Incidence of stillbirth and perinatal mortality and their associated factors among women delivering at Harare Maternity Hospital, Zimbabwe: a cross-sectional retrospective analysis

BACKGROUND: Death of an infant in utero or at birth has always been a devastating experience for the mother and of concern in clinical practice. Infant mortality remains a challenge in the care of pregnant women worldwide, but particularly for developing countries and the need to understand contributory factors is crucial for addressing appropriate perinatal health. METHODS: Using information available in obstetric records for all deliveries (17,072 births) at Harare Maternity Hospital, Zimbabwe, we conducted a cross-sectional retrospective analysis of a one-year data, (1997–1998) to assess demographic and obstetric risk factors for stillbirth and early neonatal death. We estimated risk of stillbirth and early neonatal death for each potential risk factor. RESULTS: The annual frequency of stillbirth was 56 per 1,000 total births. Women delivering stillbirths and early neonatal deaths were less likely to receive prenatal care (adjusted relative risk [RR] = 2.54; 95% confidence intervals [CI] 2.19–2.94 and RR = 2.52; 95% CI 1.63–3.91), which for combined stillbirths and early neonatal deaths increased with increasing gestational age (Hazard Ratio [HR] = 3.98, HR = 7.49 at 28 and 40 weeks of gestation, respectively). Rural residence was associated with risk of infant dying in utero, (RR = 1.33; 95% CI 1.12–1.59), and the risk of death increased with increasing gestational age (HR = 1.04, HR = 1.69, at 28 and 40 weeks of gestation, respectively). Older maternal age was associated with risk of death (HR = 1.50; 95% CI 1.21–1.84). Stillbirths were less likely to be delivered by Cesarean section (RR = 0.64; 95% CI 0.51–0.79), but more likely to be delivered as breech (RR = 4.65; 95% CI 3.88–5.57, as were early neonatal deaths (RR = 3.38; 95% CI 1.64–6.96). CONCLUSION: The frequency of stillbirth, especially macerated, is high, 27 per 1000 total births. Early prenatal care could help reduce perinatal death linking the woman to the health care system, increasing the probability that she would seek timely emergency care that would reduce the likelihood of death of her infant in utero. Improved quality of obstetric care during labor and delivery may help reduce the number of fresh stillbirths and early neonatal deaths

Meteorological Controls on Local and Regional Volcanic Ash Dispersal

Volcanic ash has the capacity to impact human health, livestock, crops and infrastructure, including international air traffic. For recent major eruptions, information on the volcanic ash plume has been combined with relatively coarse-resolution meteorological model output to provide simulations of regional ash dispersal, with reasonable success on the scale of hundreds of kilometres. However, to predict and mitigate these impacts locally, significant improvements in modelling capability are required. Here, we present results from a dynamic meteorological-ash-dispersion model configured with sufficient resolution to represent local topographic and convectively-forced flows. We focus on an archetypal volcanic setting, Soufrière, St Vincent, and use the exceptional historical records of the 1902 and 1979 eruptions to challenge our simulations. We find that the evolution and characteristics of ash deposition on St Vincent and nearby islands can be accurately simulated when the wind shear associated with the trade wind inversion and topographically-forced flows are represented. The wind shear plays a primary role and topographic flows a secondary role on ash distribution on local to regional scales. We propose a new explanation for the downwind ash deposition maxima, commonly observed in volcanic eruptions, as resulting from the detailed forcing of mesoscale meteorology on the ash plume

Computational approaches for modeling human intestinal absorption and permeability

Human intestinal absorption (HIA) is an important roadblock in the formulation of new drug substances. Computational models are needed for the rapid estimation of this property. The measurements are determined via in vivo experiments or in vitro permeability studies. We present several computational models that are able to predict the absorption of drugs by the human intestine and the permeability through human Caco-2 cells. The training and prediction sets were derived from literature sources and carefully examined to eliminate compounds that are actively transported. We compare our results to models derived by other methods and find that the statistical quality is similar. We believe that models derived from both sources of experimental data would provide greater consistency in predictions. The performance of several QSPR models that we investigated to predict outside the training set for either experimental property clearly indicates that caution should be exercised while applying any of the models for quantitative predictions. However, we are able to show that the qualitative predictions can be obtained with close to a 70% success rate

The Impact of the Human DNA Topoisomerase II C-Terminal Domain on Activity

Type II DNA topoisomerases (topos) are essential enzymes needed for the resolution of topological problems that occur during DNA metabolic processes. Topos carry out an ATP-dependent strand passage reaction whereby one double helix is passed through a transient break in another. Humans have two topoII isoforms, alpha and beta, which while enzymatically similar are differentially expressed and regulated, and are thought to have different cellular roles. The C-terminal domain (CTD) of the enzyme has the most diversity, and has been implicated in regulation. We sought to investigate the impact of the CTD domain on activity.We have investigated the role of the human topoII C-terminal domain by creating constructs encoding C-terminally truncated recombinant topoIIalpha and beta and topoIIalpha+beta-tail and topoIIbeta+alpha-tail chimeric proteins. We then investigated function in vivo in a yeast system, and in vitro in activity assays. We find that the C-terminal domain of human topoII isoforms is needed for in vivo function of the enzyme, but not needed for cleavage activity. C-terminally truncated enzymes had similar strand passage activity to full length enzymes, but the presence of the opposite C-terminal domain had a large effect, with the topoIIalpha-CTD increasing activity, and the topoIIbeta-CTD decreasing activity.In vivo complementation data show that the topoIIalpha C-terminal domain is needed for growth, but the topoIIbeta isoform is able to support low levels of growth without a C-terminal domain. This may indicate that topoIIbeta has an additional localisation signal. In vitro data suggest that, while the lack of any C-terminal domain has little effect on activity, the presence of either the topoIIalpha or beta C-terminal domain can affect strand passage activity. Data indicates that the topoIIbeta-CTD may be a negative regulator. This is the first report of in vitro data with chimeric human topoIIs

Robustness and uncertainties in global multivariate wind-wave climate projections

Understanding climate-driven impacts on the multivariate global wind-wave climate is paramount to effective offshore/coastal climate adaptation planning. However, the use of single-method ensembles and variations arising from different methodologies has resulted in unquantified uncertainty amongst existing global wave climate projections. Here, assessing the first coherent, community-driven, multi-method ensemble of global wave climate projections, we demonstrate widespread ocean regions with robust changes in annual mean significant wave height and mean wave period of 5–15% and shifts in mean wave direction of 5–15°, under a high-emission scenario. Approximately 50% of the world’s coastline is at risk from wave climate change, with ~40% revealing robust changes in at least two variables. Furthermore, we find that uncertainty in current projections is dominated by climate model-driven uncertainty, and that single-method modelling studies are unable to capture up to ~50% of the total associated uncertainty

DONSON and FANCM associate with different replisomes distinguished by replication timing and chromatin domain

Eukaryotic replisomes are multiprotein complexes. Here the authors reveal two distinct stressed replisomes, associated with DONSON and FANCM, displaying a bias in replication timing and chromatin domain

Effects of Ionomycin on Egg Activation and Early Development in Starfish

Ionomycin is a Ca2+-selective ionophore that is widely used to increase intracellular Ca2+ levels in cell biology laboratories. It is also occasionally used to activate eggs in the clinics practicing in vitro fertilization. However, neither the precise molecular action of ionomycin nor its secondary effects on the eggs' structure and function is well known. In this communication we have studied the effects of ionomycin on starfish oocytes and zygotes. By use of confocal microscopy, calcium imaging, as well as light and transmission electron microscopy, we have demonstrated that immature oocytes exposed to ionomycin instantly increase intracellular Ca2+ levels and undergo structural changes in the cortex. Surprisingly, when microinjected into the cells, ionomycin produced no Ca2+ increase. The ionomycin-induced Ca2+ rise was followed by fast alteration of the actin cytoskeleton displaying conspicuous depolymerization at the oocyte surface and in microvilli with concomitant polymerization in the cytoplasm. In addition, cortical granules were disrupted or fused with white vesicles few minutes after the addition of ionomycin. These structural changes prevented cortical maturation of the eggs despite the normal progression of nuclear envelope breakdown. At fertilization, the ionomycin-pretreated eggs displayed reduced Ca2+ response, no elevation of the fertilization envelope, and the lack of orderly centripetal translocation of actin fibers. These alterations led to difficulties in cell cleavage in the monospermic zygotes and eventually to a higher rate of abnormal development. In conclusion, ionomycin has various deleterious impacts on egg activation and the subsequent embryonic development in starfish. Although direct comparison is difficult to make between our findings and the use of the ionophore in the in vitro fertilization clinics, our results call for more defining investigations on the issue of a potential risk in artificial egg activation

Timbre from Sound Synthesis and High-level Control Perspectives

International audienceExploring the many surprising facets of timbre through sound manipulations has been a common practice among composers and instrument makers of all times. The digital era radically changed the approach to sounds thanks to the unlimited possibilities offered by computers that made it possible to investigate sounds without physical constraints. In this chapter we describe investigations on timbre based on the analysis by synthesis approach that consists in using digital synthesis algorithms to reproduce sounds and further modify the parameters of the algorithms to investigate their perceptual relevance. In the first part of the chapter timbre is investigated in a musical context. An examination of the sound quality of different wood species for xylophone making is first presented. Then the influence of instrumental control on timbre is described in the case of clarinet and cello performances. In the second part of the chapter, we mainly focus on the identification of sound morphologies, so called invariant sound structures responsible for the evocations induced by environmental sounds by relating basic signal descriptors and timbre descriptors to evocations in the case of car door noises, motor noises, solid objects, and their interactions

Prion Protein Accumulation In Lipid Rafts of Mouse Aging Brain

The cellular form of the prion protein (PrP(C)) is a normal constituent of neuronal cell membranes. The protein misfolding causes rare neurodegenerative disorders known as transmissible spongiform encephalopathies or prion diseases. These maladies can be sporadic, genetic or infectious. Sporadic prion diseases are the most common form mainly affecting aging people. In this work, we investigate the biochemical environment in which sporadic prion diseases may develop, focusing our attention on the cell membrane of neurons in the aging brain. It is well established that with aging the ratio between the most abundant lipid components of rafts undergoes a major change: while cholesterol decreases, sphingomyelin content rises. Our results indicate that the aging process modifies the compartmentalization of PrP(C). In old mice, this change favors PrP(C) accumulation in detergent-resistant membranes, particularly in hippocampi. To confirm the relationship between lipid content changes and PrP(C) translocation into detergent-resistant membranes (DRMs), we looked at PrP(C) compartmentalization in hippocampi from acid sphingomyelinase (ASM) knockout (KO) mice and synaptosomes enriched in sphingomyelin. In the presence of high sphingomyelin content, we observed a significant increase of PrP(C) in DRMS. This process is not due to higher levels of total protein and it could, in turn, favor the onset of sporadic prion diseases during aging as it increases the PrP intermolecular contacts into lipid rafts. We observed that lowering sphingomyelin in scrapie-infected cells by using fumonisin B1 led to a 50% decrease in protease-resistant PrP formation. This may suggest an involvement of PrP lipid environment in prion formation and consequently it may play a role in the onset or development of sporadic forms of prion diseases