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Hayley S. Mountford Dorothy V. M. Bishop Paul A. Thompson Nuala H. Simpson Dianne F. Newbury 《American journal of medical genetics. Part C, Seminars in medical genetics》2020,184(2):256-266
Sex chromosome trisomies (SCTs) (XXX, XXY, and XYY karyotypes) are associated with an elevated risk of neurodevelopmental disorders. The range of severity of the phenotype is substantial. We considered whether this variable outcome was related to the presence of copy number variants (CNVs)—stretches of duplicated or deleted DNA. A sample of 125 children with an SCT were compared with 181 children of normal karyotype who had been given the same assessments. First, we compared the groups on measures of overall CNV burden: number of CNVs, total span of CNVs, and likely functional impact (probability of loss‐of‐function intolerance, pLI, summed over CNVs). Differences between groups were small relative to within‐group variance and not statistically significant on overall test. Next, we considered whether a measure of general neurodevelopmental impairment was predicted by pLI summed score, SCT versus comparison group, or the interaction between them. There was a substantial effect of SCT/comparison status but the pLI score was not predictive of outcomes in either group. We conclude that variable presence of CNVs is not a likely explanation for the wide phenotypic variation in children with SCTs. We discuss methodological challenges of testing whether CNVs are implicated in causing neurodevelopmental problems. 相似文献
3.
Resistance mechanisms to plant viruses: an overview 总被引:18,自引:0,他引:18
To obtain virus-resistant host plants, a range of operational strategies can be followed nowadays. While for decades plant breeders have been able to introduce natural resistance genes in susceptible genotypes without knowing precisely what these resistance traits were, currently a growing number of (mostly) dominant resistance genes have been cloned and analyzed. This has led not only to a better understanding of the plant's natural defence systems, but also opened the way to use these genes beyond species borders. Besides using natural resistance traits, also several novel, "engineered" forms of virus resistance have been developed over the past 15 years. The first successes were obtained embarking from the principle of pathogen-derived resistance (PDR) by transforming host plants with viral genes or sequences with the purpose to block a specific step during virus multiplication in the plant. As an unforeseen spin-off of these investments, the phenomenon of post-translational gene silencing (PTGS) was discovered, which to date is by far the most successful way to engineer resistance. It is generally believed that PTGS reflects a natural defence system of the plant, and part of the hypothesized components required for PTGS have been identified. As counteracting strategy, and confirming PTGS to be a natural phenomenon, a considerable number of viruses have acquired gene functions by which they can suppress PTGS. In addition to PDR and PTGS, further strategies for engineered virus resistance have been explored, including the use of pokeweed antiviral protein (PAP), 2',5'-oligoadenylate synthetase and "plantibodies". This paper will give a brief overview of the major strategies that have become operational during the past 10 years. 相似文献
4.
O. E. Scholten H. Paul D. Peters J. W. M. Van Lent R. W. Goldbach 《Archives of virology》1994,136(3-4):349-361
Summary Mechanisms of resistance to beet necrotic yellow vein virus (BNYVV) were studied by comparing the multiplication and distribution of BNYVV in root tissue of some beet accessions. Seedlings were infected either by soil containing resting spores ofPolymyxa betae with BNYVV, or by a viruliferous zoospore suspension. With both inoculation methods high virus concentrations were obtained in rootlets of the susceptible cultivar Regina. Using infested soil, low virus concentrations were found in the partially resistant cultivar Rima and in the resistant accessions Holly and WB42. When a zoospore suspension was used, similar virus concentrations occurred in Rima and Holly as in Regina, while a low virus concentration was found in WB42. By in situ localisation studies, using immunogold-silver labelling, virus was detected in Regina after infection by soil or a zoospore suspension, but it could only be detected in the resistant accessions after infection by a zoospore suspension. In rootlets of Regina, Rima and Holly, virus was found in the epidermis, cortex parenchyma, endodermis, and interstitial parenchyma, but in general not inside the vascular tissue. In WB42 the virus, occurring in small aggregates, seemed to be restricted to the epidermis and some cortex parenchyma cells. Comparing both the multiplication and distribution of BNYVV in rootlets of the accessions studied, it is concluded that the virus resistance mechanism in Rima and Holly is different from that in WB42. 相似文献
5.
Leah R. Ketcheson Erin E. Centeio Erin E. Snapp Hayley B. McKown Jeffrey J. Martin 《Disability and health journal》2021,14(1):100952
BackgroundChildren with intellectual and developmental disabilities (IDD) often experience increased barriers to engaging in physical activity (PA) which can stem from lack of gross motor function (GMF) development. Intervening on GMF at an early age can create better opportunities for children with IDD to engage in regular PA. In turn, increased PA can improve health outcomes and increase social skills.ObjectiveThe primary objective of this pilot study was to explore the effectiveness of a community-based GMF-focused PA intervention for improving overall motor skills and PA for children with IDD.MethodsAll study participants (n = 24) engaged in 10 weeks of programming for 1 h each week. A convenience sample was utilized.ResultsResults indicated no statistically significant changes pre to post for motor skill scores. However, a visual analysis of mean changes showed a consistent pattern of increased scores from pre to post on most skills. Additionally, we found that a change in participant locomotor skills significantly predicted change in Moderate to Vigorous Physical Activity (MVPA), F (1,11) = 5.16, Adj R2 = .26, p = .04.ConclusionsThese results suggest individualized attention on GMF may help to increase motor skills for children with IDD. This study adds to the small but growing amount of research examining the efficacy of community based adapted PA interventions. Further, study results should support continued exploration of effective approaches to address the motor delays experienced by children with IDD. 相似文献
6.
Summary Sequence analysis of iris severe mosaic potyvirus genomic RNA revealed an unusual E/G cleavage site between the deduced large nuclear-inclusion protein and coat protein sequences. The latter showed an N-terminus of only 15 amino acids. The 3 non-translated region of the viral RNA was 340 nucleotides long. 相似文献
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Danny Azucar Joshua A Rusow Lindsay Slay Mariam Taiwo Aracely Rodriguez Ali Johnson Sam Calvetti Deja Wright Su Wu Bethany Bray Jeremy T Goldbach Michele D Kipke 《JMIR Research Protocols》2022,11(11)
BackgroundAs we enter the fifth decade of the AIDS epidemic, health researchers and AIDS activists reflect both on the progress that has been made and the importance of continued prevention efforts for those most at risk. As HIV infection rates continue to fluctuate across communities, a trend has emerged with new HIV infections becoming increasingly concentrated—with cascading effects—among people aged <30 years, from marginalized racial and ethnic groups, and who are sexual or gender minorities.ObjectiveIn this paper, we discuss the renewal of the Healthy Young Men’s (HYM) Cohort Study and the addition of a subcohort—TRUTH: A Transgender Youth of Color Study. The overarching aim of our renewed study was to inform new intervention strategies; understand linkage to care; and examine changes over time with respect to minority-related stress and intersectional identities and their relationship with substance use, mental health, and HIV risk. Findings from this study will help to inform the development of new interventions designed to engage African American and Black and Latino young men who have sex with men (YMSM) and transgender and gender minority youth in the HIV prevention and care continua and to reduce risk by addressing pathways of minority-related stress and intersectional stigma.MethodsLongitudinal study (baseline and follow-up assessments every 6 months for a total of 8 waves of data collection) is ongoing with reconsented cohort from the last iteration of HYM Cohort Study. This study protocol includes self-report survey, collection of urine to assess recent use of illicit drugs, and collection of blood and rectal and throat swabs to test for current sexually transmitted infection and HIV infection. An additional sample of blood and plasma (10 mL for 4 aliquots and 1 pellet) is also collected and stored in the HYM Cohort Study biorepository for future studies. This mixed methods study design includes collection of triangulated analysis of quantitative, qualitative, and biological measures (ie, drug use, sexually transmitted infection and HIV testing, and adherence to antiretroviral therapy among participants who are HIV+) at baseline and every 6 months.ResultsAs of February 2022, participants from the past 4 years of the HYM Cohort Study and TRUTH: A Transgender Youth of Color Study Cohort have been reconsented and enrolled into the renewal period of longitudinal data collection, which is projected from summer of 2020 until summer of 2025. Recruitment is ongoing to reach our target enrollment goal of YMSM and transgender minority youth.ConclusionsThe findings from this study are being used to inform the development of new, and adaptation of existing, evidence-based HIV prevention interventions designed to engage populations of transgender and gender minority youth and YMSM in the HIV prevention and care continua.International Registered Report Identifier (IRRID)DERR1-10.2196/39232 相似文献
9.
Jim Maas Garry Barton Vivienne Maskrey Hayley Pinto Richard Holland 《Drug and alcohol dependence》2013
Background
The cost of opiate substitution is usually considered lower in cost when methadone is used, as compared to that of buprenorphine, however the overall cost effectiveness of substitution programmes comparing the two drugs remains largely unknown.Methods
We evaluated the treatment cost and effectiveness of methadone and buprenorphine when used in an opiate substitution programme in Norfolk, UK. All programme costs, estimated from the perspective of the drug treatment clinic, were collected on 361 opiate-dependent participants over a six-month period. Total costs comprised medication (methadone or buprenorphine) costs, pharmacy supervision and dispensing costs, and drug service clinic costs. Effectiveness was measured in terms of (1) each programmes ability to retain participants in the programme for six months, and (2) the ability of the programme to accomplish complete abstinence from illicit opiate consumption.Results
Overall, mean medication-only costs of methadone were lower than that of buprenorphine, however, pharmacy and clinic costs were lower for the buprenorphine programme. The covariate-adjusted mean total cost of the two programmes was not significantly different. Mean six-month retention rates were higher on the methadone programme, therefore, the methadone programme “dominates” the buprenorphine programme as it was slightly more effective for the same cost. Conversely, when ability to stop taking illicit opiates concomitant with opiate substitution medication was considered, the buprenorphine programme was more effective with an additional cost of £903 per individual who stopped illicit opiate use.Conclusions
The provision of buprenorphine should be considered an appropriate treatment if cessation of illicit opiate use, concomitant with programme retention is considered an important outcome. 相似文献10.
Kenneth Shulman Nathan Herrmann Hayley Peglar Daniel Dochylo Clare Burns Carmelle Peisah 《Revue canadienne de psychiatrie》2021,66(3):255
Objectives:Physicians and other mental health experts are increasingly called on to assist the courts with the determination of testamentary capacity. We aim to improve the understanding of the retrospective assessment of testamentary capacity for medical experts in order to provide more useful reports for the court’s determinations and to provide a methodology for the retrospective assessment of testamentary capacity.Method:Medical experts with experience in the retrospective assessment of testamentary capacity collaborated with lawyers who practice estate litigation. The medical literature on the assessment of testamentary capacity was reviewed and integrated. The medical experts provided a clinical perspective, while the lawyers ensured that the case law and legal perspective were integrated into this review.Results:The focus and limitations of the medical expert are outlined including the need to be objective, nonpartisan, and fair. For the benefit of the court, the medical expert should describe the nature and severity of relevant medical, psychiatric, and cognitive disorders, and how they may impact on the specific criteria for testamentary capacity as defined by the leading case of Banks v Goodfellow. Medical experts should opine only on the issue of vulnerability to influence and defer to the court to determine the facts of the case regarding any influence that may have been exerted.Conclusions:Although the ultimate determination of testamentary capacity is a legal one, medical experts can help the court achieve the most informed legal decision by providing relevant information on clinical issues that may impact the criteria for testamentary capacity. 相似文献