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Accurate diagnosis of bipolar disorder (BPD) is difficult in clinical practice, with an average delay between symptom onset and diagnosis of about 7 years. A depressive episode often precedes the first manic episode, making it difficult to distinguish BPD from unipolar major depressive disorder (MDD).
Aims
We use genome-wide association analyses (GWAS) to identify differential genetic factors and to develop predictors based on polygenic risk scores (PRS) that may aid early differential diagnosis.
Method
Based on individual genotypes from case–control cohorts of BPD and MDD shared through the Psychiatric Genomics Consortium, we compile case–case–control cohorts, applying a careful quality control procedure. In a resulting cohort of 51 149 individuals (15 532 BPD patients, 12 920 MDD patients and 22 697 controls), we perform a variety of GWAS and PRS analyses.
Results
Although our GWAS is not well powered to identify genome-wide significant loci, we find significant chip heritability and demonstrate the ability of the resulting PRS to distinguish BPD from MDD, including BPD cases with depressive onset (BPD-D). We replicate our PRS findings in an independent Danish cohort (iPSYCH 2015, N = 25 966). We observe strong genetic correlation between our case–case GWAS and that of case–control BPD.
Conclusions
We find that MDD and BPD, including BPD-D are genetically distinct. Our findings support that controls, MDD and BPD patients primarily lie on a continuum of genetic risk. Future studies with larger and richer samples will likely yield a better understanding of these findings and enable the development of better genetic predictors distinguishing BPD and, importantly, BPD-D from MDD.
White matter hyperintensity (WMH) burden is greater, has a frontal-temporal distribution, and is associated with proxies of exposure to repetitive head impacts (RHI) in former American football players. These findings suggest that in the context of RHI, WMH might have unique etiologies that extend beyond those of vascular risk factors and normal aging processes. The objective of this study was to evaluate the correlates of WMH in former elite American football players. We examined markers of amyloid, tau, neurodegeneration, inflammation, axonal injury, and vascular health and their relationships to WMH. A group of age-matched asymptomatic men without a history of RHI was included to determine the specificity of the relationships observed in the former football players.
Participants and Methods:
240 male participants aged 45-74 (60 unexposed asymptomatic men, 60 male former college football players, 120 male former professional football players) underwent semi-structured clinical interviews, magnetic resonance imaging (structural T1, T2 FLAIR, and diffusion tensor imaging), and lumbar puncture to collect cerebrospinal fluid (CSF) biomarkers as part of the DIAGNOSE CTE Research Project. Total WMH lesion volumes (TLV) were estimated using the Lesion Prediction Algorithm from the Lesion Segmentation Toolbox. Structural equation modeling, using Full-Information Maximum Likelihood (FIML) to account for missing values, examined the associations between log-TLV and the following variables: total cortical thickness, whole-brain average fractional anisotropy (FA), CSF amyloid ß42, CSF p-tau181, CSF sTREM2 (a marker of microglial activation), CSF neurofilament light (NfL), and the modified Framingham stroke risk profile (rFSRP). Covariates included age, race, education, APOE z4 carrier status, and evaluation site. Bootstrapped 95% confidence intervals assessed statistical significance. Models were performed separately for football players (college and professional players pooled; n=180) and the unexposed men (n=60). Due to differences in sample size, estimates were compared and were considered different if the percent change in the estimates exceeded 10%.
Results:
In the former football players (mean age=57.2, 34% Black, 29% APOE e4 carrier), reduced cortical thickness (B=-0.25, 95% CI [0.45, -0.08]), lower average FA (B=-0.27, 95% CI [-0.41, -.12]), higher p-tau181 (B=0.17, 95% CI [0.02, 0.43]), and higher rFSRP score (B=0.27, 95% CI [0.08, 0.42]) were associated with greater log-TLV. Compared to the unexposed men, substantial differences in estimates were observed for rFSRP (Bcontrol=0.02, Bfootball=0.27, 994% difference), average FA (Bcontrol=-0.03, Bfootball=-0.27, 802% difference), and p-tau181 (Bcontrol=-0.31, Bfootball=0.17, -155% difference). In the former football players, rFSRP showed a stronger positive association and average FA showed a stronger negative association with WMH compared to unexposed men. The effect of WMH on cortical thickness was similar between the two groups (Bcontrol=-0.27, Bfootball=-0.25, 7% difference).
Conclusions:
These results suggest that the risk factor and biological correlates of WMH differ between former American football players and asymptomatic individuals unexposed to RHI. In addition to vascular risk factors, white matter integrity on DTI showed a stronger relationship with WMH burden in the former football players. FLAIR WMH serves as a promising measure to further investigate the late multifactorial pathologies of RHI.
Australian conservation cropping systems are practiced on very large farms (approximately 3,000 ha) where herbicides are relied on for effective and timely weed control. In many fields, though, there are low weed densities (e.g., <1.0 plant 10 m−2) and whole-field herbicide treatments are wasteful. For fallow weed control, commercially available weed detection systems provide the opportunity for site-specific herbicide treatments, removing the need for whole-field treatment of fallow fields with low weed densities. Concern about the sustainability of herbicide-reliant weed management systems remain and there has not been interest in the use of weed detection systems for alternative weed control technologies, such as targeted tillage. In this paper, we discuss the use of a targeted tillage technique for site-specific weed control in large-scale crop production systems. Three small-scale prototypes were used for engineering and weed control efficacy testing across a range of species and growth stages. With confidence established in the design approach and a demonstrated 100% weed-control potential, a 6-m wide pre-commercial prototype, the “Weed Chipper,” was built incorporating commercially available weed-detection cameras for practical field-scale evaluation. This testing confirmed very high (90%) weed control efficacies and associated low levels (1.8%) of soil disturbance where the weed density was fewer than 1.0 plant 10 m−2 in a commercial fallow. These data established the suitability of this mechanical approach to weed control for conservation cropping systems. The development of targeted tillage for fallow weed control represents the introduction of site-specific, nonchemical weed control for conservation cropping systems.
The rocky shores of the north-east Atlantic have been long studied. Our focus is from Gibraltar to Norway plus the Azores and Iceland. Phylogeographic processes shape biogeographic patterns of biodiversity. Long-term and broadscale studies have shown the responses of biota to past climate fluctuations and more recent anthropogenic climate change. Inter- and intra-specific species interactions along sharp local environmental gradients shape distributions and community structure and hence ecosystem functioning. Shifts in domination by fucoids in shelter to barnacles/mussels in exposure are mediated by grazing by patellid limpets. Further south fucoids become increasingly rare, with species disappearing or restricted to estuarine refuges, caused by greater desiccation and grazing pressure. Mesoscale processes influence bottom-up nutrient forcing and larval supply, hence affecting species abundance and distribution, and can be proximate factors setting range edges (e.g., the English Channel, the Iberian Peninsula). Impacts of invasive non-native species are reviewed. Knowledge gaps such as the work on rockpools and host–parasite dynamics are also outlined.
The straw itch mite, Pyemotes tritici Lagrèze-Fossat and Montané (Acari: Pyemotidae), was discovered parasitising the goldspotted oak borer, Agrilus auroguttatus Schaeffer (Coleoptera: Buprestidae), an invasive exotic species to California, United States of America, and the Mexican goldspotted oak borer, Agrilus coxalis Waterhouse (Coleoptera: Buprestidae), during surveys for natural enemies for a classical biological control programme for A. auroguttatus. Pyemotes tritici caused low levels of mortality to each species of flatheaded borer, but it will likely not be a good candidate for a biological control programme because it is a generalist parasitoid with deleterious human health effects.
Resilience after a nuclear power plant or other radiation emergency requires response and recovery activities that are appropriately safe, timely, effective, and well organized. Timely informed decisions must be made, and the logic behind them communicated during the evolution of the incident before the final outcome is known. Based on our experiences in Tokyo responding to the Fukushima Daiichi nuclear power plant crisis, we propose a real-time, medical decision model by which to make key health-related decisions that are central drivers to the overall incident management. Using this approach, on-site decision makers empowered to make interim decisions can act without undue delay using readily available and high-level scientific, medical, communication, and policy expertise. Ongoing assessment, consultation, and adaption to the changing conditions and additional information are additional key features. Given the central role of health and medical issues in all disasters, we propose that this medical decision model, which is compatible with the existing US National Response Framework structure, be considered for effective management of complex, large-scale, and large-consequence incidents. (Disaster Med Public Health Preparedness. 2012;0:1-10)
In order to determine the impact of garlic on total cholesterol (TC), TAG levels, as well as LDL and HDL, and establish if any variables have an impact on the magnitude of this effect, a meta-analysis was conducted. A systematic literature search of MEDLINE, CINAHL and the Cochrane Database from the earliest possible date through to November 2007 was conducted to identify randomised, placebo-controlled trials of garlic that reported effects on TC, TAG concentrations, LDL or HDL. The weighted mean difference of the change from baseline (with 95 % CI) was calculated as the difference between the means in the garlic groups and the control groups using a random-effects model. Subgroup and sensitivity analyses were performed to determine the effects on type, brand and duration of garlic therapy as well as baseline TC and TAG levels, the use of dietary modification, and study quality on the meta-analysis's conclusions. Twenty-nine trials were included in the analysis. Upon meta-analysis garlic was found to significantly reduce TC ( − 0·19; 95 % CI − 0·33, − 0·06 mmol/l) and TAG ( − 0·11; 95 % CI − 0·19, − 0·06 mmol/l) but exhibited no significant effect on LDL or HDL. There was a moderate degree of statistical heterogeneity for the TC and TAG analyses. Garlic reduces TC to a modest extent, an effect driven mostly by the modest reductions in TAG, without appreciable LDL lowering or HDL elevation. Higher baseline line TC levels and the use of dietary modification may alter the effect of garlic on these parameters. Future studies should be conducted evaluating the impact of adjunctive garlic therapy with fibrates or statins on TAG concentrations.
Layer-by-layer films incorporating single-wall carbon nanotubes (SWNTs) with anionic or cationic coatings have been prepared. The process of self-assembly was monitored using the quartz microbalance technique, while the morphology of the resulting thin layers was studied with atomic force microscopy. A variety of different architectures have been built up. The dc conductivities of the thin films, in-plane and out-of-plane, were measured at room temperature and contrasted with reference architectures. The results show clearly that the incorporation of SWNTs into the multilayers resulted in electrically conductive thin films.
The search for extraterrestrial habitable planets will require long observation times and the intelligent selection of appropriate parent stars and target biosignatures. While life can certainly develop in the absence of photosynthesis, such life forms on earth exhibit metabolic rates several orders of magnitude less than the activity accompanying a photosynthetic-driven ecosystem. The most accessible spectral biosignatures are those accompanying a system driven away from thermodynamic equilibrium by photosynthetic activity. For example, the co-existence in a planetary atmosphere of significant amounts of ozone, oxygen, and methane would be a strong indication of biotic activity. Investigating the issue of the Habitable Zone from the standpoint of the constraints inherent in photosynthesis it appears that the absorption characteristics of photosynthetic microorganisms on this planet make it likely that photosynthetic activity can exist on planets orbiting stars to red-ward of the Sun on the H-R diagram. Such a possibility is encouraging for terrestrial planet finder efforts since stars classified red-ward of our sun (G3 to K7) account for more than 55% of our nearest neighbors.
Modern colonialism, writes Gyan Prakash, ‘instituted enduring hierarchies of subjects and knowledges — the colonizer and the colonized, the Occidental and the Oriental, the civilized and the primitive, the scientific and the superstitious, the developed and the underdeveloped’. Such dichotomies ‘reduced complex differences and interactions to the binary (self/other) logic of colonial power’, and colonial rulers ‘constituted the “native” as their inverse image’. Such perceptions of difference as ‘other’ expressed what ‘civilized’ Westerners believed themselves not to be — but also what they feared they might become, should they lose rational self-control. The ‘other’, writes Eva Kornfelt, ‘threatens the integrity of the self by offering alternative, unrealized, and suppressed possibilities’. As shown by Western fascination with the ‘noble savage’, this process could sometimes produce positive representations. Yet even these expressed the needs of the perceiver rather than the reality of the perceived. ‘Othering’, then, is a complex process, one implying deep cultural and individual needs, which may occasionally result in accurate representations, but more often produces self-justifying positive/negative dichotomies.
Hundreds of American Indian children attended schools run by the Board of Foreign Missions (BFM) of the Presbyterian Church in the United States of America (PCUSA) during the nineteenth century. Yet these young Indians left little written evidence from which to reconstruct their responses to an alien educational experience. Presbyterian missionaries, on the other hand, sent detailed reports on the schools and pupils to headquarters in New York. If subjected to careful analysis, the admittedly partisan BFM writings are a rich source for discovering how Indian pupils responded to their teachers and to the whole BFM program.