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Gene therapy uses a vector to deliver a gene to its required site, where expression of the protein can produce a therapeutic effect. In the last decade there have been significant therapeutic breakthroughs, with clinical trials of postnatal gene therapy showing efficacy for a variety of diseases, such as hemophilia, congenital blindness, congenital immunodeficiency and neuromuscular disorders, and the first gene therapy for familial hyperlipidemia was approved in the European Union (EU) in 2012.
Teotihuacan's Tlajinga district is a cluster of neighborhoods on the southern periphery of the city best known for earlier investigations at Compound 33:S3W1. New research includes excavations at two other apartment compounds and along the southern extension of the Street of the Dead. Excavation contexts, major finds, chronology, and preliminary interpretations are the subject of this article. We highlight evidence attesting to a major obsidian-blade workshop at Compound 17:S3E1, offerings, and other features at that compound and Compound 18:S3E1, and the tempo and processes of urbanization viewed through well-recorded stratigraphic sequences of the compounds and the Street of the Dead. We conclude that significant occupation began in the Miccaotli phase, but it was not until some point in the Early Tlamimilolpa phase that the dominant housing type became apartment compounds; the continuation of the axis of Street of the Dead in the district was accomplished by excavating in the volcanic tuft substrate (tepetate) and could have been undertaken by the inhabitants of the district themselves; and the presence of items such as a sculpted stone face, marine shell, and polychrome pottery demonstrates that commoners at Teotihuacan enjoyed some access to finer items within the interregional economy.
Chylothorax after paediatric cardiac surgery incurs significant morbidity; however, a detailed understanding that does not rely on single-centre or administrative data is lacking. We described the present clinical epidemiology of postoperative chylothorax and evaluated variation in rates among centres with a multicentre cohort of patients treated in cardiac ICU.
This was a retrospective cohort study using prospectively collected clinical data from the Pediatric Cardiac Critical Care Consortium registry. All postoperative paediatric cardiac surgical patients admitted from October, 2013 to September, 2015 were included. Risk factors for chylothorax and association with outcomes were evaluated using multivariable logistic or linear regression models, as appropriate, accounting for within-centre clustering using generalised estimating equations.
A total of 4864 surgical hospitalisations from 15 centres were included. Chylothorax occurred in 3.8% (n=185) of hospitalisations. Case-mix-adjusted chylothorax rates varied from 1.5 to 7.6% and were not associated with centre volume. Independent risk factors for chylothorax included age <1 year, non-Caucasian race, single-ventricle physiology, extracardiac anomalies, longer cardiopulmonary bypass time, and thrombosis associated with an upper-extremity central venous line (all p<0.05). Chylothorax was associated with significantly longer duration of postoperative mechanical ventilation, cardiac ICU and hospital length of stay, and higher in-hospital mortality (all p<0.001).
Chylothorax after cardiac surgery in children is associated with significant morbidity and mortality. A five-fold variation in chylothorax rates was observed across centres. Future investigations should identify centres most adept at preventing and managing chylothorax and disseminate best practices.
The interactions between religious and secular elites differ across societies, and those interactions may evolve differently even in the face of similarly controversial issues. What explains variation in relations between religious and secular elites in comparative settings? We highlight the links between religious change, political incentives, and the level of conflict or cooperation between religious and secular actors in public life. We illustrate distinct patterns of religious-secular relations with a paired comparison of two democracies with an intertwined history: the United States and the Philippines. In the United States, religious-secular relations have becoming increasingly conflictual as political incentives have changed in response to religious change. In the Philippines, in contrast, religious and secular actors maintain cooperative ties in part because relative religious stability has diminished political incentives to stoke religious-secular tensions.
The provision of financial services through mobile phones is a powerful tool to foster financial inclusion, and thus economic growth, in developing countries. However, it raises important regulatory issues. Given the vulnerability of most potential customers of these services, the protection of customer funds is important. In common law countries, trust accounts are an effective response to these concerns. In civil law jurisdictions however, in the absence of trusts, protection of customer funds is more difficult. This paper identifies the theoretical and practical problems that regulators in civil law jurisdictions might face when trying to protect customer funds and explores how fiduciary contracts, mandate contracts and direct regulation might be used to achieve this goal. It offers a series of practical recommendations for policymakers in developing countries that provide a range of regulatory options that combine private law and regulation.
We present spectropolarimetric observations of the eclipsing cataclysmic variable 1H1752+08. Modelling of the line intensity and polarisation spectra of 1H1752+08 shows that the magnetic field structure of the white dwarf is off-centre and the mean photospheric field strength is about 7 MG, the lowest measured in a cataclysmic variable (CV). We argue that 1H1752+08 is most probably a low-field AM Herculis system.
Screening measures such as the 15-item Geriatric Depression Scale (GDS-15) (Sheikh and Yesavage, 1986) and the Hospital Anxiety and Depression Scale (HADS) (Zigmond and Snaith, 1983) are important tools in the recognition of depressive symptoms in older people. While these measures are widely used, there is evidence of specific weaknesses in some cohorts and contexts, with the GDS-15 showing limitations in the context of cognitive impairment (Gilley and Wilson, 1997), and the depression subscale of the HADS (HADS-D) losing sensitivity in the context of older participants in hospital inpatient settings (Davies et al., 1993).
Autobiographical memory (ABM), personal semantic memory (PSM), and autonoetic consciousness are affected in individuals with mild cognitive impairment (MCI) but their relationship with Alzheimer's disease (AD) biomarkers are unclear.
Forty-five participants (healthy controls (HC) = 31, MCI = 14) completed the Episodic ABM Interview and a battery of memory tests. Thirty-one (HC = 22, MCI = 9) underwent β-amyloid positron emission tomography (PET) and magnetic resonance (MR) imaging. Fourteen participants (HC = 9, MCI = 5) underwent one imaging modality.
Unlike PSM, ABM differentiated between diagnostic categories but did not relate to AD biomarkers. Personal semantic memory was related to neocortical β-amyloid burden after adjusting for age and apolipoprotein E (APOE) ɛ4. Autonoetic consciousness was not associated with AD biomarkers, and was not impaired in MCI.
Autobiographical memory was impaired in MCI participants but was not related to neocortical amyloid burden, suggesting that personal memory systems are impacted by differing disease mechanisms, rather than being uniformly underpinned by β-amyloid. Episodic and semantic ABM impairment represent an important AD prodrome.
The United Kingdom aims to decarbonize its national electricity generation in order to transition to a low carbon economy. Solar, wind, hydro and thermal energy conversion are renewable alternatives to fossil fuels and are currently being explored that may form part of the future generation mix of the country.
How does materials scientist's work addressing energy research challenges for solar and storage (for example) translate into the adoption of new technology? How appropriate are the technology usage visions of the scientists? How can technology users better inform the materials science motivations? This report will focus on how a multidisciplinary team of researchers from the Universities of Sheffield and University of Durham, community members and industry representatives are jointly developing renewable energy projects to try to answer these and other questions. The history of the project will be presented as well as the methodology used to collaboratively engage the community participants.
This work is supported by a grant provided by the Engineering and Physical Sciences Research Council (EPSRC) of the United Kingdom.
The nitrogen-vacancy (NV) center in diamond offers the opportunity to develop quantum technologies that leverage the defect’s atom-like properties using established engineering techniques from the semiconductor industry. While many NV center applications are motivated by the remarkable properties of isolated NV centers in bulk diamond, realizing these technologies requires addressing a number of device and materials engineering challenges unique to creating and controlling individual semiconductor spins. We review recent advances in interfacing NV centers with on-chip electronics that enable control over the defect’s spin and orbital degrees of freedom and review fabrication techniques for creating single NV centers with nanometer-scale placement accuracies. We also discuss efforts, motivated by the success of diamond NV center applications, to identify defect spins with similar properties to the NV center in more technologically mature semiconductors such as SiC.
We present a brief description of the Berkeley Visible Imaging Tube (BVIT) detector system, which is a user instrument on the 10-m Southern African Large Telescope (SALT), and include some preliminary observational results gained in mid-2011. The data show that BVIT is capable of revealing emission features occurring on time-scales of < 0.1 sec, thus opening up for the general user a window of high time-resolution astronomy at visible wavelengths.
We carried out a population-based study of dystrophin mutations in patients followed by members of the Canadian Paediatric Neuromuscular Group (CPNG) over a ten-year period.
We aimed to describe the changes in diagnostic testing for dystrophinopathy and to determine the frequency of dystrophin mutations from 2000 to 2009.
De-identified data containing the clinical phenotypes, diagnostic methods, and mutational reports from dystrophinopathy patients followed by CPNG centres from January 2000 to December 2009 were analyzed using descriptive statistics.
773 patients had a confirmed diagnosis of dystrophinopathy based on genetic testing (97%), muscle biopsy (2%), or family history (1%). 573 (74%) had complete deletion/duplication analysis of all 79 exons or whole gene sequencing, resulting in 366 (64%) deletions, 64 (11%) duplications, and 143 (25%) point mutations. The percentage of patients who were diagnosed using currently accepted genetic testing methods varied across Canada, with a mean of 63% (SD 23). 246 (43%) mutations involved exons 45 to 53. The top ten deletions (n=147, 26%) were exons 45-47, 45-48, 45, 45-50, 45-55, 51, 45-49, 45-52, 49-50, and 46-47. 169 (29%) mutations involved exons 2 to 20. The most common duplications (n=29, 5.1%) were exons 2, 2-7, 2-17, 3-7, 8-11, 10, 10-11, and 12.
This is the most comprehensive report of dystrophin mutations in Canada. Consensus guidelines regarding the diagnostic approach to dystrophinopathy will hopefully reduce the geographical variation in mutation detection rates in the coming decade.
A 10-metre class telescope project on African soil is ending its commissioning period and is transitioning to science mode. We present the current status of the Southern African Large Telescope and its instruments. We will also briefly discuss the SALT capabilities for extragalactic astronomy in particular.
T1-weighted dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) is an experimental technique designed to measure tissue hemodynamic parameters.[1–3] For this purpose, contrast medium (the tracer) is rapidly injected intravenously. The passage of the bolus through the tissue causes changes in the longitudinal relaxation rate R1 (1/T1) that are measured with a dynamic T1-weighted imaging technique (Fig. 9.1). The principles of MRI signal theory are used to determine tracer concentration–time curves from the measured signal changes. In a second step, tracer kinetic principles [4,5] are applied to derive the relevant perfusion and/or blood–brain barrier (BBB) permeability parameters.
Perfusion and permeability parameters
Perfusion parameters characterize the state of the microvasculature (Fig. 9.2). Cerebral blood flow (CBF) quantifies tissue perfusion and is conventionally expressed in units of milliliters of blood per minute per 100 g tissue. Cerebral blood volume (CBV) quantifies the volume of the microvasculature and has the units of milliliters of blood per 100 g tissue. Compared with other organs, normal brain tissue is characterized by low blood volumes, with CBV in the range 2–4 ml/100 g.