Design of Agriculture Drainage Under Uncertainty: 1. Background and Chance Constraint Approach

The problems of waterlogging and salinity on agricultural lands has led to the installation of agricultural drainage systems. The effect of soil property uncertainty on drainage system design and thus drain performance is not implicitly considered by present design procedures. This is the first in a series of papers that will present methods for analyzing the effect of soil property uncertainty on drainage system design. An analysis of the nature of uncertainty and spatial variability in recharge rate and soil permeability is presented. A First Order--Second Moment (FOSM) approach is developed for the Hooghoudt steady-state drainage design equation to provide an estimate of the of the uncertainty of the dewatering zone between the drains as a function of the design variables and the uncertainty in the soil properties. Based upon the FOSM approach, a Chance Constraint model for optimal design of drains is developed which incorporates uncertainty in recharge rate, permeability, dewatering zone with the economics of drain installation to provide the least cost design for given reliabilities of drain performance

Design of Agriculture Drainage Under Uncertainty: 2. A Stochastic Programming Approach

The effect of soil property uncertainty on drainage system design was presented in the first of a series of papers on methods for optimal design of agricultural drains. A First Order--Second Moment (FOSM) approach was developed for the Hooghoudt steady-state drainage design ,equation to provide an estimate of the of the uncertainty of the dewatering zone between the drains as a function of the design variables and the uncertainty in the soil properties. In this paper, a Stochastic Programming Model for optimal design of drains under uncertainty, based upon the FOSM approach, is developed. The Stochastic Programming Model incorporates uncertainty in the objective function of the model as the expected loss in crop production as a function of uncertainty in the dewatering zone. The Stochastic Programming model is extended to included a multiple cropping situation and finally, the Chance Constraint approach, presented in the first paper, is compared with the Stochastic Programming Approach to drainage design and advantages of each are presented

Developing a tool to assess trainees during crisis management training for major risks

International audienceOften based on simulation exercises, crisis management training helps prepare decision-makers to manage crises better. However, this training has definite limits in terms of trainee assessment and the feed-back given during the debriefing phase. This paper presents a method for better organising the assessment of trainees involved in a real time crisis management training exercises and for giving them feedback during the debriefing phase. The approach presented is based on creating a typology of training objectives in order to or-ganise the assessment. The assessment includes expected outcomes techniques as well as the human and or-ganisational factors that can be observed within a group. The assessment tools developed were then experi-mented within crisis management exercises completed with trainees. Beyond the basic results, these tools helped redefine the basic roles played by observers and trainers during training exercises

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types

Formal ratification of subseries for the Pleistocene Series of the Quaternary System

The Pleistocene Series/Epoch of the Quaternary System/ Period has been divided unofficially into three subseries/ subepochs since at least the 1870s. On 30th January, 2020, the Executive Committee of the International Union of Geological Sciences ratified two proposals approved by the International Commission on Stratigraphy formalizing: 1) the Lower Pleistocene Subseries, comprising the Gelasian Stage and the superjacent Calabrian Stage, with a base defined by the GSSP for the Gelasian Stage, the Pleistocene Series, and the Quaternary System, and currently dated at 2.58 Ma; and 2) the term Upper Pleistocene, at the rank of subseries, with a base currently undefined but provisionally dated at ~129 ka. Defining the Upper Pleistocene Subseries and its corresponding stage with a GSSP is in progress. The Middle Pleistocene Subseries is defined by the recently ratified GSSP for the Chibanian Stage currently dated at 0.774 Ma. These ratifications complete the official division of the Pleistocene into three subseries/ subepochs, in uniformity with the similarly subdivided Holocene Series/Epoch.</p

The differential diagnosis of chronic daily headaches: an algorithm-based approach

Chronic daily headaches (CDHs) refers to primary headaches that happen on at least 15 days per month, for 4 or more hours per day, for at least three consecutive months. The differential diagnosis of CDHs is challenging and should proceed in an orderly fashion. The approach begins with a search for “red flags” that suggest the possibility of a secondary headache. If secondary headaches that mimic CDHs are excluded, either on clinical grounds or through investigation, the next step is to classify the headaches based on the duration of attacks. If the attacks last less than 4 hours per day, a trigeminal autonomic cephalalgia (TAC) is likely. TACs include episodic and chronic cluster headache, episodic and chronic paroxysmal hemicrania, SUNCT, and hypnic headache. If the duration is ≥4 h, a CDH is likely and the differential diagnosis encompasses chronic migraine, chronic tension-type headache, new daily persistent headache and hemicrania continua. The clinical approach to diagnosing CDH is the scope of this review

Improving lung health in low-income and middle-income countries: from challenges to solutions

Low-income and middle-income countries (LMICs) bear a disproportionately high burden of the global morbidity and mortality caused by chronic respiratory diseases (CRDs), including asthma, chronic obstructive pulmonary disease, bronchiectasis, and post-tuberculosis lung disease. CRDs are strongly associated with poverty, infectious diseases, and other non-communicable diseases (NCDs), and contribute to complex multi-morbidity, with major consequences for the lives and livelihoods of those affected. The relevance of CRDs to health and socioeconomic wellbeing is expected to increase in the decades ahead, as life expectancies rise and the competing risks of early childhood mortality and infectious diseases plateau. As such, the World Health Organization has identified the prevention and control of NCDs as an urgent development issue and essential to the achievement of the Sustainable Development Goals by 2030. In this Review, we focus on CRDs in LMICs. We discuss the early life origins of CRDs; challenges in their prevention, diagnosis, and management in LMICs; and pathways to solutions to achieve true universal health coverage

Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990-2015: A systematic analysis for the Global Burden of Disease Study 2015

Background: The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 provides an up-to-date synthesis of the evidence for risk factor exposure and the attributable burden of disease. By providing national and subnational assessments spanning the past 25 years, this study can inform debates on the importance of addressing risks in context. Methods: We used the comparative risk assessment framework developed for previous iterations of the Global Burden of Disease Study to estimate attributable deaths, disability-adjusted life-years (DALYs), and trends in exposure by age group, sex, year, and geography for 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks from 1990 to 2015. This study included 388 risk-outcome pairs that met World Cancer Research Fund-defined criteria for convincing or probable evidence. We extracted relative risk and exposure estimates from randomised controlled trials, cohorts, pooled cohorts, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. We developed a metric that allows comparisons of exposure across risk factors—the summary exposure value. Using the counterfactual scenario of theoretical minimum risk level, we estimated the portion of deaths and DALYs that could be attributed to a given risk. We decomposed trends in attributable burden into contributions from population growth, population age structure, risk exposure, and risk-deleted cause-specific DALY rates. We characterised risk exposure in relation to a Socio-demographic Index (SDI). Findings: Between 1990 and 2015, global exposure to unsafe sanitation, household air pollution, childhood underweight, childhood stunting, and smoking each decreased by more than 25%. Global exposure for several occupational risks, high body-mass index (BMI), and drug use increased by more than 25% over the same period. All risks jointly evaluated in 2015 accounted for 57·8% (95% CI 56·6–58·8) of global deaths and 41·2% (39·8–42·8) of DALYs. In 2015, the ten largest contributors to global DALYs among Level 3 risks were high systolic blood pressure (211·8 million [192·7 million to 231·1 million] global DALYs), smoking (148·6 million [134·2 million to 163·1 million]), high fasting plasma glucose (143·1 million [125·1 million to 163·5 million]), high BMI (120·1 million [83·8 million to 158·4 million]), childhood undernutrition (113·3 million [103·9 million to 123·4 million]), ambient particulate matter (103·1 million [90·8 million to 115·1 million]), high total cholesterol (88·7 million [74·6 million to 105·7 million]), household air pollution (85·6 million [66·7 million to 106·1 million]), alcohol use (85·0 million [77·2 million to 93·0 million]), and diets high in sodium (83·0 million [49·3 million to 127·5 million]). From 1990 to 2015, attributable DALYs declined for micronutrient deficiencies, childhood undernutrition, unsafe sanitation and water, and household air pollution; reductions in risk-deleted DALY rates rather than reductions in exposure drove these declines. Rising exposure contributed to notable increases in attributable DALYs from high BMI, high fasting plasma glucose, occupational carcinogens, and drug use. Environmental risks and childhood undernutrition declined steadily with SDI; low physical activity, high BMI, and high fasting plasma glucose increased with SDI. In 119 countries, metabolic risks, such as high BMI and fasting plasma glucose, contributed the most attributable DALYs in 2015. Regionally, smoking still ranked among the leading five risk factors for attributable DALYs in 109 countries; childhood underweight and unsafe sex remained primary drivers of early death and disability in much of sub-Saharan Africa. Interpretation: Declines in some key environmental risks have contributed to declines in critical infectious diseases. Some risks appear to be invariant to SDI. Increasing risks, including high BMI, high fasting plasma glucose, drug use, and some occupational exposures, contribute to rising burden from some conditions, but also provide opportunities for intervention. Some highly preventable risks, such as smoking, remain major causes of attributable DALYs, even as exposure is declining. Public policy makers need to pay attention to the risks that are increasingly major contributors to global burden. Funding: Bill & Melinda Gates Foundation

Driver Fusions and Their Implications in the Development and Treatment of Human Cancers.

Gene fusions represent an important class of somatic alterations in cancer. We systematically investigated fusions in 9,624 tumors across 33 cancer types using multiple fusion calling tools. We identified a total of 25,664 fusions, with a 63% validation rate. Integration of gene expression, copy number, and fusion annotation data revealed that fusions involving oncogenes tend to exhibit increased expression, whereas fusions involving tumor suppressors have the opposite effect. For fusions involving kinases, we found 1,275 with an intact kinase domain, the proportion of which varied significantly across cancer types. Our study suggests that fusions drive the development of 16.5% of cancer cases and function as the sole driver in more than 1% of them. Finally, we identified druggable fusions involving genes such as TMPRSS2, RET, FGFR3, ALK, and ESR1 in 6.0% of cases, and we predicted immunogenic peptides, suggesting that fusions may provide leads for targeted drug and immune therapy