976 research outputs found
Teprotumumab for Thyroid-Associated Ophthalmopathy
BACKGROUND: Thyroid-associated ophthalmopathy, a condition commonly associated with Graves’ disease, remains inadequately treated. Current medical therapies, which primarily consist of glucocorticoids, have limited efficacy and present safety concerns. Inhibition of the insulin-like growth factor I receptor (IGF-IR) is a new therapeutic strategy to attenuate the underlying autoimmune pathogenesis of ophthalmopathy. / METHODS: We conducted a multicenter, double-masked, randomized, placebo-controlled trial to determine the efficacy and safety of teprotumumab, a human monoclonal antibody inhibitor of IGF-IR, in patients with active, moderate-to-severe ophthalmopathy. A total of 88 patients were randomly assigned to receive placebo or active drug administered intravenously once every 3 weeks for a total of eight infusions. The primary end point was the response in the study eye. This response was defined as a reduction of 2 points or more in the Clinical Activity Score (scores range from 0 to 7, with a score of ≥3 indicating active thyroid-associated ophthalmopathy) and a reduction of 2 mm or more in proptosis at week 24. Secondary end points, measured as continuous variables, included proptosis, the Clinical Activity Score, and results on the Graves’ ophthalmopathy–specific quality-of-life questionnaire. Adverse events were assessed. / RESULTS: In the intention-to-treat population, 29 of 42 patients who received teprotumumab (69%), as compared with 9 of 45 patients who received placebo (20%), had a response at week 24 (P<0.001). Therapeutic effects were rapid; at week 6, a total of 18 of 42 patients in the teprotumumab group (43%) and 2 of 45 patients in the placebo group (4%) had a response (P<0.001). Differences between the groups increased at subsequent time points. The only drug-related adverse event was hyperglycemia in patients with diabetes; this event was controlled by adjusting medication for diabetes. / CONCLUSIONS: In patients with active ophthalmopathy, teprotumumab was more effective than placebo in reducing proptosis and the Clinical Activity Score. (Funded by River Vision Development and others; ClinicalTrials.gov number, NCT01868997.
Digital media usage and prevalence of internet addiction among undergraduate students in South Africa
The use of Internet and digital media in the academic sector has significantly improved knowledge creation. The Internet has
particularly proven itself to be a valuable resource in the enhancement of knowledge production and dissemination. The purpose
of the study on which this chapter is based was to establish how excessive non-academic use of the Internet detrimentally affects
daily lives of undergraduate students. A survey was conducted of 390 university undergraduate students, comprising mainly of
adolescents or young adults, who were selected using stratified random sampling at two South African universities. The universities
selected were Fort Hare and Nelson Mandela. Data was collected using the Modified Internet Addiction Test for Undergraduates
(MIATU), a modification of Internet Addiction Test (IAT) questionnaire. 282 (72.3%) of the respondents indicated that they
make use of the Internet daily with 34.8% spending more than 10 hours. More than 60% have access to at least two electronic
devices. Most of the respondents stayed online longer than intended (x̅ 2.88), slept less at night due to Internet use (x̅ 2.63) and
hence spent less time studying owing to Internet surfing (x̅ 2.27). Furthermore, the amount of time spent on the Internet had a
significant relationship with the level of influence the use of the Internet had on respondents (B = 0.250, t = 4.850, p<0.05).
The findings are indications that the excessive amount of time spent on the Internet served as a distraction from school work; a
situation that disadvantaged students in academic productivity. These findings suggest that the uncontrolled use of new media is
both a hazard and a potential danger to academic productivity. This is the first study in South Africa that empirically investigates
Internet use pattern by undergraduate students, Internet use rate and problematic Internet use among undergraduate students.
Keywords: Internet addiction, Internet use, Undergraduate Students, Problematic Internet use, South Africa
The fundamental pro-groupoid of an affine 2-scheme
A natural question in the theory of Tannakian categories is: What if you
don't remember \Forget? Working over an arbitrary commutative ring , we
prove that an answer to this question is given by the functor represented by
the \'etale fundamental groupoid \pi_1(\spec(R)), i.e.\ the separable
absolute Galois group of when it is a field. This gives a new definition
for \'etale \pi_1(\spec(R)) in terms of the category of -modules rather
than the category of \'etale covers. More generally, we introduce a new notion
of "commutative 2-ring" that includes both Grothendieck topoi and symmetric
monoidal categories of modules, and define a notion of for the
corresponding "affine 2-schemes." These results help to simplify and clarify
some of the peculiarities of the \'etale fundamental group. For example,
\'etale fundamental groups are not "true" groups but only profinite groups, and
one cannot hope to recover more: the "Tannakian" functor represented by the
\'etale fundamental group of a scheme preserves finite products but not all
products.Comment: 46 pages + bibliography. Diagrams drawn in Tik
Mapping the disease-specific LupusQoL to the SF-6D
Purpose
To derive a mapping algorithm to predict SF-6D utility scores from the non-preference-based LupusQoL and test the performance of the developed algorithm on a separate independent validation data set.
Method
LupusQoL and SF-6D data were collected from 320 patients with systemic lupus erythematosus (SLE) attending routine rheumatology outpatient appointments at seven centres in the UK. Ordinary least squares (OLS) regression was used to estimate models of increasing complexity in order to predict individuals’ SF-6D utility scores from their responses to the LupusQoL questionnaire. Model performance was judged on predictive ability through the size and pattern of prediction errors generated. The performance of the selected model was externally validated on an independent data set containing 113 female SLE patients who had again completed both the LupusQoL and SF-36 questionnaires.
Results
Four of the eight LupusQoL domains (physical health, pain, emotional health, and fatigue) were selected as dependent variables in the final model. Overall model fit was good, with R2 0.7219, MAE 0.0557, and RMSE 0.0706 when applied to the estimation data set, and R2 0.7431, MAE 0.0528, and RMSE 0.0663 when applied to the validation sample.
Conclusion
This study provides a method by which health state utility values can be estimated from patient responses to the non-preference-based LupusQoL, generalisable beyond the data set upon which it was estimated. Despite concerns over the use of OLS to develop mapping algorithms, we find this method to be suitable in this case due to the normality of the SF-6D data
Of Mice and ‘Convicts’: Origin of the Australian House Mouse, Mus musculus
The house mouse, Mus musculus, is one of the most ubiquitous invasive species worldwide and in Australia is particularly common and widespread, but where it originally came from is still unknown. Here we investigated this origin through a phylogeographic analysis of mitochondrial DNA sequences (D-loop) comparing mouse populations from Australia with those from the likely regional source area in Western Europe. Our results agree with human historical associations, showing a strong link between Australia and the British Isles. This outcome is of intrinsic and applied interest and helps to validate the colonization history of mice as a proxy for human settlement history
Coordination of opposing sex-specific and core muscle groups regulates male tail posture during Caenorhabditis elegans male mating behavior
Background
To survive and reproduce, animals must be able to modify their motor behavior in response to changes in the environment. We studied a complex behavior of Caenorhabditis elegans, male mating behavior, which provided a model for understanding motor behaviors at the genetic, molecular as well as circuit level. C. elegans male mating behavior consists of a series of six sub-steps: response to contact, backing, turning, vulva location, spicule insertion, and sperm transfer. The male tail contains most of the sensory structures required for mating, in addition to the copulatory structures, and thus to carry out the steps of mating behavior, the male must keep his tail in contact with the hermaphrodite. However, because the hermaphrodite does not play an active role in mating and continues moving, the male must modify his tail posture to maintain contact. We provide a better understanding of the molecular and neuro-muscular pathways that regulate male tail posture during mating.
Results
Genetic and laser ablation analysis, in conjunction with behavioral assays were used to determine neurotransmitters, receptors, neurons and muscles required for the regulation of male tail posture. We showed that proper male tail posture is maintained by the coordinated activity of opposing muscle groups that curl the tail ventrally and dorsally. Specifically, acetylcholine regulates both ventral and dorsal curling of the male tail, partially through anthelmintic levamisole-sensitive, nicotinic receptor subunits. Male-specific muscles are required for acetylcholine-driven ventral curling of the male tail but dorsal curling requires the dorsal body wall muscles shared by males and hermaphrodites. Gamma-aminobutyric acid activity is required for both dorsal and ventral acetylcholine-induced curling of the male tail and an inhibitory gamma-aminobutyric acid receptor, UNC-49, prevents over-curling of the male tail during mating, suggesting that cross-inhibition of muscle groups helps maintain proper tail posture.
Conclusion
Our results demonstrated that coordination of opposing sex-specific and core muscle groups, through the activity of multiple neurotransmitters, is required for regulation of male tail posture during mating. We have provided a simple model for regulation of male tail posture that provides a foundation for studies of how genes, molecular pathways, and neural circuits contribute to sensory regulation of this motor behavior
Strong signature of natural selection within an FHIT intron implicated in prostate cancer risk
Previously, a candidate gene linkage approach on brother pairs affected with prostate cancer identified a locus of prostate cancer susceptibility at D3S1234 within the fragile histidine triad gene (FHIT), a tumor suppressor that induces apoptosis. Subsequent association tests on 16 SNPs spanning approximately 381 kb surrounding D3S1234 in Americans of European descent revealed significant evidence of association for a single SNP within intron 5 of FHIT. In the current study, resequencing and genotyping within a 28.5 kb region surrounding this SNP further delineated the association with prostate cancer risk to a 15 kb region. Multiple SNPs in sequences under evolutionary constraint within intron 5 of FHIT defined several related haplotypes with an increased risk of prostate cancer in European-Americans. Strong associations were detected for a risk haplotype defined by SNPs 138543, 142413, and 152494 in all cases (Pearson's χ2 = 12.34, df 1, P = 0.00045) and for the homozygous risk haplotype defined by SNPs 144716, 142413, and 148444 in cases that shared 2 alleles identical by descent with their affected brothers (Pearson's χ2 = 11.50, df 1, P = 0.00070). In addition to highly conserved sequences encompassing SNPs 148444 and 152413, population studies revealed strong signatures of natural selection for a 1 kb window covering the SNP 144716 in two human populations, the European American (π = 0.0072, Tajima's D= 3.31, 14 SNPs) and the Japanese (π = 0.0049, Fay & Wu's H = 8.05, 14 SNPs), as well as in chimpanzees (Fay & Wu's H = 8.62, 12 SNPs). These results strongly support the involvement of the FHIT intronic region in an increased risk of prostate cancer. © 2008 Ding et al
The quest for the solar g modes
Solar gravity modes (or g modes) -- oscillations of the solar interior for
which buoyancy acts as the restoring force -- have the potential to provide
unprecedented inference on the structure and dynamics of the solar core,
inference that is not possible with the well observed acoustic modes (or p
modes). The high amplitude of the g-mode eigenfunctions in the core and the
evanesence of the modes in the convection zone make the modes particularly
sensitive to the physical and dynamical conditions in the core. Owing to the
existence of the convection zone, the g modes have very low amplitudes at
photospheric levels, which makes the modes extremely hard to detect. In this
paper, we review the current state of play regarding attempts to detect g
modes. We review the theory of g modes, including theoretical estimation of the
g-mode frequencies, amplitudes and damping rates. Then we go on to discuss the
techniques that have been used to try to detect g modes. We review results in
the literature, and finish by looking to the future, and the potential advances
that can be made -- from both data and data-analysis perspectives -- to give
unambiguous detections of individual g modes. The review ends by concluding
that, at the time of writing, there is indeed a consensus amongst the authors
that there is currently no undisputed detection of solar g modes.Comment: 71 pages, 18 figures, accepted by Astronomy and Astrophysics Revie
Author Correction: Cross-ancestry genome-wide association analysis of corneal thickness strengthens link between complex and Mendelian eye diseases.
Emmanuelle Souzeau, who contributed to analysis of data, was inadvertently omitted from the author list in the originally published version of this Article. This has now been corrected in both the PDF and HTML versions of the Article
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