Introduction
The UNAIDS 90‐90‐90 targets for the cascade of care are widely used to monitor the success of HIV care programmes but there are few studies in children. We assessed the cascade for ...children and adolescents living with HIV in the national Collaborative HIV Paediatric Study (CHIPS) in the UK and Ireland.
Methods
Utilizing longitudinal data from CHIPS we compared the cascade of care for 2010, 2013 and 2016. Among children diagnosed with HIV and not known to be lost to follow‐up at the start of each calendar year, we summarized the proportion in active paediatric care during that year (defined as having ≥1 clinic visit, CD4 or viral load measurement, or change to antiretroviral therapy (ART) regimen), and of these, the proportion on ART at last visit in that year. Among those on ART, the proportion with viral suppression (<200 copies/mL) and good immune status (WHO immunological stage none‐/mild‐for‐age) at last visit in the year were summarized. Among those in care in 2016, outcomes were compared by current age, place of birth (born abroad vs. UK/Ireland) and sex.
Results
Of children in paediatric HIV care at the start of 2010, 2013 and 2016 (n = 1249, 1157, 905 respectively), the proportion in active care during that calendar year was high throughout at 97 to 99%. Of those in active care, the proportion on ART increased from 79% to 85% and 92% respectively (p < 0.001). Among those on ART, the proportion with viral suppression and good immune status was stable at 83% to 86% and 85% to 88%, respectively, across the years. Among children in care in 2016, those aged ≥15 years were less likely to be virally suppressed (79% vs. 91%, p < 0.001) or to have good immune status (78% vs. 94%, p < 0.001) compared to younger children; there were no differences by place of birth or sex.
Conclusions
Children and adolescents in the UK and Ireland national cohort had high retention in care. The proportion on ART increased significantly over time although there was no change in viral suppression or good immune status. Poorer outcomes among adolescents highlight the need for targeted support for this population.
•A track of differentiation was identified as time progress.•While osteoblast genes were upregulated, stem cell genes were down-regulated.•Microarray results were confirmed by PCR analysis.•Skeletal ...development was significantly dysregulated by cadmium sulfate.•Transcriptomics can detect toxic effects at earlier time points.
The mouse embryonic stem cell test (mEST) is a promising in vitro assay for predicting developmental toxicity. In the current study, early differentiation of D3 mouse embryonic stem cells (mESCs) under osteoblast culture conditions and embryotoxicity of cadmium sulfate were examined. D3 mESCs were exposed to cadmium sulfate for 24, 48 or 72h, and whole genome transcriptional profiles were determined. The results indicate a track of differentiation was identified as mESCs differentiate. Biological processes that were associated with differentiation related genes included embryonic development and, specifically, skeletal system development. Cadmium sulfate inhibited mESC differentiation at all three time points. Functional pathway analysis indicated biological pathways affected included those related to skeletal development, renal and reproductive function. In summary, our results suggest that transcriptional profiles are a sensitive indicator of early mESC differentiation. Transcriptomics may improve the predictivity of the mEST by suggesting possible modes of action for tested chemicals.
To compare visual evoked potentials (VEPs) and contrast sensitivity in adults with early- or late-onset strabismic amblyopia.
Twelve adults with early- and 12 with late-onset strabismic amblyopia ...with similar ranges of visual acuity were studied. Pattern-onset VEPs to 30-minute checks were recorded at a range of contrast levels. Contrast sensitivity (CS) was measured at 3.2 cyc/deg using a two-alternative, forced-choice staircase method.
There was no significant difference in VEP CII latency or amplitude between amblyopic and fellow eyes across all contrast levels for the early-onset group, but in the late-onset group, CII latencies were significantly longer and amplitudes smaller in the amblyopic eye. CII responses in both amblyopic and fellow eyes of the early-onset amblyopes were of significantly shorter latency and smaller amplitude than normal. In the late-onset group the CII responses from the amblyopic eye were of significantly increased latency and reduced amplitude compared with normal, whereas latency and amplitude of fellow eye responses did not differ significantly from normal. Late-onset amblyopes showed reduced CS across the central field for the amblyopic eye, but increased CS for the fellow eye compared with normal. In the early-onset group, central CS did not differ between amblyopic and fellow eyes or from normal.
There are significant differences in the electrophysiological and psychophysical characteristics of adults with early- and late-onset strabismic amblyopia.
To examine changes in color- and motion-related visual function in patients with strabismic amblyopia.
Motion-onset and color visual-evoked potentials (VEPs) were recorded in 16 adult patients with ...strabismic amblyopia which had an early onset, before 18 months of age, and 14 patients with amblyopia of later onset. The results are compared with those from 21 normal adults.
The peak times of motion-onset VEPs in the amblyopic eye were longer those than in the fellow eye in patients with both early- and late-onset strabismic amblyopia, but peak times in both amblyopic and fellow eyes were shorter than those in normal eyes. In patients with late- but not early-onset amblyopia, the peak times for color VEPs were significantly longer in amblyopic than in fellow and normal eyes.
The patterns of abnormality for motion-onset and color VEPs in patients with strabismic amblyopia are different, probably indicating differential changes in function in magno- and parvocellular pathways. These abnormalities affect both the amblyopic and fellow eyes and are different in patients with an onset of amblyopia before or after 18 months of age.
Normal muscle precursor cells, prepared by the enzymatic disaggregation of neonatal mouse muscle, were implanted into an area of regenerating muscle in a genetically different inbred strain. This was ...done in an attempt to determine, first, whether donor muscle precursor cells prepared in this way would fuse with the developing muscle fibres of the host; and second, whether in the "mosaic" muscle fibres thus formed donor as well as host genes were expressed. As markers of the host and donor genes we used the allelic isoenzyme variants of glucose-6-phosphate isomerase (GPI). In 43 out of 60 grafts we detected the presence of a "hybrid" isoenzyme intermediate between host and donor types. This "hybrid" indicated that donor muscle precursor cells had fused with regenerating host muscle cells, and had expressed their GPI genes within the resulting mosaic muscle fibres. We have developed this technique with a view to inserting normal genes into genetically abnormal myopathic muscle.
Configuration and control of the ATLAS trigger and data acquisition Miotto, Giovanna Lehmann; Aleksandrov, Igor; Amorim, Antonio ...
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
11/2010, Letnik:
623, Številka:
1
Journal Article
Recenzirano
Odprti dostop
ATLAS is a general purpose experiment aimed at studying high-energy particle interactions at the Large Hadron Collider (LHC). This paper describes the evolution of the Controls and Configuration ...system of the ATLAS Trigger and Data Acquisition from the Technical Design Report to the first events taken with circulating beams. We present the lessons learned during the development.
The optic chiasm is one of the most popular models for studying axon guidance. Here axons make a key binary decision either to cross the midline to innervate the contralateral hemisphere or to remain ...uncrossed. In rodents, midline interactions between axons from the two eyes are critical for normal development, as early removal of one eye systematically disrupts hemispheric projections from the remaining eye, increasing the crossed projection at the expense of the uncrossed. This is similar to the abnormal decussation pattern seen in albinos. This pattern is markedly different in marsupials where early eye removal has no impact on projections from the remaining eye. These differences are related to the location of the uncrossed projection through the chiasm. In rodents these axons approach the midline whereas in marsupials they remain segregated laterally. We provide anatomical evidence in man suggesting that, unlike in rodents, uncrossed axons are confined laterally and do not mix in each hemi‐chiasm, which is a pattern similar to that found in marsupials. Further, we demonstrate electrophysiologically, using visual cortical evoked potentials, that the failure of one eye to develop in man has no impact on the hemispheric projections from the remaining eye. These data demonstrate that the mechanisms regulating chiasmal development in man differ from those in rodents but may be similar to those in marsupials. We suggest that mouse models of the organization and development of the optic chiasm are not common to placental mammals in general.
A total of 195 children were randomised to zidovudine (immediate) or matching placebo (deferred) in a multicentre double blind trial in vertically HIV infected children with early disease (the PENTA ...1 trial). Median follow up in the blinded phase was 1.9 years. Thereafter, individual children were unblinded following the results of adult trials showing a benefit of combination antiretroviral therapy (ART) over monotherapy, but follow up continued and is reported here until December 1998 (total follow up 4.6 years). Median time to starting ART in the deferred group was 2.7 years; 19% of deferred children had not started ART by 1999. Throughout follow up, the percentage of time spent on no ART, monotherapy, dual, and triple ART was 21%, 44%, 29%, and 6% respectively for immediate and 62%, 12%, 18%, and 8% for deferred groups. During the blinded phase eight (7.8%) immediate and 12 (13.3%) deferred children developed AIDS or died (log rank p = 0.24); overall 21 immediate and 20 deferred children progressed. In an analysis including all children regardless of original allocation, the risk of progression to AIDS or death, adjusting for age and time since trial entry was significantly lower during 1997–98 (2.4 per 100 child years) than during 1992–96 (6.6 per 100 child years), most likely a result of increased use of combination ART.
To compare the binocular enhancement of contrast sensitivity and stereoacuity in patients with Duane syndrome and normal subjects.
Monocular and binocular contrast sensitivity functions were ...determined using a two-alternative, forced-choice method in 14 patients with Duane syndrome and 14 normal subjects. Monocular and binocular log minimum angle of resolution (logMAR) acuities were measured, and stereoacuity was determined using the Titmus and TNO stereotests.
In the patients with Duane syndrome, the binocular enhancement of contrast sensitivity was increased across all spatial frequencies, although stereoacuity was reduced compared to that of the normal subjects. The increased enhancement was caused by a reduction in monocular contrast sensitivity rather than an increase in binocular contrast sensitivity. The patients with Duane syndrome also showed a generalized reduction of contrast sensitivity at high spatial frequencies.
It is suggested that the combination of reduced stereoacuity and increased binocular enhancement of contrast sensitivity seen in Duane syndrome can be explained by a partial loss of binocular cortical cells, caused by intermittent misalignment of the eyes during early visual development.
To evaluate the contribution of electrodiagnostic testing (EDT) to the management of children in a paediatric ophthalmology service using the Greenwich Grading System (GGS).
A retrospective analysis ...was performed of the case notes of 105 of the 113 paediatric patients referred from the Strabismus and Paediatric Service at Moorfields Eye Hospital for electrophysiological testing over a 1-year period. The GGS was used to quantify the contribution of EDT to the diagnosis, overall investigation, and treatment of each patient. Patients were further subdivided into different diagnostic groups to allow comparison of the value of EDT in different conditions.
EDT was found to be of value in 91% of the children tested and was considered an essential investigation in 71%. EDT made a new diagnosis in 7% of patients, changed it in 5%, and confirmed or excluded a diagnosis in 79%. EDT made a useful contribution to the overall investigation of 89% of the patients and was considered the only test that could provide the required information in 71%. The results of EDT allowed reassurance and/or explanation with regard to the diagnosis, prognosis, and treatment in 91% of children. In one patient, treatment was changed as a result of EDT. The clinical outcome was not adversely affected in any patient.
EDT was of value to the clinical management of most of the children reviewed, mainly by confirming or excluding a clinical diagnosis and allowing explanation and reassurance to children and parents. Electrodiagnostic information gave a new or changed diagnosis in 12% of the children.
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