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The Psychiatric Genomics Consortium (PGC) has made major advances in the molecular etiology of MDD, confirming that MDD is highly polygenic. Pathway enrichment results from PGC meta-analyses can also be used to help inform molecular drug targets. Prior to any knowledge of molecular biomarkers for MDD, drugs targeting molecular pathways (MPs) proved successful in treating MDD. It is possible that examining polygenicity within specific MPs implicated in MDD can further refine molecular drug targets.
Using a large case–control GWAS based on low-coverage whole genome sequencing (N = 10 640) in Han Chinese women, we derived polygenic risk scores (PRS) for MDD and for MDD specific to each of over 300 MPs previously shown to be relevant to psychiatric diagnoses. We then identified sets of PRSs, accounting for critical covariates, significantly predictive of case status.
Over and above global MDD polygenic risk, polygenic risk within the GO: 0017144 drug metabolism pathway significantly predicted recurrent depression after multiple testing correction. Secondary transcriptomic analysis suggests that among genes in this pathway, CYP2C19 (family of Cytochrome P450) and CBR1 (Carbonyl Reductase 1) might be most relevant to MDD. Within the cases, pathway-based risk was additionally associated with age at onset of MDD.
Results indicate that pathway-based risk might inform etiology of recurrent major depression. Future research should examine whether polygenicity of the drug metabolism gene pathway has any association with clinical presentation or treatment response. We discuss limitations to the generalizability of these preliminary findings, and urge replication in future research.
A recent paper, “Parkinson's disease mild cognitive impairment classifications and neurobehavioral symptoms” (McDermott et al., 2017), provides an interesting comparison of the influence of different criteria for Parkinson's disease with mild cognitive impairment (PD-MCI) on progression to dementia (PDD). Unfortunately, McDermott et al. (2017) incorrectly stated that “only 21% of PD-MCI participants (identified with a 1.5 SD cut-off) converted to PDD within four years” (p.6) in our study (Wood et al., 2016). However, the important point made by Wood et al. (2016) was that the proportion of conversions to PDD was 51% when the PD-MCI diagnosis required a minimum of two 1.5 SD impairments within any single cognitive domain, whereas additional PD-MCI patients classified with one impairment at 1.5 SD in each of the two domains (but never two impairments in the same domain) had a non-significant risk of dementia relative to non-MCI patients (11% vs. 6% converted, respectively). Our PDD conversion rate was 38% when combining both 1.5 SD criteria (21/56 PD-MCI patients vs. 4/65 non-MCI patients converted); McDermott et al. (2017) found a 42% conversion rate over three years for similarly described PD-MCI patients (10/24 PD-MCI patients vs. 0/27 non-MCI patients converted). Our study was also part of a multinational study (n = 467) showing that PD-MCI has predictive validity beyond known demographic and PD-specific factors of influence (Hoogland et al., 2017). All three studies found that multiple cognitive domain impairments are common in PD-MCI. Nonetheless, the research community needs to clarify the association between PD-MCI subtypes and, especially, the optimal cognitive markers for dementia risk in PD patients.
We read the findings by Cecato et al. (2016) with great interest. In their study, naming the rhinoceros discriminated between patients with amnestic mild cognitive impairment (aMCI) and Alzheimer's disease (AD) but not healthy controls (HC). Of note, HC participants were significantly younger than aMCI and AD patients. All participants were administered the original version of the Montreal Cognitive Assessment (MoCA) instrument.
Studies using acute tryptophan depletion (ATD) to examine the effects of a rapid reduction in serotonin function have shown a reduction in global cognitive status during ATD in Alzheimer's disease (AD) and Parkinson's disease (PD). Based on the severe cholinergic loss evident in dementia with Lewy bodies (DLB) and Parkinson's disease and dementia (PDD), we predicted that a reduction of global cognitive status during ATD would be greater in these conditions than in AD.
Patients having DLB or PDD underwent ATD in a double-blind, placebo-controlled, randomized, counterbalanced, crossover design.
While the study intended to test 20 patients, the protocol was poorly tolerated and terminated after six patients attempted, but only four patients – three with DLB and one with PDD – completed the protocol. The Modified Mini-Mental State Examination (3MSE) score was reduced in all three DLB patients and unchanged in the PDD and dementia patient during ATD compared with placebo.
This reduction in global cognitive function and the poor tolerability may fit with the hypothesis that people with dementia with Lewy bodies have sensitivity to the effects of reduced serotonin function.
The sensitivity of glaciers to climatic change is key information in assessing the response and sea-level implications of projected future warming. New Zealand glaciers are important globally as an example of how maritime glaciers will contribute to sea-level rise. A spatially distributed energy-balance model is applied to Brewster Glacier, New Zealand, in order to calculate glacier mass balance, run-off and sensitivity to climate change. The model successfully simulates four annual mass-balance cycles. Close to half (52%) of the energy available for melt on the glacier is supplied by turbulent heat fluxes, with radiation less important, except during the winter. Model sensitivity to temperature change is one of the largest reported on Earth, at −2.0 m w.e. a−1 °C−1. In contrast, a 50% change in precipitation is required to offset the mass-balance change resulting from a 1 °C temperature change. Meltwater runoff sensitivity is also very high, increasing 60% with a 1°C warming. The extreme sensitivity of mass balance to temperature change suggests that significant ice loss will occur with even moderate climate warming.
To evaluate the feasibility of undertaking a food skills intervention study in areas of social deprivation aimed at altering cooking confidence, food preparation methods and dietary choices.
A standardised skills programme was implemented in community-based settings. Pre- (T1) and post-intervention (T2) and 6-month follow-up (T3) measures (7-day diaries and self-administered questionnaires) were undertaken in intervention and comparison groups.
Eight urban communities in Scotland.
One hundred and thirteen adults living in areas of social deprivation.
It was clear that many subjects led fragmented lives and found commitment to intervention classes problematic. Sixty-three subjects completed the final (T3) assessments. The response to each component varied due to inability to attend sessions, illness, study requirements, employment, moving out of the area, change in circumstances, loss of interest and loss of postal questionnaires. At baseline, reported consumption of fruit and vegetables was low (mean frequency 8.1 ± 4.78 times per week). Fruit intake increased significantly (P < 0.05) between T1 and T2 in the intervention group (1.7 ± 2.36 to 2.7 ± 3.28 times per week) only. Between T1 and T3, there was a significant increase (P < 0.05) in intervention subjects who reported confidence in following a recipe (67–90%,).
This exploratory trial shows that a food skills intervention is likely to have a small but positive effect on food choice and confidence in food preparation. A full-scale randomised controlled trial in this hard-to-reach group would require a range of flexible approaches rather than a fully defined intervention, and presents challenges for trial design.
Hydride-Metalorganic Vapor Phase Epitaxy (H-MOVPE) was used to grow a series of films on c-Al2O3 substrates. Depending on the growth temperature and HCl/TMIn molar ratio, InN deposited as a continuous film or a collection of micro or nanorods, or no InN growth was observed. A chemical equilibrium analysis of the In-N-H-Cl system predicts both InN growth and etching regimes with the nanorod growth observed near the growth-etching transition. All InN rod structures demonstrated well faceted hexagonal structure with a near random orientation of the rods, while the films were polycrystalline.
The representations formed by the ventral and dorsal streams of a prelinguistic agent will tend to be too qualitatively similar to support the distinct roles required by PREDICATE(x) structure. We suggest that the attachment of qualities to objects is not a product of the combination of these separate processing streams, but is instead a part of the processing required in each. In addition, we suggest that the formation of objective predicates is inextricably bound up with the emergence of language itself, and so cannot be cleanly identified with any prelinguistic cognitive capacities.
Ice-sheet basal ice is warmer than that above because of the heat from the Earth’s interior. The stresses acting on the basal ice are greatest. In addition, the basal ice often contains debris consisting of silt and small stones picked up from the rock over which the ice flows. Because the base is the warmest part of an ice sheet and the stress there is greatest, flow rates in the basal ice are large and often contribute most of the ice movement. It is therefore important, for accurate modelling of the ice sheets, to know whether the debris within the basal ice enhances or retards the flow of the ice. In this paper, we describe laboratory deformation tests in uniaxial compression and in simple shear, on sand-laden ice. We find no significant dependence of flow rate on sand content (up to 15% volume) in the stress range 0.13–0.5 MPa and temperature range –0.02 to –18.0°C. Further work needs to include laboratory tests on debris-laden ice extracted from the polar ice sheets. This work is underway.
Interdiffusion of Si/Si0.85Ge0.15 heterojunctions subjected to annealing in inert and oxidizing ambients was investigated as a function of temperature (900 to 1200 °C) and time, allowing comparison between intrinsic diffusion and diffusion under interstitial injection. The Ge diffusivity was extracted using the process simulation program FLOOPS. A time-independent diffusivity was observed for all temperatures. The calculated Ge diffusivity in oxidizing ambient was comparable to that in inert ambient indicating that the interstitial concentration plays a minimal role in interdiffusion. A fractional interstitial component, f1, equal to 0.10 is estimated for annealing temperatures in the range 900 to 1100 °C, while f1 increases to approximately 0.17 at 1200 °C. This may indicate a change in diffusion mechanism at a temperature greater than 1100 °C
CuInSe2 thin films have been synthesized from binary precursors by Rapid Thermal Processing (RTP) at a set-point temperature of 290°C for 70 s. With appropriate processing conditions no detrimental Cu2-xSe phase was detected in the CIS films. The novel binary precursor approach consisted of a bilayer structure of In-Se and Cu-Se compounds. This bilayer structure was deposited by migration enhanced physical vapor deposition at a low temperature (200°C) and the influence of deposition parameters on the precursor film composition was determined. The bilayer structure was then processed by RTP and characterized for constitution by X-ray diffraction and for composition by Wavelength Dispersive X-ray Spectroscopy.
It is shown that in a variety of (not necessarily associative) algebras which satisfies a variant of Andrunakievich's Lemma, a class C containing no solvable algebras is the semi-simple class corresponding to some supernilpotent radical class if and only ifCis hereditary and is closed under extensions and sub-direct products. Semi-simple classes in general are not characterized by these properties. If the variety satisfies the further condition that some proper power of every ideal is an ideal, then analogous results hold for the semi-simple classes corresponding to radical classes containing no solvable algebras. In particular, for algebras over a field in the latter situation, all semi-simple classes are characterized by the three closure properties mentioned.
The Levitzki radical, which is fundamental in the study of algebras satisfying a polynomial identity, has been shown to exist in the varieties of alternative and Jordan algebras (see Zhevlakov , Zwier , and Tsai — for an important application of this radical to alternative algebras satisfying a polynomial identity, see Slater ). In fact, Hartley  even investigated local nilpotence for Lie algebras, though this property can not be radical in the sense of Kurosh-Amitsur  for these algebras.
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