Spatial clusters of gonorrhoea in England with particular reference to the outcome of partner notification: 2012 and 2013

Background: This study explored spatial-temporal variation in diagnoses of gonorrhoea to identify and quantify endemic areas and clusters in relation to patient characteristics and outcomes of partner notification (PN) across England, UK. Methods: Endemic areas and clusters were identified using a two-stage analysis with Kulldorff’s scan statistics (SaTScan). Results Of 2,571,838 tests, 53,547 diagnoses were gonorrhoea positive (positivity = 2.08%). The proportion of diagnoses in heterosexual males was 1.5 times that in heterosexual females. Among index cases, men who have sex with men (MSM) were 8 times more likely to be diagnosed with gonorrhoea than heterosexual males (p<0.0001). After controlling for age, gender, ethnicity and deprivation rank, 4 endemic areas were identified including 11,047 diagnoses, 86% of which occurred in London. 33 clusters included 17,629 diagnoses (34% of total diagnoses in 2012 and 2013) and spanned 21 locations, some of which were dominated by heterosexually acquired infection, whilst others were MSM focused. Of the 53,547 diagnoses, 14.5% (7,775) were the result of PN. The proportion of patients who attended services as a result of PN varied from 0% to 61% within different age, gender and sexual orientation cohorts. A third of tests resulting from PN were positive for gonorrhoea. 25% of Local Authorities (n = 81, 95% CI: 20.2, 29.5) had a higher than expected proportion for female PN diagnoses as compared to 16% for males (n = 52, 95% CI: 12.0, 19.9). Conclusions: The English gonorrhoea epidemic is characterised by spatial-temporal variation. PN success varied between endemic areas and clusters. Greater emphasis should be placed on the role of PN in the control of gonorrhoea to reduce the risk of onward transmission, re-infection, and complications of infection

Identification of Candidate Genes for Dyslexia Susceptibility on Chromosome 18

Background: Six independent studies have identified linkage to chromosome 18 for developmental dyslexia or general reading ability. Until now, no candidate genes have been identified to explain this linkage. Here, we set out to identify the gene(s) conferring susceptibility by a two stage strategy of linkage and association analysis. Methodology/Principal Findings: Linkage analysis: 264 UK families and 155 US families each containing at least one child diagnosed with dyslexia were genotyped with a dense set of microsatellite markers on chromosome 18. Association analysis: Using a discovery sample of 187 UK families, nearly 3000 SNPs were genotyped across the chromosome 18 dyslexia susceptibility candidate region. Following association analysis, the top ranking SNPs were then genotyped in the remaining samples. The linkage analysis revealed a broad signal that spans approximately 40 Mb from 18p11.2 to 18q12.2. Following the association analysis and subsequent replication attempts, we observed consistent association with the same SNPs in three genes; melanocortin 5 receptor (MC5R), dymeclin (DYM) and neural precursor cell expressed, developmentally down-regulated 4-like (NEDD4L). Conclusions: Along with already published biological evidence, MC5R, DYM and NEDD4L make attractive candidates for dyslexia susceptibility genes. However, further replication and functional studies are still required.Publisher PDFPeer reviewe

Biallelic Variants in PYROXD2 Cause a Severe Infantile Metabolic Disorder Affecting Mitochondrial Function

Pyridine Nucleotide-Disulfide Oxidoreductase Domain 2 (PYROXD2; previously called YueF) is a mitochondrial inner membrane/matrix-residing protein and is reported to regulate mitochondrial function. The clinical importance of PYROXD2 has been unclear, and little is known of the protein’s precise biological function. In the present paper, we report biallelic variants in PYROXD2 identified by genome sequencing in a patient with suspected mitochondrial disease. The child presented with acute neurological deterioration, unresponsive episodes, and extreme metabolic acidosis, and received rapid genomic testing. He died shortly after. Magnetic resonance imaging (MRI) brain imaging showed changes resembling Leigh syndrome, one of the more common childhood mitochondrial neurological diseases. Functional studies in patient fibroblasts showed a heightened sensitivity to mitochondrial metabolic stress and increased mitochondrial superoxide levels. Quantitative proteomic analysis demonstrated decreased levels of subunits of the mitochondrial respiratory chain complex I, and both the small and large subunits of the mitochondrial ribosome, suggesting a mitoribosomal defect. Our findings support the critical role of PYROXD2 in human cells, and suggest that the biallelic PYROXD2 variants are associated with mitochondrial dysfunction, and can plausibly explain the child’s clinical presentation

Teprotumumab Efficacy in Retreatment and Longer-Term Thyroid Eye Disease: OPTIC-X Study Results

Teprotumumab, an insulin-like growth factor I receptor inhibitory antibody, improves proptosis, diplopia, inflammatory signs/symptoms, and quality of life in thyroid eye disease (TED) patients.1,2 In the phase 3, randomized, placebo-controlled trial (OPTIC), 83% receiving teprotumumab were responders (≥2 mm proptosis reduction) after 24 weeks (vs. 10% placebo).2 Extension of this trial (OPTIC-X) examined benefit of retreatment (additional 24-week treatment) in those who had disease exacerbation (flare) or were placebo/teprotumumab non-responders, and whether longer disease duration impacts treatment response

Teprotumumab Efficacy in Retreatment and Longer-Term Thyroid Eye Disease: OPTIC-X Study Results

Teprotumumab, an insulin-like growth factor I receptor inhibitory antibody, improves proptosis, diplopia, inflammatory signs/symptoms, and quality of life in thyroid eye disease (TED) patients.1,2 In the phase 3, randomized, placebo-controlled trial (OPTIC), 83% receiving teprotumumab were responders (≥2 mm proptosis reduction) after 24 weeks (vs. 10% placebo).2 Extension of this trial (OPTIC-X) examined benefit of retreatment (additional 24-week treatment) in those who had disease exacerbation (flare) or were placebo/teprotumumab non-responders, and whether longer disease duration impacts treatment response

GpsTunes: controlling navigation via audio feedback

We combine the functionality of a mobile Global Positioning System (GPS) with that of an MP3 player, implemented on a PocketPC, to produce a handheld system capable of guiding a user to their desired target location via continuously adapted music feedback. We illustrate how the approach to presentation of the audio display can benefit from insights from control theory, such as predictive 'browsing' elements to the display, and the appropriate representation of uncertainty or ambiguity in the display. The probabilistic interpretation of the navigation task can be generalised to other context-dependent mobile applications. This is the first example of a completely handheld location- aware music player. We discuss scenarios for use of such systems

Quarterly gonorrhoea diagnosis rate with regions grouped by Local Authority (LA), England: 2013.

<p>Regions are compared to the English average (12.6/100,000 people) as higher, similar or lower. Similar regions were denoted as those within 20% above or below the English average (12.6–15.1 and 10.1–12.6/100,000 people, respectively).</p

Teprotumumab Effect on Proptosis, Diplopia and Quality of Life in Active Thyroid Eye Disease (TED) (PDF)

Active thyroid eye disease (TED), a progressive, autoimmune condition, produces retro-orbital inflammation/tissue expansion. Patients present with ocular pain, redness, and swelling. Retro-orbital fat/muscle expansion produces subsequent proptosis, diplopia, and strabismus. These manifestations can persist after inflammation is no longer evident. A phase 3 placebo-controlled trial recently confirmed that teprotumumab, an IGF-1R inhibitory antibody, significantly reduced TED-associated proptosis and improved other outcomes.[1] Key TED outcomes (proptosis [mm], subjective Bahn/Gorman diplopia grade, and GO-QOL) from the teprotumumab phase 2 and 3 trials are reported here.[1,2

Teprotumumab Effect on Proptosis, Diplopia and Quality of Life in Active Thyroid Eye Disease (TED) (Slides)

Active thyroid eye disease (TED), a progressive, autoimmune condition, produces retro-orbital inflammation/tissue expansion. Patients present with ocular pain, redness, and swelling. Retro-orbital fat/muscle expansion produces subsequent proptosis, diplopia, and strabismus. These manifestations can persist after inflammation is no longer evident. A phase 3 placebo-controlled trial recently confirmed that teprotumumab, an IGF-1R inhibitory antibody, significantly reduced TED-associated proptosis and improved other outcomes.[1] Key TED outcomes (proptosis [mm], subjective Bahn/Gorman diplopia grade, and GO-QOL) from the teprotumumab phase 2 and 3 trials are reported here.[1,2