Objectives
We sought to compare all‐cause mortality of people living with HIV and accessing care in Canada and the UK.
Methods
Individuals from the Canadian Observational Cohort (CANOC) collaboration ...and UK Collaborative HIV Cohort (UK CHIC) study who were aged ≥ 18 years, had initiated antiretroviral therapy (ART) for the first time between 2000 and 2012 and who had acquired HIV through sexual transmission were included in the analysis. Cox regression was used to investigate the difference in mortality risk between the two cohort collaborations, accounting for loss to follow‐up as a competing risk.
Results
A total of 19 960 participants were included in the analysis (CANOC, 4137; UK CHIC, 15 823). CANOC participants were more likely to be older median age 39 years (interquartile range (IQR): 33, 46 years) vs. 36 years (IQR: 31, 43 years) for UK CHIC participants, to be male (86 vs. 73%, respectively), and to report men who have sex with men (MSM) sexual transmission risk (72 vs. 56%, respectively) (all P < 0.001). Overall, 762 deaths occurred during 98 798 person‐years (PY) of follow‐up, giving a crude mortality rate of 7.7 per 1000 PY 95% confidence interval (CI): 7.1, 8.3 per 1000 PY. The crude mortality rates were 8.6 (95% CI: 7.4, 10.0) and 7.5 (95% CI: 6.9, 8.1) per 1000 PY among CANOC and UK CHIC study participants, respectively. No statistically significant difference in mortality risk was observed between the cohort collaborations in Cox regression accounting for loss to follow‐up as a competing risk (adjusted hazard ratio 0.86; 95% CI: 0.72–1.03).
Conclusions
Despite differences in national HIV care provision and treatment guidelines, mortality risk did not differ between CANOC and UK CHIC study participants who acquired HIV through sexual transmission.
Presents a case study of a persistent widespread oral candidosis in a diabetic patient. Discusses the range of oral conditions, which have been associated with the disease. Source: National Library ...of New Zealand Te Puna Matauranga o Aotearoa, licensed by the Department of Internal Affairs for re-use under the Creative Commons Attribution 3.0 New Zealand Licence.
Shelf seas play an important role in the global carbon cycle, absorbing atmospheric carbon dioxide (CO
) and exporting carbon (C) to the open ocean and sediments. The magnitude of these processes is ...poorly constrained, because observations are typically interpolated over multiple years. Here, we used 298500 observations of CO
fugacity (fCO
) from a single year (2015), to estimate the net influx of atmospheric CO
as 26.2 ± 4.7 Tg C yr
over the open NW European shelf. CO
influx from the atmosphere was dominated by influx during winter as a consequence of high winds, despite a smaller, thermally-driven, air-sea fCO
gradient compared to the larger, biologically-driven summer gradient. In order to understand this climate regulation service, we constructed a carbon-budget supplemented by data from the literature, where the NW European shelf is treated as a box with carbon entering and leaving the box. This budget showed that net C-burial was a small sink of 1.3 ± 3.1 Tg C yr
, while CO
efflux from estuaries to the atmosphere, removed the majority of river C-inputs. In contrast, the input from the Baltic Sea likely contributes to net export via the continental shelf pump and advection (34.4 ± 6.0 Tg C yr
).
The aim of this study was to determine prospectively the frequency of pathogenic chromosomal microdeletions and microduplications in a large group of referred patients with developmental delay (DD), ...intellectual disability (ID) or autism spectrum disorders (ASD) within a genetic diagnostic service. First tier testing was applied using a standardised oligo-array comparative genomic hybridization (CGH) platform, replacing conventional cytogenetic testing that would have been used in the past. Copy number variants (CNVs) found to be responsible for the clinical condition on the request form could all be subdivided into three groups: well established pathogenic microdeletion/microduplication/aneuploidy syndromes, predicted pathogenic CNVs as interpreted by the laboratory, and recently established pathogenic disease susceptibility CNVs. Totalled from these three groups, with CNVs of uncertain significance excluded, detection rates were: DD (13.0%), ID (15.6%), ASD (2.3%), ASD with DD (8.2%), ASD with ID (12.7%) and unexplained epilepsy with DD, ID and ASD (10.9%). The greater diagnostic sensitivity arising from routine application of array CGH, compared with previously used conventional cytogenetics, outweighs the interpretative issues for the reporting laboratory and referring clinician arising from detection of CNVs of uncertain significance. Precise determination of any previously hidden molecular defect responsible for the patient’s condition is translated to improved genetic counselling.
Cell Biology and Imaging 1 and Divisions of Retrovirology 2 , Virology 3 and Immunobiology 4 , National Institute for Biological Standards & Control, Blanche Lane, South Mimms, Potters Bar, Herts EN6 ...3QG, UK
CAMR, Porton Down, Salisbury, Wilts SP4 0JG, UK 5
Author for correspondence: Neil Almond. Fax +44 1707 649865. e-mail nalmond{at}nibsc.ac.uk
The distribution of virus-infected cells in cynomolgus macaques was determined at 4, 7, 14 and 28 days following intravenous challenge with 1000 TCID 50 of the wild-type simian immunodeficiency virus SIVmacJ5 (stock J5C). At each time-point, pairs of macaques were killed humanely and the presence of SIV was determined and quantified in blood, spleen, peripheral and mesenteric lymph nodes, thymus, lung and ileum by virus co-cultivation with C8166 cells, by quantitative DNA PCR or by in situ hybridization (ISH). At day 4 post-infection (p.i.), detection of the virus was sporadic. By day 7 p.i., however, significant SIV loads were detected in the blood and lymphoid tissues by DNA PCR and virus co-cultivation. Large numbers of cells expressing SIV RNA were detected in mesenteric lymph nodes by ISH and significantly fewer ( P <0·05) in the spleen. Significant numbers of ISH-positive cells were also observed in sections of ileum. By day 14 p.i., the distribution of SIV was more even in all lymphoid tissues analysed. By day 28, most of the tissues were negative by ISH, but all remained positive by virus isolation and DNA PCR. Immunolabelling of sections of mesenteric lymph node with monoclonal antibodies specific for SIV envelope and Nef largely confirmed the observations from ISH. These results indicate that, even following intravenous challenge, a major site of the initial replication of SIV is gut-associated lymphoid tissue. Vaccines that induce protection at this site may therefore be superior, even against parenteral challenge.
Stop or nonsense mutations are known to disrupt gene function in a number of different ways. We have studied the effects of the stop mutation R553X in exon 11 of the CFTR gene by analyzing mRNA ...extracted from nasal epithelial cells harvested from patients with cystic fibrosis. Four patients who were compound heterozygotes for the R553X mutation were studied. Ten non-CF control subjects were also studied. In all four patients, full-length CFTR mRNA was identified, but only a very small proportion of this was derived from the R553X allele. A smaller transcript, lacking exon 11, was also seen in the R553X patients but not in the controls. Most of this transcript was derived from the R553X allele. These results suggest that the R553X mutation results in skipping of the exon in which it is located.
Three different putative splicing mutations in the CFTR gene have been studied by analysing mRNA extracted from nasal epithelial cells harvested from patients with cystic fibrosis. Six patients were ...analysed, all of whom had classical symptoms of cystic fibrosis (CF). Two patients carried the 621 + 1G-->T mutation, 3 patients carried the 1717 - 1G-->A mutation and 1 patient carried the 1898 + 1G-->A mutation. All patients carried the delta F508 mutation on the other chromosome. Ten non-CF control subjects were also studied. The 621 + 1G-->T mutation resulted in activation of an alternative splice site within exon 4 in one patient and activation of this site or skipping of exon 4 in the other patient. The 1717 - 1G-->A mutation resulted in skipping of exon 11 in all 3 patients studied and the 1898 + 1G-->T mutation resulted in skipping of exon 12. These experiments demonstrate that these mutations do result in aberrant splicing of CFTR mRNA as predicted from the changes in genomic sequence.
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