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Jürgen Habermas’ discourse theory of morality should be understood, in metaethical terms, as a constructivist theory. All constructivist theories face a Euthyphro-like dilemma arising from how they classify the constraints on their metaethical construction procedures: are they moral or non-moral? Many varieties of Kantian constructivism, such as Christine Korsgaard’s, classify the constraints as moral, albeit constitutive of human reason and agency in general. However, this constitutivist strategy is vulnerable to David Enoch’s ‘shmagency’ objection. The discourse theory of morality, by classifying the constraints on the metaethical construction procedure (principles (D) and (U)) as non-moral, can avoid this problem.
Iron deficiency is common in pregnant and lactating women and is associated with reduced cognitive development of the offspring. Since iron affects lipid metabolism, the availability of fatty acids, particularly the polyunsaturated fatty acids required for early neural development, was investigated in the offspring of female rats fed iron-deficient diets during gestation and lactation. Subsequent to the dams giving birth, one group of iron-deficient dams was recuperated by feeding an iron-replete diet. Dams and neonates were killed on postnatal days 1, 3 and 10, and the fatty acid composition of brain and stomach contents was assessed by gas chromatography. Changes in the fatty acid profile on day 3 became more pronounced on day 10 with a decrease in the proportion of saturated fatty acids and a compensatory increase in monounsaturated fatty acids. Long-chain polyunsaturated fatty acids in the n-6 family were reduced, but there was no change in the n-3 family. The fatty acid profiles of neonatal brain and stomach contents were similar, suggesting that the change in milk composition may be related to the changes in the neonatal brain. When the dams were fed an iron-sufficient diet at birth, the effects of iron deficiency on the fatty acid composition of lipids in both dam’s milk and neonates’ brains were reduced. This study showed an interaction between maternal iron status and fatty acid composition of the offspring’s brain and suggests that these effects can be reduced by iron repletion of the dam’s diet at birth.
Nutritional science has traditionally used the reductionist approach to understand the roles of individual nutrients in growth and development. The macronutrient dense but micronutrient poor diets consumed by many in the Western world may not result in an overt deficiency; however, there may be situations where multiple mild deficiencies combine with excess energy to alter cellular metabolism. These interactions are especially important in pregnancy as changes in early development modify the risk of developing non-communicable diseases later in life. Nutrient interactions affect all stages of fetal development, influencing endocrine programming, organ development and the epigenetic programming of gene expression. The rapidly developing field of stem cell metabolism reveals new links between cellular metabolism and differentiation. This review will consider the interactions between nutrients in the maternal diet and their influence on fetal development, with particular reference to energy metabolism, amino acids and the vitamins in the B group.
Recent ground surveys in the Samtskhe-Javakheti region of southern Georgia have investigated a previously undocumented group of sites along a ridge overlooking the upper Kura river valley. Features and artefacts recorded at Varneti suggest long but episodic occupation from the Chalcolithic to the later medieval periods, with prominent phases in the Early to Middle Bronze Age and the Late Bronze Age to Early Iron Age. Varneti has the potential to contribute to understanding economic and strategic aspects of the long-term settlement pattern in the southern Caucasus, especially the interplay between lowland and highland zones. Its position in the landscape, at a transitional point between the river valley and the upland pasture (yayla), may explain its persistent use by agro-pastoral communities that operated in varied cultural situations. The survey results help us frame a series of questions regarding economic and social dynamics at a local and regional scale and the continuity and discontinuity of practice in highland environments through long timespans.
Understanding the underlying mechanisms of recovery from insomnia is an important goal for improving existing treatments. In a randomised controlled trial, 57 participants with insomnia disorder were given either cognitive therapy (CT) or mindfulness-based therapy (MBT) following 4 sessions of CBT. Each participant was assessed on process measures related to CT and MBT. MBT resulted in improvement on mindfulness process measures and the size of the improvement was significantly greater than achieved in the CT condition. Interestingly, CT and MBT both resulted in significant improvement on the cognitive process measures. Treatment outcome on the primary outcome measure (Insomnia Severity Index) was not predicted by type of treatment but was predicted by posttreatment scores on the cognitive process measures. The results suggest that changes in cognitive processes are especially important in treating insomnia, and that there are different therapeutic modalities through which this can be achieved.
The demographic composition of Kazakhstan after the fall of the Soviet Union presented a dilemma to the new Kazakhstani government: Should it advance a Kazakh identity as paramount, possibly alienating the large non-Kazakh population? Or should it advocate for a non-ethnicized national identity? How would those decisions be made in light of global norms of liberal multiculturalism? And, critically, would citizens respond to new frames of identity? This paper provides an empirical look at supraethnic identity-building in Kazakhstan – that is, at the development of a national identity that individuals place above or alongside their ethnic identification. We closely examine the Assembly of People of Kazakhstan to describe how Kazakhstani policies intersect with theories of nationalism and nation-building. We then use ordered probit models to analyze data from a 2014 survey to examine how citizens of Kazakhstan associate with a “Kazakhstani” supraethnic identity. Our findings suggest that despite the Assembly of People's rhetoric, there are still significant barriers to citizen-level adoption of a supraethnic identity in Kazakhstan, particularly regarding language. However, many individuals do claim an association with Kazakhstani identity, especially those individuals who strongly value citizenship in the abstract.
Increasingly, ambulance services offer alternatives to transfer to the emergency department (ED), when this is better for patients. The introduction of electronic health records (EHR) in ambulance services is encouraged by national policy across the United Kingdom (UK) but roll-out has been variable and complex.
Electronic Records in Ambulances (ERA) is a two-year study which aims to investigate and describe the opportunities and challenges of implementing EHR and associated technology in ambulances to support a safe and effective shift to out of hospital care, including the implications for workforce in terms of training, role and clinical decision-making skills.
Our study includes a scoping review of relevant issues and a baseline assessment of progress in all UK ambulance services in implementing EHR. These will inform four in-depth case studies of services at different stages of implementation, assessing current usage, and examining context.
The scoping review identified themes including: there are many perceived potential benefits of EHR, such as improved safety and remote diagnostics, but as yet little evidence of them; technical challenges to implementation may inhibit uptake and lead to increased workload in the short term; staff implementing EHR may do so selectively or devise workarounds; and EHR may be perceived as a tool of staff surveillance.
Our scoping review identified some complex issues around the implementation of EHR and the relevant challenges, opportunities and workforce implications. These will help to inform our fieldwork and subsequent data analysis in the case study sites, to begin early in 2017. Lessons learned from the experience of implementing EHR so far should inform future development of information technology in ambulance services, and help service providers to understand how best to maximize the opportunities offered by EHR to redesign care.
Euclid is a Europe-led cosmology space mission dedicated to a visible and near infrared survey of the entire extra-galactic sky. Its purpose is to deepen our knowledge of the dark content of our Universe. After an overview of the Euclid mission and science, this contribution describes how the community is getting organized to face the data analysis challenges, both in software development and in operational data processing matters. It ends with a more specific account of some of the main contributions of the Swiss Science Data Center (SDC-CH).
This paper describes a preliminary investigation of the extent to which the normalised difference vegetation index (NDVI), derived from satellite optical imagery, can indicate the extent of damage to upland tundra (fruticose lichen and dwarf shrub) vegetation. We combine the results of a previously reported classification of Landsat multispectral scanner imagery from Kol'skiy Poluostrov, Russia, with field measurements of the biomass and spectral reflectance of tundra vegetation. The results show that the NDVI is not strongly influenced by biomass, but that differences in species composition and ground cover are significant. Other workers have concluded that vegetation indices are not useful for boreal forests. It is therefore suggested that the use of the NDVI by itself as an indicator of the state of disturbed vegetation in Arctic regions is not recommended.
Previously we have examined the effects of diets deficient in folic acid ( − F) or folate deficient with low methionine and choline ( − F LM LC) on the relative abundance of soluble proteins in the liver of the pregnant rat. In the present study we report the corresponding changes in the fetal liver at day 21 of gestation. The abundance of eighteen proteins increased when dams were fed the − F diet. When dams were fed the − F LM LC diet, thirty-three proteins increased and eight decreased. Many of the differentially abundant proteins in the fetal liver could be classified into the same functional groups as those previously identified in the maternal liver, namely protein synthesis, metabolism, lipid metabolism and proteins associated with the cytoskeleton and endoplasmic reticulum. The pattern was consistent with reduced cell proliferation in the − F LM LC group but not in the − F group. Metabolic enzymes associated with lipid metabolism changed in both the − F and − F LM LC groups. The mRNA for carnitine palmitoyl transferase were up-regulated and CD36 (fatty acid translocase) down-regulated in the − F group, suggesting increased mitochondrial oxidation of fatty acids as an indirect response to altered maternal lipid metabolism. In the − F LM LC group the mRNA for acetyl CoA carboxylase was down-regulated, suggesting reduced fatty acid synthesis. The mRNA for transcriptional regulators including PPARα and sterol response element-binding protein-1c were unchanged. These results suggest that an adequate supply of folic acid and the related methyl donors may benefit fetal development directly by improving lipid metabolism in fetal as well as maternal tissues.
In humans poor maternal folate status is associated with a decrease in infant birth weight. As low birth weight increases the risk of cardiovascular and metabolic disease in adults, an inadequate supply of folic acid in the mother's diet may increase the susceptibility of the offspring to disease. We have fed laboratory rats diets deficient in folic acid and the related methyl donors methionine and choline to examine the effects on growth, blood pressure and insulin action in the offspring. Poor folate status transiently increased fetal growth but did not produce a long-term change in body weight. There were, however, small changes in the hearts of the female offspring. When folate deficiency was combined with low intakes of methionine and choline, the kidneys of the male offspring were proportionately smaller, probably because of the limited availability of methionine. There was no effect on the blood pressure of either the male or female offspring. The pancreatic insulin content of fetuses from animals fed the folate-deficient diets were higher than those of the controls. Following an oral glucose challenge, there was a weak trend for glucose-stimulated insulin release to be increased in the offspring of dams fed the folate-deficient diet. The changes in insulin concentrations were, however, much smaller than the corresponding changes observed in the offspring of animals fed protein-deficient diets. These results suggest that folate deficiency during gestation causes modest changes to the insulin axis of the fetus.
The importance of folic acid and the methionine cycle in fetal development is well recognised even though the mechanism has not been established. Since the cycle is active in the maternal liver, poor folate status may modify hepatic metabolism. Pregnant rats were fed diets deficient in folic acid (–F) or in three key methyl donors, folic acid, choline and methionine (–FLMLC) and the maternal liver was analysed on day 21 of gestation. Two-dimensional gel electrophoresis of soluble proteins identified differentially abundant proteins, which could be allocated into nine functional groups. Five involved in metabolic processes, namely, folate/methionine cycle, tyrosine metabolism, protein metabolism, energy metabolism and lipid metabolism, and three in cellular processes, namely, endoplasmic reticulum function, bile production and antioxidant defence. The mRNA for sterol regulatory element-binding protein-1c and acetyl-CoA carboxylase-1 (fatty acid synthesis) were decreased by both –F and –FLMLC diets. The mRNA for PPARα and PPARγ and carnitine palmitoyl transferase (fatty acid oxidation) were increased in the animals fed the –FLMLC diets. Changes in the abundance of proteins associated with intracellular lipid transport suggest that folate deficiency interferes with lipid export. Reduced fatty acid synthesis appeared to prevent steatosis in animals fed the –F diet. Even with increased oxidation, TAG concentrations were approximately three-fold higher in animals fed the –FLMLC diet and were associated with an increase in the relative abundance of proteins associated with oxidative stress. Fetal development may be indirectly affected by these changes in hepatic lipid metabolism.
The methionine cycle and methyl group metabolism are implicated in the long-term programming of metabolism. Diets deficient in folic acid, methionine and choline have been fed to pregnant rats to examine the effects on amino acid metabolism, choline reserves and DNA methylation in dam and fetuses. Animals were fed folate-deficient, folate-deficient with low methionine, folate-deficient with low choline and folate-deficient, low-methionine, low-choline diets starting 2 weeks before mating. The dams and their fetuses were subsequently killed on day 21 of gestation for analysis. Diets low in methionine reduced fetal and maternal weight. Folate deficiency increased the concentrations of homocysteine, glycine, serine and threonine in the maternal plasma, and this was exacerbated by the low-methionine diets. The changes in the amino acid profile in the fetal serum were similar but less pronounced. This result suggests that fetal metabolism was less perturbed. Folate deficiency increased free choline in the maternal liver at the expense of phosphocholine stores. It has been suggested that a deficiency in methyl donors in the diet during pregnancy may impact on key methylation reactions, including the methylation of DNA. Despite widespread changes in the metabolism of choline and amino acids, there was no change in the global methylation of cytosine in DNA from either maternal or fetal livers. This suggests a more indirect mechanism in which gene–nutrient interactions modify the process of differential methylation during development
The available evidence suggests that metabolic control mechanisms are programmed early in life. Previous studies of pregnant rats fed low-protein diets have suggested that the vegetable oils used in the experimental diets influence the outcome. The present study investigated the offspring of female rats fed semi-synthetic diets containing either 180 or 90 g casein/kg with 70 g/kg (w/w) of either corn oil or soya oil during gestation. During lactation, the dams received stock diet, and the offspring were subsequently weaned onto the stock diet. The offspring of dams fed the low-protein diets were smaller at birth. At 25 weeks of age, the offspring were subjected to an oral glucose tolerance test. In the offspring of dams fed the diet containing soya oil, the area under the insulin curve was affected by the protein content of the maternal diet. There was no effect of protein on the area under the insulin curve in the offspring of dams fed the diet prepared with corn oil. There were no differences in plasma glucose concentrations. The levels of mRNA for acetyl-CoA carboxylase-1 in the livers of female offspring were affected by the protein and oil content of the maternal diet. The level of carnitine palmitoyl transferase mRNA was affected by the protein content of the maternal diet. The present study suggests that PUFA in the maternal diet can interact with protein metabolism to influence the development of the offspring. This may involve the higher content of α-linolenic acid in soya oil compared with corn oil.
During fetal life, there are periods of rapid cell proliferation, which are uniquely sensitive to nutritional perturbation. Feeding the pregnant rat a protein-restricted diet alters the growth trajectory of major fetal organs such as the kidney. By day 21 of gestation, the ratio of kidney weight to total body weight is reduced in the fetuses of dams fed a protein-deficient diet. In contrast, the ratio of fetal liver weight to total body weight is unchanged. To investigate the mechanisms underlying this disproportionate change in organ growth in the low-protein group, cell proliferation and differentiation have been assessed in the liver and kidney. The steady-state levels of mRNA for the growth-arrest and DNA-damage gene gadd153/CHOP-10, CCAAT enhancer-binding proteins α and β were unaffected by maternal diet in both fetal liver and kidney. The mRNA for alpha-fetoprotein, albumin and hepatic glucokinase were unchanged in the liver, suggesting that maternal protein deficiency does not alter the state of differentiation. The steady-state levels of the mRNA coding for the cyclin-dependent protein kinase inhibitors (p15INK4a, p19INK4d, p21CIP1, p27KIP1 and p57KIP2) were unchanged in the fetal livers but were significantly increased in the kidneys of fetuses from dams fed the low-protein diet. These results show that the asymmetrical growth of the kidney is associated with increases in mRNA for the Cip/Kip cyclin-dependent kinase inhibitors and that these may reflect specific lesions in organ development.
A multi-technique approach was used to map the spatial distribution of seabed biotopes (i.e. physical habitats and their associated benthic assemblages) in the vicinity of Hastings Shingle Bank in the eastern English Channel, part of which is licensed for the extraction of marine aggregates for the construction industry. An area of seabed, approximately 12×4 km in size, was surveyed using a high-resolution sidescan sonar system, and a mosaic of the output was produced, covering 100% of the survey area. The area was then divided into acoustically distinct regions based on the sidescan sonar data, and the benthic communities and sediment types within each of the regions were ground-truthed using a Hamon grab fitted with a video camera, and using a heavy duty 2-m beam trawl. Additional information concerning the seabed was obtained through the application of video and photographic techniques. Sediments within the survey area ranged from cobbles and coarse gravels on the Shingle Bank, to various grades of sands to the north and south. Analysis of faunal data revealed the presence of statistically distinct biological assemblages within each acoustic region. Using all available data, four discrete biotopes were identified and their spatial distribution mapped across the survey area.