Disentangling ADHD's Presentation-Related Decision-Making-A Meta-Analytic Approach on Predominant Presentations

Background: Deficient decision-making (DM) in attention deficit/hyperactivity disorder (ADHD) is marked by altered reward sensitivity, higher risk taking, and aberrant reinforcement learning. Previous meta-analysis aggregate findings for the ADHD combined presentation (ADHD-C) mostly, while the ADHD predominantly inattentive presentation (ADHD-I) and the predominantly hyperactive/impulsive presentation (ADHD-H) were not disentangled. The objectives of the current meta-analysis were to aggregate findings from DM for each presentation separately. Methods: A comprehensive literature search of the PubMed (Medline) and Web of Science Database took place using the keywords "ADHD," "attention-deficit/hyperactivity disorder," "decision-making," "risk-taking," "reinforcement learning," and "risky." Random-effects models based on correlational effect-sizes were conducted. Heterogeneity analysis and sensitivity/outlier analysis were performed, and publication biases were assessed with funnel-plots and the egger intercept. Results: Of 1,240 candidate articles, seven fulfilled criteria for analysis of ADHD-C (N = 193), seven for ADHD-I (N = 256), and eight for ADHD-H (N = 231). Moderate effect-size were found for ADHD-C (r = 0.34; p = 0.0001; 95% CI = [0.19, 0.49]). Small effect-sizes were found for ADHD-I (r = 0.09; p = 0.0001; 95% CI = [0.008, 0.25]) and for ADHD-H (r = 0.1; p = 0.0001; 95% CI = [-0.012, 0.32]). Heterogeneity was moderate for ADHD-H. Sensitivity analyses show robustness of the analysis, and no outliers were detected. No publication bias was evident. Conclusion: This is the first study that uses a meta-analytic approach to investigate the relationship between the different presentations of ADHD separately. These findings provide first evidence of lesser pronounced impairment in DM for ADHD-I and ADHD-I compared to ADHD-C. While the exact factors remain elusive, the current study can be considered as a starting point to reveal the relationship of ADHD presentations and DM more detailed

The Acquisition of Physical Knowledge in Generative Neural Networks

As children grow older, they develop an intuitive understanding of the physical processes around them. Their physical understanding develops in stages, moving along developmental trajectories which have been mapped out extensively in previous empirical research. Here, we investigate how the learning trajectories of deep generative neural networks compare to children's developmental trajectories using physical understanding as a testbed. We outline an approach that allows us to examine two distinct hypotheses of human development - stochastic optimization and complexity increase. We find that while our models are able to accurately predict a number of physical processes, their learning trajectories under both hypotheses do not follow the developmental trajectories of children.Comment: Published as a conference paper at ICML 202

In-situ characterization of tool temperatures using in-tool integrated thermoresistive thin-film sensors

Metal cutting is characterized by high temperatures at the tool-workpiece interface. Although valuable information could be provided by the temperature values, their direct measurement still presents a challenge due to the high contact pressure and the inaccessibility of the process kinematic. In this research work, the current state of thin-film sensors for measuring temperatures on the chip-tool interface has been analyzed with a focus on the measuring phenomena: thermoelectricity and thermoresistivity. Thin-film sensors placed on the cutting tools in or close to the tool-chip contact area are expected to obtain accurate temperature information at the expense of a short lifetime. New insights into thin-film sensors manufacturing, design and calibration are presented, and a new concept of a three-point thermoresistive thin-film sensor is proposed. During orthogonal cutting tests the workpiece deformations were measured through high-speed imaging and the process temperatures were measured with thin-film sensors. In order to validate the temperatures and to obtain the temperature distribution on the cutting edge, Finite Element simulations were carried out. Finally, the potential of using cutting tools with integrated thin-film sensors for in-situ characterization is investigated and a statement for its limitations and potential applications is given

Bio-energy retains its mitigation potential under elevated CO2

Background If biofuels are to be a viable substitute for fossil fuels, it is essential that they retain their potential to mitigate climate change under future atmospheric conditions. Elevated atmospheric CO2 concentration [CO2] stimulates plant biomass production; however, the beneficial effects of increased production may be offset by higher energy costs in crop management. Methodology/Main findings We maintained full size poplar short rotation coppice (SRC) systems under both current ambient and future elevated [CO2] (550 ppm) and estimated their net energy and greenhouse gas balance. We show that a poplar SRC system is energy efficient and produces more energy than required for coppice management. Even more, elevated [CO2] will increase the net energy production and greenhouse gas balance of a SRC system with 18%. Managing the trees in shorter rotation cycles (i.e. 2 year cycles instead of 3 year cycles) will further enhance the benefits from elevated [CO2] on both the net energy and greenhouse gas balance. Conclusions/significance Adapting coppice management to the future atmospheric [CO2] is necessary to fully benefit from the climate mitigation potential of bio-energy systems. Further, a future increase in potential biomass production due to elevated [CO2] outweighs the increased production costs resulting in a northward extension of the area where SRC is greenhouse gas neutral. Currently, the main part of the European terrestrial carbon sink is found in forest biomass and attributed to harvesting less than the annual growth in wood. Because SRC is intensively managed, with a higher turnover in wood production than conventional forest, northward expansion of SRC is likely to erode the European terrestrial carbon sink

An epigenome-wide association study in whole blood of measures of adiposity among Ghanaians: the RODAM study.

BACKGROUND: Epigenome-wide association studies (EWAS) have identified DNA methylation loci involved in adiposity. However, EWAS on adiposity in sub-Saharan Africans are lacking despite the high burden of adiposity among African populations. We undertook an EWAS for anthropometric indices of adiposity among Ghanaians aiming to identify DNA methylation loci that are significantly associated. METHODS: The Illumina 450k DNA methylation array was used to profile DNA methylation in whole blood samples of 547 Ghanaians from the Research on Obesity and Diabetes among African Migrants (RODAM) study. Differentially methylated positions (DMPs) and differentially methylation regions (DMRs) were identified for BMI and obesity (BMI ≥ 30 kg/m2), as well as for waist circumference (WC) and abdominal obesity (WC ≥ 102 cm in men, ≥88 cm in women). All analyses were adjusted for age, sex, blood cell distribution estimates, technical covariates, recruitment site and population stratification. We also did a replication study of previously reported EWAS loci for anthropometric indices in other populations. RESULTS: We identified 18 DMPs for BMI and 23 for WC. For obesity and abdominal obesity, we identified three and one DMP, respectively. Fourteen DMPs overlapped between BMI and WC. DMP cg00574958 annotated to gene CPT1A was the only DMP associated with all outcomes analysed, attributing to 6.1 and 5.6% of variance in obesity and abdominal obesity, respectively. DMP cg07839457 (NLRC5) and cg20399616 (BCAT1) were significantly associated with BMI, obesity and with WC and had not been reported by previous EWAS on adiposity. CONCLUSIONS: This first EWAS for adiposity in Africans identified three epigenome-wide significant loci (CPT1A, NLRC5 and BCAT1) for both general adiposity and abdominal adiposity. The findings are a first step in understanding the role of DNA methylation in adiposity among sub-Saharan Africans. Studies on other sub-Saharan African populations as well as translational studies are needed to determine the role of these DNA methylation variants in the high burden of adiposity among sub-Saharan Africans

Reduced Skin Blistering in Experimental Epidermolysis Bullosa Acquisita After Anti-TNF Treatment

Epidermolysis bullosa acquisita (EBA) is a difficult-to-treat subepidermal autoimmune blistering skin disease (AIBD) with circulating and tissue-bound anti-type VII collagen antibodies. Different reports have indicated increased concentration of tumor necrosis factor a (TNF) in the serum and blister fluid of patients with subepidermal AIBD. Furthermore, successful anti-TNF treatment has been reported for individual patients with AIBD. Here we show that in mice, induction of experimental EBA by repeated injections of rabbit anti-mouse type VII collagen antibodies led to increased expression of TNF in skin, as determined by real-time polymerase chain reaction (PCR) and immunohistochemistry. To investigate whether the increased TNF expression is of functional relevance in experimental EBA, we inhibited TNF function using the soluble TNF receptor fusion protein etanercept (Enbrel) or a monoclonal antibody to murine TNF. Interestingly, mice that received either of these treatments showed significantly milder disease progression than controls. In addition, immunohistochemical staining demonstrated reduced numbers of macrophages in lesional skin in mice treated with TNF inhibitors compared with controls. Furthermore, etanercept treatment significantly reduced disease progression in immunization-induced EBA. In conclusion, increased expression of TNF in experimental EBA is of functional relevance, as both the prophylactic blockade of TNF and the therapeutic use of etanercept impaired induction and progression of experimental EBA. Thus, TNF is likely to serve as a new therapeutic target for EBA and AIBDs with a similar pathogenesis

PI(18:1/18:1) is a SCD1-derived lipokine that limits stress signaling

Cytotoxic stress activates stress-activated kinases, initiates adaptive mechanisms, including the unfolded protein response (UPR) and autophagy, and induces programmed cell death. Fatty acid unsaturation, controlled by stearoyl-CoA desaturase (SCD)1, prevents cytotoxic stress but the mechanisms are diffuse. Here, we show that 1,2-dioleoyl-sn-glycero-3-phospho-(1’-myo-inositol) [PI(18:1/18:1)] is a SCD1-derived signaling lipid, which inhibits p38 mitogen-activated protein kinase activation, counteracts UPR, endoplasmic reticulum-associated protein degradation, and apoptosis, regulates autophagy, and maintains cell morphology and proliferation. SCD1 expression and the cellular PI(18:1/18:1) proportion decrease during the onset of cell death, thereby repressing protein phosphatase 2 A and enhancing stress signaling. This counter-regulation applies to mechanistically diverse death-inducing conditions and is found in multiple human and mouse cell lines and tissues of Scd1-defective mice. PI(18:1/18:1) ratios reflect stress tolerance in tumorigenesis, chemoresistance, infection, high-fat diet, and immune aging. Together, PI(18:1/18:1) is a lipokine that links fatty acid unsaturation with stress responses, and its depletion evokes stress signaling

Premorbid body weight predicts weight loss in both anorexia nervosa and atypical anorexia nervosa: Further support for a single underlying disorder.

OBJECTIVE For adolescents, DSM-5 differentiates anorexia nervosa (AN) and atypical AN with the 5th BMI-centile-for-age. We hypothesized that the diagnostic weight cut-off yields (i) lower weight loss in atypical AN and (ii) discrepant premorbid BMI distributions between the two disorders. Prior studies demonstrate that premorbid BMI predicts admission BMI and weight loss in patients with AN. We explore these relationships in atypical AN. METHOD Based on admission BMI-centile < or ≥5th, participants included 411 female adolescent inpatients with AN and 49 with atypical AN from our registry study. Regression analysis and t-tests statistically addressed our hypotheses and exploratory correlation analyses compared interrelationships between weight loss, admission BMI, and premorbid BMI in both disorders. RESULTS Weight loss in atypical AN was 5.6 kg lower than in AN upon adjustment for admission age, admission height, premorbid weight and duration of illness. Premorbid BMI-standard deviation scores differed by almost one between both disorders. Premorbid BMI and weight loss were strongly correlated in both AN and atypical AN. DISCUSSION Whereas the weight cut-off induces discrepancies in premorbid weight and adjusted weight loss, AN and atypical AN overall share strong weight-specific interrelationships that merit etiological consideration. Epidemiological and genetic associations between AN and low body weight may reflect a skewed premorbid BMI distribution. In combination with prior findings for similar psychological and medical characteristics in AN and atypical AN, our findings support a homogenous illness conceptualization. We propose that diagnostic subcategorization based on premorbid BMI, rather than admission BMI, may improve clinical validity. PUBLIC SIGNIFICANCE Because body weights of patients with AN must drop below the 5th BMI-centile per DSM-5, they will inherently require greater weight loss than their counterparts with atypical AN of the same sex, age, height and premorbid weight. Indeed, patients with atypical AN had a 5.6 kg lower weight loss after controlling for these variables. In comparison to the reference population, we found a lower and higher mean premorbid weight in patients with AN and atypical AN, respectively. Considering previous psychological and medical comparisons showing little differences between AN and atypical AN, we view a single disorder as the most parsimonious explanation. Etiological models need to particularly account for the strong relationship between weight loss and premorbid body weight