ObjectiveTo generate a global reference for caesarean section (CS) rates at health facilities.DesignCross‐sectional study.SettingHealth facilities from 43 countries.Population/SampleThirty eight thousand three hundred and twenty‐four women giving birth from 22 countries for model building and 10 045 875 women giving birth from 43 countries for model testing.MethodsWe hypothesised that mathematical models could determine the relationship between clinical‐obstetric characteristics and CS. These models generated probabilities of CS that could be compared with the observed CS rates. We devised a three‐step approach to generate the global benchmark of CS rates at health facilities: creation of a multi‐country reference population, building mathematical models, and testing these models.Main outcome measuresArea under the ROC curves, diagnostic odds ratio, expected CS rate, observed CS rate.ResultsAccording to the different versions of the model, areas under the ROC curves suggested a good discriminatory capacity of C‐Model, with summary estimates ranging from 0.832 to 0.844. The C‐Model was able to generate expected CS rates adjusted for the case‐mix of the obstetric population. We have also prepared an e‐calculator to facilitate use of C‐Model (www.who.int/reproductivehealth/publications/maternal_perinatal_health/c-model/en/).ConclusionsThis article describes the development of a global reference for CS rates. Based on maternal characteristics, this tool was able to generate an individualised expected CS rate for health facilities or groups of health facilities. With C‐Model, obstetric teams, health system managers, health facilities, health insurance companies, and governments can produce a customised reference CS rate for assessing use (and overuse) of CS.Tweetable abstractThe C‐Model provides a customized benchmark for caesarean section rates in health facilities and systems.
Exposure of cells to carcinogenic Cr(VI) compounds results in the formation of several types of DNA lesions such as strand breaks, DNA-protein crosslinks and uncharacterized DNA-Cr adducts. Hexavalent chromium compounds are positive in most bacterial and eukaryotic mutagenic systems, although the nature of DNA modifications underlying the chromium-induced mutagenesis is not known. Hexavalent chromate(VI) is very active in cellular systems because it is actively transported into cells, but intracellularly it is ultimately reduced to Cr(III). Here we show that exposure of Chinese hamster ovary (CHO) cells to potassium chromate(VI) leads to the formation of stable complexes between DNA and amino acids or glutathione. Cysteine, glutamic acid and histidine were the major amino acids crosslinked to DNA in chromate-treated cells. Incubation of purified DNA in the presence of EDTA dissociated SDS stable amino acid-DNA complexes, which indicates that these DNA adducts are most likely to represent ternary coordination complexes mediated by Cr(III) rather than covalent linkage between amino acids/glutathione and DNA. The amino acids that were found complexed with DNA purified from chromate-exposed cells did not orginate from previously crosslinked proteins during DNA isolation, but represented authentic reactions of free amino acids and glutathione with chromium and DNA in cells. Ternary complexes of glutathione or amino acids with Cr(III) and DNA were estimated to account for as much as 50% of DNA-bound chromium following exposure to < or = 25 microM chromate.
Crystalline nickel sulfide (alpha NiS) and cobalt sulfide (CoS2) particles can cause greater cell transformation and cellular toxicity than the respective amorphous metal sulfide particles. Cultured mammalian cells phagocytose the crystalline metal sulfide particles more readily than the amorphous ones. In the case of the nickel sulfides, the crystalline metal sulfide particles had negatively charged surfaces (Zeta potential: -27.012 mV) in contrast to the amorphous particles, which were positively charge (Zeta potential: +9.174 mV). X-ray photoelectron spectroscopy analysis of amorphous and crystalline NiS particles revealed that the outermost surface (1-4 nm) of the two particles had striking differences in Ni/S ratios and in their sulfur oxidation states. Rendering particles' surfaces more negative by reduction with lithium aluminum hydride enhanced their phagocytosis, and in the case of amorphous NiS chemical reduction resulted in an incidence of morphological transformation of Syrian hamster embryo cells comparable to that observed with untreated crystalline alpha NiS.
Dichlorofluorescein (DCF) was used as a fluorescent probe to detect oxidants formed in cultured CHO cells during nickel treatment. Crystalline Ni3S2 specifically enhanced the formation of oxidants in the nuclei of these living cells, but Ni3S2 particles did not enhance DCF fluorescence as much when added in vitro to isolated nuclei. Our results add to the emerging concept that oxidants mediated by nickel compounds may play an important role in nickel-induced genotoxicity.
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