Detectable clonal mosaicism and its relationship to aging and cancer

In an analysis of 31,717 cancer cases and 26,136 cancer-free controls from 13 genome-wide association studies, we observed large chromosomal abnormalities in a subset of clones in DNA obtained from blood or buccal samples. We observed mosaic abnormalities, either aneuploidy or copy-neutral loss of heterozygosity, of >2 Mb in size in autosomes of 517 individuals (0.89%), with abnormal cell proportions of between 7% and 95%. In cancer-free individuals, frequency increased with age, from 0.23% under 50 years to 1.91% between 75 and 79 years (P = 4.8 × 10(-8)). Mosaic abnormalities were more frequent in individuals with solid tumors (0.97% versus 0.74% in cancer-free individuals; odds ratio (OR) = 1.25; P = 0.016), with stronger association with cases who had DNA collected before diagnosis or treatment (OR = 1.45; P = 0.0005). Detectable mosaicism was also more common in individuals for whom DNA was collected at least 1 year before diagnosis with leukemia compared to cancer-free individuals (OR = 35.4; P = 3.8 × 10(-11)). These findings underscore the time-dependent nature of somatic events in the etiology of cancer and potentially other late-onset diseases

Female chromosome X mosaicism is age-related and preferentially affects the inactivated X chromosome

To investigate large structural clonal mosaicism of chromosome X, we analysed the SNP microarray intensity data of 38,303 women from cancer genome-wide association studies (20,878 cases and 17,425 controls) and detected 124 mosaic X events42Mb in 97 (0.25%) women. Here we show rates for X-chromosome mosaicism are four times higher than mean autosomal rates; X mosaic events more often include the entire chromosome and participants with X events more likely harbour autosomal mosaic events. X mosaicism frequency increases with age (0.11% in 50-year olds; 0.45% in 75-year olds), as reported for Y and autosomes. Methylation array analyses of 33 women with X mosaicism indicate events preferentially involve the inactive X chromosome. Our results provide further evidence that the sex chromosomes undergo mosaic events more frequently than autosomes, which could have implications for understanding the underlying mechanisms of mosaic events and their possible contribution to risk for chronic diseases

Expanding provider-initiated HIV testing at STI clinics in China

Despite expanding sexually transmitted epidemics in South China, the majority of patients presenting to sexually transmitted infection (STI) clinics are not routinely screened for HIV infection. Identifying barriers to offering HIV testing among STI care providers is an important public health priority. The aim of this study was to investigate the frequency of offering HIV testing among STI care providers in South China and reported physician barriers to offering HIV testing. More detailed operational data regarding HIV test offer frequency and barriers to testing may enhance routine HIV testing at STI clinics. A sample of 62 STI care providers within the Pearl River Delta Region of South China completed a survey including socio-demographic and training background information (including sex, age, medical education, year of terminal medical degree, HIV-specific training), reasons for not offering HIV testing routinely, and physical examination and sexual history taking practices. Frequency of offering HIV testing was calculated based on reports from research assistants and operational data. STI care providers offered HIV testing to 3011/10592 (28.4%) of their patients. There was substantial variability across providers in the frequency of offering testing, ranging from 3% to 100%. None of the identified physician factors were associated with offering HIV testing 100% of the time in the multivariate model. The most commonly physician reported barriers to HIV testing included: 1) low perceived prevalence of disease; and 2) not recommended by current guidelines. Forty-seven providers (76%) reported asking about same sex behaviors rarely or never. Further research on HIV screening practices of STI care providers may help scale up HIV provider-initiated testing and counseling programs

Reduced risk of low weight births among indigent women receiving care from nurse-midwives

STUDY OBJECTIVE—To examine the effect of a comprehensive prenatal and delivery programme administered by nurse-midwives on the risk of low weight births among indigent women.
STUDY DESIGN—Historical prospective study. Birth outcomes among the cohort were compared with all county births during the same period, adjusting for maternal age and race. Results are expressed as relative risks with 95% confidence intervals.
SETTING—An enhanced Medicaid funded pre-natal programme administered by nurse-midwives from 1992 to 1994 in Westchester County, New York.
PARTICIPANTS—Indigent mothers (n=1443), between the ages of 15 and 44, who were residents of Westchester County and indicated having Medicaid or no health care coverage.
RESULTS—There were 1474 live births among cohort mothers. Mean (SD) gestational age was 39.4 (1.9) weeks. Less than 6% of births occurred before 37 weeks gestation. The mean birth weight of cohort infants was 3365.6 (518.6) g. Only 4.1% of the cohort births were less than 2500 g. Compared with all county births, the cohort showed a 41% reduction in the risk of low weight births (RR(lbw)=0.59, 95%CI: 0.46 to 0.73, p<.001 ) and a 56% reduction when compared with county Medicaid births only (RR=0.44, 95%CI: 0.34 to 0.57,( )p<.005) adjusting for maternal age and race. Larger reductions were found for very low weight births.
CONCLUSIONS—Mothers need not be considered at high risk for adverse pregnancy outcomes based on their socioeconomic status alone. Moreover, a comprehensive prenatal programme administered by nurse-midwifes may promote a reduction in adverse pregnancy outcomes among indigent mothers.


Keywords: low birth weight; prenatal care; indigent mothers; nurse-midwif

The International Sexual Health And REproductive Health during COVID-19 (I-SHARE) Study: A Multicountry Analysis of Adults from 30 Countries Prior to and During the Initial Coronavirus Disease 2019 Wave

BACKGROUND: There is limited evidence to date about changes to sexual and reproductive health (SRH) during the initial wave of coronavirus disease 2019 (COVID-19). To address this gap, our team organized a multicountry, cross-sectional online survey as part of a global consortium. METHODS: Consortium research teams conducted online surveys in 30 countries. Sampling methods included convenience, online panels, and population-representative. Primary outcomes included sexual behaviors, partner violence, and SRH service use, and we compared 3 months prior to and during policy measures to mitigate COVID-19. We conducted meta-analyses for primary outcomes and graded the certainty of the evidence. RESULTS: Among 4546 respondents with casual partners, condom use stayed the same for 3374 (74.4%), and 640 (14.1%) reported a decline. Fewer respondents reported physical or sexual partner violence during COVID-19 measures (1063 of 15 144, 7.0%) compared to before COVID-19 measures (1469 of 15 887, 9.3%). COVID-19 measures impeded access to condoms (933 of 10 790, 8.7%), contraceptives (610 of 8175, 7.5%), and human immunodeficiency virus/sexually transmitted infection (HIV/STI) testing (750 of 1965, 30.7%). Pooled estimates from meta-analysis indicate that during COVID-19 measures, 32.3% (95% confidence interval [CI], 23.9%-42.1%) of people needing HIV/STI testing had hindered access, 4.4% (95% CI, 3.4%-5.4%) experienced partner violence, and 5.8% (95% CI, 5.4%-8.2%) decreased casual partner condom use (moderate certainty of evidence for each outcome). Meta-analysis findings were robust in sensitivity analyses that examined country income level, sample size, and sampling strategy. CONCLUSIONS: Open science methods are feasible to organize research studies as part of emergency responses. The initial COVID-19 wave impacted SRH behaviors and access to services across diverse global settings.SCOPUS: ar.jinfo:eu-repo/semantics/publishe