Periconceptional maternal and paternal alcohol consumption and embryonic and fetal development:the Rotterdam periconception cohort

Research question: What is the impact of maternal and paternal alcohol consumption in the periconception period on embryonic and fetal development assessed using three-dimensional ultrasound and virtual reality techniques? Design: This prospective observational study was embedded in the Rotterdam periconception cohort (Predict study). Participating women received longitudinal three-dimensional transvaginal ultrasound examinations from week 7 to week 12 of gestation to measure crown–rump length and embryonic volume. Mid-pregnancy fetal size parameters and birth weight were retrieved from medical files. Participants completed a periconception exposure questionnaire and a validated food frequency questionnaire. Linear mixed models were used to analyse the association between parental alcohol consumption, and embryonic and fetal developmental parameters. Results: In total, 1141 female and 987 male participants were included in the analyses. Moderate maternal alcohol consumption in the periconception period resulted in a smaller head circumference (β = -1.85, SE = 0.84, P = 0.03), abdominal circumference (β = -2.65, SE = 0.93, P = 0.004), femur length (β = -0.56, SE = 0.22, P = 0.01) and estimated fetal weight (β = -9.36, SE = 4.35, P = 0.03) at 20 weeks of gestation. Paternal alcohol consumption showed significant positive associations, mainly with fetal size parameters (abdominal circumference: β = 0.033, SE = 0.01, P = 0.008; estimated fetal weight: β = 0.131, SE = 0.06, P = 0.03). Conclusions: Moderate maternal alcohol consumption is negatively associated with fetal growth parameters. Moreover, alcohol is proven to be a strong teratogen, and its consumption before and during pregnancy should be discouraged in both women and men as it affects several parameters of embryonic and fetal development.</p

Explaining inconsistencies between data on condom use and condom sales

BACKGROUND: Several HIV prevention programs use data on condom sales and survey-based data on condom prevalence to monitor progress. However, such indicators are not always consistent. This paper aims to explain these inconsistencies and to assess whether the number of sex acts and the number of condoms used can be estimated from survey data. This would be useful for program managers, as it would enable estimation of the number of condoms needed for different target groups. METHODS: We use data from six Demographic and Health Surveys to estimate the total annual number of sex acts and number of condoms used. Estimates of the number of sex acts are based on self-reported coital frequency, the proportion reporting intercourse the previous day, and survival methods. Estimates of the number of condoms used are based on self-reported frequency of use, the proportion reporting condom use the previous day and in last intercourse. The estimated number of condoms used is then compared with reported data on condom sales and distribution. RESULTS: Analysis of data on the annual number of condoms sold and distributed to the trade reveals very erratic patterns, which reflect stock-ups at various levels in the distribution chain. Consequently, condom sales data are a very poor indicator of the level of condom use. Estimates of both the number of sexual acts and the number of condoms used vary enormously based on the estimation method used. For several surveys, the highest estimate of the annual number of condoms used is tenfold that of the lowest estimate. CONCLUSIONS: Condom sales to the trade are a poor indicator of levels of condom use, and are therefore insufficient to monitor HIV prevention programs. While survey data on condom prevalence allow more detailed monitoring, converting such data to an estimated number of sex acts and condoms used is not straightforward. The estimation methods yield widely different results, and it is impossible to determine which method is most accurate. Until the reliability of these various estimation methods can be established, estimating the annual number of condoms used from survey data will not be feasible. Collecting survey data on the number of sex acts and the number of condoms used in a fixed time period may enable the calculation of more reliable estimates of the number of sex acts and condoms used

Chronologically dating the early assembly of the Milky Way

The standard cosmological model predicts that galaxies are built through hierarchical assembly on cosmological timescales1,2. The Milky Way, like other disk galaxies, underwent violent mergers and accretion of small satellite galaxies in its early history. Owing to Gaia Data Release 23 and spectroscopic surveys4, the stellar remnants of such mergers have been identified5–7. The chronological dating of such events is crucial to uncover the formation and evolution of the Galaxy at high redshift, but it has so far been challenging due to difficulties in obtaining precise ages for these oldest stars. Here we combine asteroseismology—the study of stellar oscillations—with kinematics and chemical abundances to estimate precise stellar ages (~11%) for a sample of stars observed by the Kepler space mission8. Crucially, this sample includes not only some of the oldest stars that were formed inside the Galaxy but also stars formed externally and subsequently accreted onto the Milky Way. Leveraging this resolution in age, we provide compelling evidence in favour of models in which the Galaxy had already formed a substantial population of its stars (which now reside mainly in its thick disk) before the infall of the satellite galaxy Gaia-Enceladus/Sausage5,6 around 10 billion years ago

Assessing effects of a media campaign on HIV/AIDS awareness and prevention in Nigeria: results from the VISION Project

BACKGROUND: In response to the growing HIV epidemic in Nigeria, the U.S. Agency for International Development (USAID) initiated the VISION Project, which aimed to increase use of family planning, child survival, and HIV/AIDS services. The VISION Project used a mass-media campaign that focused on reproductive health and HIV/AIDS prevention. This paper assesses to what extent program exposure translates into increased awareness and prevention of HIV/AIDS. METHODS: This analysis is based on data from the 2002 and 2004 Nigeria (Bauchi, Enugu, and Oyo) Family Planning and Reproductive Health Surveys, which were conducted among adults living in the VISION Project areas. To correct for endogeneity, two-stage logistic regression is used to investigate the effect of program exposure on 1) discussion of HIV/AIDS with a partner, 2) awareness that consistent condom use reduces HIV risk, and 3) condom use at last intercourse. RESULTS: Exposure to the VISION mass media campaign was high: 59%, 47%, and 24% were exposed to at least 1 VISION radio, printed advertisement, or TV program about reproductive health, respectively. The differences in outcome variables between 2002 baseline data and the 2004 follow-up data were small. However, those with high program exposure were almost one and a half (Odds Ratio [O.R.] = 1.47, 95% Confidence Interval [C.I.] 1.01–2.16) times more likely than those with no exposure to have discussed HIV/AIDS with a partner. Those with high program exposure were over twice (O.R. = 2.20, C.I. 1.49–3.25) as likely as those with low exposure to know that condom use can reduce risk of HIV infection. Program exposure had no effect on condom use at last sex. CONCLUSION: The VISION Project reached a large portion of the population and exposure to mass media programs about reproductive health and HIV prevention topics can help increase HIV/AIDS awareness. Programs that target rural populations, females, and unmarried individuals, and disseminate information on where to obtain condoms, are needed to reduce barriers to condom use. Improvements in HIV/AIDS prevention behaviour are likely to require that these programmatic efforts be continued, scaled up, done in conjunction with other interventions, and targeted towards individuals with specific socio-demographic characteristics

Neonatal cranial ultrasound abnormalities in LBW infants: Relation to cognitive outcomes at age six

bjective: To assess the independent relation of neonatal cranial ultrasound (US) abnormalities in low birth weight (LBW) infants to cognitive outcomes at 6 years of age.Design: Prospective cohort study.Sample and Methods: Six-year follow-up data were obtained on a regional birth cohort of LBW infants (\u3c 2 kg) systematically screened as neonates with serial US. US abnormalities were dichotomized into isolated germinal matrix/intraventricular hemorrhage (GM/IVH) and parenchymal lesions/ventricular enlargement (PL/VE). Global cognitive outcomes (mental retardation, borderline intelligence, and normal intelligence) and selected specific cognitive abilities were assessed at 6 years of age with standardized instruments. Multivariate techniques were used to assess the effects of US independent of maternal social disadvantage at birth and other perinatal and neonatal risk factors.Results: The sample as a whole had a significantly elevated rate of mental retardation (MR; 5%), almost all moderate to profound in severity. PL/VE was independently related to MR (odds ratio [OR], 65.8; confidence interval [CI], 19.1 to 22.4) and borderline intelligence (OR, 3.7; CI, 1.3 to 10.8); isolated GM/IVH was more modestly related to MR (OR, 4.6; CI, 1.2 to 18.6) but not related to borderline intelligence. Approximately half of the cases of MR were attributable to PL/VE independent of other factors. Of non-US factors, the number of days receiving mechanical ventilation increased the risk for MR. Maternal social disadvantage increased the risk for borderline intelligence but not MR. Among children of normal intelligence, those with PL/VE, but not isolated GM/IVH, performed more poorly than those without US abnormalities on tests of visual perceptual organization but not on tests of language, memory, or quantitative skills.Conclusion: Prevention of white matter injury would substantially improve cognitive outcomes for LBW infants

Two Days Versus Five Days of Postoperative Antibiotics for Complex Appendicitis:Cost Analysis of a Randomized, Noninferiority Trial

Objective: To compare costs for 2 days versus 5 days of postoperative antibiotics within the antibiotics after an aPPendectomy In Complex appendicitis trial. Background: Recent studies suggest that restrictive antibiotic use leads to a significant reduction in hospital stays without compromising patient safety. Its potential effect on societal costs remains underexplored. Methods: This was a pragmatic, open-label, multicenter clinical trial powered for noninferiority. Patients with complex appendicitis (age ≥ 8 years) were randomly allocated to 2 days or 5 days of intravenous antibiotics after appendectomy. Patient inclusion lasted from June 2017 to June 2021 in 15 Dutch hospitals. The final follow-up was on September 1, 2021. The primary trial endpoint was a composite endpoint of infectious complications and mortality within 90 days. In the present study, the main outcome measures were overall societal costs (comprising direct health care costs and costs related to productivity loss) and cost-effectiveness. Direct health care costs were recorded based on data in the electronic patient files, complemented by a telephone follow-up at 90 days. In addition, data on loss of productivity were acquired through the validated Productivity Cost Questionnaire at 4 weeks after surgery. Cost estimates were based on prices for the year 2019. Results: In total, 1005 patients were evaluated in the "intention-to-treat" analysis: 502 patients were allocated to the 2-day group and 503 to the 5-day group. The mean difference in overall societal costs was - €625 (95% CI: -€ 958 to -€ 278) to the advantage of the 2-day group. This difference was largely explained by reduced hospital stay. Productivity losses were similar between the study groups. Restricting postoperative antibiotics to 2 days was cost-effective, with estimated cost savings of €31,117 per additional infectious complication. Conclusions: Two days of postoperative antibiotics for complex appendicitis results in a statistically significant and relevant cost reduction, as compared with 5 days. Findings apply to laparoscopic appendectomy in a well-resourced health care setting.</p

Two Days Versus Five Days of Postoperative Antibiotics for Complex Appendicitis:Cost Analysis of a Randomized, Noninferiority Trial

Objective: To compare costs for 2 days versus 5 days of postoperative antibiotics within the antibiotics after an aPPendectomy In Complex appendicitis trial. Background: Recent studies suggest that restrictive antibiotic use leads to a significant reduction in hospital stays without compromising patient safety. Its potential effect on societal costs remains underexplored. Methods: This was a pragmatic, open-label, multicenter clinical trial powered for noninferiority. Patients with complex appendicitis (age ≥ 8 years) were randomly allocated to 2 days or 5 days of intravenous antibiotics after appendectomy. Patient inclusion lasted from June 2017 to June 2021 in 15 Dutch hospitals. The final follow-up was on September 1, 2021. The primary trial endpoint was a composite endpoint of infectious complications and mortality within 90 days. In the present study, the main outcome measures were overall societal costs (comprising direct health care costs and costs related to productivity loss) and cost-effectiveness. Direct health care costs were recorded based on data in the electronic patient files, complemented by a telephone follow-up at 90 days. In addition, data on loss of productivity were acquired through the validated Productivity Cost Questionnaire at 4 weeks after surgery. Cost estimates were based on prices for the year 2019. Results: In total, 1005 patients were evaluated in the "intention-to-treat" analysis: 502 patients were allocated to the 2-day group and 503 to the 5-day group. The mean difference in overall societal costs was - €625 (95% CI: -€ 958 to -€ 278) to the advantage of the 2-day group. This difference was largely explained by reduced hospital stay. Productivity losses were similar between the study groups. Restricting postoperative antibiotics to 2 days was cost-effective, with estimated cost savings of €31,117 per additional infectious complication. Conclusions: Two days of postoperative antibiotics for complex appendicitis results in a statistically significant and relevant cost reduction, as compared with 5 days. Findings apply to laparoscopic appendectomy in a well-resourced health care setting.</p

Chronologically dating the early assembly of the Milky Way

The standard cosmological model predicts that galaxies are built through hierarchical assembly on cosmological timescales1,2. The Milky Way, like other disk galaxies, underwent violent mergers and accretion of small satellite galaxies in its early history. Owing to Gaia Data Release 23 and spectroscopic surveys4, the stellar remnants of such mergers have been identified5,6,7. The chronological dating of such events is crucial to uncover the formation and evolution of the Galaxy at high redshift, but it has so far been challenging due to difficulties in obtaining precise ages for these oldest stars. Here we combine asteroseismology—the study of stellar oscillations—with kinematics and chemical abundances to estimate precise stellar ages (~11%) for a sample of stars observed by the Kepler space mission8. Crucially, this sample includes not only some of the oldest stars that were formed inside the Galaxy but also stars formed externally and subsequently accreted onto the Milky Way. Leveraging this resolution in age, we provide compelling evidence in favour of models in which the Galaxy had already formed a substantial population of its stars (which now reside mainly in its thick disk) before the infall of the satellite galaxy Gaia-Enceladus/Sausage5,6 around 10 billion years ago

Lentiviral gene therapy corrects platelet phenotype and function in patients with Wiskott-Aldrich syndrome

BACKGROUND: Thrombocytopenia is a serious issue for all patients with classical Wiskott-Aldrich syndrome (WAS) and X-linked thrombocytopenia (XLT) because it causes severe and life-threatening bleeding. Lentiviral gene therapy (GT) for WAS has shown promising results in terms of immune reconstitution. However, despite the reduced severity and frequency of bleeding events, platelet counts remain low in GT-treated patients. OBJECTIVE: We carefully investigated platelet defects in terms of phenotype and function in untreated patients with WAS and assessed the effect of GT treatment on platelet dysfunction. METHODS: We analyzed a cohort of 20 patients with WAS/XLT, 15 of them receiving GT. Platelet phenotype and function were analyzed by using electron microscopy, flow cytometry, and an aggregation assay. Platelet protein composition was assessed before and after GT by means of proteomic profile analysis. RESULTS: We show that platelets from untreated patients with WAS have reduced size, abnormal ultrastructure, and a hyperactivated phenotype at steady state, whereas activation and aggregation responses to agonists are decreased. GT restores platelet size and function early after treatment and reduces the hyperactivated phenotype proportionally to WAS protein expression and length of follow-up. CONCLUSIONS: Our study highlights the coexistence of morphologic and multiple functional defects in platelets lacking WAS protein and demonstrates that GT normalizes the platelet proteomic profile with consequent restoration of platelet ultrastructure and phenotype, which might explain the observed reduction of bleeding episodes after GT. These results are instrumental also from the perspective of a future clinical trial in patients with XLT only presenting with microthrombocytopenia