are publicly available and can be used by practitioners in the water-energy-food nexus to assess the water sustainability of our food and energy systems at multiple spatial (local to global) and temporal (seasonal to multi-year) scales

    Socio-Environmental Effects of Large-Scale Land Acquisition in Mozambique

    No full text
    The growing global demand for food, fibers, and biofuels and the consequently, increasing prices of agricultural products have made investments in agriculture a priority for some governments and corporations. Since 2008, about 50 million ha of arable land have been purchased or leased worldwide, with an alarming and unprecedented increase in the number of land negotiations. When land acquisitions occur disregarding the rights of former land users and the socio-environmental impacts of these investments, they are often termed “land grabs.” Not only do large-scale land acquisitions (LSLAs) entail the purchase of fertile land but also the appropriation of land-based resources, such as water, with potential effects on the local population and the environment. Recently, a number of studies and reports have documented the process of LSLAs, while the associated effects on land and water resource availability to local communities have remained poorly investigated. Here, we develop an in-depth analysis of each land deal from the standpoint of land fertility, water scarcity, distance from roads, rivers, and villages. We focus on the case of Mozambique, a country affected by intense large-scale land acquisition, malnourishment, and demographic growth. Results show that, presently, LSLA in Mozambique covers an area of about 2 million hectares that account for roughly 30% of the currently cultivated land. Water resources appropriated through LSLAs are estimated around 39 billion m3 y−1, including 31 billion m3 y−1 for rainfed agriculture (green water) and a potential use of 8 billion m3 y−1 of water for irrigation (blue water), which corresponds to about 8 times the blue water currently used for agriculture across the country. The majority of land deals (29 out of 51) target fertile land and/or land with easy access to water resources and infrastructures
    corecore