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Background. Frequency and quantity of alcohol consumption are metrics commonly used to measure alcohol consumption behaviors. Epidemiological studies indicate that these alcohol consumption measures are differentially associated with (mental) health outcomes and socioeconomic status (SES). The current study aims to elucidate to what extent genetic risk factors are shared between frequency and quantity of alcohol consumption, and how these alcohol consumption measures are genetically associated with four broad phenotypic categories: (i) SES; (ii) substance use disorders; (iii) other psychiatric disorders; and (iv) psychological/personality traits.
Methods. Genome-Wide Association analyses were conducted to test genetic associations with alcohol consumption frequency (N = 438 308) and alcohol consumption quantity (N = 307 098 regular alcohol drinkers) within UK Biobank. For the other phenotypes, we used genome-wide association studies summary statistics. Genetic correlations (rg) between the alcohol measures and other phenotypes were estimated using LD score regression.
Results. We found a substantial genetic correlation between the frequency and quantity of alcohol consumption (rg = 0.52). Nevertheless, both measures consistently showed opposite genetic correlations with SES traits, and many substance use, psychiatric, and psychological/personality traits. High alcohol consumption frequency was genetically associated with high SES and low risk of substance use disorders and other psychiatric disorders, whereas the opposite applies for high alcohol consumption quantity.
Conclusions. Although the frequency and quantity of alcohol consumption show substantial genetic overlap, they consistently show opposite patterns of genetic associations with SES-related phenotypes. Future studies should carefully consider the potential influence of SES on the shared genetic etiology between alcohol and adverse (mental) health outcomes.
Use of artificial light resulted in relative independence from the natural light–dark (LD) cycle, allowing human subjects to shift the timing of food intake and work to convenient times. However, the increase in artificial light exposure parallels the increase in obesity prevalence. Light is the dominant Zeitgeber for the central circadian clock, which resides within the hypothalamic suprachiasmatic nucleus, and coordinates daily rhythm in feeding behaviour and metabolism. Eating during inappropriate light conditions may result in metabolic disease via changes in the biological clock. In this review, we describe the physiological role of light in the circadian timing system and explore the interaction between the circadian timing system and metabolism. Furthermore, we discuss the acute and chronic effects of artificial light exposure on food intake and energy metabolism in animals and human subjects. We propose that living in synchrony with the natural daily LD cycle promotes metabolic health and increased exposure to artificial light at inappropriate times of day has adverse effects on metabolism, feeding behaviour and body weight regulation. Reducing the negative side effects of the extensive use of artificial light in human subjects might be useful in the prevention of metabolic disease.
The primary aim of this experiment was to evaluate the intestinal barrier permeability in vivo in rainbow trout (Oncorhynchus mykiss) fed increasing levels of soyabean meal (SBM). The relationship between SBM-induced enteritis (SBMIE) and the permeability markers was also investigated. Our results showed that the mean score of morphological parameters was significantly higher as a result of 37·5 % SBM inclusion in the diet, while the scores of fish fed 25 % SBM or lower were not different from those of the fish meal-fed controls (P < 0·05). SBMIE was found in the distal intestine (DI) in 18 % of the fish (eleven of sixty): ten in the 37·5 % SBM-fed group and one in the 25 % SBM-fed group. Sugar markers in plasma showed large variation among individuals probably due to variation in feed intake. We found, however, a significant linear increase in the level of plasma d-lactate with increasing SBM inclusion level (P < 0·0001). Plasma concentration of endotoxin was not significantly different in groups with or without SBMIE. Some individual fish showed high values of endotoxin in blood, but the same individuals did not show any bacterial translocation. Plasma bacterial DNA was detected in 28 % of the fish with SBMIE, and 8 % of non-SBMIE fish (P = 0·07). Plasma concentration of d-lactate was significantly higher in fish with SBMIE (P < 0·0001). To conclude, SBMIE in the DI of rainbow trout was associated with an increase in bacterial translocation and plasma d-lactate concentration, suggesting that these permeability markers can be used to evaluate intestinal permeability in vivo.
Low-glycaemic index diets reduce glycated Hb (HbA1c) in patients with type 2 diabetes, but require intensive dietary support. Using a liquid meal replacement with a low glycaemic response (GR) may be an alternative dietary approach. In the present study, we investigated whether breakfast replacement with a low-GR liquid meal would reduce postprandial glycaemia and/or improve long-term glycaemia. In the present randomised, controlled, cross-over design, twenty patients with type 2 diabetes consumed either a breakfast replacement consisting of an isoenergetic amount of Glucerna SR or a free-choice breakfast for 3 months. Postprandial AUC levels were measured using continuous glucose measurement at home. After the 3-month dietary period, meal profiles and oral glucose tolerance were assessed in the clinical setting. The low-GR liquid meal replacement reduced the AUC of postprandial glucose excursions at home compared with a free-choice control breakfast (estimated marginal mean 141 (95 % CI 114, 174) v. estimated marginal mean 259 (95 % CI 211, 318) mmol × min/l; P= 0·0002). The low-GR liquid meal replacement also reduced glucose AUC levels in the clinical setting compared with an isoenergetic control breakfast (low GR: median 97 (interquartile range (IQR) 60–188) mmol × min/l; control: median 253 (IQR 162–386) mmol × min/l; P< 0·001). However, the 3-month low-GR liquid meal replacement did not affect fasting plasma glucose, HbA1c or lipid levels, and even slightly reduced oral glucose tolerance. In conclusion, the low-GR liquid meal replacement is a potential dietary approach to reduce postprandial glycaemia in patients with type 2 diabetes. However, clinical trials into the effects of replacing multiple meals on long-term glycaemia in poorly controlled patients are required before a low-GR liquid meal replacement can be adopted as a dietary approach to the treatment of type 2 diabetes.
In this chapter we discuss the potential failure of simple management models. Analysing components of a complex adaptive system in isolation is often misleading. The fundamental complexity of the social and natural environment has to be fully accounted for if unpleasant surprises are to be avoided. We examine a list of general management tools used in real-world fisheries, arguing that the success of a given instrument depends not only on its inherent properties but also on the way these instruments are administered. Similarly, we address how uncertainty and the biological complexity of the resource system may result in unintended consequences, including unanticipated costs. This demonstrates that for each resource system, the informational constraints have to be considered. Hence, interdisciplinary research is mandatory in order to reach adequate management decisions for social–ecological systems.
Marine fish stocks are renewable natural resources. They have the potential to provide food, income, and other services to mankind on a sustainable basis (Smith et al. 2010). Yet in reality, overfishing – the wasteful exploitation of marine resources – is a widespread observable fact (Jackson et al. 2001, Hilborn et al. 2003, Myers and Worm 2003, Worm and Myers 2004). On the one hand, there is no doubt that globally fisheries are in crisis (Clark 2006). On the other hand, how we can manage to rebuild global fisheries is still under debate (Worm et al. 2009).
The Groningen Overweight and Lifestyle (GOAL) study primarily aims at preventing weight gain by nurse practitioners (NP) guided by a standardized computerized software program. Since favourable changes in physical activity (PA) and diet may improve health independently of weight (loss), insight into effects on lifestyle habits is essential. We examined the 1-year effects of lifestyle counselling by NP on PA and diet, compared with usual care from the general practitioner (GP-UC).
A randomized controlled trial.
Eleven general practice locations in the Netherlands.
A total of 341 GOAL participants with overweight or obesity and either hypertension or dyslipidaemia, or both, who completed an FFQ and Short Questionnaire to Assess Health-Enhancing Physical Activity (SQUASH) at baseline and after 1 year.
After 1 year, the NP group spent 33 min/week more on walking compared with the GP-UC group who spent −5 min/week on walking (P = 0·05). No significant differences were found between the NP and GP-UC groups on the percentage of persons complying with the PA guidelines. In both groups, nutrient intake changed in a favourable direction and participants complied more often with dietary guidelines, but without overall difference between the NP and GP-UC groups.
With the exception of an increase in walking (based on self-reported data) in the NP group, no intervention effects on PA and diet occurred. Positive changes in nutrient intake were seen in both groups.
Aim – Delinquency among adolescents and antecedent conduct disorder among children has been recognized as a growing public mental health problem in contemporary societies. The contribution of the neighbourhood environment to delinquent behaviour was examined in a cohort of Dutch adolescents (aged approximately 11 years at baseline; n=394). Methods – Multilevel regression analyses estimated associations between baseline neighbourhood socioeconomic status and social capital, and delinquent behaviour two years later controlling for individual-level variables. Results – A significant interaction effect was found between neighbourhood environment variables and gender in models of delinquency, indicating that associations between neighbourhood environment variables and delinquency were apparent, for the most part, in girls only. However, higher level of neighbourhood informal social control was associated with increased delinquency rates in boys. Conclusion – In girls there is a longitudinal association between neighbourhood characteristics and delinquency, suggesting complex gender differences in the way the wider social environment impacts on behavioural outcomes.
RESEARCH AND THE CONTINUING EVOLUTION OF MOLECULAR MEDICINE
Andries J Oelofse, BSc, BSc (Hons), MSc (Bioinformatics), held the position of Bioinformatics Consultant at Wits Bioinformatics, a node of the National Bioinformatics Network, at the time of writing. He has a keen interest in the contribution of bioinformatics to molecular medicine.,
Michèle Ramsay, PhD (Human Genetics), is currently Professor and Head of the Molecular Genetics Laboratory, Division of Human Genetics, National Health Laboratory Service and University of the Witwatersrand.
To study life at the molecular level, various types of data must be in a ‘human readable format’. There are many tools and techniques with which we can determine the sequences of the nucleic acids and proteins that allow us to draw parallels between what we physically observe and what is happening at the molecular level. The amount of data these tools generate is vast. The data can amount to several gigabytes per experiment, and all must be correctly stored and interpreted in order to be useful. There are also several related types of information that assist in the better understanding of the function of genes and proteins in the organism.
Bioinformatics is the discipline that deals with the problem of massive data sets with diverse data in molecular research. It concerns the storage, visualisation, manipulation, analysis and integration of biological information using computers. Initially, the biological information that was required to be managed by bioinformaticists was the nucleotide and amino acid data derived from DNA and protein sequencing, but today with new technologies and approaches there are many more diverse data types that must be managed.
A paradigm shift is starting to occur in molecular research. The emphasis on hypo - thesis-driven research is declining, and is shifting towards exploratory observations. These observations are typically done in a very high-throughput way, meaning that in some cases literally billions of data points are considered per experiment over a relatively short period of time. This would be impossible if all the observations had to be made by human observers, and computers are extremely important for data capturing, management and analysis in experiments of this type.
A very good example of technology that requires computers for data capture, management and analysis is microarray technology. This technology enables the determination of miRNA expression levels for all genes in a sample at a given time point. It is utilised by com paring the gene expression levels between a test and a reference sample, and then identifying the genes that are up-regulated in terms of their expression as well as those that are down-regulated. These genes are very interesting to examine, since (usually in combination) they determine how the phenotype of a test sample would differ from the reference sample.
The garnet Ca3Sc2Si3O12 (CSSO) and the silico-carnotite Ca3Y2Si3O12 (CYSO) and Ca3Lu2Si3O12 (CLSO) materials, both undoped and doped with Pr3+, have been synthesized by solid state reaction at high temperature. The luminescence spectroscopy and the excited state dynamics of the materials have been studied upon VUV and X-ray excitation using synchrotron radiation. All doped samples have shown efficient 5d-4f emission upon direct VUV excitation of 5d levels, but only CSSO:Pr3+ shows luminescence upon interband VUV or X-ray excitation. The VUV excited emission spectra of CYSO:Pr3+ and CLSO:Pr3+ show features attributed to emission from two distinct sites accommodating the Pr3+ dopant. The decay kinetics of the Pr3+ 5d-4f emission in CSSO:Pr3+ upon VUV excitation across the conduction band are characterized by decay times in the range 25-28 ns with no significant rise after the excitation pulse. They appear to be faster upon X-ray irradiation than for VUV excitation. Weak afterglow components are attributed to defect luminescence.
This paper describes an investigation towards very fast emitting oxidic luminescent materials doped with Pr3+. Such materials have the potential to be applied as scintillators in Positron Emission Tomography.
As the limits of traditional CMOS scaling are approached, process integration has become increasingly difficult and resulting in a diminished rate of performance improvement over time. Consequently, the search for new two- and three- dimensional sub-system solutions has been pursued. One such solution is a silicon carrier-based System-on-Package (SOP) that enables high-density interconnection of heterogeneous die beyond current first level packaging densities. Silicon carrier packaging contains through silicon vias (TSV), fine pitch Cu wiring and high-density solder pads/joins, all of which are compatible with traditional semiconductor methods and tools. These same technology elements, especially the through silicon via process, also enable three dimensional stacking and integration. An approach to fabricating electrical through-vias in silicon is described, featuring annular-shaped vias instead of the more conventional cylindrical via. This difference enables large-area, uniform arrays to be produced with high yield as it is simpler to integrate into a conventional CMOS back-end-of-line (BEOL) process flow. Furthermore, the CTE-matched silicon core provides improved mechanical stability and the dimensions of the annular via allows for metallization by various means including copper electroplating or CVD tungsten deposition. An annular metal conductor process flow will be described. Through-via resistance measurements of 50, 90, and 150μm deep tungsten-filled annular vias will be compared. Two silicon carrier test vehicle designs, containing more than 2,200 and 9,600 electrical through-vias, respectively, were built to determine process yield and uniformity of via resistance. Through silicon via resistances range from 15-40 mΩ, and yields in excess of 99.99% have been demonstrated.
The influence of a constant coronal magnetic field on solar global oscillations is investigated for a simple planar equilibrium model. The model consists of an atmosphere with a constant horizontal magnetic field on top of a unmagnetized solar interior. The focus is on the possible resonant coupling of global solar oscillation modes to local slow continuum modes of the atmosphere and the consequent damping of the global oscillations.
Nanocrystalline ZnS:Pb2+ is synthesized via a precipitation method. The luminescence is studied and the influence of the size of the nanocrystals on the luminescence properties is investigated. Nanocrystalline ZnS:Pb2+ shows a white emission under UV excitation. At least two luminescence centers are involved. One center is identified as a Pb2+ ion located on a regular Zn2+ site and gives a red emission under 480 nm excitation. The luminescence properties of this emission are characteristic for transitions on Pb2+ ions. The other centers are not as well defined and give a broad green emission band under 380 nm excitation and also show luminescence properties typically observed for Pb2+. The green emission probably originates from a charge-transfer like D-band emission of Pb2+ in ZnS close to a defect (e.g. an S2− vacancy or an O2− ion on an S2− site). A relation between the temperature quenching of the emissions and the band gap is observed and indicates that photoionization occurs.
This paper presents for the first time a comparison between the luminescence properties (viz. emission and excitation spectra, lifetimes, and concentration quenching) of nanocrystalline and microcrystalline Lu2O3:xTm3+ (x= 0.1– 5 mol%). The results show that the most important difference between the two size regimes is the higher defect concentration in the nanoparticles. These defects give rise to a broadband emission (λmax = 430 nm), and to partial quenching of the Tm3+ emission, in addition to the expected concentration quenching by cross-relaxation between Tm3+ ions. The defect concentration seems to be similar in all nanocrystalline samples, so that those with the lowest Tm3+ concentrations experience the most pronounced quenching. The nature of these defects is as yet unknown. The local structure around the Tm3+ ions is not noticeably different in the two size regimes. No evidence of phonon confinement or quantum size effects was observed in the Tm3+luminescence.
Clozapine (Leponex®) has been shown to be therapeutically effective in patients resistant to long-term medication with classical antipsychotics. The mode of action of clozapine is not clear, but several cerebral receptors have been implicated, including the dopamine D2, D3 and D4 types, α-adrenergic, serotonin (type 2A) and glutamate (NMDA-type) receptors. Moreover, clozapine has anti-cholinergic and antihistaminergic potencies. Thusfar, receptor profiles are based virtually exclusively on in vitro binding assays. It appeared, that pharmacological and physiological stimuli activate particular gene expression, in vivo, so at cellular level the action of e.g. antipsychotics can now be traced. In this communication we present data on the in vivo profile of clozapine as revealed with Fos-protein expression. The immediate early gene c-fos is, as other members of the class of such genes, rapidly and transiently induced in the brain. The prototypic members of this class all encode nuclear proteins that regulate gene transcription. Recent studies have shown that the antipsychotics haloperidol (Haldol®) and clozapine, when given acutely, induce different patterns of Fos-like immunoreactivity in the forebrain of the rat. The most marked effects of haloperidol were found in the striatum, the nucleus accumbens and the lateral septum.
In this chapter, we examine secular trends in diet, metabolism and body composition, including changes in the type of food consumed (‘country’ versus ‘market’ sources), the energy costs of ‘country’ versus urban activities, developing problems from the contamination of local food and water resources, secular trends in body composition, and specific indicators of metabolic health such as glucose tolerance and the blood lipid profile.
One major nutritional change associated with the ‘modernization’ of indigenous circumpolar populations has been a progressive shift from ‘country’ to ‘market’ foods. There has also been a decrease in the total food needs of the individual as daily energy expenditures have declined, and in at least a substantial minority of the population, a substantial intake of refined carbohydrates and/or alcohol has displaced more nutritious food items. Nevertheless, serious malnutrition remains much less common in the arctic than in many developing countries, in part because of financial support from central governments, and in part because many of the indigenous communities continue to supplement store purchases by protein-rich items of ‘country’ food. However, the continuing isolation of arctic settlements and the high costs of air-freight have precluded substantial purchases of fresh fruit and green vegetables by the average villager, so that deficiencies in the blood levels of certain vitamins are common. In some communities, a high intake of refined carbohydrate and lack of vegetable fibre has also had an adverse effect upon dental health.
‘Modernization’ has brought a multitude of changes in social structures and behaviour patterns to the indigenous circumpolar populations – a process that some authors have termed ‘acculturation’ (Berry, 1976; Forsius, 1980; Sampath, 1976). This chapter looks at objective measures of acculturation and the resulting acculturative stress or alienation, examining the extent and the social effects of cultural change in groups that, until recently, have followed a neolithic hunter-gatherer or pastoral lifestyle.
Measures of acculturation
In a study of Inuit living at Baker Lake and Lake Harbour, Freeman (1971a) measured acculturation in terms of sources of income (Table 1.1). He demonstrated a substantial change in the type of employment from 1951/52 to the late 1960s.
At the time of the 1969/70 IBP-HAP survey of Igloolik, Rode & Shephard (1973b) made a three-level classification of the occupation of adult men, based on extensive observation of the villagers and discussion with the community elders. The population was divided into those who were persisting with a traditional hunting lifestyle, those who had accepted wage-earning employment within the settlement, and an intermediate, transitional group who were accepting occasional paid work, but still persisted with some hunting. This classification, although simple, revealed substantial inter-category differences in aerobic power and skinfold thicknesses, both in summer and in winter (Table 3.1). The association between acculturation and measures of fitness became even more marked when the hunters were subdivided, based upon the frequency of their long (two to three week) hunting trips.
This chapter begins by describing certain features of fitness patterns that were observed among indigenous circumpolar residents at the time of the IBP-HAP surveys, particularly seasonal effects and inter- and intra-community differences related to the early phases of acculturation to a sedentary, urban lifestyle. Information on secular trends in aerobic power, anaerobic power and capacity, lean tissue mass and muscle strength is then drawn from communities where cross-sectional surveys have been repeated or longitudinal analyses undertaken. Changes in cold tolerance are considered in similar fashion, and finally the possibility of developing community programmes to conserve physical fitness is explored in the context of indigenous societies.
Lifestyle, season and fitness: the IBP-HAP findings
Early information on the physical fitness of circumpolar populations, obtained mainly by non-standard methodology, was summarized in Chapter 1. Despite limitations in the available data, the conclusion was drawn that in the 1950s and 1960s, the small samples of people that were tested had a higher fitness level than would have been expected in sedentary city dwellers of similar age. However, it was unclear whether those examined were representative of their communities, and it was also uncertain how much the individual fitness levels may have been biased downward by such factors as malnutrition and the ravages of chronic disease, particularly tuberculosis (Andersen & Hart, 1963).
The IBP-HAP data on aerobic power is summarized in Table 5.1 and Fig. 5.1. At most of the circumpolar test sites, direct measurements of maximal oxygen intake were only obtained on small samples of subjects, with younger adults preponderating.