3,199 research outputs found
Perinatal Gene Transfer to the Liver
The liver acts as a host to many functions hence raising the possibility that any one may be compromised by a single gene defect.
Inherited or de novo mutations in these genes may result in relatively mild diseases or be so devastating that death within the first
weeks or months of life is inevitable. Some diseases can be managed using conventional medicines whereas others are, as yet, untreatable.
In this review we consider the application of early intervention gene therapy in neonatal and fetal preclinical studies. We appraise
the tools of this technology, including lentivirus, adenovirus and adeno-associated virus (AAV)-based vectors. We highlight the application
of these for a range of diseases including hemophilia, urea cycle disorders such as ornithine transcarbamylase deficiency, organic
acidemias, lysosomal storage diseases including mucopolysaccharidoses, glycogen storage diseases and bile metabolism. We conclude by
assessing the advantages and disadvantages associated with fetal and neonatal liver gene transfer
Sir Patrick Manson: good medicine for the people of Hong Kong
published_or_final_versio
Generic master equations for quasi-normal frequencies
Generic master equations governing the highly-damped quasi-normal frequencies
[QNFs] of one-horizon, two-horizon, and even three-horizon spacetimes can be
obtained through either semi-analytic or monodromy techniques. While many
technical details differ, both between the semi-analytic and monodromy
approaches, and quite often among various authors seeking to apply the
monodromy technique, there is nevertheless widespread agreement regarding the
the general form of the QNF master equations. Within this class of generic
master equations we can establish some rather general results, relating the
existence of "families" of QNFs of the form omega_{a,n} = (offset)_a + i n
(gap) to the question of whether or not certain ratios of parameters are
rational or irrational.Comment: 23 pages; V2: Minor additions, typos fixed. Matches published versio
New Experimental Limits on Macroscopic Forces Below 100 Microns
Results of an experimental search for new macroscopic forces with Yukawa
range between 5 and 500 microns are presented. The experiment uses 1 kHz
mechanical oscillators as test masses with a stiff conducting shield between
them to suppress backgrounds. No signal is observed above the instrumental
thermal noise after 22 hours of integration time. These results provide the
strongest limits to date between 10 and 100 microns, improve on previous limits
by as much as three orders of magnitude, and rule out half of the remaining
parameter space for predictions of string-inspired models with low-energy
supersymmetry breaking. New forces of four times gravitational strength or
greater are excluded at the 95% confidence level for interaction ranges between
200 and 500 microns.Comment: 25 Pages, 7 Figures: Minor Correction
Semi-analytic results for quasi-normal frequencies
The last decade has seen considerable interest in the quasi-normal
frequencies [QNFs] of black holes (and even wormholes), both asymptotically
flat and with cosmological horizons. There is wide agreement that the QNFs are
often of the form omega_n = (offset) + i n (gap), though some authors have
encountered situations where this behaviour seems to fail. To get a better
understanding of the general situation we consider a semi-analytic model based
on a piecewise Eckart (Poeschl-Teller) potential, allowing for different
heights and different rates of exponential falloff in the two asymptotic
directions. This model is sufficiently general to capture and display key
features of the black hole QNFs while simultaneously being analytically
tractable, at least for asymptotically large imaginary parts of the QNFs. We
shall derive an appropriate "quantization condition" for the asymptotic QNFs,
and extract as much analytic information as possible. In particular, we shall
explicitly verify that the (offset)+ i n (gap) behaviour is common but not
universal, with this behaviour failing unless the ratio of rates of exponential
falloff on the two sides of the potential is a rational number. (This is
"common but not universal" in the sense that the rational numbers are dense in
the reals.) We argue that this behaviour is likely to persist for black holes
with cosmological horizons.Comment: V1: 28 pages, no figures. V2: 3 references added, no physics changes.
V3: 29 pages, 9 references added, no physics changes; V4: reformatted, now 27
pages. Some clarifications, comparison with results obtained by monodromy
techniques. This version accepted for publication in JHEP. V5: Minor typos
fixed. Compatible with published versio
Heart and liver R2 and R2* measurements in patients with thalassaemia major at 3T
Myocardial Tissue Characterization: Fat, Hemorrhage & Edema - Poster presentationTo determine the feasibility of measurements of transverse relaxation times for assessment of tissue iron overload at high field, we compared results of determinations of R2 and R2* using breathhold multi-echo spin-echo (MESE) and multi-echo gradient echo (MEGE) sequences, respectively, at 3T and at 1.5T in normal subjects and patients with thalassaemia major. Our results, the first reported measurements of R2 at both 3T and 1.5T in iron overloaded patients, demonstrate significant correlations in heart and liver at the two field strengths. These results provide evidence that myocardial and hepatic R2 can be measured at 3T as indicators of iron overload.published_or_final_versionThe 17th Scientific Meeting & Exhibition of the International Society of Magnetic Resonance in Medicine (ISMRM), Honolulu, HI., 18-24 April 2009. In Proceedings of ISMRM 17th Scientific Meeting & Exhibition, 2009, p. 375
A few things we do not know about stars and model atmospheres
We list a few things that we do not understand about stars and that most
people ignore. These are all hard problems. We can learn more cosmology by
working on them to reduce the systematic errors they introduce than by trying
to derive cosmological results that are highly uncertain.Comment: 12 pages. Presented at the conference, The Link between Stars and
Cosmology, 26-30 March, 2001, Puerto Vallarta, Mexico. To be published by
Kluwer, eds. M. Chavez, A. Bressan, A. Buzzoni, and D. Mayy
Combined mirror visual and auditory feedback therapy for upper limb phantom pain: a case report
<p>Abstract</p> <p>Introduction</p> <p>Phantom limb sensation and phantom limb pain is a very common issue after amputations. In recent years there has been accumulating data implicating 'mirror visual feedback' or 'mirror therapy' as helpful in the treatment of phantom limb sensation and phantom limb pain.</p> <p>Case presentation</p> <p>We present the case of a 24-year-old Caucasian man, a left upper limb amputee, treated with mirror visual feedback combined with auditory feedback with improved pain relief.</p> <p>Conclusion</p> <p>This case may suggest that auditory feedback might enhance the effectiveness of mirror visual feedback and serve as a valuable addition to the complex multi-sensory processing of body perception in patients who are amputees.</p
National Surveillance of Home-Based HIV Testing Among Australian Gay and Bisexual Men, 2018–2020: Uptake After Commercial Availability of HIV Self-Tests
HIV self-testing allows people to collect samples and test themselves at home, addressing known barriers to facility-based testing. We aimed to measure the uptake of home HIV testing among Australian gay and bisexual men (GBM). Using national cross-sectional data from the Australian Gay Community Periodic Surveys, we assessed trends in home HIV testing among non-HIV positive GBM between 2018 and 2020. Overall, the use of home HIV testing was low, but slightly increased during 2018–2020 (from 0.3 to 0.8%, RR = 1.54, 95%CI = 1.23–1.92, p-trend < 0.001). Testing at home was more likely among non-HIV-positive GBM who were born overseas and recently arrived in Australia, at higher risk of HIV, and infrequent HIV testers. Given the greater use of home testing by men at higher risk of HIV, recent migrants and infrequent testers, all priority groups in Australia’s HIV epidemic, we recommend increasing access to HIV self-testing to enhance uptake in these and other groups of GBM
Effect of D222G Mutation in the Hemagglutinin Protein on Receptor Binding, Pathogenesis and Transmissibility of the 2009 Pandemic H1N1 Influenza Virus
Influenza viruses isolated during the 2009 H1N1 pandemic generally lack known molecular determinants of virulence associated with previous pandemic and highly pathogenic avian influenza viruses. The frequency of the amino acid substitution D222G in the hemagglutinin (HA) of 2009 H1N1 viruses isolated from severe but not mild human cases represents the first molecular marker associated with enhanced disease. To assess the relative contribution of this substitution in virus pathogenesis, transmission, and tropism, we introduced D222G by reverse genetics in the wild-type HA of the 2009 H1N1 virus, A/California/04/09 (CA/04). A dose-dependent glycan array analysis with the D222G virus showed a modest reduction in the binding avidity to human-like (α2-6 sialylated glycan) receptors and an increase in the binding to avian-like (α2-3 sialylated glycan) receptors in comparison with wild-type virus. In the ferret pathogenesis model, the D222G mutant virus was found to be similar to wild-type CA/04 virus with respect to lethargy, weight loss and replication efficiency in the upper and lower respiratory tract. Moreover, based on viral detection, the respiratory droplet transmission properties of these two viruses were found to be similar. The D222G virus failed to productively infect mice inoculated by the ocular route, but exhibited greater viral replication and weight loss than wild-type CA/04 virus in mice inoculated by the intranasal route. In a more relevant human cell model, D222G virus replicated with delayed kinetics compared with wild-type virus but to higher titer in human bronchial epithelial cells. These findings suggest that although the D222G mutation does not influence virus transmission, it may be considered a molecular marker for enhanced replication in certain cell types.Centers for Disease Control and Prevention (U.S.)United States. National Institutes of Health (merit award R37 GM057073-13)Singapore-MIT Alliance for Research and Technolog
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