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In engineering and architecture, different approaches have been developed that share the use of graph transformation to automate design processes or to search for design solutions by means of computational design synthesis. In order to give an overview of these approaches, we provide a review of articles published in the last decade. Forty-eight articles were reviewed to determine similarities and differences of these approaches. Research fields in method development for the representation of design problems and the processing of graph transformations, as well as the application of graph transformations in engineering, architecture, and shape grammars were identified. Different approaches for the documentation of the vocabulary and the rules were examined. Finally, different approaches for rule applications were analyzed. Based on found limitations, future research directions are suggested.
To mitigate the risk of wake vortex encounters during final approach, so-called plate lines have been developed. Data collected during a six-month measurement campaign at Vienna International Airport are used to assess the potential for reducing minimum aircraft separations facilitated by plate lines during approach and landing following the re-categorisation (RECAT-EU) methodology for revised wake turbulence categorisation. To ensure that no other parameters controlling wake vortex decay bias the analysis, it is verified that wind speed, atmospheric turbulence, thermal stratification and flight altitude reside in similar ranges with and without the plates. The analysis follows the steps of the RECAT-EU method to generate non-dimensional so-called reasonable worst-case circulation decay curves; one as a reference for nominal operations without plates and one representing the accelerated wake vortex decay brought about by the plate lines. The difference between the two circulation decay curves corresponds to the non-dimensional time-based aircraft separation reduction potential that can be translated into distance-based separation gains. Depending on the particular RECAT-EU category combination, the attained aircraft separation reduction potential ranges between 12% and 15%. Constricting the analysis to wake vortices generated by one aircraft type representing the Upper Heavy RECAT-EU category, the separation reduction potential amounts up to 24%.
Response to lithium in patients with bipolar disorder is associated with clinical and transdiagnostic genetic factors. The predictive combination of these variables might help clinicians better predict which patients will respond to lithium treatment.
Aims
To use a combination of transdiagnostic genetic and clinical factors to predict lithium response in patients with bipolar disorder.
Method
This study utilised genetic and clinical data (n = 1034) collected as part of the International Consortium on Lithium Genetics (ConLi+Gen) project. Polygenic risk scores (PRS) were computed for schizophrenia and major depressive disorder, and then combined with clinical variables using a cross-validated machine-learning regression approach. Unimodal, multimodal and genetically stratified models were trained and validated using ridge, elastic net and random forest regression on 692 patients with bipolar disorder from ten study sites using leave-site-out cross-validation. All models were then tested on an independent test set of 342 patients. The best performing models were then tested in a classification framework.
Results
The best performing linear model explained 5.1% (P = 0.0001) of variance in lithium response and was composed of clinical variables, PRS variables and interaction terms between them. The best performing non-linear model used only clinical variables and explained 8.1% (P = 0.0001) of variance in lithium response. A priori genomic stratification improved non-linear model performance to 13.7% (P = 0.0001) and improved the binary classification of lithium response. This model stratified patients based on their meta-polygenic loadings for major depressive disorder and schizophrenia and was then trained using clinical data.
Conclusions
Using PRS to first stratify patients genetically and then train machine-learning models with clinical predictors led to large improvements in lithium response prediction. When used with other PRS and biological markers in the future this approach may help inform which patients are most likely to respond to lithium treatment.
While converging evidence suggests that both environmental and genetic factors underlie variations in diurnal cortisol, the extent to which these sources of influence vary according to socioeconomic status (SES) has seldom been investigated, particularly in adolescence. To investigate whether a distinct genetic and environmental contribution to youth’s diurnal cortisol secretion emerges according to family SES and whether the timing of these experiences matters. Participants were 592 twin pairs, who mostly came from middle-income and intact families and for whom SES was measured in childhood and adolescence. Diurnal cortisol was assessed at age 14 at awakening, 30 min later, in the afternoon and evening over four nonconsecutive days. SES–cortisol phenotypic associations were specific to the adolescence period. Specifically, higher awakening cortisol levels were detected in wealthier backgrounds, whereas higher cortisol awakening response (CAR) and diurnal changes were present at both ends of the SES continuum. Moreover, smaller genetic contributions emerged for awakening cortisol in youth from poorer compared to wealthier backgrounds. The results suggest that the relative contribution of inherited factors to awakening cortisol secretion may be enhanced or suppressed depending on the socio-family context, which may help to decipher the mechanisms underlying later adjustment.
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.
Alcohol use disorder (AUD) and schizophrenia (SCZ) frequently co-occur, and large-scale genome-wide association studies (GWAS) have identified significant genetic correlations between these disorders.
Methods
We used the largest published GWAS for AUD (total cases = 77 822) and SCZ (total cases = 46 827) to identify genetic variants that influence both disorders (with either the same or opposite direction of effect) and those that are disorder specific.
Results
We identified 55 independent genome-wide significant single nucleotide polymorphisms with the same direction of effect on AUD and SCZ, 8 with robust effects in opposite directions, and 98 with disorder-specific effects. We also found evidence for 12 genes whose pleiotropic associations with AUD and SCZ are consistent with mediation via gene expression in the prefrontal cortex. The genetic covariance between AUD and SCZ was concentrated in genomic regions functional in brain tissues (p = 0.001).
Conclusions
Our findings provide further evidence that SCZ shares meaningful genetic overlap with AUD.
Introduction: Postpartum weight management is difficult for many mothers due to the demands of parenthood. Women have highlighted a need for support but experience barriers to engaging with lifestyle interventions hence more adaptable approaches are required. This work examined participants’ engagement with a 12-month, theory-based, automated, text message (SMS) delivered, intervention supporting postpartum weight management.
Methods: SMS content was informed by: 1) the ‘Health Action Process Approach’ (HAPA)1; 2) behaviour change techniques associated with effectiveness in weight management interventions2; 3) women's accounts of postpartum weight-related experiences; and 4) personal and public involvement. A two-arm pilot RCT recruited women within two years postpartum, with a BMI ≥ 25 kg/m2, through community sources and social media. Women were randomised via a secure remote system to receive the intervention or an active control delivering child development messages. Participants received 353 messages during the 12 month intervention. Two-way messages were used to assess engagement: 50 messages prompted women to respond with their weight; 36 interactive messages requested participants’ to respond ‘Yes/No’ to a question which then triggered a feedback message. Participant engagement with two-way messages was calculated as a percentage of replies sent by women and was categorised as ‘high’ or ‘low’ according to the median number of replies sent. Weight was measured at 0, 3, 6, 9 and 12 months.
Results: 51 of 100 women recruited were randomised to receive the intervention. In months 0–6, (47%) and (95%) of participants responded to the weight messages and the ‘Yes/No’ messages respectively. In months 7–12, the responses were (77%) and (86%) respectively. Participants who were high engagers with weight messages had greater mean weight loss compared with low engagers at all time points: at 12 months high engagers (n = 18) lost -2.66 kg and had a reduction in waist circumference at 12 months of -8.9 cm, compared to changes in low engagers (n = 18) of -0.84 kg and -3.6 cm. Likewise, high engagers with ‘Yes/No’ messages had greater mean weight loss compared with low engagers at all time points: at 12 months high engagers (n = 16) lost -2.87 kg and had a reduction in waist circumference of -9.4 cm, compared to changes in low engagers (n = 20) of -0.86 kg and -3.6 cm.
Discussion: The use of two-way text messages was a useful way to encourage engagement with this SMS-delivered intervention. Higher engagement resulted in more weight loss compared to low engagement.
Waterfall Bluff is a rock shelter in eastern Pondoland, South Africa, adjacent to a narrow continental shelf that limited coastline movements across glacial/interglacial cycles. The archaeological deposits are characterized by well-preserved stratigraphy, faunal, and botanical remains alongside abundant stone artifacts and other materials. A comprehensive dating protocol consisting of 5 optically stimulated luminescence ages and 51 accelerator mass spectrometry 14C ages shows that the record of hunter-gatherer occupations at Waterfall Bluff persisted from the late Pleistocene to the Holocene, spanning the last glacial maximum and the transition from the Pleistocene to the Holocene. Here, we provide detailed descriptions about the sedimentary sequence, chronology, and characteristics of the archaeological deposits at Waterfall Bluff. Remains of marine mollusks and marine fish also show, for the first time, that coastal foraging was a component of some hunter-gatherer groups’ subsistence practices during glacial phases in the late Pleistocene. The presence of marine fish and shellfish further demonstrates that hunter-gatherers selectively targeted coastal resources from intertidal and estuarine habitats. Our results therefore underscore the idea that Pondoland's coastline remained a stable and predictable point on the landscape over the last glacial/interglacial transition being well positioned for hunter-gatherers to access resources from the nearby coastline, narrow continental shelf, and inland areas.
We prove that the continuous function${\rm{\hat \Omega }}:2^\omega \to $ that is defined via$X \mapsto \mathop \sum \limits_n 2^{ - K\left( {Xn} \right)} $ for all $X \in {2^\omega }$ is differentiable exactly at the Martin-Löf random reals with the derivative having value 0; that it is nowhere monotonic; and that $\mathop \smallint \nolimits _0^1{\rm{\hat{\Omega }}}\left( X \right)\,{\rm{d}}X$ is a left-c.e. $wtt$-complete real having effective Hausdorff dimension ${1 / 2}$.
We further investigate the algorithmic properties of ${\rm{\hat{\Omega }}}$. For example, we show that the maximal value of ${\rm{\hat{\Omega }}}$ must be random, the minimal value must be Turing complete, and that ${\rm{\hat{\Omega }}}\left( X \right) \oplus X{ \ge _T}\emptyset \prime$ for every X. We also obtain some machine-dependent results, including that for every $\varepsilon > 0$, there is a universal machine V such that ${{\rm{\hat{\Omega }}}_V}$ maps every real X having effective Hausdorff dimension greater than ε to a real of effective Hausdorff dimension 0 with the property that $X{ \le _{tt}}{{\rm{\hat{\Omega }}}_V}\left( X \right)$; and that there is a real X and a universal machine V such that ${{\rm{\Omega }}_V}\left( X \right)$ is rational.
Two laboratory emission spectrometers have been designed and described previously. Here, we present a follow-up study with special focus on absolute intensity calibration of the new SURFER-spectrometer (SUbmillimeter Receiver For Emission spectroscopy of Rotational transitions), operational between 300 and 400 GHz and coincident with ALMA (Atacama Large Millimeter/submillimeter Array) Band 7.
Furthermore, we present a feasibility study to extend the detection frequencies up to 2 THz. First results have been obtained using the SOFIA (Stratospheric Observatory for IR Astronomy) upGREAT laboratory setup which is located at the University of Cologne. Pure rotational spectra of the complex molecule vinyl cyanide have been obtained and are used to give an estimate on the sensitivity to record ro-vibrational transitions of molecules with astrophysical importance at 2 THz.
Background: Based on the vulnerability model, several studies indicate that low self-esteem seems to contribute to depressive symptoms. Aims: The aim of this study was to treat depressive symptoms in a cognitive behavioural group therapy, focusing on the enhancement of self-esteem, and to explore co-variation in depressive symptoms and the level of self-esteem. Method: The Multidimensional Self-esteem Scale (MSWS) and the Beck Depression Inventory (BDI) were administered to 147 psychiatric in-patients with current depressive symptoms due to an affective disorder (major depression, bipolar I, dysthymia). Self-esteem was measured pre-treatment (t0) and post-treatment (t4, after 5 weeks of eight group sessions); the BDI was applied weekly. A linear mixed growth analysis was conducted to estimate the change in depressive symptoms including interactions with self-esteem. Results: Within the 5 weeks of group therapy, depressive symptoms showed a linear decline, which was stronger for patients with higher gains in self-esteem between t0 and t4. Self-esteem at t0 was unrelated to the change in depression but predicted self-esteem at t4. Conclusions: Treating depressive symptoms in a cognitive behavioural group therapy in a naturalistic setting might have a positive effect on the process of recovery. Moreover, depressive symptoms and level of self-esteem seemed to co-vary.
Field experiments were conducted in 1989 and 1990 to evaluate seasonal effects of herbicide application, smutgrass (Sporobolus indicus) growth stage, and herbicide rate on smutgrass control. The experimental design was a split–split plot, with season (late spring, midsummer, and fall) as the whole plot, physiological stage at application (uncut, 15-, and 30-cm regrowth) the subplot, and hexazinone rate (0.0, 0.56, 0.84, and 1.12 kg ai/ha) as the sub-subplot treatment. Whole plots were arranged in three randomized complete blocks. Smutgrass control for the mean of the hexazinone treatments (1989 and 1990) was 95%. Application of 0.56 kg/ha hexazinone during late spring, midsummer, and fall seasons provided 77, 92, and 92% smutgrass control, respectively. Generally, the influence of plant stage at time of hexazinone application had no effect (P > 0.05) on smutgrass control. At 20 d after treatment (DAT), hexazinone had injured bahiagrass (Paspalum notatum) plants by yellowing them, but the plants reverted to their usual dark green color by 40 DAT. Total nonstructural carbohydrates were lower for the 30-cm regrowth than for the uncut plants, regardless of season; however, 30-cm regrowth had little effect on smutgrass control.
We present first results of a new heterodyne spectrometer dedicated to high-resolution spectroscopy of molecules of astrophysical importance. The spectrometer, based on a room-temperature heterodyne receiver, is sensitive to frequencies between 75 and 110 GHz with an instantaneous bandwidth of currently 2.5 GHz in a single sideband. The system performance, in particular the sensitivity and stability, is evaluated. Proof of concept of this spectrometer is demonstrated by recording the emission spectrum of methyl cyanide, CH3CN. Compared to state-of-the-art radio telescope receivers the instrument is less sensitive by about one order of magnitude. Nevertheless, the capability for absolute intensity measurements can be exploited in various experiments, in particular for the interpretation of the ever richer spectra in the ALMA era. The ease of operation at room-temperature allows for long time integration, the fast response time for integration in chirped pulse instruments or for recording time dependent signals. Future prospects as well as limitations of the receiver for the spectroscopy of complex organic molecules (COMs) are discussed.
Bipolar disorder is a highly heritable polygenic disorder. Recent
enrichment analyses suggest that there may be true risk variants for
bipolar disorder in the expression quantitative trait loci (eQTL) in the
brain.
Aims
We sought to assess the impact of eQTL variants on bipolar disorder risk
by combining data from both bipolar disorder genome-wide association
studies (GWAS) and brain eQTL.
Method
To detect single nucleotide polymorphisms (SNPs) that influence
expression levels of genes associated with bipolar disorder, we jointly
analysed data from a bipolar disorder GWAS (7481 cases and 9250 controls)
and a genome-wide brain (cortical) eQTL (193 healthy controls) using a
Bayesian statistical method, with independent follow-up replications. The
identified risk SNP was then further tested for association with
hippocampal volume (n = 5775) and cognitive performance
(n = 342) among healthy individuals.
Results
Integrative analysis revealed a significant association between a brain
eQTL rs6088662 on chromosome 20q11.22 and bipolar disorder (log Bayes
factor = 5.48; bipolar disorder P =
5.85×10–5). Follow-up studies across multiple independent
samples confirmed the association of the risk SNP (rs6088662) with gene
expression and bipolar disorder susceptibility (P =
3.54×10–8). Further exploratory analysis revealed that
rs6088662 is also associated with hippocampal volume and cognitive
performance in healthy individuals.
Conclusions
Our findings suggest that 20q11.22 is likely a risk region for bipolar
disorder; they also highlight the informative value of integrating
functional annotation of genetic variants for gene expression in
advancing our understanding of the biological basis underlying complex
disorders, such as bipolar disorder.