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We here present a comparison of methods for the pretreatment of a batch of tree rings for high-precision measurement of radiocarbon at the Aarhus AMS Centre (AARAMS), Aarhus University, Denmark. The aim was to develop an efficient and high-throughput method able to pretreat ca. 50 samples at a time. We tested two methods for extracting α-cellulose from wood to find the most optimal for our use. One method used acetic acid, the other used HCl acid for the delignification. The testing was conducted on background 14C samples, in order to assess the effect of the different pretreatment methods on low-activity samples. Furthermore, the extracted wood and cellulose fractions were analyzed using Fourier transform infrared (FTIR) spectroscopy, which showed a successful extraction of α-cellulose from the samples. Cellulose samples were pretreated at AARAMS, and the graphitization and radiocarbon analysis of these samples were done at both AARAMS and the radiocarbon dating laboratory at Lund University to compare the graphitization and AMS machine performance. No significant offset was found between the two sets of measurements. Based on these tests, the pretreatment of tree rings for high-precision radiocarbon analysis at AARAMS will henceforth use HCI for the delignification.
A design rationale is a representation of the reasoning behind a design concept, explaining why the solution is designed the way it is. This makes design rationale a critical part of concept development. However, there is little exploration on how to build a design rationale. This study sheds light on professional designers’ reasoning in conceptual design, as we examine how design rationales for different concepts are built based on a longitudinal study in the context of two design studios. Particularly the study provides insight into how a design rationale is initiated, matured and finalized.
Cognitive disturbances are common and disabling features of major depressive disorder (MDD). Previous studies provide limited insight into the co-occurrence of hot (emotion-dependent) and cold (emotion-independent) cognitive disturbances in MDD. Therefore, we here map both hot and cold cognition in depressed patients compared to healthy individuals.
We collected neuropsychological data from 92 antidepressant-free MDD patients and 103 healthy controls. All participants completed a comprehensive neuropsychological test battery assessing hot cognition including emotion processing, affective verbal memory and social cognition as well as cold cognition including verbal and working memory and reaction time.
The depressed patients showed small to moderate negative affective biases on emotion processing outcomes, moderate increases in ratings of guilt and shame and moderate deficits in verbal and working memory as well as moderately slowed reaction time compared to healthy controls. We observed no correlations between individual cognitive tasks and depression severity in the depressed patients. Lastly, an exploratory cluster analysis suggested the presence of three cognitive profiles in MDD: one characterised predominantly by disturbed hot cognitive functions, one characterised predominantly by disturbed cold cognitive functions and one characterised by global impairment across all cognitive domains. Notably, the three cognitive profiles differed in depression severity.
We identified a pattern of small to moderate disturbances in both hot and cold cognition in MDD. While none of the individual cognitive outcomes mapped onto depression severity, cognitive profile clusters did. Overall cognition-based stratification tools may be useful in precision medicine approaches to MDD.
The Danish National Schizophrenia project for persons with a first episode psychosis within the schizophrenia spectrum (F20-29) has initially collected data for 562 persons, included consecutively in a 2 years period (1997-1999). The investigation covers 45% of the Danish population.
To present a prospectively investigation of three types of treatment: Psychodynamic Psychotherapy, Integrated Treatment and Treatment as usual.
Measurements of psychopathology, social functioning, and psychological functions (Rorschach and WAIS) showed that the group of patients who were treated by the intervention methods did better than the group who received the Treatment as usual. Preliminary 5 years data will also be indicated.
After two years patients receiving integrated treatment and the psychodynamic treatment will do better than the group of patients getting Treatment as usual. Integrated treatment is superior compared with the two other modes of treatment. After five years only minor advantages of adding psychodynamic treatment to Treatment as usual can be shown on the general symptom and social functioning scales.
To describe the rationale, design and methods of the Danish national Schoizophrenia Project, and to characterise the sample at inclusion and after 1 and 2 ys.
Prospective, comparative,longitudinal multicenter-study (16 centers distributed all over Denmark), including 562 patients with a first episode psychosis, ICD 10 F- 2, sduccessively referred during two years.
Patients were treated with three different intervention types
1. supportive psychodynamic as a supplement to treatmen as usual, including antipsychotics (TAU), 2. assertive, integrated treatment with psychosocial and psychoeducation and antipsychotics 3. Treatment as usual. Data included psychopathology, social fundtion and sociodemographic data, at baseline, years 1 and 2.
Comparing the three interventions showed a significantly better outcome for the interventions 1 and 2 than 3, TAU.
DSM-5 includes two conceptualizations of personality disorders (PDs). The classification in Section II is identical to the one found in DSM-IV, and includes 10 categorical PDs. The Alternative Model (Section III) includes criteria for dimensional measures of maladaptive personality traits organized into five domains. The degree to which the two conceptualizations reflect the same etiological factors is not known.
We use data from a large population-based sample of adult twins from the Norwegian Institute of Public Health Twin Panel on interview-based DSM-IV PDs and a short self-report inventory that indexes the five domains of the DSM-5 Alternative Model plus a domain explicitly targeting compulsivity. Schizotypal, Paranoid, Antisocial, Borderline, Avoidant, and Obsessive-compulsive PDs were assessed at the same time as the maladaptive personality traits and 10 years previously. Schizoid, Histrionic, Narcissistic, and Dependent PDs were only assessed at the first interview. Biometric models were used to estimate overlap in genetic and environmental risk factors.
When measured concurrently, there was 100% genetic overlap between the maladaptive trait domains and Paranoid, Schizotypal, Antisocial, Borderline, and Avoidant PDs. For OCPD, 43% of the genetic variance was shared with the domains. Genetic correlations between the individual domains and PDs ranged from +0.21 to +0.91.
The pathological personality trait domains, which are part of the Alternative Model for classification of PDs in DSM-5 Section III, appears to tap, at an aggregate level, the same genetic risk factors as the DSM-5 Section II classification for most of the PDs.
Cognitive dysfunction in depression and bipolar disorder (BD) is insufficiently targeted by available treatments. Erythropoietin (EPO) increases neuroplasticity and may improve cognition in mood disorders, but the neuronal mechanisms of these effects are unknown. This functional magnetic resonance imaging (fMRI) study investigated the effects of EPO on neural circuitry activity during working memory (WM) performance.
Patients with treatment-resistant major depression, who were moderately depressed, or with BD in partial remission, were randomized to eight weekly infusions of EPO (40 000 IU) (N = 30) or saline (N = 26) in a double-blind, parallel-group design. Patients underwent fMRI, mood ratings and blood tests at baseline and week 14. During fMRI patients performed an n-back WM task.
EPO improved WM accuracy compared with saline (p = 0.045). Whole-brain analyses revealed that EPO increased WM load-related activity in the right superior frontal gyrus (SFG) compared with saline (p = 0.01). There was also enhanced WM load-related deactivation of the left hippocampus in EPO-treated compared to saline-treated patients (p = 0.03). Across the entire sample, baseline to follow-up changes in WM performance correlated positively with changes in WM-related SFG activity and negatively with hippocampal response (r = 0.28–0.30, p < 0.05). The effects of EPO were not associated with changes in mood or red blood cells (p ⩾0.08).
The present findings associate changes in WM-load related activity in the right SFG and left hippocampus with improved executive function in EPO-treated patients. Clinical trial registration: clinicaltrials.gov: NCT00916552.
Antisocial personality disorder (ASPD) and borderline personality disorder (BPD) share genetic and environmental risk factors. Little is known about the temporal stability of these etiological factors in adulthood.
DSM-IV criteria for ASPD and BPD were assessed using structured interviews in 2282 Norwegian twins in early adulthood and again approximately 10 years later. Longitudinal biometric models were used to analyze the number of endorsed criteria.
The mean criterion count for ASPD and BPD decreased 40% and 28%, respectively, from early to middle adulthood. Rank-order stability was 0.58 for ASPD and 0.45 for BPD. The best-fitting longitudinal twin model included only genetic and individual-specific environmental factors. Genetic effects, both those shared by ASPD and BPD, and those specific to each disorder remained completely stable. The unique environmental effects, however, changed substantially, with a correlation across time of 0.19 for the shared effects, and 0.39 and 0.15, respectively, for those specific to ASPD and BPD. Genetic effects accounted for 71% and 72% of the stability over time for ASPD and BPD, respectively. The genetic and environmental correlations between ASPD and BPD were 0.73, and 0.43, respectively, at both time points.
ASPD and BPD traits were moderately stable from early to middle adulthood, mostly due to genetic risk factors which did not change over the 10-year assessment period. Environmental risk factors were mostly transient, and appear to be the main source of phenotypic change. Genetic liability factors were, to a large extent, shared by ASPD and BPD.
While cluster A personality disorders (PDs) have been shown to be moderately heritable, we know little about the temporal stability of these genetic risk factors.
Paranoid PD (PPD) and schizotypal PD (STPD) were assessed using the Structured Interview for DSM-IV Personality in 2793 young adult twins from the Norwegian Institute of Public Health Twin Panel at wave 1 and 2282 twins on average 10 years later at wave 2. Using the program Mx, we fitted a longitudinal latent factor model using the number of endorsed criteria for PPD and STPD.
The stability over time of the criteria counts for PPD and STPD, estimated as polychoric correlations, were +0.34 and +0.40, respectively. The best-fit longitudinal model included only additive genetic and individual-specific environmental factors with parameter estimates constrained to equality across the two waves. The cross-wave genetic and individual-specific environmental correlations for a latent cluster A factor were estimated to equal +1.00 and +0.13, respectively. The cross-time correlations for genetic and environmental effects specific to the individual PDs were estimated at +1.00 and +0.16–0.20, respectively. We found that 68% and 71% of the temporal stability of PPD and STPD derived, respectively, from the effect of genetic factors.
Shared genetic risk factors for two of the cluster A PDs are highly stable in adults over a 10-year period while environmental risk factors are relatively transient. Over two-thirds of the long-term stability of the common cluster A PD liability can be attributed to genetic influences.
Healthy first-degree relatives of patients with major depression (rMD+) show brain structure and functional response anomalies and have elevated risk for developing depression, a disorder linked to abnormal serotonergic neurotransmission and reward processing.
In a two-step functional magnetic resonance imaging (fMRI) investigation, we first evaluated whether positive and negative monetary outcomes were differentially processed by rMD+ individuals compared to healthy first-degree relatives of control probands (rMD−). Second, in a double-blinded placebo-controlled randomized trial we investigated whether a 4-week intervention with the selective serotonergic reuptake inhibitor (SSRI) escitalopram had a normalizing effect on behavior and brain responses of the rMD+ individuals.
Negative outcomes increased the probability of risk-averse choices in the subsequent trial in rMD+ but not in rMD− individuals. The orbitofrontal cortex (OFC) displayed a stronger neural response when subjects missed a large reward after a low-risk choice in the rMD+ group compared to the rMD− group. The enhanced orbitofrontal response to negative outcomes was reversed following escitalopram intervention compared to placebo. Conversely, for positive outcomes, the left hippocampus showed attenuated response to high wins in the rMD+ compared to the rMD− group. The SSRI intervention reinforced the hippocampal response to large wins. A subsequent structural analysis revealed that the abnormal neural responses were not accounted for by changes in gray matter density in rMD+ individuals.
Our study in first-degree relatives of depressive patients showed abnormal brain responses to aversive and rewarding outcomes in regions known to be dysfunctional in depression. We further confirmed the reversal of these aberrant activations with SSRI intervention.
Objective: There is clear evidence of a genetic component in major depression, and several studies indicate that neuropeptide Y (NPY) could play an important role in the pathophysiology of the disease. A well-known polymorphism encoding the substitution of leucine to proline in the signal peptide sequence of NPY (Leu7Pro variation) was previously found to protect against depression. Our study aimed at replicating this association in a large Danish population with major depression.
Method: Leu7Pro was studied in a sample of depressed patients and ethnically matched controls, as well as psychiatric disease controls with schizophrenia. Possible functional consequences of Leu7Pro were explored in vitro.
Results: In contrast to previous studies, Pro7 appeared to be a risk allele for depression, being significantly more frequent in the depression sample (5.5%, n = 593; p = 0.009; odds ratio, OR: 1.46) as compared to ethnically matched controls (3.8%, n = 2912), while schizophrenia patients (4.1%, n = 503) did not differ. In vitro, the Pro7 substitution appeared to be associated with reduced levels of NPY without affecting its mRNA level.
Conclusion: The Leu7Pro variation may increase the risk of major depression, possibly by affecting the biosynthesis of NPY.
A trial of protective efficacy which compared medium–titre Edmonston-Zagreb (EZ) measles vaccine (104.6 p.f.u.) from the age of 4 months with the standard Schwarz (SW) measles vaccine given from the age of 9 months was started in an urban community in Guinea-Bissau in 1985. Because trials of high–titre measles vaccine have found increased mortality among female recipients, we examined whether EZ medium–titre vaccine was associated with any long-term impact on mortality, suppression of T–cells, or growth. The mortality rate ratio over 5 years of follow–up was 1.12 for EZ children compared with children in the standard group (P = 0.63). Seventy–five percent of the children still residing in the area at 5 years of age took part in an immunological and anthropometric examination. There was no difference in T–cell subsets between the two groups. There was no difference in mid–upper–arm circumference, but EZ children were significantly shorter than the children in the standard group. In conclusion, medium–titre EZ was not associated with reduced survival or persistent immunosuppression.
Molecular gas has now been detected in 15 z>2 QSOs. These detections are commonly obtained by observing high–J CO transitions due to their relatively high peak fluxes and observing frequencies in the millimeter atmospheric windows. However, only observations of the CO ground-state transition, CO(1–0), have the potential to trace the molecular gas at lower excitations, which may give a better estimate of the total molecular gas mass of high–z QSOs. Here we present first z>4 CO(1–0) observations obtained with the NRAO Green Bank Telescope and the MPIfR Effelsberg telescope (Riechers et al. 2006). With these two 100m telescopes, we detect the CO(1–0) transition in the high–redshift QSOs BR 1202-0725 (z = 4.7), PSS J2322+1944 (z = 4.1), and APM 08279+5255 (z = 3.9). We find that the CO/FIR luminosity ratios of these high-z sources follow the same trend as seen for low-z galaxies. Utilizing large velocity gradient (LVG) models based on previous results for higher–J CO transitions, we derive that all CO emission can be described by a single gas component and that all molecular gas appears to be concentrated in a compact nuclear region. We thus find no evidence for luminous, extended CO(1–0) components in the molecular gas reservoirs around our target quasars.
The effect of large dose boron implantation in single crystal CdTe has been investigated by Rutherford Backscattering Spectrometry with channeling (RBS), double crystal x-ray diffraction (DCD) and photoreflectance spectroscopy (PR). Comparisons are made with the results of identical B implantations of Si and GaAs crystals. Multiple energy implantations were performed at room temperature and liquid nitrogen temperature with total doses up to 1.5×1016 B+ ions/cm2. The implanted B distribution was measured with neutron depth profiling (NDP) and found to agree well with Monte-Carlo ion range calculations. The RBS results showed that the CdTe crystals had not been rendered completely amorphous even for the highest dose implantation, unlike GaAs and Si. Furthermore, the DCD results showed little implantation induced structure in the rocking curves from the implanted CdTe crystals, in contrast to GaAs. The consequences of annealing at 500°C in an attempt to regrow the crystal structure are also discussed.
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