The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

Longitudinal clinical and biomarker characteristics of non-manifesting LRRK2 G2019S carriers in the PPMI cohort

We examined 2-year longitudinal change in clinical features and biomarkers in LRRK2 non-manifesting carriers (NMCs) versus healthy controls (HCs) enrolled in the Parkinson’s Progression Markers Initiative (PPMI). We analyzed 2-year longitudinal data from 176 LRRK2 G2019S NMCs and 185 HCs. All participants were assessed annually with comprehensive motor and non-motor scales, dopamine transporter (DAT) imaging, and biofluid biomarkers. The latter included cerebrospinal fluid (CSF) Abeta, total tau and phospho-tau; serum urate and neurofilament light chain (NfL); and urine bis(monoacylglycerol) phosphate (BMP). At baseline, LRRK2 G2019S NMCs had a mean (SD) age of 62 (7.7) years and were 56% female. 13% had DAT deficit (defined as <65% of age/sex-expected lowest putamen SBR) and 11% had hyposmia (defined as ≤15th percentile for age and sex). Only 5 of 176 LRRK2 NMCs developed PD during follow-up. Although NMCs scored significantly worse on numerous clinical scales at baseline than HCs, there was no longitudinal change in any clinical measures over 2 years or in DAT binding. There were no longitudinal differences in CSF and serum biomarkers between NMCs and HCs. Urinary BMP was significantly elevated in NMCs at all time points but did not change longitudinally. Neither baseline biofluid biomarkers nor the presence of DAT deficit correlated with 2-year change in clinical outcomes. We observed no significant 2-year longitudinal change in clinical or biomarker measures in LRRK2 G2019S NMCs in this large, well-characterized cohort even in the participants with baseline DAT deficit. These findings highlight the essential need for further enrichment biomarker discovery in addition to DAT deficit and longer follow-up to enable the selection of NMCs at the highest risk for conversion to enable future prevention clinical trials

The Guiding Principles in international human rights courts

The Guiding Principles have potential to support and complement international human rights law on internal displacement but they have had little explicit consideration by international and regional human rights courts and commissions

Information and reputation mechanisms in auctions of remanufactured goods

We investigate how feedback scores and alternative reputation mechanisms can mitigate asymmetric information in auctions of second-hand electronic items. In contrast to previous studies, we exploit the information available across heterogeneous goods and avoid the problems caused by different degrees of wear and tear by studying remanufactured products. We find the presence of relevant scale effects in the value of such reputation mechanisms that become complements or substitutes depending on the value of the transactions. Feedback scores are not valuable when alternative contractual devices are in place, such as refurbishment by a manufacturer-approved vendor and the availability of return policies. However, when we partition the sample according to the value of the auctions, feedback scores become effective for cheap items, whereas return policies are important for expensive goods

Diode-pumped femtosecond oscillators using ultra-broad-band Yb-doped crystals and modelocked using low-temperature grown or ion implanted saturable-absorber mirrors

Femtosecond modelocked lasers using new ytterbium-doped borate crystals (Yb:Sr3Y(BO3)(3), Yb: Ca4GdO(BO3)(3) and Yb: Ca4YO(BO3)(3)) are demonstrated. Pulse duration as short as 69 fs has been obtained. To modelock such lasers, fast saturable absorbers need to be used. Two different types of fast saturable absorbers have been studied: low-temperature-grown semiconductor mirrors ( SESAM) and high-energy-ion-implanted semiconductor Bragg reflectors (SBR). We demonstrated, for the. first time to our knowledge, that ion-implanted SBR can be used to modelock oscillators using Yb-doped materials

Temperament and behaviour problems in children : A multilevel analysis of cross-cultural differences

Early temperament attributes have been linked to emerging behaviour problems and significant long-term consequences; however, these relations are rarely examined cross-culturally. The present study addresses this gap, employing multilevel modelling to explain within- and between-culture variances with respect to temperament predicting a spectrum of behaviour problems across 14 nations from the Joint Effort Toddler Temperament Consortium (JETTC). A total of 865 children between 17 and 40 months, with approximately equal age distribution across this developmental period and about equivalent representation of genders, were recruited from 14 nations. Greater negative emotionality was associated with more internalizing problems, whereas higher surgency and effortful control predicted fewer internalizing difficulties. Controlling for age and gender, temperament explained significant within- and between-culture variances in internalizing and externalizing problems (at the broad-band and fine-grained levels), as well as sleep problems. For internalizing difficulties, temperament accounted for more between-culture variance. In contrast, for externalizing difficulties, temperament accounted more for how individuals within the same culture differed from their same-culture counterparts. The within-culture findings suggest universal patterns of temperament-problem relations, informing cultural adaptation of interventions; between-culture findings enhance understanding of the implications of the cultural niche for normative behaviour and adjustment.Peer reviewe

Parental Attachment Dimensions and Parenting Stress: The Mediating Role of Parental Reflective Functioning

Research suggests that parental reflective functioning—the parent’s capacity to envision the mind of his/her child—may play an important role in the intergenerational transmission of attachment and reflective functioning. Studies also suggest the importance of this capacity for the transition to parenthood, and particularly parents’ capacity to deal with parenting stress. This study focused on the potential mediating role of PRF dimensions in the relationship between parental attachment dimensions (attachment anxiety and avoidance) and parenting stress, using data from a 1-year longitudinal study in biological first-time parents (N = 106). Structural equation modeling showed that parents’ use of prementalizing modes of reflecting upon their child (PM) fully mediated the relationship between attachment anxiety and three parenting stress dimensions (marital relationship, role restriction, and social isolation) across a 1-year interval, while attachment avoidance was indirectly related to these parenting stress dimensions through PM. Further, PM partially mediated the relationship between parental attachment anxiety and avoidance and a fourth dimension of parenting stress, lack of trust in parental competence. In addition, multi-group analyses revealed some interesting gender differences. Implications of these findings for the conceptualization of the relationship between parental attachment, PRF, and parenting stress are discussed