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Cognitive deficits at the first episode of schizophrenia are predictive of functional outcome. Interventions that improve cognitive functioning early in schizophrenia are critical if we hope to prevent or limit long-term disability in this disorder.
Methods
We completed a 12-month randomized controlled trial of cognitive remediation and of long-acting injectable (LAI) risperidone with 60 patients with a recent first episode of schizophrenia. Cognitive remediation involved programs focused on basic cognitive processes as well as more complex, life-like situations. Healthy behavior training of equal treatment time was the comparison group for cognitive remediation, while oral risperidone was the comparator for LAI risperidone in a 2 × 2 design. All patients were provided supported employment/education to encourage return to work or school.
Results
Both antipsychotic medication adherence and cognitive remediation contributed to cognitive improvement. Cognitive remediation was superior to healthy behavior training in the LAI medication condition but not the oral medication condition. Cognitive remediation was also superior when medication adherence and protocol completion were covaried. Both LAI antipsychotic medication and cognitive remediation led to significantly greater improvement in work/school functioning. Effect sizes were larger than in most prior studies of first-episode patients. In addition, cognitive improvement was significantly correlated with work/school functional improvement.
Conclusions
These results indicate that consistent antipsychotic medication adherence and cognitive remediation can significantly improve core cognitive deficits in the initial period of schizophrenia. When combined with supported employment/education, cognitive remediation and LAI antipsychotic medication show separate significant impact on improving work/school functioning.
We present a detailed analysis of the radio galaxy PKS
$2250{-}351$
, a giant of 1.2 Mpc projected size, its host galaxy, and its environment. We use radio data from the Murchison Widefield Array, the upgraded Giant Metre-wavelength Radio Telescope, the Australian Square Kilometre Array Pathfinder, and the Australia Telescope Compact Array to model the jet power and age. Optical and IR data come from the Galaxy And Mass Assembly (GAMA) survey and provide information on the host galaxy and environment. GAMA spectroscopy confirms that PKS
$2250{-}351$
lies at
$z=0.2115$
in the irregular, and likely unrelaxed, cluster Abell 3936. We find its host is a massive, ‘red and dead’ elliptical galaxy with negligible star formation but with a highly obscured active galactic nucleus dominating the mid-IR emission. Assuming it lies on the local M–
$\sigma$
relation, it has an Eddington accretion rate of
$\lambda_{\rm EDD}\sim 0.014$
. We find that the lobe-derived jet power (a time-averaged measure) is an order of magnitude greater than the hotspot-derived jet power (an instantaneous measure). We propose that over the lifetime of the observed radio emission (
${\sim} 300\,$
Myr), the accretion has switched from an inefficient advection-dominated mode to a thin disc efficient mode, consistent with the decrease in jet power. We also suggest that the asymmetric radio morphology is due to its environment, with the host of PKS
$2250{-}351$
lying to the west of the densest concentration of galaxies in Abell 3936.
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.
Methods
We conducted an individual patient data meta-analysis. We fit bivariate random-effects models to assess diagnostic accuracy.
Results
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).
Conclusions
PHQ-8 and PHQ-9 total scores were similar. Sensitivity may be minimally reduced with the PHQ-8, but specificity is similar.
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.
Aims
To evaluate the association between interview method and odds of major depression classification, controlling for depressive symptom scores and participant characteristics.
Method
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.
Results
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).
Conclusions
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.
Methods
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).
Results
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.
Conclusions
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.
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.
In 2005 we obtained very precise interferometric measurements of the pole-on rapid rotator Vega (A0 V) with the longest baselines of the Center for High Angular Angular Resolution (CHARA) Array and the Fiber Linked Unit for Optical Recombination (FLUOR). For the analysis of these data, we developed a code for mapping sophisticated PHOENIX model atmospheres on to the surface of rotationally distorted stars described by a Roche-von Zeipel formalism. Given a set of input parameters for a star or binary pair, this code predicts the interferometric visibility, spectral energy distribution and high-resolution line spectrum expected for the system. For the gravity-darkened Vega, our model provides a very good match to the K-band interferometric data, a good match to the spectral energy distribution – except below 160 nm – and a rather poor match to weak lines in the high dispersion spectrum where the model appears overly gravity darkened. In 2006, we used the CHARA Array and FLUOR to obtain high precision measurements of the massive, non-eclipsing, double-line spectroscopic binary Spica, a 4-day period system where both components are gravity darkened rapid rotators. These data supplement recent data obtained with the Sydney University Stellar Interferometer (SUSI). Our study follows the classic 1971 study by Herbison-Evans et al. who resolved Spica as a binary with the Narrabri Stellar Intensity Interferometer (NSII). We will report on our progress modeling the new interferometric and archival spectroscopic data, with the goal towards better constraining the apsidal constant.
The Lyot Project near-infrared JHK coronagraph achieved first light on the Advanced Electro-Optical System (AEOS) in March 2004. Optical pupil plane imaging at video rates from this coronagraph provides data on atmospheric scintillation and quasi-static pupil intensity variations. We examine the effect of these variations on coronagraphic performance. Early simulations suggested Strehl ratio reductions of the order of 2–3% due to residual uncorrected phase aberrations in H-band. We find that static or quasi-static pupil illumination non-uniformity in I-band reduces Strehl by $\sim$2%. A lower bound on the effects of dynamic illumination variation over the pupil is also $\sim$2% in I-band. Some of the static intensity variations in the pupil are due to pinned deformable mirror (DM) actuators. We simulate the effects a pinned actuator has on the coronagraph. The resultant speckles in simulated coronagraphic images show similarities to some Lyot Project PSFs. This highlights the importance of knowledge of the pupil in next-generation extreme AO coronagraphs in order to realize the predicted photometric dynamic range of their images.
Lipids play varied and critical roles in metabolism, with function dramatically modulated by the individual fatty acid moities in complex lipid entities. In particular, the fatty acid composition of membrane lipids greatly influences membrane function. Here we consider the role of dietary fatty acid profile on membrane composition and, in turn, its impact on prevalent disease clusters of the metabolic syndrome and mental illness. Applying the classical physiological conformer-regulator paradigm to quantify the influence of dietary fats on membrane lipid composition (i.e. where the membrane variable is plotted against the same variable in the environment – in this case dietary fats), membrane lipid composition appears as a predominantly regulated parameter. Membranes remain relatively constant in their saturated (SFA) and monounsaturated (MUFA) fatty acid levels over a wide range of dietary variation for these fatty acids. Membrane composition was found to be more responsive to n-6 and n-3 polyunsaturated fatty acid (PUFA) levels in the diet and most sensitive to n-3 PUFA and to the n-3/n-6 ratio. These differential responses are probably due to the fact that both n-6 and n-3 PUFA classes cannot be synthesised de novo by higher animals. Diet-induced modifications in membrane lipid composition are associated with changes in the rates of membrane-linked cellular processes that are major contributors to energy metabolism. For example, in the intrinsic activity of fundamental processes such as the Na+/K+ pump and proton pump-leak cycle. Equally, dietary lipid profile impacts substantially on diseases of the metabolic syndrome with evidence accruing for changes in metabolic rate and neuropeptide regulation (thus influencing both sides of the energy balance equation), in second messenger generation and in gene expression influencing a range of glucose and lipid handling pathways. Finally, there is a growing literature relating changes in dietary fatty acid profile to many aspects of mental health. The understanding of dietary lipid profile and its influence on membrane function in relation to metabolic dysregulation has exciting potential for the prevention and treatment of a range of prevalent disease states.
We discuss the mechanism by which gastric mucin forms a gel at low pH, which serves to protect the stomach from being damaged by the acidic gastric juice that it secretes. Frequency dependence of viscoelastic moduli of pig gastric mucin gels obtained by microscopic dynamic light scattering is presented. Atomic Force Microscopy provides direct visual evidence to indicate that mucin broken into its subunits does not gel at low pH.
Automated three-dimensional (3-D) image analysis methods are
presented for tracing of dye-injected neurons imaged by fluorescence
confocal microscopy and HRP-stained neurons imaged by transmitted-light
brightfield microscopy. An improved algorithm for adaptive 3-D
skeletonization of noisy images enables the tracing. This algorithm
operates by performing connectivity testing over large N × N
× N voxel neighborhoods exploiting the sparseness of the
structures of interest, robust surface detection that improves upon
classical vacant neighbor schemes, improved handling of process ends or
tips based on shape collapse prevention, and thickness-adaptive
thinning. The confocal image stacks were skeletonized directly. The
brightfield stacks required 3-D deconvolution. The results of
skeletonization were analyzed to extract a graph representation.
Topological and metric analyses can be carried out using this
representation. A semiautomatic method was developed for reconnection
of dendritic fragments that are disconnected due to insufficient dye
penetration, an imaging deficiency, or skeletonization errors.