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Positive symptoms are a useful predictor of aggression in schizophrenia. Although a similar pattern of abnormal brain structures related to both positive symptoms and aggression has been reported, this observation has not yet been confirmed in a single sample.
To study the association between positive symptoms and aggression in schizophrenia on a neurobiological level, a prospective meta-analytic approach was employed to analyze harmonized structural neuroimaging data from 10 research centers worldwide. We analyzed brain MRI scans from 902 individuals with a primary diagnosis of schizophrenia and 952 healthy controls.
The result identified a widespread cortical thickness reduction in schizophrenia compared to their controls. Two separate meta-regression analyses revealed that a common pattern of reduced cortical gray matter thickness within the left lateral temporal lobe and right midcingulate cortex was significantly associated with both positive symptoms and aggression.
These findings suggested that positive symptoms such as formal thought disorder and auditory misperception, combined with cognitive impairments reflecting difficulties in deploying an adaptive control toward perceived threats, could escalate the likelihood of aggression in schizophrenia.
Item 9 of the Patient Health Questionnaire-9 (PHQ-9) queries about thoughts of death and self-harm, but not suicidality. Although it is sometimes used to assess suicide risk, most positive responses are not associated with suicidality. The PHQ-8, which omits Item 9, is thus increasingly used in research. We assessed equivalency of total score correlations and the diagnostic accuracy to detect major depression of the PHQ-8 and PHQ-9.
We conducted an individual patient data meta-analysis. We fit bivariate random-effects models to assess diagnostic accuracy.
16 742 participants (2097 major depression cases) from 54 studies were included. The correlation between PHQ-8 and PHQ-9 scores was 0.996 (95% confidence interval 0.996 to 0.996). The standard cutoff score of 10 for the PHQ-9 maximized sensitivity + specificity for the PHQ-8 among studies that used a semi-structured diagnostic interview reference standard (N = 27). At cutoff 10, the PHQ-8 was less sensitive by 0.02 (−0.06 to 0.00) and more specific by 0.01 (0.00 to 0.01) among those studies (N = 27), with similar results for studies that used other types of interviews (N = 27). For all 54 primary studies combined, across all cutoffs, the PHQ-8 was less sensitive than the PHQ-9 by 0.00 to 0.05 (0.03 at cutoff 10), and specificity was within 0.01 for all cutoffs (0.00 to 0.01).
PHQ-8 and PHQ-9 total scores were similar. Sensitivity may be minimally reduced with the PHQ-8, but specificity is similar.
The flora of Mediterranean ecosystems contains families with species having fully and under-developed embryos in their seeds. After-ripening for physiological dormancy release and smoke influence germination in many species. We investigated how after-ripening and embryo growth interact with smoke to influence the temporal dynamics of seedling emergence among fire ephemerals. Seeds were placed in the field and under standardized (50% relative humidity, 30°C) laboratory conditions to test the effects of summer conditions on physiological dormancy loss. Germination was tested with water or smoke compounds (smoke water, KAR1) at a simulated autumn/winter temperature (18/7°C). The timing and amount of seedling emergence with smoke was observed for seeds exposed to near-natural conditions. During summer, physiological dormancy was broken in all species, enabling germination at autumn/winter but not summer temperatures; no embryo growth occurred in seeds with under-developed embryos. At the start of the wet season, seedling emergence from seeds with fully developed embryos occurred earlier than from seeds with under-developed embryos. In a non-consistent manner among our study species, smoke and smoke compounds influenced the rate of embryo growth and amount of germination. Effects of smoke were noticeable in terms of number of emergents in the first emergence season. Among ecologically similar species, we have shown (1) that both thermal and embryo traits exclude germination in the summer, (2) how embryo size influences the timing of seedling emergence in autumn–winter, and (3) a reduced requirement for smoke in the second emergence season after a fire with a shift to reliance on seasonal cues for emergence.
Different diagnostic interviews are used as reference standards for major depression classification in research. Semi-structured interviews involve clinical judgement, whereas fully structured interviews are completely scripted. The Mini International Neuropsychiatric Interview (MINI), a brief fully structured interview, is also sometimes used. It is not known whether interview method is associated with probability of major depression classification.
To evaluate the association between interview method and odds of major depression classification, controlling for depressive symptom scores and participant characteristics.
Data collected for an individual participant data meta-analysis of Patient Health Questionnaire-9 (PHQ-9) diagnostic accuracy were analysed and binomial generalised linear mixed models were fit.
A total of 17 158 participants (2287 with major depression) from 57 primary studies were analysed. Among fully structured interviews, odds of major depression were higher for the MINI compared with the Composite International Diagnostic Interview (CIDI) (odds ratio (OR) = 2.10; 95% CI = 1.15–3.87). Compared with semi-structured interviews, fully structured interviews (MINI excluded) were non-significantly more likely to classify participants with low-level depressive symptoms (PHQ-9 scores ≤6) as having major depression (OR = 3.13; 95% CI = 0.98–10.00), similarly likely for moderate-level symptoms (PHQ-9 scores 7–15) (OR = 0.96; 95% CI = 0.56–1.66) and significantly less likely for high-level symptoms (PHQ-9 scores ≥16) (OR = 0.50; 95% CI = 0.26–0.97).
The MINI may identify more people as depressed than the CIDI, and semi-structured and fully structured interviews may not be interchangeable methods, but these results should be replicated.
Declaration of interest
Drs Jetté and Patten declare that they received a grant, outside the submitted work, from the Hotchkiss Brain Institute, which was jointly funded by the Institute and Pfizer. Pfizer was the original sponsor of the development of the PHQ-9, which is now in the public domain. Dr Chan is a steering committee member or consultant of Astra Zeneca, Bayer, Lilly, MSD and Pfizer. She has received sponsorships and honorarium for giving lectures and providing consultancy and her affiliated institution has received research grants from these companies. Dr Hegerl declares that within the past 3 years, he was an advisory board member for Lundbeck, Servier and Otsuka Pharma; a consultant for Bayer Pharma; and a speaker for Medice Arzneimittel, Novartis, and Roche Pharma, all outside the submitted work. Dr Inagaki declares that he has received grants from Novartis Pharma, lecture fees from Pfizer, Mochida, Shionogi, Sumitomo Dainippon Pharma, Daiichi-Sankyo, Meiji Seika and Takeda, and royalties from Nippon Hyoron Sha, Nanzando, Seiwa Shoten, Igaku-shoin and Technomics, all outside of the submitted work. Dr Yamada reports personal fees from Meiji Seika Pharma Co., Ltd., MSD K.K., Asahi Kasei Pharma Corporation, Seishin Shobo, Seiwa Shoten Co., Ltd., Igaku-shoin Ltd., Chugai Igakusha and Sentan Igakusha, all outside the submitted work. All other authors declare no competing interests. No funder had any role in the design and conduct of the study; collection, management, analysis and interpretation of the data; preparation, review or approval of the manuscript; and decision to submit the manuscript for publication.
Our understanding of the complex relationship between schizophrenia symptomatology and etiological factors can be improved by studying brain-based correlates of schizophrenia. Research showed that impairments in value processing and executive functioning, which have been associated with prefrontal brain areas [particularly the medial orbitofrontal cortex (MOFC)], are linked to negative symptoms. Here we tested the hypothesis that MOFC thickness is associated with negative symptom severity.
This study included 1985 individuals with schizophrenia from 17 research groups around the world contributing to the ENIGMA Schizophrenia Working Group. Cortical thickness values were obtained from T1-weighted structural brain scans using FreeSurfer. A meta-analysis across sites was conducted over effect sizes from a model predicting cortical thickness by negative symptom score (harmonized Scale for the Assessment of Negative Symptoms or Positive and Negative Syndrome Scale scores).
Meta-analytical results showed that left, but not right, MOFC thickness was significantly associated with negative symptom severity (βstd = −0.075; p = 0.019) after accounting for age, gender, and site. This effect remained significant (p = 0.036) in a model including overall illness severity. Covarying for duration of illness, age of onset, antipsychotic medication or handedness weakened the association of negative symptoms with left MOFC thickness. As part of a secondary analysis including 10 other prefrontal regions further associations in the left lateral orbitofrontal gyrus and pars opercularis emerged.
Using an unusually large cohort and a meta-analytical approach, our findings point towards a link between prefrontal thinning and negative symptom severity in schizophrenia. This finding provides further insight into the relationship between structural brain abnormalities and negative symptoms in schizophrenia.
This paper presents the results of a detailed experimental investigation into the effectiveness of sinusoidal leading edge serrations on aerofoils for the reduction of the noise generated by the interaction with turbulent flow. A detailed parametric study is performed to investigate the sensitivity of the noise reductions to the serration amplitude and wavelength. The study is primarily performed on flat plates in an idealized turbulent flow, which we demonstrate captures the same behaviour as when identical serrations are introduced onto three-dimensional aerofoils. The influence on the noise reduction of the turbulence integral length scale is also studied. An optimum serration wavelength is identified whereby maximum noise reductions are obtained, corresponding to when the transverse integral length scale is approximately one-fourth the serration wavelength. This paper proves that, at the optimum serration wavelength, adjacent valley sources are excited incoherently. One of the most important findings of this paper is that, at the optimum serration wavelength, the sound power radiation from the serrated aerofoil varies inversely proportional to the Strouhal number
are frequency, serration amplitude and flow speed, respectively. A simple model is proposed to explain this behaviour. Noise reductions are observed to generally increase with increasing frequency until the frequency at which aerofoil self-noise dominates the interaction noise. Leading edge serrations are also shown to reduce aerofoil self-noise. The mechanism for this phenomenon is explored through particle image velocimetry measurements. Finally, the lift and drag of the serrated aerofoil are obtained through direct measurement and compared against the straight edge baseline aerofoil. It is shown that aerodynamic performance is not substantially degraded by the introduction of the leading edge serrations on the aerofoil.
Childhood early life stress (ELS) increases risk of adulthood major depressive disorder (MDD) and is associated with altered brain structure and function. It is unclear whether specific ELSs affect depression risk, cognitive function and brain structure.
This cross-sectional study included 64 antidepressant-free depressed and 65 never-depressed individuals. Both groups reported a range of ELSs on the Early Life Stress Questionnaire, completed neuropsychological testing and 3T magnetic resonance imaging (MRI). Neuropsychological testing assessed domains of episodic memory, working memory, processing speed and executive function. MRI measures included cortical thickness and regional gray matter volumes, with a priori focus on the cingulate cortex, orbitofrontal cortex (OFC), amygdala, caudate and hippocampus.
Of 19 ELSs, only emotional abuse, sexual abuse and severe family conflict independently predicted adulthood MDD diagnosis. The effect of total ELS score differed between groups. Greater ELS exposure was associated with slower processing speed and smaller OFC volumes in depressed subjects, but faster speed and larger volumes in non-depressed subjects. In contrast, exposure to ELSs predictive of depression had similar effects in both diagnostic groups. Individuals reporting predictive ELSs exhibited poorer processing speed and working memory performance, smaller volumes of the lateral OFC and caudate, and decreased cortical thickness in multiple areas including the insula bilaterally. Predictive ELS exposure was also associated with smaller left hippocampal volume in depressed subjects.
Findings suggest an association between childhood trauma exposure and adulthood cognitive function and brain structure. These relationships appear to differ between individuals who do and do not develop depression.
We describe the performance of the Boolardy Engineering Test Array, the prototype for the Australian Square Kilometre Array Pathfinder telescope. Boolardy Engineering Test Array is the first aperture synthesis radio telescope to use phased array feed technology, giving it the ability to electronically form up to nine dual-polarisation beams. We report the methods developed for forming and measuring the beams, and the adaptations that have been made to the traditional calibration and imaging procedures in order to allow BETA to function as a multi-beam aperture synthesis telescope. We describe the commissioning of the instrument and present details of Boolardy Engineering Test Array’s performance: sensitivity, beam characteristics, polarimetric properties, and image quality. We summarise the astronomical science that it has produced and draw lessons from operating Boolardy Engineering Test Array that will be relevant to the commissioning and operation of the final Australian Square Kilometre Array Path telescope.
From June 15 to 28, 1991 the Compton Gamma-Ray Observatory (CGRO) observed the radio-loud quasar 3C 273. All four CGRO instruments detected radiation from this quasar in their relevant energy range (from 20 keV to 5 GeV). Simultaneous and quasi-simultaneous observations (spanning the time period May 27 – July 25, 1991) by instruments sensitive at other wavelengths have also been obtained. The data from all these observations spanning the frequency range from ∼ 109 Hz to ∼ 1026 Hz were collected and analysed. The resulting energy-density spectrum is shown in the figure below. It shows two maxima, one in the UV, another one at low-energy γ-rays which have nearly the same strength (the corresponding luminosities per decade of frequency for H0 = 60(km/s)/Mpc are 3.2·1046 erg/s and 2.7·1046 erg/s, respectively). A break of the spectrum at low-energy γ-rays is evident. From a detailed analysis a break energy of (2±1.5) MeV could be derived corresponding to a frequency of (4.8±3.6)·1020 Hz. The observed spectral break between X- and γ-rays is ∼ 0.8, much higher than the value of 0.5 predicted by some models. A more detailed paper on this topic is in preparation (Lichti et al.).
Blazar OJ 287 is one of the best observed extragalactic objects. It's historical light curve goes back to 1890′s. Based on the historical behaviour Sillanpää et al. (1988) showed that OJ 287 displays large periodic outbursts, with a period of 11.7 years. We have monitored OJ 287 intensively for two years, during the OJ-94 project. This project was created for monitoring OJ 287 during its predicted new outburst in 1994. In the data archive we have over 7000 observations on OJ 287, in the radio, infrared and optical bands. This data archive contains the best ever obtained light curves for any extragalactic object. The optical light curve shows continuous variability down to time scales of tens of minutes. The variability observed in OJ 287 can be broken down to (at least) four different categories:
The short period and small amplitude of pulsation for the 1d.95 Cepheid SU Cas make it an excellent candidate for pulsation in a purely excited mode, and, as summarized by Gieren (1982), there is some evidence from recent radius determinations for this variable which suggests that it is indeed an overtone pulsator.