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Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.
Aims
To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.
Method
Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.
Results
Earlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.
Conclusions
AAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.
Objective: Focal cortical dysplasia (FCD) is a common cause of refractory, focal onset epilepsy in children. Interictal, scalp electroencephalograph (EEG) markers have been associated with these pathologies and epilepsy surgery may be an option for some patients. We aim to study how scalp EEG and magnetic resonance imaging (MRI) markers of FCD affect referral of these patients for surgical evaluation. Methods: A single-center, retrospective review of children with focal onset epilepsy. Patients were included if they were between 1 month and 18 years of age, had focal onset seizures, prolonged scalp EEG monitoring, and an MRI conducted after 2 years of age. Statistics were carried out using the chi-squared and student’s t-test, as well as a logistic regression model. Results: Sixty-eight patients were included in the study. Thirty-seven of these patients were referred to a comprehensive pediatric epilepsy program (CPEP) for surgical evaluation, and of these 22% showed FCD EEG markers, 32% FCD MRI markers, and 10% had both. These markers were also present in patients not referred to a CPEP. The MRI markers were significantly associated with CPEP referral, whereas EEG markers were not. Neither marker type was associated with epilepsy surgery. Conclusion: This study found that children with focal onset epilepsy were more likely to be referred for surgical evaluation if they were medically refractory, or were diagnosed with FCD or tumor on MRI. Scalp EEG markers of FCD were not associated with CPEP referral. The online tool CASES may be a useful physician guide for identifying appropriate children for epilepsy surgery referral.
A new deep level transient spectroscopy (DLTS) technique is described, called half-width at variable intensity analysis. This method utilizes the width and normalized intensity of a DLTS signal to determine the activation energy and capture cross section of the trap that generated the signal via a variable, kO. This constant relates the carrier emission rates giving rise to the differential capacitance signal associated with a given trap at two different temperatures: the temperature at which the maximum differential capacitance is detected, and an arbitrary temperature at which some nonzero differential capacitance signal is detected. The extracted activation energy of the detected trap center is used along with the position of the peak maximum to extract the capture cross section of the trap center.
The Taipan galaxy survey (hereafter simply ‘Taipan’) is a multi-object spectroscopic survey starting in 2017 that will cover 2π steradians over the southern sky (δ ≲ 10°, |b| ≳ 10°), and obtain optical spectra for about two million galaxies out to z < 0.4. Taipan will use the newly refurbished 1.2-m UK Schmidt Telescope at Siding Spring Observatory with the new TAIPAN instrument, which includes an innovative ‘Starbugs’ positioning system capable of rapidly and simultaneously deploying up to 150 spectroscopic fibres (and up to 300 with a proposed upgrade) over the 6° diameter focal plane, and a purpose-built spectrograph operating in the range from 370 to 870 nm with resolving power R ≳ 2000. The main scientific goals of Taipan are (i) to measure the distance scale of the Universe (primarily governed by the local expansion rate, H0) to 1% precision, and the growth rate of structure to 5%; (ii) to make the most extensive map yet constructed of the total mass distribution and motions in the local Universe, using peculiar velocities based on improved Fundamental Plane distances, which will enable sensitive tests of gravitational physics; and (iii) to deliver a legacy sample of low-redshift galaxies as a unique laboratory for studying galaxy evolution as a function of dark matter halo and stellar mass and environment. The final survey, which will be completed within 5 yrs, will consist of a complete magnitude-limited sample (i ⩽ 17) of about 1.2 × 106 galaxies supplemented by an extension to higher redshifts and fainter magnitudes (i ⩽ 18.1) of a luminous red galaxy sample of about 0.8 × 106 galaxies. Observations and data processing will be carried out remotely and in a fully automated way, using a purpose-built automated ‘virtual observer’ software and an automated data reduction pipeline. The Taipan survey is deliberately designed to maximise its legacy value by complementing and enhancing current and planned surveys of the southern sky at wavelengths from the optical to the radio; it will become the primary redshift and optical spectroscopic reference catalogue for the local extragalactic Universe in the southern sky for the coming decade.
The rapid growth and co-option of the local agriculture movement highlights a need to deepen connections to place-based culture. Selection of plant varieties specifically adapted to regional production and end-use is an important component of building a resilient food system. Doing so will facilitate a defetishization of food systems by increasing the cultural connection to production and consumption. Today's dominant model of plant breeding relies on selection for centralized production and end-use, thereby limiting opportunity for regional differentiation. On the other hand, end-user-driven selection of heirloom varieties with strong cultural and culinary significance may limit productivity while failing to promote continued advances in end-use quality. Farmer-based selection may directly reflect local food culture; however, increasing genetic gains may require increased exchange of germplasm, and collaboration with trained plant breeders. Participatory farmer–breeder–chef collaborations are an emerging model for overcoming these limitations and adding the strength of culturally based plant breeding to the alternative food movement. These models of variety selection are examined within the context of small grain and dry bean production in Western Washington.
(See the commentary by Pfeiffer and Beldavs, on pages 984–986.)
Objective
Describe the epidemiology of carbapenem-resistant Enterobacteriaceae (CRE) and examine the effect of lower carbapenem breakpoints on CRE detection.
Design
Retrospective cohort.
Setting
Inpatient care at community hospitals.
Patients
All patients with CRE-positive cultures were included.
Methods
CRE isolated from 25 community hospitals were prospectively entered into a centralized database from January 2008 through December 2012. Microbiology laboratory practices were assessed using questionnaires.
Results
A total of 305 CRE isolates were detected at 16 hospitals (64%). Patients with CRE had symptomatic infection in 180 cases (59%) and asymptomatic colonization in the remainder (125 cases; 41%). Klebsiella pneumoniae (277 isolates; 91%) was the most prevalent species. The majority of cases were healthcare associated (288 cases; 94%). The rate of CRE detection increased more than fivefold from 2008 (0.26 cases per 100,000 patient-days) to 2012 (1.4 cases per 100,000 patient-days; incidence rate ratio (IRR), 5.3 [95% confidence interval (CI), 1.22–22.7]; P = .01). Only 5 hospitals (20%) had adopted the 2010 Clinical and Laboratory Standards Institute (CLSI) carbapenem breakpoints. The 5 hospitals that adopted the lower carbapenem breakpoints were more likely to detect CRE after implementation of breakpoints than before (4.1 vs 0.5 cases per 100,000 patient-days; P < .001; IRR, 8.1 [95% CI, 2.7–24.6]). Hospitals that implemented the lower carbapenem breakpoints were more likely to detect CRE than were hospitals that did not (3.3 vs 1.1 cases per 100,000 patient-days; P = .01).
Conclusions
The rate of CRE detection increased fivefold in community hospitals in the southeastern United States from 2008 to 2012. Despite this, our estimates are likely underestimates of the true rate of CRE detection, given the low adoption of the carbapenem breakpoints recommended in the 2010 CLSI guidelines.
Several studies have suggested that neuropsychological and structural brain deficits are implicated in poor insight. Few insight studies however have combined neurocognitive and structural neuroanatomical measures.
Aims
Focusing on the ability to relabel psychotic symptoms as pathological, we examined insight, brain structure and neurocognition in first-onset psychosis.
Method
Voxel-based magnetic resonance imaging data were acquired from 82 individuals with psychosis and 91 controls assessed with a brief neuropsychological test battery. Insight was measured using the Schedule for the Assessment of Insight.
Results
The principal analysis showed reduced general neuropsychological function was linked to poor symptom relabelling ability. A subsequent between-psychosis group analysis found those with no symptom relabelling ability had significant global and regional grey matter deficits primarily located at the posterior cingulate gyrus and right precuneus/cuneus.
Conclusions
The cingulate gyrus (as part of a midline cortical system) along with right hemisphere regions may be involved in illness and symptom self-appraisal in first-onset psychosis.
Soil erosion due to annual cropping on highly erodible farmland is a major ecological concern in the wheat growing regions of Washington State. In response to requests from farmers, the winter wheat breeding program at Washington State University has been developing perennial wheat selected from crosses between wild wheatgrass species and commonly grown annual wheat cultivars. In 2005/06, we conducted field trials of the most promising perennial wheat breeding lines derived from interspecific crosses between tall wheatgrass (Thinopyrum elongatum) and bread wheat (Triticum aestivum). Thirty-one perennial breeding lines and two annual winter wheat cultivars were evaluated for nutritional value in the form of grain mineral concentration, multiple baking and milling quality traits, and ease of grain threshability. The objective of this study was to identify the strengths and weaknesses of these post-harvest traits in the perennial wheat lines derived from these interspecific crosses. Mineral nutrient concentrations in the perennial lines were 44, 40, 24, 23, 32, 30 and 33% higher than the annual control cultivars for calcium, copper, iron, magnesium, manganese, phosphorus and zinc, respectively. The annual cultivars had a higher grain mineral content per unit area of land than the perennial lines, due primarily to the higher grain yields of the annual cultivars. Compared to the annual wheat cultivars, the perennial lines produced grain with smaller seed size, lower test weight and reduced flour yield, mix time and loaf volume. Protein content was 3.5–4.5% higher in the perennial lines than in the annual cultivars. The threshability index (TI) ranged from 0.63 to 0.89 in the perennials (μ=0.75); significantly lower than the mean TI of the annual cultivars (μ=0.97). The significant genotype×location interaction found for TI suggests that the variation in annual precipitation positively influenced some perennial lines to express greater threshability. In addition to transferring traits important to the perennial growth habit in wheat, the wild wheatgrass species also introduced beneficial characteristics (i.e. increased protein and mineral concentration) and deleterious traits (poor threshing grain and inferior baking qualities). This research gives researchers a platform from which to direct further research and selection in the development of perennial wheat.
Edited by
Judith M. Rumsey, National Institute of Mental Health, Bethesda, Maryland,Monique Ernst, National Institute of Mental Health, Bethesda, Maryland