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The staging model of mental illness is developing beyond the clinical level aiming to include biological processes and markers that may reflect the dynamic biological processes of stages of mental illness. The neurobiology of inflammation in mental illness has gained much attention in recent years. Since neuroinflammation has been shown to be an important possible feature of psychosis, schizophrenia and depression, in this chapter it is attempted to map changes and dysregulation of the immune system and inflammation to the different clinical stages of severe mental illness. The literature suggests that an increased inflammatory response may define a subgroup of individuals in ultra-high-risk states, in acute disease episodes and in those with severe mental illness. In addition, the literature clearly points to the dynamic nature of the immune response in mental illness and shows an involvement of both the innate and adaptive immune system in mental illness. A focus on inflammation only might be insufficient and a broader understanding of the interaction between innate and adaptive immune systems and the complex neuroimmune interaction is required.
Childhood maltreatment (CM) plays an important role in the development of major depressive disorder (MDD). The aim of this study was to examine whether CM severity and type are associated with MDD-related brain alterations, and how they interact with sex and age.
Within the ENIGMA-MDD network, severity and subtypes of CM using the Childhood Trauma Questionnaire were assessed and structural magnetic resonance imaging data from patients with MDD and healthy controls were analyzed in a mega-analysis comprising a total of 3872 participants aged between 13 and 89 years. Cortical thickness and surface area were extracted at each site using FreeSurfer.
CM severity was associated with reduced cortical thickness in the banks of the superior temporal sulcus and supramarginal gyrus as well as with reduced surface area of the middle temporal lobe. Participants reporting both childhood neglect and abuse had a lower cortical thickness in the inferior parietal lobe, middle temporal lobe, and precuneus compared to participants not exposed to CM. In males only, regardless of diagnosis, CM severity was associated with higher cortical thickness of the rostral anterior cingulate cortex. Finally, a significant interaction between CM and age in predicting thickness was seen across several prefrontal, temporal, and temporo-parietal regions.
Severity and type of CM may impact cortical thickness and surface area. Importantly, CM may influence age-dependent brain maturation, particularly in regions related to the default mode network, perception, and theory of mind.
Cognitive impairments reported across psychiatric conditions (ie, major depressive disorder, bipolar disorder, schizophrenia, and posttraumatic stress disorder) strongly impair the quality of life of patients and the recovery of those conditions. There is therefore a great need for consideration for cognitive dysfunction in the management of psychiatric disorders. The redundant pattern of cognitive impairments across such conditions suggests possible shared mechanisms potentially leading to their development. Here, we review for the first time the possible role of inflammation in cognitive dysfunctions across psychiatric disorders. Raised inflammatory processes (microglia activation and elevated cytokine levels) across diagnoses could therefore disrupt neurobiological mechanisms regulating cognition, including Hebbian and homeostatic plasticity, neurogenesis, neurotrophic factor, the HPA axis, and the kynurenine pathway. This redundant association between elevated inflammation and cognitive alterations across psychiatric disorders hence suggests that a cross-disorder approach using pharmacological and nonpharmacological (ie, physical activity and nutrition) anti-inflammatory/immunomodulatory strategies should be considered in the management of cognition in psychiatry.
During the past two decades, it has been amply documented that neuropsychiatric disorders (NPDs) disproportionately account for burden of illness attributable to chronic non-communicable medical disorders globally. It is also likely that human capital costs attributable to NPDs will disproportionately increase as a consequence of population aging and beneficial risk factor modification of other common and chronic medical disorders (e.g., cardiovascular disease). Notwithstanding the availability of multiple modalities of antidepressant treatment, relatively few studies in psychiatry have primarily sought to determine whether improving cognitive function in MDD improves patient reported outcomes (PROs) and/or is cost effective. The mediational relevance of cognition in MDD potentially extrapolates to all NPDs, indicating that screening for, measuring, preventing, and treating cognitive deficits in psychiatry is not only a primary therapeutic target, but also should be conceptualized as a transdiagnostic domain to be considered regardless of patient age and/or differential diagnosis.
The electrical reliability of multilayer high density interconnection printed circuit boards (HDI-PCBs) is mainly affected by the thermo-mechanical stability of stacked micro via interconnections. Here, a critical failure mode is the stress related crack between the electrolytically filled via and the target pad, commonly known as target pad separation. The junction includes two Cu-Cu-interfaces, one between the target Cu pad and the thin electroless Cu layer and the second between electroless Cu and electrolytic Cu. In this paper we will show that state-of-the-art electroless Cu plating processes are able to provide solid, completely recrystallized and highly reliable stacked via junctions. Defect free interfaces were achieved by using ionic Pd-activators and electroless Cu baths with a cyanide based stabilizer system. Cyanide free electroless Cu baths tend more to the formation of nanometer sized defects, discovered via Transmission Electron Microscopy (TEM). In this case a precise adjustment of single stabilizer components is mandatory to achieve defect free layers. The defects are hollow and were identified as “nano voids”. A critical density of these nano voids weakens the interface, predefines the crack path and reduces the overall reliability of the junction. A precise localization of the nano voids within the junction was enabled by detecting the Ni-containing electroless Cu layer via TEM-Ni mapping. Slower volume exchange of the electroless Cu solution within the blind micro via (BMV) substantially increases the nano void density. The ability of nano voids to migrate and coalesce at elevated temperatures was investigated as well.
Dementia is a leading cause of morbidity and mortality without pharmacologic prevention or cure. Mounting evidence suggests that adherence to a Mediterranean dietary pattern may slow cognitive decline, and is important to characterise in at-risk cohorts. Thus, we determined the reliability and validity of the Mediterranean Diet and Culinary Index (MediCul), a new tool, among community-dwelling individuals with mild cognitive impairment (MCI). A total of sixty-eight participants (66 % female) aged 75·9 (sd 6·6) years, from the Study of Mental and Resistance Training study MCI cohort, completed the fifty-item MediCul at two time points, followed by a 3-d food record (FR). MediCul test–retest reliability was assessed using intra-class correlation coefficients (ICC), Bland–Altman plots and κ agreement within seventeen dietary element categories. Validity was assessed against the FR using the Bland–Altman method and nutrient trends across MediCul score tertiles. The mean MediCul score was 54·6/100·0, with few participants reaching thresholds for key Mediterranean foods. MediCul had very good test–retest reliability (ICC=0·93, 95 % CI 0·884, 0·954, P<0·0001) with fair-to-almost-perfect agreement for classifying elements within the same category. Validity was moderate with no systematic bias between methods of measurement, according to the regression coefficient (y=−2·30+0·17x) (95 % CI −0·027, 0·358; P=0·091). MediCul over-estimated the mean FR score by 6 %, with limits of agreement being under- and over-estimated by 11 and 23 %, respectively. Nutrient trends were significantly associated with increased MediCul scoring, consistent with a Mediterranean pattern. MediCul provides reliable and moderately valid information about Mediterranean diet adherence among older individuals with MCI, with potential application in future studies assessing relationships between diet and cognitive function.
We present our new investigation aimed to estimate the mass-loss and dust production rates of carbon-rich stars (C-stars) in the Magellanic Clouds (MCs). We compute dust growth and radiative transfer in circumstellar envelopes of C-stars for a grid of stellar parameters and for selected optical constants that simultaneously reproduce the main colour–colour diagrams in the infrared. We employ these grids of spectra to fit the spectral energy distribution of C-stars in the MCs. We find that our estimates can be significantly different from the other ones in the literature.
The term ‘mood stabiliser’ is ill-defined and lacks clinical utility. We propose a framework to evaluate medications and effectively communicate their mood stabilising properties – their acute and prophylactic efficacy across the domains of mania and depression. The standardised framework provides a common definition to facilitate research and clinical practice.
Declaration of interest
The Treatment Algorithm Group (TAG) was supported logistically by Servier who provided financial assistance with travel and accommodation for those TAG members travelling interstate or overseas to attend the meeting in Sydney (held on 18 November 2017). None of the committee were paid to participate in this project and Servier have not had any input into the content, format or outputs from this project.
This study assesses how political parties’ candidate selection strategies influence women’s descriptive parliamentary representation. Focusing on proportional elections, it explores what determines whether parties place women in viable list positions. Evaluating party rankings at the individual level, it directly examines a mechanism – party nomination – central to prevailing explanations of empirical patterns in women’s representation. Moreover, it jointly evaluates how incumbency and gender affect nomination. This study uses European Parliament elections to compare a plethora of parties, operating under numerous institutions, in the context of a single legislature. It finds that gender differences in candidate selection are largely explained by incumbency bias, although party ideology and female labor force participation help explain which parties prioritize the placement of novice women.
Patients with major depression show reduced hippocampal volume compared to healthy controls. However, the contribution of patients’ cumulative illness severity to hippocampal volume has rarely been investigated. It was the aim of our study to find a composite score of cumulative illness severity that is associated with hippocampal volume in depression.
We estimated hippocampal gray matter volume using 3-tesla brain magnetic resonance imaging in 213 inpatients with acute major depression according to DSM-IV criteria (employing the SCID interview) and 213 healthy controls. Patients’ cumulative illness severity was ascertained by six clinical variables via structured clinical interviews. A principal component analysis was conducted to identify components reflecting cumulative illness severity. Regression analyses and a voxel-based morphometry approach were used to investigate the influence of patients’ individual component scores on hippocampal volume.
Principal component analysis yielded two main components of cumulative illness severity: Hospitalization and Duration of Illness. While the component Hospitalization incorporated information from the intensity of inpatient treatment, the component Duration of Illness was based on the duration and frequency of illness episodes. We could demonstrate a significant inverse association of patients’ Hospitalization component scores with bilateral hippocampal gray matter volume. This relationship was not found for Duration of Illness component scores.
Variables associated with patients’ history of psychiatric hospitalization seem to be accurate predictors of hippocampal volume in major depression and reliable estimators of patients’ cumulative illness severity. Future studies should pay attention to these measures when investigating hippocampal volume changes in major depression.
Tuberculosis (TB) has been known to affect elephants for thousands of years. It was put into spotlight when few circus elephants were diagnosed carrying Mycobacterium (M.) tuberculosis. Because of the zoonotic risk and high susceptibility to M. tuberculosis, periodic testing was enacted since, in captive breeding programmes. Presently, trunk wash is the recommended diagnostic procedure for TB. Trunk wash, however, puts the operator at risk, has low sensitivity, and is prone to contamination. Here, bronchoalveolar lavage is described for the first time for TB diagnosis in elephants. Bronchial, trunk and mouth fluids were investigated using bacterial culture, M. tuberculosis complex (MTC)-specific real-time quantitative PCR (qPCR) and mycobacterial genus-specific qPCR for overall presence of mycobacteria or mycobacterial DNA including bacteria or DNA of closely related genera, respectively, in 14 elephants. Neither bacteria of the MTC nor their DNA were identified in any of the elephants. Yet, 25% of the cultures grew non-tuberculous mycobacteria (NTM) or closely related bacterial species. Furthermore, 85% of the samples contained DNA of NTM or closely related bacterial genera. This finding might explain continued false-positive results from various serological tests. From a zoonotic point of view, bronchoalveolar lavage is safer for the testing personal, has higher probability of capturing MTC and, through PCR, identifies DNA NTM in elephants. Yet, necessary endoscopic equipment, animal sedation and access to a TB reference laboratory might pose challenging requirements in remote conditions in some elephant range countries.
Glacier surface mass-balance measurements on Greenland started more than a century ago, but no compilation exists of the observations from the ablation area of the ice sheet and local glaciers. Such data could be used in the evaluation of modelled surface mass balance, or to document changes in glacier melt independently from model output. Here, we present a comprehensive database of Greenland glacier surface mass-balance observations from the ablation area of the ice sheet and local glaciers. The database spans the 123 a from 1892 to 2015, contains a total of ~3000 measurements from 46 sites, and is openly accessible through the PROMICE web portal (http://www.promice.dk). For each measurement we provide X, Y and Z coordinates, starting and ending dates as well as quality flags. We give sources for each entry and for all metadata. Two thirds of the data were collected from grey literature and unpublished archive documents. Roughly 60% of the measurements were performed by the Geological Survey of Denmark and Greenland (GEUS, previously GGU). The data cover all regions of Greenland except for the southernmost part of the east coast, but also emphasize the importance of long-term time series of which there are only two exceeding 20 a. We use the data to analyse uncertainties in point measurements of surface mass balance, as well as to estimate surface mass-balance profiles for most regions of Greenland.
Cytokines and vitamin D both have a role in modulating the immune system, and are also potentially useful biomarkers in mental illnesses such as major depressive disorder (MDD) and schizophrenia. Studying the variability of cytokines and vitamin D in a healthy population sample may add to understanding the association between these biomarkers and mental illness. To assess genetic and environmental contributions to variation in circulating levels of cytokines and vitamin D (25-hydroxy vitamin D: 25(OH)D3), we analyzed data from a healthy adolescent twin cohort (mean age 16.2 years; standard deviation 0.25). Plasma cytokine measures were available for 400 individuals (85 MZ, 115 DZ pairs), dried blood spot sample vitamin D measures were available for 378 individuals (70 MZ, 118 DZ pairs). Heritability estimates were moderate but significant for the cytokines transforming growth factor-β1 (TGF-β1), 0.57 (95% CI 0.26–0.80) and tumor necrosis factor-receptor type 1 (TNFR1), 0.50 (95% CI 0.11–0.63) respectively. Measures of 25(OH)D3 were within normal range and heritability was estimated to be high (0.86, 95% CI 0.61–0.94). Assays of other cytokines did not generate meaningful results. These potential biomarkers may be useful in mental illness, with further research warranted in larger sample sizes. They may be particularly important in adolescents with mental illness where diagnostic uncertainty poses a significant clinical challenge.
Templates and models of galaxy spectra are often essential for determining the physical properties of galaxies. Many commonly used templates have large systematic errors, which significantly impact photometric redshifts and k-corrections. We present a new library of 110 galaxy template spectra spanning from the ultraviolet to the mid-infrared. The templates combine optical, Spitzer and Akari spectra with MAGPHYS models, all normalised and verified with matched aperture photometry. Our library contains more galaxies, spans a broader range of colours and has smaller systematic errors than previous libraries of galaxy spectra.
In this work high quality ferroelectric PZT films have been prepared in-situ by hot RF magnetron sputtering. 200 mm wafer were coated with PZT films of 1 μm and 2 μm thickness at sputter rates of 45 nm/min in a high volume production sputtering tool. The films were grown on oxidized Si substrates prepared either with sputtered Ti/TiO2/Pt, sputtered Ti/TiO2/Pt/TiO2 or evaporated Ti/Pt bottom electrodes at substrate holder temperatures in the range from 550 °C to 700 °C. At these temperatures, the material nucleates in the requisite piezoelectric perovskite phase without need of an additional post annealing treatment.
The films were investigated with respect to their chemical composition and their crystallographic, piezoelectric and dielectric properties. At an intermediate chuck temperature of 600 °C the PZT thin films were characterized by a minimum volume fraction of secondary nonpiezoelectric phases. A Zr/(Zr+Ti) ratio of 0.53 has been achieved matching the morphotropic phase boundary. By improving the deposition process and poling procedure, a notable high e31,f coefficient of -17.3 C/m2 has been obtained. The corresponding longitudinal piezoelectric constant was determined to have an effective longitudinal piezoelectric coefficient d33,f of 160 pm/V.
We have constructed a new digital elevation model (DEM) of the 1995 surface of Black Rapids Glacier, a surge-type glacier in the central Alaska Range, using ERS-1/-2 repeat-pass interferometry. We isolated the topographic phase from three interferograms with contrasting perpendicular baselines. Numerous phase-unwrapping errors caused by areas of poor coherence were corrected in all three interferograms, using a novel, iterative, semi-automated approach that capitalizes on the multi-baseline nature of the dataset. Comparison of our DEM with a 1949 US Geological Survey DEM and with 1973–95 ground survey data shows the gradual return of Black Rapids Glacier to a pre-surge hypsometry following a surge in 1936/37. Maximum elevation changes along the glacier center line in the ablation and accumulation areas are, respectively, −249 and +63 m (−5.4 and +1.4 m a−1). Maximum elevation changes of survey points at nearby locations are −4.9 m a−1 (1975–84) and +0.5 m a−1 (1975–85). Center-line thickening of +62 m between 1949 and 1995 (+1.4 m a−1), just above the Loket tributary in the upper part of the ablation zone, indicates dynamic thickening following the 1936/37 surge.