Intelligence quotient in paediatric sickle cell disease: a systematic review and meta-analysis

AIM: Sickle cell disease (SCD) is the commonest cause of childhood stroke worldwide. Magnetic resonance imaging (MRI) is routinely used to detect additional silent cerebral infarction (SCI), as IQ is lower in SCI as well as stroke. This review assesses the effect of infarction on IQ, and specifically whether, compared to healthy controls, IQ differences are seen in children with SCI with no apparent MRI abnormality. METHOD: A systematic review was conducted to include articles with an SCD paediatric population, MRI information, and Wechsler IQ. A meta-analysis of 19 articles was performed to compare IQ in three groups: stroke vs SCI; SCI vs no SCI; and no SCI vs healthy controls. RESULTS: Mean differences in IQ between all three groups were significant: stroke patients had lower IQ than patients with SCI by 10 points (six studies); patients with SCI had lower IQ than no patients with SCI by 6 points (17 studies); and no patients with SCI had lower IQ than healthy controls by 7 points (seven studies). INTERPRETATION: Children with SCD and no apparent MRI abnormality have significantly lower IQ than healthy controls. In this chronic condition, other biological, socioeconomic, and environmental factors must play a significant role in cognition

Past water flow beneath Pine Island and Thwaites glaciers, West Antarctica

Abstract. Outburst floods from subglacial lakes beneath the Antarctic Ice Sheet modulate ice-flow velocities over periods of months to years. Although subglacial lake drainage events have been observed from satellite-altimetric data, little is known about their role in the long-term evolution of ice-sheet basal hydrology. Here, we systematically map and model past water flow through an extensive area containing over 1000 subglacial channels and 19 former lake basins exposed on over 19 000 km2 of seafloor by the retreat of Pine Island and Thwaites glaciers, West Antarctica. At 507 m wide and 43 m deep on average, the channels offshore of present-day Pine Island and Thwaites glaciers are approximately twice as deep, 3 times as wide, and cover an area over 400 times larger than the terrestrial meltwater channels comprising the Labyrinth in the Antarctic Dry Valleys. The channels incised into bedrock offshore of contemporary Pine Island and Thwaites glaciers would have been capable of accommodating discharges of up to 8.8×106 m3 s−1. We suggest that the channels were formed by episodic discharges from subglacial lakes trapped during ice-sheet advance and retreat over multiple glacial periods. Our results document the widespread influence of episodic subglacial drainage events during past glacial periods, in particular beneath large ice streams similar to those that continue to dominate contemporary ice-sheet discharge. UK Natural Environment Research Council’s iSTAR programme (grant nos. NE/J005703/1, NE/J005746/1, and NE/J005770/1). James D. Kirkham: Debenham Scholarship from the Scott Polar Research Institute, University of Cambridge, and a UK Natural Environment Research Council Ph.D. studentship awarded through the Cambridge Earth System Science Doctoral Training Partnership (grant no. NE/L002507/1

Revealing the former bed of Thwaites Glacier using sea-floor bathymetry: Implications for warm-water routing and bed controls on ice flow and buttressing

Abstract. The geometry of the sea floor immediately beyond Antarctica's marine-terminating glaciers is a fundamental control on warm-water routing, but it also describes former topographic pinning points that have been important for ice-shelf buttressing. Unfortunately, this information is often lacking due to the inaccessibility of these areas for survey, leading to modelled or interpolated bathymetries being used as boundary conditions in numerical modelling simulations. At Thwaites Glacier (TG) this critical data gap was addressed in 2019 during the first cruise of the International Thwaites Glacier Collaboration (ITGC) project. We present more than 2000 km2 of new multibeam echo-sounder (MBES) data acquired in exceptional sea-ice conditions immediately offshore TG, and we update existing bathymetric compilations. The cross-sectional areas of sea-floor troughs are under-predicted by up to 40 % or are not resolved at all where MBES data are missing, suggesting that calculations of trough capacity, and thus oceanic heat flux, may be significantly underestimated. Spatial variations in the morphology of topographic highs, known to be former pinning points for the floating ice shelf of TG, indicate differences in bed composition that are supported by landform evidence. We discuss links to ice dynamics for an overriding ice mass including a potential positive feedback mechanism where erosion of soft erodible highs may lead to ice-shelf ungrounding even with little or no ice thinning. Analyses of bed roughnesses and basal drag contributions show that the sea-floor bathymetry in front of TG is an analogue for extant bed areas. Ice flow over the sea-floor troughs and ridges would have been affected by similarly high basal drag to that acting at the grounding zone today. We conclude that more can certainly be gleaned from these 3D bathymetric datasets regarding the likely spatial variability of bed roughness and bed composition types underneath TG. This work also addresses the requirements of recent numerical ice-sheet and ocean modelling studies that have recognised the need for accurate and high-resolution bathymetry to determine warm-water routing to the grounding zone and, ultimately, for predicting glacier retreat behaviour. </jats:p

Raman spectroscopy and advanced mathematical modelling in the discrimination of human thyroid cell lines

Raman spectroscopy could offer non-invasive, rapid and an objective nature to cancer diagnostics. However, much work in this field has focused on resolving differences between cancerous and non-cancerous tissues, and lacks the reproducibility and interpretation to be put into clinical practice. Much work is needed on basic cellular differences between malignancy and normal. This would allow the establishment of a clinically relevant cellular based model to translate to tissue classification. Raman spectroscopy provides a very detailed biochemical analysis of the target material and to 'unlock' this potential requires sophisticated mathematical modelling such as neural networks as an adjunct to data interpretation. Commercially obtained cancerous and non-cancerous cells, cultured in the laboratory were used in Raman spectral measurements. Data trends were visualised through PCA and then subjected to neural network analysis based on self-organising maps; consisting of m maps, where m is the number of classes to be recognised. Each map approximates the statistical distribution of a given class. The neural network analysis provided a 95% accuracy for identification of the cancerous cell line and 92% accuracy for normal cell line. In this preliminay study we have demonstrated th ability to distinguish between "normal" and cancerous commercial cell lines. This encourages future work to establish the reasons underpinning these spectral differences and to move forward to more complex systems involving tissues. We have also shown that the use of sophisticated mathematical modelling allows a high degree of discrimination of 'raw' spectral data

Clathrin and LRP-1-Independent Constitutive Endocytosis and Recycling of uPAR

Background: The urokinase receptor (uPAR/CD87) is highly expressed in malignant tumours. uPAR, as a GPI anchored protein, is preferentially located at the cell surface, where it interacts with its ligands urokinase (uPA) and the extracellular matrix protein vitronectin, thus promoting plasmin generation, cell-matrix interactions and intracellular signalling events. Interaction with a complex formed by uPA and its inhibitor PAI-1 induces cell surface down regulation and recycling of the receptor via the clathrin-coated pathway, a process dependent on the association to LRP-1. Methodology/Principal Findings: In this study, we have found that along with the ligand-induced down-regulation, uPAR also internalizes and recycles constitutively through a second pathway that is independent of LRP-1 and clathrin but shares some properties with macropinocytosis. The ligand-independent route is amiloride-sensitive, does not require uPAR partitioning into lipid rafts, is independent of the activity of small GTPases RhoA, Rac1 and Cdc42, and does not require PI3K activity. Constitutively endocytosed uPAR is found in EEA1 positive early/recycling endosomes but does not reach lysosomes in the absence of ligands. Electron microscopy analysis reveals the presence of uPAR in ruffling domains at the cell surface, in macropinosome-like vesicles and in endosomal compartments. Conclusions/Significance: These results indicate that, in addition to the ligand-induced endocytosis of uPAR, efficient surface expression and membrane trafficking might also be driven by an uncommon macropinocytic mechanism couple

An exploration of influences on women’s birthplace decision-making in New Zealand: a mixed methods prospective cohort within the Evaluating Maternity Units study

BACKGROUND: There is worldwide debate surrounding the safety and appropriateness of different birthplaces for well women. One of the primary objectives of the Evaluating Maternity Units prospective cohort study was to compare the clinical outcomes for well women, intending to give birth in either an obstetric-led tertiary hospital or a free-standing midwifery-led primary maternity unit. This paper addresses a secondary aim of the study – to describe and explore the influences on women’s birthplace decision-making in New Zealand, which has a publicly funded, midwifery-led continuity of care maternity system. METHODS: This mixed method study utilised data from the six week postpartum survey and focus groups undertaken in the Christchurch area in New Zealand (2010–2012). Christchurch has a tertiary hospital and four primary maternity units. The survey was completed by 82% of the 702 study participants, who were well, pregnant women booked to give birth in one of these places. All women received midwifery-led continuity of care, regardless of their intended or actual birthplace. RESULTS: Almost all the respondents perceived themselves as the main birthplace decision-makers. Accessing a ‘specialist facility’ was the most important factor for the tertiary hospital group. The primary unit group identified several factors, including ‘closeness to home’, ‘ease of access’, the ‘atmosphere’ of the unit and avoidance of ‘unnecessary intervention’ as important. Both groups believed their chosen birthplace was the right and ‘safe’ place for them. The concept of ‘safety’ was integral and based on the participants’ differing perception of safety in childbirth. CONCLUSIONS: Birthplace is a profoundly important aspect of women’s experience of childbirth. This is the first published study reporting New Zealand women’s perspectives on their birthplace decision-making. The groups’ responses expressed different ideologies about childbirth. The tertiary hospital group identified with the ‘medical model’ of birth, and the primary unit group identified with the ‘midwifery model’ of birth. Research evidence affirming the ‘clinical safety’ of primary units addresses only one aspect of the beliefs influencing women’s birthplace decision-making. In order for more women to give birth at a primary unit other aspects of women’s beliefs need addressing, and much wider socio-political change is required

A role for the cell-wall protein silacidin in cell size of the diatom Thalassiosira pseudonana

Diatoms contribute 20% of global primary production and form the basis of many marine food webs. Although their species diversity correlates with broad diversity in cell size, there is also an intraspecific cell-size plasticity due to sexual reproduction and varying environmental conditions. However, despite the ecological significance of the diatom cell size for food-web structure and global biogeochemical cycles, our knowledge about genes underpinning the size of diatom cells remains elusive. Here, a combination of reverse genetics, experimental evolution and comparative RNA8 sequencing analyses enabled us to identify a previously unknown genetic control of cell size in the diatom Thalassiosira pseudonana. In particular, the targeted deregulation of the expression of the cell-wall protein silacidin caused a significant increase in valve diameter. Remarkably, the natural downregulation of the silacidin gene transcript due to experimental evolution under low temperature also correlated with cell-size increase. Our data give first evidence for a genetically controlled regulation of cell size in Thalassiosira pseudonana and possibly other centric diatoms as they also encode the silacidin gene in their genomes

Decreased Reward Sensitivity in Rats from the Fischer344 Strain Compared to Wistar Rats Is Paralleled by Differences in Endocannabinoid Signaling

BACKGROUND: The aim of the present study was to examine if differences in the endocannabinoid (ECB) system might be linked to strain specific variations in reward-related behavior in Fischer344 (Fischer) and Wistar rats. METHODOLOGY/PRINCIPAL FINDINGS: Two rat strains, the Fischer and the Wistar strain, were tested for different aspects of reward sensitivity for a palatable food reward (sweetened condensed milk, SCM) in a limited-access intake test, a progressive ratio (PR) schedule and the pleasure-attenuated startle (PAS) paradigm. Additionally, basic differences in the ECB system and cannabinoid pharmacology were examined in both rat strains. Fischer rats were found to express lower reward sensitivity towards SCM compared to Wistar rats. These differences were observed for consummatory, motivational and hedonic aspects of the palatable food reward. Western blot analysis for the CB1 receptor and the ECB degrading enzyme fatty acid amide hydrolase (FAAH) revealed a lower expression of both proteins in the hippocampus (HPC) of Fischer rats compared to the Wistar strain. Furthermore, increased cannabinoid-stimulated extracellular-regulated kinase (ERK) phosphorylation was detected in Wistar rats compared to the Fischer strain, indicating alterations in ECB signaling. These findings were further supported by the pharmacological results, where Fischer rats were found to be less sensitive towards the effects of the CB1 receptor antagonist/inverse agonist SR141716 and the cannabinoid agonist WIN 55,212-2. CONCLUSIONS/SIGNIFICANCE: Our present findings indicate differences in the expression of the CB1 receptor and FAAH, as well as the activation of ECB signaling pathways between Fischer and Wistar rats. These basic differences in the ECB system might contribute to the pronounced differences observed in reward sensitivity between both rat strains