Objectives Hereditary haemorrhagic telangiectasia (HHT) affects 1 in 5–8000 individuals. Pregnancy outcomes are rarely reported. The major reason is that most women do not have their HHT diagnosed ...prior to pregnancy. Using a large well‐characterised series, we studied all pregnancies known to have occurred in HHT‐affected women, whether or not their diagnosis was known at the time of pregnancy. Our aim was to estimate rates and types of major complications of HHT in pregnancy, to guide management decisions.
Design Cohort study, with prospective, retrospective and familial components.
Setting/Population Tertiary referral centre population.
Methods All 262 pregnancies in the 111 women with HHT and pulmonary arteriovenous malformations (PAVMs) reviewed between 1999 and 2005 were studied. Eighty‐two women (74%) did not have a diagnosis of HHT/PAVM at the time of pregnancy. 222 pregnancies in their 86 HHT‐affected relatives were also studied.
Main outcome measures PAVM bleed, stroke and maternal death.
Results Thirteen women experienced life‐threatening events during pregnancy: 1.0% (95% CI 0.1–1.9) of pregnancies resulted in a major PAVM bleed; 1.2% (0.3–2.2%) in stroke (not all were HHT related); and 1.0% (0.13–1.9%) in maternal death. All deaths occurred in women previously considered well. In women experiencing a life‐threatening event, prior awareness of HHT or PAVM diagnosis was associated with improved survival (P = 0.041, Fisher’s exact test).
Conclusions Most HHT pregnancies proceed normally. Rare major complications, and improved survival outcome following prior recognition, means that pregnancy in a woman with HHT should be considered high risk. Recommendations for pregnancy management are provided.
Bicontinuous cubic structures offer enormous potential in applications ranging from protein crystallisation to drug delivery systems and have been observed in cellular membrane structures. One of the ...current bottlenecks in understanding and exploiting these structures is that cubic scaffolds produced in vitro are considerably smaller in size than those observed in biological systems, differing by almost an order of magnitude in some cases. We have addressed this technological bottleneck and developed a methodology capable of manufacturing highly swollen bicontinuous cubic membranes with length scales approaching those seen in vivo. Crucially, these cubic systems do not require the presence of proteins. We have generated highly swollen Im3m symmetry bicontinuous cubic phases with lattice parameters of up to 480 Å, composed of ternary mixtures of monoolein, cholesterol and negatively charged lipid (DOPS or DOPG) and we have been able to tune their lattice parameters. The swollen cubic phases are highly sensitive to both temperature and pressure; these structural changes are likely to be controlled by a fine balance between lipid headgroup repulsions and lateral pressure in the hydrocarbon chain region.
The Laser Interferometer Gravitational Wave Observatory (LIGO) has been directly detecting gravitational waves from compact binary mergers since 2015. We report on the first use of squeezed vacuum ...states in the direct measurement of gravitational waves with the Advanced LIGO H1 and L1 detectors. This achievement is the culmination of decades of research to implement squeezed states in gravitational-wave detectors. During the ongoing O3 observation run, squeezed states are improving the sensitivity of the LIGO interferometers to signals above 50 Hz by up to 3 dB, thereby increasing the expected detection rate by 40% (H1) and 50% (L1).
To conduct an analysis of associations between eating behaviours and weight status in 2-year-old children.
Data were collected prospectively in the maternal-infant dyad Cork BASELINE Birth Cohort ...Study. The weight status of children aged 2 years (n=1189) was assigned using the International Obesity Task Force BMI cutoffs using measured heights and weights. Eating behaviours were assessed using the Children's Eating Behaviour Questionnaire (CEBQ).
Eighty percent of children were of normal weight, 14% were overweight or obese and 6% were underweight. From the CEBQ, food approach behaviours including Enjoyment of Food (odds ratio (OR)=1.90, 95% confidence interval (CI)=1.46-2.48) and Food Responsiveness (OR=1.73, 95% CI=1.47-2.03) were associated with overweight/obesity (all P<0.001). The food avoidant behaviours of Satiety Responsiveness (OR=2.03, 95% CI=1.38-2.98) and Slowness in Eating (OR=1.44, 95% CI=1.01-2.04) were associated with underweight at 2 years (all P<0.05).
Eating behaviours are associated with weight status as early as 2 years of age.
A persistent challenge in membrane biophysics has been to quantitatively predict how membrane physical properties change upon addition of new amphiphiles (e.g., lipids, alcohols, peptides, or ...proteins) in order to assess whether the changes are large enough to plausibly result in biological ramifications. Because of their roles as general anesthetics, n-alcohols are perhaps the best-studied amphiphiles of this class. When n-alcohols are added to model and cell membranes, changes in membrane parameters tend to be modest. One striking exception is found in the large decrease in liquid-liquid miscibility transition temperatures (T
) observed when short-chain n-alcohols are incorporated into giant plasma membrane vesicles (GPMVs). Coexisting liquid-ordered and liquid-disordered phases are observed at temperatures below T
in GPMVs as well as in giant unilamellar vesicles (GUVs) composed of ternary mixtures of a lipid with a low melting temperature, a lipid with a high melting temperature, and cholesterol. Here, we find that when GUVs of canonical ternary mixtures are formed in aqueous solutions of short-chain n-alcohols (n ≤ 10), T
increases relative to GUVs in water. This shift is in the opposite direction from that reported for cell-derived GPMVs. The increase in T
is robust across GUVs of several types of lipids, ratios of lipids, types of short-chain n-alcohols, and concentrations of n-alcohols. However, as chain lengths of n-alcohols increase, nonmonotonic shifts in T
are observed. Alcohols with chain lengths of 10-14 carbons decrease T
in ternary GUVs of dioleoyl-PC/dipalmitoyl-PC/cholesterol, whereas 16 carbons increase T
again. Gray et al. observed a similar influence of the length of n-alcohols on the direction of the shift in T
. These results are consistent with a scenario in which the relative partitioning of n-alcohols between liquid-ordered and liquid-disordered phases evolves as the chain length of the n-alcohol increases.
Objective
Primary synovial chondromatosis (PSC) is a rare disorder characterised by cartilage formation in synovium-lined joints, tendon sheaths and bursae. It is thought that PSC cartilage arises ...from the proliferation of mesenchymal cells, which exhibit cartilaginous metaplasia in subintimal connective tissue. There are reports of transformation of PSC to chondrosarcoma, although the precise incidence and nature of this complication is uncertain. In this study we carried out a retrospective review PSC to determine the incidence of sarcomatous change in this condition, in addition to the clinical, radiological and pathological features that characterise this complication
Materials and Methods
We reviewed 155 cases of PSC and identified 4 cases (3 in the hip joint; 1 in the elbow joint) of aggressive behaviour and chondrosarcoma-like histology.
Results
Radiologically, these cases were all reported as showing features consistent with PSC and aggressive extra-articular soft tissue/bone involvement. Histologically, in addition to typical features of PSC, there was morphological evidence of peri-articular soft tissue and, in 2 cases, bone involvement by an infiltrating cartilaginous tumour. These tumours all behaved as locally aggressive neoplasms and did not give rise to metastasis.
Conclusion
Our findings show that chondrosarcoma arises infrequently in PSC (approximately 2.5 %), and that this complication occurs most commonly in the hip joint (approximately 11 % of cases of hip PSC). These tumours behaved mainly as low-grade, locally aggressive tumours analogous to atypical cartilaginous tumour of bone/grade 1 chondrosarcoma of bone.
Objective
To investigate the parental physical and lifestyle determinants of newborn body composition.
Design
Prospective cohort study.
Setting
Cork University Maternity Hospital, a tertiary referral ...hospital in Cork, Ireland.
Population
All babies were recruited as part of a prospective birth cohort, Babies After SCOPE: Evaluating the Longitudinal Impact Using Neurological and Nutritional Endpoints (BASELINE). These babies were recruited from women who had participated in the Screening of Pregnancy Endpoints (SCOPE) study Ireland, a prospective, multicentre cohort study
Methods
Multivariate linear regression was used to analyse the effect of a range of maternal and paternal physical and lifestyle features on neonatal body fat percentage (BF%).
Main outcome measures
Neonatal BF%. Neonatal adiposity was assessed within 48 hours of birth using air displacement plethysmography (PEAPOD®).
Results
In all, 1243 infants were enrolled in the study. Increasing maternal body mass index (adjusted mean difference 0.09; 0.04, 0.15) and waist height ratio (adjusted mean difference 6.59; 0.27, 12.92) were significantly associated with increased neonatal BF%. In contrast, maternal smoking was associated with reduced neonatal BF% compared with non smokers (adjusted mean difference –0.55; –1.07, –0.03). Infant sex significantly altered neonatal BF%, with female infants having higher neonatal BF% compared with male infants (adjusted mean difference 1.98; 1.54, 2.53). No association was observed between paternal body mass index (BMI), paternal age or paternal smoking and neonatal BF%.
Conclusions
Maternal smoking, BMI, waist height ratio and infant sex were associated with altered BF%.
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Maternal smoking, BMI, waist height ratio and infant sex are associated with altered neonatal body fat percentage.
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Maternal smoking, BMI, waist height ratio and infant sex are associated with altered neonatal body fat percentage.
Ceramides are a group of sphingolipids that act as highly important signaling molecules in a variety of cellular processes including differentiation and apoptosis. The predominant in vivo synthetic ...pathway for ceramide formation is via sphingomyelinase catalyzed hydrolysis of sphingomyelin. The biochemistry of this essential pathway has been studied in detail; however, there is currently a lack of information on the structural behavior of sphingomyelin- and ceramide-rich model membrane systems, which is essential for developing a bottom-up understanding of ceramide signaling and platform formation. We have studied the lyotropic phase behavior of sphingomyelin–ceramide mixtures in excess water as a function of temperature (30–70 °C) and pressure (1–200 MPa) by small- and wide-angle X-ray scattering. At low ceramide concentrations the mixtures form the ripple gel phase (Pβ′) below the gel transition temperature for sphingomyelin, and this observation has been confirmed by atomic force microscopy. Formation of the ripple gel phase can also be induced at higher temperatures via the application of hydrostatic pressure. At high ceramide concentration an inverse hexagonal phase (HII) is formed coexisting with a cubic phase.
The measurement of minuscule forces and displacements with ever greater precision is inhibited by the Heisenberg uncertainty principle, which imposes a limit to the precision with which the position ...of an object can be measured continuously, known as the standard quantum limit
. When light is used as the probe, the standard quantum limit arises from the balance between the uncertainties of the photon radiation pressure applied to the object and of the photon number in the photoelectric detection. The only way to surpass the standard quantum limit is by introducing correlations between the position/momentum uncertainty of the object and the photon number/phase uncertainty of the light that it reflects
. Here we confirm experimentally the theoretical prediction
that this type of quantum correlation is naturally produced in the Laser Interferometer Gravitational-wave Observatory (LIGO). We characterize and compare noise spectra taken without squeezing and with squeezed vacuum states injected at varying quadrature angles. After subtracting classical noise, our measurements show that the quantum mechanical uncertainties in the phases of the 200-kilowatt laser beams and in the positions of the 40-kilogram mirrors of the Advanced LIGO detectors yield a joint quantum uncertainty that is a factor of 1.4 (3 decibels) below the standard quantum limit. We anticipate that the use of quantum correlations will improve not only the observation of gravitational waves, but also more broadly future quantum noise-limited measurements.
Osteoarthritis is the most common musculoskeletal disease and the leading cause of disability globally. Here, we performed a genome-wide association study for osteoarthritis (77,052 cases and 378,169 ...controls), analyzing four phenotypes: knee osteoarthritis, hip osteoarthritis, knee and/or hip osteoarthritis, and any osteoarthritis. We discovered 64 signals, 52 of them novel, more than doubling the number of established disease loci. Six signals fine-mapped to a single variant. We identified putative effector genes by integrating expression quantitative trait loci (eQTL) colocalization, fine-mapping, and human rare-disease, animal-model, and osteoarthritis tissue expression data. We found enrichment for genes underlying monogenic forms of bone development diseases, and for the collagen formation and extracellular matrix organization biological pathways. Ten of the likely effector genes, including TGFB1 (transforming growth factor beta 1), FGF18 (fibroblast growth factor 18), CTSK (cathepsin K), and IL11 (interleukin 11), have therapeutics approved or in clinical trials, with mechanisms of action supportive of evaluation for efficacy in osteoarthritis.
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