The contribution of X-linked coding variation to severe developmental disorders

Abstract: Over 130 X-linked genes have been robustly associated with developmental disorders, and X-linked causes have been hypothesised to underlie the higher developmental disorder rates in males. Here, we evaluate the burden of X-linked coding variation in 11,044 developmental disorder patients, and find a similar rate of X-linked causes in males and females (6.0% and 6.9%, respectively), indicating that such variants do not account for the 1.4-fold male bias. We develop an improved strategy to detect X-linked developmental disorders and identify 23 significant genes, all of which were previously known, consistent with our inference that the vast majority of the X-linked burden is in known developmental disorder-associated genes. Importantly, we estimate that, in male probands, only 13% of inherited rare missense variants in known developmental disorder-associated genes are likely to be pathogenic. Our results demonstrate that statistical analysis of large datasets can refine our understanding of modes of inheritance for individual X-linked disorders

An investigation into the occurrence of ecdysteroids and the ecdysteroid receptor complex in the marine copepod Calanus finmarchicus (Gunnerus)

EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Architecture Providing a Sustainable Community

Architecture is more than creating a unique design or an attractive building. Architecture is about creating spaces that will endure time. With the building industry being one of the largest energy resource users on this planet, architects have the responsibility to reduce its reliance on these precious resources. A renowned architect, Richard Rogers, once said, “I believe we - architects - can affect the quality of life of the people.” Missionaries in Costa Rica approached us to design a community that is a safe haven for local orphans and refugees. The architecture we created focused on making a space for people to heal, and emotionally rehabilitate. Architecture has the ability to create emotion, to influence the thoughts and ideas a person has. The significance of our architecture was to produce a space where interaction, opportunity and healing encourage a community to grow and function as one. It became essential to design a community that was sustainable and self-sufficient. Bringing together sustainable design and our ideas of a community go together harmoniously. Sustainability philosophy focuses on creating prosperity and hope in our communities. It is through careful investigation and awareness that we achieved a design that had a positive environmental impact, and one that also is socially and emotionally responsive to the community

Positive end-expiratory pressure improves elastic working pressure in anesthetized children

Abstract Background Positive end-expiratory pressure (PEEP) has been demonstrated to decrease ventilator-induced lung injury in patients under mechanical ventilation (MV) for acute respiratory failure. Recently, some studies have proposed some beneficial effects of PEEP in ventilated patients without lung injury. The influence of PEEP on respiratory mechanics in children is not well known. Our aim was to determine the effects on respiratory mechanics of setting PEEP at 5 cmH2O in anesthetized healthy children. Methods Patients younger than 15 years old without history of lung injury scheduled for elective surgery gave informed consent and were enrolled in the study. After usual care for general anesthesia, patients were placed on volume controlled MV. Two sets of respiratory mechanics studies were performed using inspiratory and expiratory breath hold, with PEEP 0 and 5 cmH2O. The maximum inspiratory and expiratory flow (QI and QE) as well as peak inspiratory pressure (PIP), plateau pressure (PPL) and total PEEP (tPEEP) were measured. Respiratory system compliance (CRS), inspiratory and expiratory resistances (RawI and RawE) and time constants (KTI and KTE) were calculated. Data were expressed as median and interquartile range (IQR). Wilcoxon sign test and Spearman’s analysis were used. Significance was set at P < 0.05. Results We included 30 patients, median age 39 (15–61.3) months old, 60% male. When PEEP increased, PIP increased from 12 (11,14) to 15.5 (14,18), and CRS increased from 0.9 (0.9,1.2) to 1.2 (0.9,1.4) mL·kg− 1·cmH2O− 1; additionally, when PEEP increased, driving pressure decreased from 6.8 (5.9,8.1) to 5.8 (4.7,7.1) cmH2O, and QE decreased from 13.8 (11.8,18.7) to 11.7 (9.1,13.5) L·min− 1 (all P < 0.01). There were no significant changes in resistance and QI. Conclusions Analysis of respiratory mechanics in anesthetized healthy children shows that PEEP at 5 cmH2O places the respiratory system in a better position in the P/V curve. A better understanding of lung mechanics may lead to changes in the traditional ventilatory approach, limiting injury associated with MV

Scottish cocaine users: wealthy snorters or delinquent smokers?

Ninty-two cocaine users were interviewed in Scotland. Most were middle-class nasal users, also used other drugs and generally gave cocaine a positive rating. One half of them had at some time used cocaine more than once a week. For some, this period lasted some months, when as much as 30 'lines' of cocaine were used per day of cocaine use. More of these heavy users reported adverse effects of cocaine than was the case for light users. Nonetheless, most heavy users had reduced their use by themselves to the point that their current cocaine use was no different from that of light users. Possible explanations for this apparently spontaneous reduction are discussed