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- Pantazis, N, et al.
(författare)
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Determining the likely place of HIV acquisition for migrants in Europe combining subject-specific information and biomarkers data
- 2019
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Ingår i: Statistical methods in medical research. - : SAGE Publications. - 1477-0334 .- 0962-2802. ; 28:7, s. 1979-1997
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Tidskriftsartikel (refereegranskat)abstract
- In most HIV-positive individuals, infection time is only known to lie between the time an individual started being at risk for HIV and diagnosis time. However, a more accurate estimate of infection time is very important in certain cases. For example, one of the objectives of the Advancing Migrant Access to Health Services in Europe (aMASE) study was to determine if HIV-positive migrants, diagnosed in Europe, were infected pre- or post-migration. We propose a method to derive subject-specific estimates of unknown infection times using information from HIV biomarkers’ measurements, demographic, clinical, and behavioral data. We assume that CD4 cell count (CD4) and HIV-RNA viral load trends after HIV infection follow a bivariate linear mixed model. Using post-diagnosis CD4 and viral load measurements and applying the Bayes’ rule, we derived the posterior distribution of the HIV infection time, whereas the prior distribution was informed by AIDS status at diagnosis and behavioral data. Parameters of the CD4–viral load and time-to-AIDS models were estimated using data from a large study of individuals with known HIV infection times (CASCADE). Simulations showed substantial predictive ability (e.g. 84% of the infections were correctly classified as pre- or post-migration). Application to the aMASE study ( n = 2009) showed that 47% of African migrants and 67% to 72% of migrants from other regions were most likely infected post-migration. Applying a Bayesian method based on bivariate modeling of CD4 and viral load, and subject-specific information, we found that the majority of HIV-positive migrants in aMASE were most likely infected after their migration to Europe.
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| 2. |
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| 3. |
- Hammarsjö, A., et al.
(författare)
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High diagnostic yield in skeletal ciliopathies using massively parallel genome sequencing, structural variant screening and RNA analyses
- 2021
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Ingår i: Journal of Human Genetics. - : Springer Nature. - 1434-5161 .- 1435-232X. ; 66:10, s. 995-1008
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Tidskriftsartikel (refereegranskat)abstract
- Skeletal ciliopathies are a heterogenous group of disorders with overlapping clinical and radiographic features including bone dysplasia and internal abnormalities. To date, pathogenic variants in at least 30 genes, coding for different structural cilia proteins, are reported to cause skeletal ciliopathies. Here, we summarize genetic and phenotypic features of 34 affected individuals from 29 families with skeletal ciliopathies. Molecular diagnostic testing was performed using massively parallel sequencing (MPS) in combination with copy number variant (CNV) analyses and in silico filtering for variants in known skeletal ciliopathy genes. We identified biallelic disease-causing variants in seven genes: DYNC2H1, KIAA0753, WDR19, C2CD3, TTC21B, EVC, and EVC2. Four variants located in non-canonical splice sites of DYNC2H1, EVC, and KIAA0753 led to aberrant splicing that was shown by sequencing of cDNA. Furthermore, CNV analyses showed an intragenic deletion of DYNC2H1 in one individual and a 6.7 Mb de novo deletion on chromosome 1q24q25 in another. In five unsolved cases, MPS was performed in family setting. In one proband we identified a de novo variant in PRKACA and in another we found a homozygous intragenic deletion of IFT74, removing the first coding exon and leading to expression of a shorter message predicted to result in loss of 40 amino acids at the N-terminus. These findings establish IFT74 as a new skeletal ciliopathy gene. In conclusion, combined single nucleotide variant, CNV and cDNA analyses lead to a high yield of genetic diagnoses (90%) in a cohort of patients with skeletal ciliopathies.
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| 4. |
- Queiroga, Henrique, et al.
(författare)
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Vertical migration behaviour in the larvae of the shore crab Carcinus maenas from a microtidal system (Gullmarsfjord,Sweden)
- 2002
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Ingår i: Marine Ecology-Progress Series. ; 237, s. 195-207
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Tidskriftsartikel (refereegranskat)abstract
- Tide-related vertical migration behaviours which assist in horizontal transport of marine larvae have been documented in many species from meso-tidal systems; however, little is known about larval behaviour in areas where the tides do not produce predictable changes in water currents. We assessed the vertical migration behaviour in larvae of the shore crab Carcinus maenas (L.) from the Swedish west coast, to explore possible transport mechanisms in a micro-tidal system. Replicated plankton samples were collected at a fixed station from 2 depths during flood and ebb tides, and analysed for effects of tides and light on temporal and vertical patterns in abundance. In a complementary experiment, first-stage zoeae were hatched in the laboratory from field-collected females and studied in constant darkness for endogenous circa-tidal or circa-diel rhythms. The abundance of different larval stages decreased from the first to the fourth zoeal stage by a factor 10, whereas megalopal densities were similar to those of the first zoea. This pattern in abundance indicates an offshore/onshore transportation of larvae during ontogeny, suggesting a behavioural component in larval dispersal. However, contrary to what has been demonstrated in larvae from meso-tidal areas, none of the larval stages displayed a vertical or temporal pattern in abundance related to the tide, although a clear semi-diurnal tidal change of approximately 0.3 m was registered throughout the sampling periods. Instead, the highest densities of all larval stages were consistently sampled during low light conditions, indicating a diel pattern in swimming behaviour. This behaviour appears to be controlled by exogenous cues, since the laboratory experiment with first zoeae in constant darkness did not indicate any consistent tidal or diel rhythm in vertical migration. The lack of an endogenous circa-tidal vertical migration rhythm suggests that Swedish shore crabs are reproductively isolated from the British Isles populations, where this behaviour has been demonstrated to be inherited. The possibility that: C. maenas larvae in micro-tidal systems may use predictable sea and land breezes as a mechanism for cross-shelf transport is discussed.
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