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A 12-year-old boy currently is followed by multiple sub-specialists for problems caused by the chromosome 22q11.2 deletion syndrome (22q11DS) (Figure). He was born via spontaneous vaginal delivery, weighing 3033 g, to a 31-year-old G3P3 mother after a full-term pregnancy complicated only by mild polyhydramnios. Family history was non-contributory. Apgar scores were 8 at 1 minute and 9 at 5 minutes. With the exception of a weak cry, the results of the infant’s initial examination were unremarkable, and he was moved to the well-baby nursery. Shortly thereafter, a cardiac murmur was noted, the cardiology department was consulted, and the child was transferred to a local tertiary care facility with a diagnosis of tetralogy of Fallot. Stable, he was discharged home at 3 days of life. Figure Mild dysmorphic facial features of a boy aged 11 years with 22q11.2DS, including a short forehead, hooded eyelids with upslanting palpebral fissures, malar flatness, bulbous nasal tip with hypoplastic alae nasi, and protuberant ears. At 5 days of life, he had jerky movements. On presentation to the local emergency department, his total calcium level was 4.7 mg/dL, and later partial hypoparathyroidism was diagnosed. At that time, a consulting geneticist suggested the diagnosis of chromosome 22q11DS. Weeks later, the family received a telephone call confirming the diagnosis with fluorescence in situ hybridization (FISH). No additional information about the diagnosis, prognosis, etiology, or recurrence risk was provided until the child was 5 months of age, when he underwent cardiac repair at a third hospital, where a comprehensive 22q11DS program was in operation. In the interim, the child had feeding difficulties requiring supplemental nasogastric tube feeds, nasal regurgitation, and gastroesophageal reflux, while the parents searched the internet for reliable information about their son’s diagnosis. Subsequent notable abnormalities and interventions included: recurrent otitis media with bilateral myringotomy tube placement at 6 months; angioplasty with left pulmonary artery stent placement after the identification of pulmonary artery stenosis with bilateral pleural effusions at age 6 years; chronic upper respiratory infections with significant T cell dysfunction requiring live viral vaccines to be held until age 7 years; velopharyngeal incompetence necessitating posterior pharyngeal flap surgery at 7 years; enamel hypoplasia and numerous caries resulting in 3 separate dental procedures under general cardiac anesthesia beginning at age 7 years; multiple cervical and thoracic vertebral anomalies with thoracic levoconvex scoliosis and upper lumbar dextroscoliosis requiring growing rod placement at age 11 years with subsequent rod extension at ages 11.5 and 12 years; postoperative hypocalcemia; short stature; constipation; and persistent idiopathic thrombocytopenia. Pertinent negative test results included normal renal ultrasound scanning and parental 22q11.2 deletion studies. On physical examination, the boy’s height and weight have consistently tracked just below the fifth percentile, with no evidence of growth hormone deficiency. His head circumference is within reference range at the 25th percentile. Dysmorphic features include: a low anterior hairline; hooded eyelids; malar flatness; normally formed but protuberant ears with attached lobes; a mildly deviated nose with a bulbous nasal tip and hypoplastic alae nasi; asymmetric crying facies with a thin upper lip; mild micrognathia; a sacral dimple; and soft tissue syndactyly of the second and third toes. Developmentally, the boy had mild delays in achieving motor milestones, sitting at 11 months and walking at 18 months. However, he exhibited significant delays in the emergence of language: he never babbled, spoke his first words at age 3 years, and only achieved full conversational speech at 7 years. However, he had relative strengths in receptive language and communicated appropriately by the use of sign language. Now quite conversant, he is mainstreamed in the seventh grade with resource room supports. Moreover, he is affable, but exhibits anxiety and perseverations. Lastly, despite numerous medical, academic, and social challenges, he participates in assisted athletics, is an avid wrestling fan, and enjoys travel. However, his exceptionally supportive parents, siblings, and extended family continue to worry about his long-term outcome and transition of care as he approaches adulthood. As demonstrated by this boy’s complicated course, practical multi-system guidelines are needed to assist the general practitioner and specialists in caring for patients with 22q11DS. Although still under-recognized, detection, including in the prenatal setting, is increasing. Moreover, the phenotypic spectrum is highly variable, and patients may present at any age. Thus, initial guidelines developed by an international panel of experts present the best practice recommendations currently available across the lifespan, with a major focus on the changing issues through childhood development.

We present the results of the first ice sheet model intercomparison project for higher-order and full Stokes ice sheet models. These models are validated in a series of six benchmark experiments of which one has an analytical solution under simplifying assumptions. Five of the tests are diagnostic and one experiment is prognostic or time dependent, for both 2-D and 3-D geometries. The results show a good convergence of the different models even for high aspect ratios. A clear distinction can be made between higher-order models and those that solve the full system of equations. The latter show a significantly better agreement with each other as well as with analytical solutions, which demonstrates that they are hardly influenced by the used numerics.

The main objective of AMICS (Antarctic ice-sheet dynamics and climatic change: Modelling and Ice Composition Studies) is to contribute to the international research effort leading to an improved understanding of the dynamic behaviour of the Antarctic ice sheet resulting from climatic change, through a better knowledge of the internal ice dynamics and the ice sheet’s interactions with the subglacial environment. To clarify the dynamic interactions between the ice sheet and the subglacial environment a new thermomechanical ice-sheet model was developed, including higher-order stress gradients. Such a model is capable of properly simulating the ice flow in areas characterized by complex basal interaction (ice streams, subglacial lakes, ...). As a contribution to the EPICA project, the model is imbedded in a large-scale model of the Antarctic ice sheet to determine the chronology and the origin of the ice within the EPICA DML ice core. A comprehensive effort to improve our understanding of the physical processes at the interface between a frozen lake and a cold-based glacier explained the complex formation of the lake ice cover. It showed how sediments become trapped in lake ice and how this lake has contributed to the formation of the basal ice layer of the adjacent damming glacier. Moreover, an isotopic model has been elaborated for basal freeze-on associated with subglacial upward flow of pore water and tested against two Antarctic outlet glaciers by studying the dD-d18O relationships in the basal ice layers of these glaciers. Investigation of the isotopic composition of the deepest part of the Vostok ice core shows the build-up of a highly deformed basal ice layer. Therefore, Lake Vostok’s behaviour has been reassessed from new and existing ice core data. In view of these results, the higher-order model was applied to the area surrounding subglacial Lake Vostok. This showed for the first time that the surface flattening and turning of the ice flow across the lake are a direct consequence of the lack of friction at the ice-water interface, and that subglacial lakes can be at the origin of enhanced ice flow and the onset of continental ice streams. A detailed numerical investigation of such streams demonstrated that a large variability in glacier response can be expected when interaction with subglacial water flow is considered. Speedup and slowdown of such large flow features may be a result of ice piracy of neighboring streams. The AMICS project has demonstrated that basal processes play an important - if not crucial - role in the ice flow of the vast interior of the ice sheet, a zone which was previously thought of being unconditionally stable. Subglacial interactions determine the onset of fast-flowing areas such as ice streams, which has its consequence for the stability of the Antarctic ice sheet with changing climate.

Arithmetic is an essential skill for further mathematical and educational development, and comprises a large part of our daily lives. Even tough, over the past few years, an increase in both functional and structural developmental neuroscientific research on mathematical cognition and arithmetic has occurred, a lot is still not fully understood. This doctoral dissertation aimed to further identify which brain regions are important for typically developing children's arithmetic fluency. Neuroimaging work in adults has shown that strategy use (i.e., fact retrieval vs. procedures) modulates the arithmetic brain network, however, this was never clearly studied in children. A first fMRI study investigated children's neural activation associated with the use of these strategies in subtraction and multiplication, and observed distinct neural networks associated with each strategy, but no differences between operations when taking strategy into account. Next, within children's multiplication fact retrieval, performance can be influenced by various effects, such as the problem size and interference effect, as evidenced by behavioral research. A second fMRI study investigated the neural basis of both effects, and, concurring with previous studies, revealed clear behavioral effects of problem size and interference, but at the neural level, only a clear effect of problem size. The interference effect was not detected; no clear neural distinctions were observed between low and high interfering items. Other than its functionality, the structure of grey matter regions has also been associated to cognitive skills. Accordingly, a third study investigated the structural grey matter correlates of children's arithmetic fluency, by looking at both volume and cortical complexity, and observed associations with various cortical grey matter structures. Furthermore, as the grey matter regions of the arithmetic brain network are spatially distant, it is also crucial to study the structural white matter connections between these regions. In a fourth study, the white matter integrity of previously observed arithmetic-related white matter pathways was correlated to children's arithmetic fluency, implementing spherical deconvolution, a novel non-tensor method which goes beyond classic DTI to tackle its methodological constraints. Clear associations were observed between the right inferior longitudinal fasciculus and arithmetic. Finally, a fifth study investigated the added value of the collected structural brain imaging data on top of well-known behavioral measures in predicting individual differences in the children's arithmetic fluency, and revealed that the neuro-anatomical measures provided the best prediction of performance, highlighting the value of brain imaging measures for the prediction of cognitive skills and striving towards a bridge between cognitive neuroscience and education. In all, the combination of both functional and structural neuroimaging in these studies has led to results which further expand our understanding of the neural substrates of children's arithmetic fluency. status: published