46 research outputs found

    Predictors of Aged Residential Care Placement in Patients Newly Diagnosed with Dementia at a New Zealand Memory Service

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    Background: Aged residential care (ARC) is a significant cost of dementia care. However, little is known about the predictors of ARC placement in New Zealand (NZ), which is important for service planning and funding. The aim of this study was to investigate the sociodemographic and clinical characteristics that predict future ARC placement among people who received a new diagnosis of dementia at a NZ memory service. Methods: Routinely collected baseline sociodemographic and clinical data in a memory service from 14/06/13 and 14/12/19 were linked with administrative LTC admission data up to 24/1/2020. Survival analysis was carried out using multivariate Cox regression models to determine significant risk factors and their association with ARC placement. Results: A total of 657 NZ European, Māori and Pacific Islander patients were included in the analyses. There were significant differences by ethnicity including age, living situation, comorbidity and ARC placement. Adjusted analyses showed that risk of ARC placement was increased by older age (HR 1.02 per year, 95%CI:1.00–1.05), moderate dementia (HR 1.45, 95%CI:1.05–1.99), severe dementia (HR 2.25, 95%CI:1.33–3.81), and antipsychotics (HR 1.55, 95%CI:1.04–2.32); while risk was reduced in Māori (HR 0.35, 95%CI:0.18–0.68) and Pacific Islanders (HR 0.32, 95%CI:0.20–0.51). Conclusions: Despite having more severe dementia and higher comorbidity, Māori and Pacific Islanders had reduced risks of ARC placement. There is an urgent need to better understand dementia care issues and to ensure culturally safe and responsive dementia services are accessible by Māori and Pacific Islanders living in the community

    Time to Switch to Second-line Antiretroviral Therapy in Children With Human Immunodeficiency Virus in Europe and Thailand.

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    Background: Data on durability of first-line antiretroviral therapy (ART) in children with human immunodeficiency virus (HIV) are limited. We assessed time to switch to second-line therapy in 16 European countries and Thailand. Methods: Children aged <18 years initiating combination ART (≄2 nucleoside reverse transcriptase inhibitors [NRTIs] plus nonnucleoside reverse transcriptase inhibitor [NNRTI] or boosted protease inhibitor [PI]) were included. Switch to second-line was defined as (i) change across drug class (PI to NNRTI or vice versa) or within PI class plus change of ≄1 NRTI; (ii) change from single to dual PI; or (iii) addition of a new drug class. Cumulative incidence of switch was calculated with death and loss to follow-up as competing risks. Results: Of 3668 children included, median age at ART initiation was 6.1 (interquartile range (IQR), 1.7-10.5) years. Initial regimens were 32% PI based, 34% nevirapine (NVP) based, and 33% efavirenz based. Median duration of follow-up was 5.4 (IQR, 2.9-8.3) years. Cumulative incidence of switch at 5 years was 21% (95% confidence interval, 20%-23%), with significant regional variations. Median time to switch was 30 (IQR, 16-58) months; two-thirds of switches were related to treatment failure. In multivariable analysis, older age, severe immunosuppression and higher viral load (VL) at ART start, and NVP-based initial regimens were associated with increased risk of switch. Conclusions: One in 5 children switched to a second-line regimen by 5 years of ART, with two-thirds failure related. Advanced HIV, older age, and NVP-based regimens were associated with increased risk of switch

    Experimental Modeling of Necrotizing Enterocolitis in Human Infant Intestinal Enteroids

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    Background: Experimental model systems are of paramount importance in advancing our understanding of human disease. Methods There are several limitations when using a single cell culture to recapitulate the findings in a complex organism and results often vary between species, when proxy animal models are studied. Results Human enteroids have allowed for study of human disease in complex multicellular culture systems. Here we present the novel use of human infant enteroids generated from premature infant intestine to study necrotizing enterocolitis (NEC), which is a devastating intestinal disorder that affects our most vulnerable pediatric population. Conclusions We demonstrate that NEC can be induced in premature human enteroids as supported by corresponding alterations in inflammation, apoptosis, tight junction expression, and permeability by treatment with lipopolysaccharide

    LD_Haploview

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    Data for Figure 3 and Figure 6 supportive information

    alpha estimates in introgressed regions

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    Data from Table 2. Alpha estimate for three introgressed P. balsamifera regions in P. trichocarpa, one in chromosome (Chr) 06 (region A) and two in chromosome 15 (B and C)

    Data from: Genomic and functional approaches reveal a case of adaptive introgression from Populus balsamifera (balsam poplar) in P. trichocarpa (black cottonwood)

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    Natural hybrid zones in forest trees provide systems to study the transfer of adaptive genetic variation by introgression. Previous landscape genomic studies in Populus trichocarpa, a keystone tree species, indicated genomic footprints of admixture with its sister species P. balsamifera and identified candidate genes for local adaptation. Here, we explored patterns of introgression and signals of local adaptation in P. trichocarpa and P. balsamifera, employing genome resequencing data from three chromosomes in pure species and admixed individuals from wild populations. Local ancestry analysis in admixed P. trichocarpa revealed a telomeric region in chromosome 15 with P. balsamifera ancestry, containing several candidate genes for local adaptation. Genomic analyses revealed signals of selection in certain genes in this region (e.g. PRR5, COMT1), and functional analyses based on gene expression variation and correlations with adaptive phenotypes suggest distinct functions of the introgressed alleles. In contrast, a block of genes in chromosome 12 paralogous to the introgressed region showed no signs of introgression or signatures of selection. We hypothesize that the introgressed region in chromosome 15 has introduced modular, or cassette-like variation into P. trichocarpa. These linked adaptive mutations are associated with a block of genes in chromosome 15 that appear to have undergone neo- or sub-functionalization relative to paralogs in a duplicated region on chromosome 12 that show no signatures of adaptive variation. The association between P. balsamifera introgressed alleles with the expression of adaptive traits in P. trichocarpa supports the hypothesis that this is a case of adaptive introgression in an ecologically important foundation species
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