932 research outputs found

    PRS3 COST ANALYSIS OF FOURTREATMENT STRATEGIES IN THE MANAGEMENT OF MODERATE-TO-SEVERE CHRONIC OBSTRUCTIVE PULMONARY DISEASE: AN APPLICATION ON NON-PARAMETRIC BOOTSTRAP

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    Socio-economic evaluation with ordinal variables: integrating counting and POSET approaches

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    The evaluation of material deprivation, quality of life and well-being very often requires to deal with multidimensional systems of ordinal variables, rather than with classical numerical datasets. This poses new statistical and methodological challenges, since classical evaluation tools are not designed to deal with this kind of data. The mainstream evaluation methodologies generally follow a counting approach, as in a recent proposal by Alkire and Foster pertaining to the evaluation of multidimensional poverty. Counting procedures are inspired by the composite indicator approach and share similar drawbacks with it, computing aggregated indicators that may be poorly reliable. A recent and alternative proposal is to address the ordinal evaluation problem through partial order theory which provides tools that prove more consistent with the discrete nature of the data. The goal of the present paper is thus to introduce the two proposals, showing how the evaluation methodology based on partial order theory can be integrated in the counting approach of Alkire and Foster

    MicroRNAs in melanoma development and resistance to target therapy

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    microRNAs constitute a complex class of pleiotropic post-transcriptional regulators of gene expression involved in the control of several physiologic and pathologic processes. Their mechanism of action is primarily based on the imperfect matching of a seed region located at the 5' end of a 21-23 nt sequence with a partially complementary sequence located in the 3' untranslated region of target mRNAs. This leads to inhibition of mRNA translation and eventually to its degradation. Individual miRNAs are capable of binding to several mRNAs and several miRNAs are capable of influencing the function of the same mRNAs. In recent years networks of miRNAs are emerging as capable of controlling key signaling pathways responsible for the growth and propagation of cancer cells. Furthermore several examples have been provided which highlight the involvement of miRNAs in the development of resistance to targeted drug therapies. In this review we provide an updated overview of the role of miRNAs in the development of melanoma and the identification of the main downstream pathways controlled by these miRNAs. Furthermore we discuss a group of miRNAs capable to influence through their respective up- or down-modulation the development of resistance to BRAF and MEK inhibitors

    The endocrine function of osteocalcin regulated by bone resorption. a lesson from reduced and increased bone mass diseases

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    Bone is a peculiar tissue subjected to a continuous process of self-renewal essential to assure the integrity of the skeleton and to explicate the endocrine functions. The study of bone diseases characterized by increased or reduced bone mass due to osteoclast alterations has been essential to understand the great role played by osteocalcin in the endocrine functions of the skeleton. The ability of osteoclasts to regulate the decarboxylation of osteocalcin and to control glucose metabolism, male fertility, and cognitive functions was demonstrated by the use of animal models. In this review we described how diseases characterized by defective and increased bone resorption activity, as osteopetrosis and osteoporosis, were essential to understand the involvement of bone tissue in whole body physiology. To translate this knowledge into humans, recently published reports on patients were described, but further studies should be performed to confirm this complex hormonal regulation in humans

    Bone control of muscle function

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    Bone and muscle represent a single functional system and are tightly connected to each other. Indeed, diseases characterized by alterations of muscle physiology have effects on bone remodeling and structure and vice versa. Muscle influence on bone has been deeply studied, and recent studies identified irisin as new molecule involved in this crosstalk. Muscle regulation by bone needs to be extensively investigated since in the last few years osteocalcin was recognized as a key molecule in the bone–muscle interaction. Osteocalcin can exist in two forms with different degrees of carboxylation. The undercarboxylated form of osteocalcin is a hormone released by the bone matrix during the osteoclast bone resorption and can bind its G-protein coupled receptor GPRC6A expressed in the muscle, thus regulating its function. Recently, this hormone was described as an antiaging molecule for its ability to regulate bone, muscle and cognitive functions. Indeed, the features of this bone-related hormone were used to test a new therapeutic approach for sarcopenia, since injection of osteocalcin in older mice induces the acquirement of physical abilities of younger animals. Even if this approach should be tested in humans, osteocalcin represents the most surprising molecule in endocrine regulation by the skeleton

    Targeting Policies for Multidimensional Poverty and Social Fragility Relief Among Migrants in Italy, Using F-FOD Analysis

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    In this paper, we apply the novel Fuzzy First-Order Dominance (F-FOD) methodology to rank migrant subpopulations in Lombardy (Italy), in terms of multidimensional poverty and social fragility, for the year 2014, with the purpose to possibly provide useful support to policy-makers, in targeting relief interventions from poverty and discomfort. The F-FOD methodology allows for the direct comparison of different distributions of poverty and fragility, assessed by means of suitable ordinal multi-indicator systems, so extending to this more complex setting, the usual univariate first-order dominance criterion. It also provides complimentary “incomparability” scores, to assess to what extent the final rankings are reliable or instead forcing. It turns out that the levels of poverty and fragility of migrant subpopulations are quite different and, in particular, that the time since migrations has a key impact, on the identification of most critical cases, which typically involve recently migrated people. Evidence also emerges that the temporal poverty/fragility trajectories of migrants, distinguished by country of origin, follow different paths, suggesting how policy interventions must be properly, and differently, tuned to be effective

    Editorial: Novel Psychoactive Drugs

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    Quantifying and Maximising the Benefits of Crops After Rice

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    At the time this project was conceived, rising watertables and subsequent salinisation were considered to be the major threats to the sustainability of irrigated agriculture in the rice growing areas of southern NSW. The biggest threat to sustainability at present is the reduced availability and higher cost of water as a result of the water reforms, and more recently prolonged drought. The hypothesis of this project was that growing crops immediately after rice would increase water use efficiency and profitability of rice-based cropping systems while reducing net recharge. Field experiments were conducted from 1998 to 2000 on two soil types to evaluate the effect of non-irrigated wheat after rice on watertables and net recharge. Rainfall during the wheat season was reasonably similar in all 3 years (270-318 mm) and higher than average (220 mm). Yield and biomass production of early sown (24 April) wheat were higher than yield of late wheat (29 June) (grain yield 4.7 vs 3.8 t/ha at 12% moisture). In the absence of irrigation, the soil profile remained wet in fallow areas, whereas there was considerable drying in areas planted to wheat. The drying created capacity in the soil profile to capture and use winter rainfall. There was a general increase in depth to the watertable during the first half of the season where non-irrigated wheat was grown after rice, but not in the fallow areas. However, in all situations, the watertable rose around the time of rice sowing each year due to a rise in the regional groundwater level. The lumped water balance studies suggested net discharge of about 1 ML/ha between the time of sowing and harvesting wheat after rice in each of the three years, mostly due to higher upflow due to crop water use. In the fallow, net discharge/recharge was close to zero. The CERES Wheat and SWAGMAN® Destiny models performed very well in simulating a wide range of crop and soil water parameters, although the validation data sets were limited in that the yield range was smaller than desirable. Consistent with the field studies, yield of nonirrigated early sown wheat (median 3.8 t/ha) was usually much higher than yield of late sown wheat (median 1.8 t/ha). With one or two irrigations yields of both early and late sown wheat almost always increased, by around 1 t/ha with one irrigation at heading, and an additional 0.5 t/ha with a second irrigation during grain filling. It was only with frequent irrigation (whenever cumulative ETo-rain since the previous irrigation reached 60 mm) that yields of late sown wheat matched (or surpassed) yields of early sown wheat. However, the irrigation requirement for late wheat irrigated at ETo-rain 60 mm was almost always much higher than for early wheat with the same irrigation management (by >100 mm in most years). While irrigation increased yield, it also increased net recharge, with final watertables generally higher by 0.5 to 0.8 m for wheat after rice (wet initial soil) with irrigation at ETo-rain 60 mm compared with no irrigation. The model simulations showed that with wheat after rice, there was net discharge in almost all years, regardless of initial watertable depth (0.5-1.5 m). In comparison, net recharge occurred in 18 to 48% of years with fallow after rice, the amount of recharge increase as initial depth to the watertable increased. For non-irrigated wheat after rice, salinity of the watertable was 2 important where the watertable was shallow (0.5 m), with yield reductions in excess of 1 t/ha in most years. However for deeper watertables, there was no effect of watertable salinity for non-irrigated wheat. With irrigation, watertable salinity had no impact on yields. Growing wheat immediately after rice was financially beneficial, with an increase in Net Present Value (NPV) ranging from 31 to 126 /ha/yrdependingontherotation.Assumingthattherateofadoptionisdoubledover20yearsasaresultoftheproject,theNPVofbenefitswasestimatedtobe/ha/yr depending on the rotation. Assuming that the rate of adoption is doubled over 20 years as a result of the project, the NPV of benefits was estimated to be 5.6 million compared with costs of $1.1 million, resulting in a benefit cost ratio of 5.3

    Quantifying and Maximising the Benefits of Crops After Rice

    Get PDF
    At the time this project was conceived, rising watertables and subsequent salinisation were considered to be the major threats to the sustainability of irrigated agriculture in the rice growing areas of southern NSW. The biggest threat to sustainability at present is the reduced availability and higher cost of water as a result of the water reforms, and more recently prolonged drought. The hypothesis of this project was that growing crops immediately after rice would increase water use efficiency and profitability of rice-based cropping systems while reducing net recharge. Field experiments were conducted from 1998 to 2000 on two soil types to evaluate the effect of non-irrigated wheat after rice on watertables and net recharge. Rainfall during the wheat season was reasonably similar in all 3 years (270-318 mm) and higher than average (220 mm). Yield and biomass production of early sown (24 April) wheat were higher than yield of late wheat (29 June) (grain yield 4.7 vs 3.8 t/ha at 12% moisture). In the absence of irrigation, the soil profile remained wet in fallow areas, whereas there was considerable drying in areas planted to wheat. The drying created capacity in the soil profile to capture and use winter rainfall. There was a general increase in depth to the watertable during the first half of the season where non-irrigated wheat was grown after rice, but not in the fallow areas. However, in all situations, the watertable rose around the time of rice sowing each year due to a rise in the regional groundwater level. The lumped water balance studies suggested net discharge of about 1 ML/ha between the time of sowing and harvesting wheat after rice in each of the three years, mostly due to higher upflow due to crop water use. In the fallow, net discharge/recharge was close to zero. The CERES Wheat and SWAGMAN® Destiny models performed very well in simulating a wide range of crop and soil water parameters, although the validation data sets were limited in that the yield range was smaller than desirable. Consistent with the field studies, yield of nonirrigated early sown wheat (median 3.8 t/ha) was usually much higher than yield of late sown wheat (median 1.8 t/ha). With one or two irrigations yields of both early and late sown wheat almost always increased, by around 1 t/ha with one irrigation at heading, and an additional 0.5 t/ha with a second irrigation during grain filling. It was only with frequent irrigation (whenever cumulative ETo-rain since the previous irrigation reached 60 mm) that yields of late sown wheat matched (or surpassed) yields of early sown wheat. However, the irrigation requirement for late wheat irrigated at ETo-rain 60 mm was almost always much higher than for early wheat with the same irrigation management (by >100 mm in most years). While irrigation increased yield, it also increased net recharge, with final watertables generally higher by 0.5 to 0.8 m for wheat after rice (wet initial soil) with irrigation at ETo-rain 60 mm compared with no irrigation. The model simulations showed that with wheat after rice, there was net discharge in almost all years, regardless of initial watertable depth (0.5-1.5 m). In comparison, net recharge occurred in 18 to 48% of years with fallow after rice, the amount of recharge increase as initial depth to the watertable increased. For non-irrigated wheat after rice, salinity of the watertable was 2 important where the watertable was shallow (0.5 m), with yield reductions in excess of 1 t/ha in most years. However for deeper watertables, there was no effect of watertable salinity for non-irrigated wheat. With irrigation, watertable salinity had no impact on yields. Growing wheat immediately after rice was financially beneficial, with an increase in Net Present Value (NPV) ranging from 31 to 126 /ha/yrdependingontherotation.Assumingthattherateofadoptionisdoubledover20yearsasaresultoftheproject,theNPVofbenefitswasestimatedtobe/ha/yr depending on the rotation. Assuming that the rate of adoption is doubled over 20 years as a result of the project, the NPV of benefits was estimated to be 5.6 million compared with costs of $1.1 million, resulting in a benefit cost ratio of 5.3

    The role of autophagy in osteoclast differentiation and bone resorption function

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    Autophagy is an evolutionary conserved and highly regulated recycling process of cellular wastes. Having a housekeeping role, autophagy through the digestion of domestic cytosolic organelles, proteins, macromolecules, and pathogens, eliminates unnecessary materials and provides nutrients and energy for cell survival and maintenance. The critical role of autophagy and autophagy-related proteins in osteoclast differentiation, bone resorption, and maintenance of bone homeostasis has previously been reported. Increasing evidence reveals that autophagy dysregulation leads to alteration of osteoclast function and enhanced bone loss, which is associated with the onset and progression of osteoporosis. In this review, we briefly consolidate the current state-of-the-art technology regarding the role of autophagy in osteoclast function in both physiologic and pathologic conditions to have a more general view on this issue
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