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Depression and obesity are highly prevalent, and major impacts on public health frequently co-occur. Recently, we reported that having depression moderates the effect of the FTO gene, suggesting its implication in the association between depression and obesity.
To confirm these findings by investigating the FTO polymorphism rs9939609 in new cohorts, and subsequently in a meta-analysis.
The sample consists of 6902 individuals with depression and 6799 controls from three replication cohorts and two original discovery cohorts. Linear regression models were performed to test for association between rs9939609 and body mass index (BMI), and for the interaction between rs9939609 and depression status for an effect on BMI. Fixed and random effects meta-analyses were performed using METASOFT.
In the replication cohorts, we observed a significant interaction between FTO, BMI and depression with fixed effects meta-analysis (β=0.12, P = 2.7 × 10−4) and with the Han/Eskin random effects method (P = 1.4 × 10−7) but not with traditional random effects (β = 0.1, P = 0.35). When combined with the discovery cohorts, random effects meta-analysis also supports the interaction (β = 0.12, P = 0.027) being highly significant based on the Han/Eskin model (P = 6.9 × 10−8). On average, carriers of the risk allele who have depression have a 2.2% higher BMI for each risk allele, over and above the main effect of FTO.
This meta-analysis provides additional support for a significant interaction between FTO, depression and BMI, indicating that depression increases the effect of FTO on BMI. The findings provide a useful starting point in understanding the biological mechanism involved in the association between obesity and depression.
Informed application of habitat management measures is crucial, especially in saltmarshes that function as last refuges for breeding waders in Europe. Despite a reduction in agricultural use of saltmarshes since the establishment of the Wadden Sea National Parks at the end of the 1980s, there remains controversy regarding management measures such as the timing of mowing. We modelled the proportion of nests and chicks that would be jeopardised by mowing at different dates, using long-term breeding data of the Common Redshank Tringa totanus – an endangered and widespread indicator species of saltmarshes – from four study sites in the German Wadden Sea. At two study sites in the western Jadebusen, the proportion of broods that were at risk of being killed when mowing began on 1 July ranged between 78% in early, to 96% in late, breeding years, averaging 87%. Although Common Redshanks in the eastern Jadebusen started breeding one week earlier, the model still predicted a loss of 73% of chicks; while 97% of broods were at risk on the island of Wangerooge. Postponement of mowing to 1 August reduced these proportions to 21%, 11% and 32%, respectively. This study is the first to model the positive effects of delayed mowing of saltmarshes on ground-nesting birds. By implementing adjusted mowing dates in addition to previously suggested reductions in artificial drainage, direct and indirect adverse effects caused by mowing and drainage, such as an increased predation risk, are likely to be reduced, such that a ’favourable conservation status’ according to the EC Habitats Directive may be achieved.
Health nudge interventions to steer people into healthier lifestyles are increasingly applied by governments worldwide, and it is natural to look to such approaches to improve health by altering what people choose to eat. However, to produce policy recommendations that are likely to be effective, we need to be able to make valid predictions about the consequences of proposed interventions, and for this, we need a better understanding of the determinants of food choice. These determinants include dietary components (e.g. highly palatable foods and alcohol), but also diverse cultural and social pressures, cognitive-affective factors (perceived stress, health attitude, anxiety and depression), and familial, genetic and epigenetic influences on personality characteristics. In addition, our choices are influenced by an array of physiological mechanisms, including signals to the brain from the gastrointestinal tract and adipose tissue, which affect not only our hunger and satiety but also our motivation to eat particular nutrients, and the reward we experience from eating. Thus, to develop the evidence base necessary for effective policies, we need to build bridges across different levels of knowledge and understanding. This requires experimental models that can fill in the gaps in our understanding that are needed to inform policy, translational models that connect mechanistic understanding from laboratory studies to the real life human condition, and formal models that encapsulate scientific knowledge from diverse disciplines, and which embed understanding in a way that enables policy-relevant predictions to be made. Here we review recent developments in these areas.
Following the surface application of granulated urea to grassland, high ammonia (NH3) losses of up to 30% have been reported. The addition of a urease inhibitor (UI) to urea granules could be a way to abate these losses. Field experiments were conducted at two intensive grassland sites in 2007 and 2008 to evaluate the potential of the new UI N-(2-nitrophenyl) phosphoric triamide (2-NPT; concentrations of 0·75, 1·0 and 1·5 g N/kg) to reduce NH3 emissions resulting from the application of granulated urea. Ammonia losses were continuously measured on plots fertilized with urea, urea + 2-NPT, calcium ammonium nitrate and a control (0N). The measurements were made with a dynamic chamber system. All measurement periods were started after a period of precipitation with a following rainless period being forecasted. Results over measurement periods of 10 days following fertilization are presented. Ammonia losses following the application of granulated urea varied between 4·6 and 11·8 kg N/ha, corresponding to 4·2 up to 14·0% of the applied nitrogen. The addition of 2-NPT to urea granules at three concentrations significantly reduced NH3 losses by 69–100%. Comparable losses of NH3 were observed for urea containing the UI 2-NPT as well as calcium ammonium nitrate, and were not significantly different from the control treatment. No relationships between losses, meteorological factors and soil moisture were observed. The addition of the UI 2-NPT to urea granules applied on grassland effectively reduced NH3 losses.
We studied the effect of a cross-conjugated bridging group (χC) on charge-transfer in a push-pull chromophore system. The hyperpolarizability of such molecules was found to be comparable to that of a fully π-conjugated molecule (πC) with the same donor and acceptor. The cross-conjugated moiety was then applied as a pendant to a fully π-conjugated chromophore containing a tricyanopyrroline acceptor (TCP). The addition of a χC moiety did not alter the intrinsic hyperpolarizability and provides an avenue for extending and aiding πC systems. The molecules were examined by X-ray diffraction (XRD), hyper-Raleigh scattering (HRS) and UV-visible (UV-vis) spectroscopy. Experimental results were compared with the predictions of density functional theory (DFT). Cross-conjugated molecules have comparable β values, relative to πC molecules, due to reduced spatial overlap between the highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO). Thus, the χC architecture could facilitate independent modification of donor and acceptor strengths while minimizing unfavorable effects on electronic transitions and dipole moments.
The use of organic nonlinear optical (ONLO) materials in electro-optic (EO) modulators requires that the active molecular components (chromophores) be acentrically oriented. The fundamental molecular constituents are in a condensed, glassy phase. Molecular orientation in such systems is typically achieved by applying a DC poling field to the glassy material. We are developing efficient coarse-grained classical Monte Carlo (MC) methods to simulate the order of such systems. The most challenging aspects of these simulations are convergence to an experimentally relevant equilibrium ensemble and verification of simulation accuracy. We use a variety of molecular descriptions and a variety of MC methods to achieve proper order in the shortest number of computational cycles possible. Herein, we illustrate a few examples of the types of calculations and compare with experimental results with representative amorphous organic materials, including electro-optic chromophores.
We report on the composition dependence of the band gap energy of strained hexagonal InxGa1−xN layers on GaN with x≤0.15, grown by metal-organic chemical vapor deposition on sapphire substrates. The composition of the (InGa)N was determined by secondary ion mass spectroscopy. High-resolution X-ray diffraction measurements confirmed that the (InGa)N layers with typical thicknesses of 30 nm are pseudomorphically strained to the in-plane lattice parameter of the underlying GaN. Room-temperature photoreflection spectroscopy and spectroscopic ellipsometry were used to determine the (InGa)N band gap energy. The composition dependence of the band gap energy of the strained (InGa)N layers was found to be given by EG(x)=3.43−3.28 × (eV) for x≤0.15. When correcting for the strain induced shift of the fundamental energy gap, a bowing parameter of 3.2 eV was obtained for the composition dependence of the gap energy of unstrained (InGa)N.
As physical activity may modify the effect of the apolipoprotein E (APOE) ε4 allele on the risk of dementia and Alzheimer's disease (AD) dementia, we tested for such a gene–environment interaction in a sample of general practice patients aged ⩾75 years.
Data were derived from follow-up waves I–IV of the longitudinal German study on Ageing, Cognition and Dementia in Primary Care Patients (AgeCoDe). The Kaplan–Meier survival method was used to estimate dementia- and AD-free survival times. Multivariable Cox regression was used to assess individual associations of APOE ε4 and physical activity with risk for dementia and AD, controlling for covariates. We tested for gene–environment interaction by calculating three indices of additive interaction.
Among the randomly selected sample of 6619 patients, 3327 (50.3%) individuals participated in the study at baseline and 2810 (42.5%) at follow-up I. Of the 2492 patients without dementia included at follow-up I, 278 developed dementia (184 AD) over the subsequent follow-up interval of 4.5 years. The presence of the APOE ε4 allele significantly increased and higher physical activity significantly decreased risk for dementia and AD. The co-presence of APOE ε4 with low physical activity was associated with higher risk for dementia and AD and shorter dementia- and AD-free survival time than the presence of APOE ε4 or low physical activity alone. Indices of interaction indicated no significant interaction between low physical activity and the APOE ε4 allele for general dementia risk, but a possible additive interaction for AD risk.
Physical activity even in late life may be effective in reducing conversion to dementia and AD or in delaying the onset of clinical manifestations. APOE ε4 carriers may particularly benefit from increasing physical activity with regard to their risk for AD.
Whether late-onset depression is a risk factor for or a prodrome of dementia remains unclear. We investigated the impact of depressive symptoms and early- v. late-onset depression on subsequent dementia in a cohort of elderly general-practitioner patients (n = 2663, mean age = 81.2 years).
Risk for subsequent dementia was estimated over three follow-ups (each 18 months apart) depending on history of depression, particularly age of depression onset, and current depressive symptoms using proportional hazard models. We also examined the additive prediction of incident dementia by depression beyond cognitive impairment.
An increase of dementia risk for higher age cut-offs of late-onset depression was found. In analyses controlling for age, sex, education, and apolipoprotein E4 genotype, we found that very late-onset depression (aged ⩾70 years) and current depressive symptoms separately predicted all-cause dementia. Combined very late-onset depression with current depressive symptoms was specifically predictive for later Alzheimer's disease (AD; adjusted hazard ratio 5.48, 95% confidence interval 2.41–12.46, p < 0.001). This association was still significant after controlling for cognitive measures, but further analyses suggested that it was mediated by subjective memory impairment with worries.
Depression might be a prodrome of AD but not of dementia of other aetiology as very late-onset depression in combination with current depressive symptoms, possibly emerging as a consequence of subjectively perceived worrisome cognitive deterioration, was most predictive. As depression parameters and subjective memory impairment predicted AD independently of objective cognition, clinicians should take this into account.
Young people with self-experienced cognitive thought and perception deficits (basic symptoms) may present with an early initial prodromal state (EIPS) of psychosis in which most of the disability and neurobiological deficits of schizophrenia have not yet occurred.
To investigate the effects of an integrated psychological intervention (IPI), combining individual cognitive–behavioural therapy, group skills training, cognitive remediation and multifamily psychoeducation, on the prevention of psychosis in the EIPS.
A randomised controlled, multicentre, parallel group trial of 12 months of IPI v. supportive counselling (trial registration number: NCT00204087). Primary outcome was progression to psychosis at 12- and 24-month follow-up.
A total of 128 help-seeking out-patients in an EIPS were randomised. Integrated psychological intervention was superior to supportive counselling in preventing progression to psychosis at 12-month follow-up (3.2% v. 16.9%; P = 0.008) and at 24-month follow-up (6.3% v. 20.0%; P = 0.019).
Integrated psychological intervention appears effective in delaying the onset of psychosis over a 24-month time period in people in an EIPS.
Symptom dimensions have not yet been comprehensively tested as predictors of the substantial heterogeneity in outcomes of antidepressant treatment in major depressive disorder.
We tested nine symptom dimensions derived from a previously published factor analysis of depression rating scales as predictors of outcome in 811 adults with moderate to severe depression treated with flexibly dosed escitalopram or nortriptyline in Genome-based Therapeutic Drugs for Depression (GENDEP). The effects of symptom dimensions were tested in mixed-effect regression models that controlled for overall initial depression severity, age, sex and recruitment centre. Significant results were tested for replicability in 3637 adult out-patients with non-psychotic major depression treated with citalopram in level I of Sequenced Treatment Alternatives to Relieve Depression (STAR*D).
The interest-activity symptom dimension (reflecting low interest, reduced activity, indecisiveness and lack of enjoyment) at baseline strongly predicted poor treatment outcome in GENDEP, irrespective of overall depression severity, antidepressant type and outcome measure used. The prediction of poor treatment outcome by the interest-activity dimension was robustly replicated in STAR*D, independent of a comprehensive list of baseline covariates.
Loss of interest, diminished activity and inability to make decisions predict poor outcome of antidepressant treatment even after adjustment for overall depression severity and other clinical covariates. The prominence of such symptoms may require additional treatment strategies and should be accounted for in future investigations of antidepressant response.
Human cytomegalovirus (CMV) is a common herpesvirus establishing lifelong persisting infection, which has been implicated in immunosenescence and mortality in the elderly. Little is known about how and when susceptibility to CMV infection is determined. We measured CMV seroprevalence in two genetically informative cohorts. From the Leiden Longevity Study (LLS) we selected long-lived sib-pairs (n=844) and their middle-aged offspring and the offspring's partners (n=1452). From the Longitudinal Study of Aging Danish Twins (LSADT) 604 (302 pairs) same-sex monozygotic (MZ) and dizygotic (DZ) twins aged 73–94 years were included (n=302 pairs). Offspring of the long-lived LLS participants had significantly lower seroprevalence of CMV compared to their partners (offspring: 42% vs. partners: 51%, P=0·003). Of 372 offspring living with a CMV-positive partner, only 58% were infected. The corresponding number for partners was 71% (P<0·001). In the LSADT, MZ and DZ twins had high and similar CMV-positive concordance rates (MZ: 90% vs. DZ: 88%, P=0·51) suggesting that shared family environment accounts for the similarity within twin pairs. Our findings suggest that susceptibility to CMV infection – even under continuous within-partnership exposure – appears to be more strongly influenced by early-life environment than by genetic factors and adult environment.
Graded (Ca,Ba)F2 layers consisting of near lattice matched CaF2 at the Si interface and of BaF2 with 14% increased lattice constant at the top surface were grown by molecular beam epitaxy (MBE) on Si(111). Smooth and crackfree layers exhibiting Rutherford backscattering (RBS) channeling minima below 5% were obtained. Device quality epitaxial layers of PbTe, PbSe and (Pb,Sn)Se were grown on top of these structures. Mechanical stress at 300K was relaxed by athermal mechanisms in the fluoride- as well as in the Pb-salt films. - In preliminary runs, epitaxial CdTe-layers were obtained on Si(111) using the same fluoride-buffer film technique and which showed clear SEM electron channeling patterns.
Multilayered WSix films for use as gates in a self-aligned refractory gate process of GaAs MESFETs have been RF sputtered onto GaAs wafers under UHV background conditions in order to study their structure and morphology as well as their contact electrical properties. Annealed films deposited at 300°C with single layer thickness of 6 and 3 nm for W and Si respectively have a smooth morphology free from cracks and blisters and show a good adhesion to the substrate. Schottky diodes prepared on n-GaAs exhibit an almost excellent I-V characteristics with a barrier height of 0.73 V and an ideality factor of 1.11. In addition E - and D-FETs fabricated on implanted s.i. wafers have good electrical parameters with transconductances of 200 mS/mm at 1 μm gate length.
Using SIMS profiling, temperature-dependent Hall measurements, electronic Raman scattering, and infra-red absorption, a detailed study is presented examining the effects of Si dopant behaviour on intersubband absorption in GaAs/Al .32Ga .68As MQW’s. The samples were grown by molecular beam epitaxy at substrate temperatures ranging from 520 to 680°C with Si doping in the GaAs quantum wells only. SIMS profiling reveals that, with increasing substrate temperature, substantial Si migration into the Al .32Ga.68 As barrier layers occurs during epitaxial growth. Hall measurements indicate that both at elevated growth temperatures and under reduced incident As4 beam fluxes, the electron sheet concentration is reduced in the QW’s. In both cases, loss of free carriers is attributed to enhanced Si compensation. Shifts in the absolute frequency of the infra-red absorption resonance, determined by electronic Raman scattering, as well as variations in the integrated absorption intensity, are both shown to directly reflect the growth-induced variations in the free-carrier concentration in the quantum wells.
We investigate the optical properties of arrays of closely spaced metal nanoparticles in view of their potential to guide electromagnetic energy with a lateral mode confinement below the diffraction limit of light. Finite-difference time-domain simulations of short arrays of noble metal nanospheres show that electromagnetic pulses at optical frequencies can propagate along the arrays due to near-field interactions between plasmon-polariton modes of adjacent nanoparticles. Near-field microscopy enables the study of energy transport in these plasmon waveguides and shows experimental evidence for energy propagation over a distance of 0.5 νm for plasmon waveguides consisting of spheroidal silver particles fabricated using electron beam lithography.
Synthesis and characterization of three classes of poly(arylene ether oxazole)s and poly(arylene ether thiazole)s with trifluoromethyl substituents in various positions is described. Based on these examples, the influence of the chemical structure of the polymers on properties such as glass transition temperature, solubility, and thermal stability will be discussed. Structural parameters studied are the number and nature of the heteroaromatic rings, the number and position of the trifluoromethyl groups, and the structure (flexibility, polarity) of various linking groups.
We report on the composition dependence of the band gap energy of strained hexagonal InGal-,N layers on GaN with x≤0.15, grown by metal-organic chemical vapor deposition on sapphire substrates. The composition of the (InGa)N was determined by secondary ion mass spectroscopy. High-resolution X-ray diffraction measurements confirmed that the (InGa)N layers with typical thicknesses of 30 nm are pseudomorphically strained to the in-plane lattice parameter of the underlying GaN. Room-temperature photoreflection spectroscopy and spectroscopic ellipsometry were used to determine the (InGa)N band gap energy. The composition dependence of the band gap energy of the strained (InGa)N layers was found to be given by EG(x)=3.43-3.28.x (eV) for x≤0.15. When correcting for the strain induced shift of the fundamental energy gap, a bowing parameter of 3.2 eV was obtained for the composition dependence of the gap energy of unstrained (InGa)N.