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Reproducibility is a defining feature of science, but the extent to which it characterizes current research is unknown. We conducted replications of 100 experimental and correlational studies published in three psychology journals using high-powered designs and original materials when available. Replication effects were half the magnitude of original effects, representing a substantial decline. Ninety-seven percent of original studies had statistically significant results. Thirty-six percent of replications had statistically significant results; 47% of original effect sizes were in the 95% confidence interval of the replication effect size; 39% of effects were subjectively rated to have replicated the original result; and if no bias in original results is assumed, combining original and replication results left 68% with statistically significant effects. Correlational tests suggest that replication success was better predicted by the strength of original evidence than by characteristics of the original and replication teams.
The Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia
(2019)
The impact of many unfavorable childhood traits or diseases, such as low birth weight and mental disorders, is not limited to childhood and adolescence, as they are also associated with poor outcomes in adulthood, such as cardiovascular disease. Insight into the genetic etiology of childhood and adolescent traits and disorders may therefore provide new perspectives, not only on how to improve wellbeing during childhood, but also how to prevent later adverse outcomes. To achieve the sample sizes required for genetic research, the Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia were established. The majority of the participating cohorts are longitudinal population-based samples, but other cohorts with data on early childhood phenotypes are also involved. Cohorts often have a broad focus and collect(ed) data on various somatic and psychiatric traits as well as environmental factors. Genetic variants have been successfully identified for multiple traits, for example, birth weight, atopic dermatitis, childhood BMI, allergic sensitization, and pubertal growth. Furthermore, the results have shown that genetic factors also partly underlie the association with adult traits. As sample sizes are still increasing, it is expected that future analyses will identify additional variants. This, in combination with the development of innovative statistical methods, will provide detailed insight on the mechanisms underlying the transition from childhood to adult disorders. Both consortia welcome new collaborations. Policies and contact details are available from the corresponding authors of this manuscript and/or the consortium websites.
Two types of electrical conductivity sensors were evaluated to prospect circular ditches surrounding former Bronze Age burial mounds, complementing aerial photography. The first sensor was based on the electrical resistivity (ER) method, while the second sensor was based on frequency-domain electromagnetic induction (FDEM). Both sensors were designed with multiple receivers, which measure several depth sensitivities simultaneously. First, the sensors were tested on an experimental site where a rectangular structure with limited dimensions was dug in a sandy soil. The structure appeared as a higher conductivity anomaly in the low-conductivity sand. Then, both methods were applied on two Bronze Age sites with different soil properties, which were discovered by aerial photography. The first site, in a sandy soil, gave only very weak anomalies. Soil augering revealed that the ditch filling consisted of the same sandy material as the surrounding, therefore this filling was not able to cause a high-conductivity contrast. Due to its lower sensitivity to noise in the low-conductive range, the ER-sensor produced a more pronounced anomaly than the FDEM-sensor. The second site was located on top of a ridge with a shallow substrate of Tertiary, coastal sediments. The ditch was very clearly visible on the sensor maps as a conductive low. At this location, the soil augering revealed that the ditch was dug through an alternating clay-sand layer and subsequently filled up with silty material from the topsoil. Overall, the shallow receiver separation produced anomalies that were both stronger and that corresponded better to the geometry of the ditches. The other receiver separations provided more information on the natural soil layering, and in the case of the ER-array they could be used to obtain a cross-section of the actual electrical conductivity with 2-D inversion modelling. The results of this study proofed that conductivity sensors can detect Bronze Age ditches, with varying contrast depending on the soil geomorphology. Moreover, the sensor maps combined with soil observations by coring provided insight in the environmental conditions that influence the contrast of the anomalies seen on the aerial photographs and the sensor maps.
Magnetic susceptibility is an important indicator of anthropogenic disturbance in the natural soil. This property is often mapped with magnetic gradiometers in archaeological prospection studies. It is also detected with frequency domain electromagnetic induction (FDEM) sensors, which have the advantage that they can simultaneously measure the electrical conductivity. The detection level of FDEM sensors for magnetic structures is very dependent on the coil configuration. Apart from theoretical modelling studies, a thorough investigation with field models has not been conducted until now. Therefore, the goal of this study was to test multiple coil configurations on a test field with naturally enhanced magnetic susceptibility in the topsoil and with different types of structures mimicking real archaeological features. Two FDEM sensors were used with coil separations between 0.5 and 2 m and with three coil orientations. First, a vertical sounding was conducted over the undisturbed soil to test the validity of a theoretical layered model, which can be used to infer the depth sensitivity of the coil configurations. The modelled sounding values corresponded well with the measured data, which means that the theoretical models are applicable to layered soils. Second, magnetic structures were buried in the site and the resulting anomalies measured to a very high resolution. The results showed remarkable differences in amplitude and complexity between the responses of the coil configurations. The 2-m horizontal coplanar and 1.1-m perpendicular coil configurations produced the clearest anomalies and resembled best a gradiometer measurement.
A novel common variant in DCST2 is associated with length in early life and height in adulthood
(2015)
Common genetic variants have been identified for adult height, but not much is known about the genetics of skeletal growth in early life. To identify common genetic variants that influence fetal skeletal growth, we meta-analyzed 22 genome-wide association studies (Stage 1; N = 28 459). We identified seven independent top single nucleotide polymorphisms (SNPs) (P < 1 x 10(-6)) for birth length, of which three were novel and four were in or near loci known to be associated with adult height (LCORL, PTCH1, GPR126 and HMGA2). The three novel SNPs were followed-up in nine replication studies (Stage 2; N = 11 995), with rs905938 in DC-STAMP domain containing 2 (DCST2) genome-wide significantly associated with birth length in a joint analysis (Stages 1 + 2; beta = 0.046, SE = 0.008, P = 2.46 x 10(-8), explained variance = 0.05%). Rs905938 was also associated with infant length (N = 28 228; P = 5.54 x 10(-4)) and adult height (N = 127 513; P = 1.45 x 10(-5)). DCST2 is a DC-STAMP-like protein family member and DC-STAMP is an osteoclast cell-fusion regulator. Polygenic scores based on 180 SNPs previously associated with human adult stature explained 0.13% of variance in birth length. The same SNPs explained 2.95% of the variance of infant length. Of the 180 known adult height loci, 11 were genome-wide significantly associated with infant length (SF3B4, LCORL, SPAG17, C6orf173, PTCH1, GDF5, ZNFX1, HHIP, ACAN, HLA locus and HMGA2). This study highlights that common variation in DCST2 influences variation in early growth and adult height.
The mechanism of action of eprenetapopt (APR-246, PRIMA-1MET) as an anticancer agent remains unresolved, al-though the clinical development of eprenetapopt focuses on its reported mechanism of action as a mutant-p53 reactivator. Using unbiased approaches, this study demonstrates that eprenetapopt depletes cellular antioxidant glutathione levels by increasing its turnover, triggering a nonapoptotic, iron-dependent form of cell death known as ferroptosis. Deficiency in genes responsible for supplying cancer cells with the substrates for de novo glutathione synthesis (SLC7A11, SHMT2, and MTHFD1L), as well as the enzymes required to synthesize glutathione (GCLC and GCLM), augments the activity of eprenetapopt. Eprenetapopt also inhibits iron-sulfur cluster biogenesis by limit-ing the cysteine desulfurase activity of NFS1, which potentiates ferroptosis and may restrict cellular proliferation. The combination of eprenetapopt with dietary serine and glycine restriction synergizes to inhibit esophageal xenograft tumor growth. These findings reframe the canonical view of eprenetapopt from a mutant-p53 reactivator to a ferroptosis inducer.