Mechanistically Guided Materials Chemistry: Synthesis of Ternary Nitrides, CaZrN2 and CaHfN2.

Recent computational studies have predicted many new ternary nitrides, revealing synthetic opportunities in this underexplored phase space. However, synthesizing new ternary nitrides is difficult, in part because intermediate and product phases often have high cohesive energies that inhibit diffusion. Here, we report the synthesis of two new phases, calcium zirconium nitride (CaZrN2) and calcium hafnium nitride (CaHfN2), by solid state metathesis reactions between Ca3N2 and MCl4 (M = Zr, Hf). Although the reaction nominally proceeds to the target phases in a 1:1 ratio of the precursors via Ca3N2 + MCl4 → CaMN2 + 2 CaCl2, reactions prepared this way result in Ca-poor materials (CaxM2-xN2, x < 1). A small excess of Ca3N2 (ca. 20 mol %) is needed to yield stoichiometric CaMN2, as confirmed by high-resolution synchrotron powder X-ray diffraction. In situ synchrotron X-ray diffraction studies reveal that nominally stoichiometric reactions produce Zr3+ intermediates early in the reaction pathway, and the excess Ca3N2 is needed to reoxidize Zr3+ intermediates back to the Zr4+ oxidation state of CaZrN2. Analysis of computationally derived chemical potential diagrams rationalizes this synthetic approach and its contrast from the synthesis of MgZrN2. These findings additionally highlight the utility of in situ diffraction studies and computational thermochemistry to provide mechanistic guidance for synthesis.

Selective Synthesis of Defect-Rich LaMnO3 by Low-Temperature Anion Cometathesis.

The synthesis of complex oxides at low temperatures brings forward aspects of chemistry not typically considered. This study focuses on perovskite LaMnO3, which is of interest for its correlated electronic behavior tied to the oxidation state and thus the spin configuration of manganese. Traditional equilibrium synthesis of these materials typically requires synthesis reaction temperatures in excess of 1000 °C, followed by subsequent annealing steps at lower temperatures and different p(O2) conditions to manipulate the oxygen content postsynthesis (e.g., LaMnO3+x). Double-ion exchange (metathesis) reactions have recently been shown to react at much lower temperatures (500-800 °C), highlighting a fundamental knowledge gap for how solids react at lower temperatures. Here, we revisit the metathesis reaction, LiMnO2 + LaOX, where X is a halide or mixture of halides, using in situ synchrotron X-ray diffraction. These experiments reveal low reaction onset temperatures (ca. 450-480 °C). The lowest reaction temperatures are achieved by a mixture of lanthanum oxyhalide precursors: 2 LiMnO2 + LaOCl + LaOBr. In all cases, the resulting products are the expected alkali halide salt and defective La1-ϵMn1-ϵO3, where ϵ = x/(3 + x). We observe a systematic variation in defect concentration, consistent with a rapid stoichiometric local equilibration of the precursors and the subsequent global thermodynamic equilibration with O2 (g), as revealed by computational thermodynamics. Together, these results reveal how the inclusion of additional elements (e.g., Li and a halide) leads to the local equilibrium, particularly at low reaction temperatures for solid-state chemistry.

Thiocyanate-Stabilized Pseudo-cubic Perovskite CH(NH2)2PbI3 from Coincident Columnar Defect Lattices.

α-FAPbI3 (FA+ = CH(NH2)2+) with a cubic perovskite structure is promising for photophysical applications. However, α-FAPbI3 is metastable at room temperature, and it transforms to the δ-phase at a certain period of time at room temperature. Herein, we report a thiocyanate-stabilized pseudo-cubic perovskite FAPbI3 with ordered columnar defects (α'-phase). This compound has a √5ap × âˆš5ap × ap tetragonal unit cell (ap: cell parameter of primitive perovskite cell) with a band gap of 1.91 eV. It is stable at room temperature in a dry atmosphere. Furthermore, the presence of the α'-phase in a mixed sample with the δ-phase drastically reduces the δ-to-α transition temperature measured on heating, suggesting the reduction of the nucleation energy of the α-phase or thermodynamic stabilization of the α-phase through epitaxy. The defect-ordered pattern in the α'-phase forms a coincidence-site lattice at the twinned boundary of the single crystals, thus hinting at an epitaxy- or strain-based mechanism of α-phase formation and/or stabilization. In this study, we developed a new strategy to control defects in halide perovskites and provided new insight into the stabilization of α-FAPbI3 by pseudo-halide and grain boundary engineering.

Correlating Broadband Photoluminescence with Structural Dynamics in Layered Hybrid Halide Perovskites.

The emission of white light from a single material is atypical and is of interest for solid-state lighting applications. Broadband light emission has been observed in some layered perovskite derivatives, A2PbBr4 (A = R-NH3+), and correlates with static structural distortions corresponding to out-of-plane tilting of the lead bromide octahedra. While materials with different organic cations can yield distinct out-of-plane tilts, the underlying origin of the octahedral tilting remains poorly understood. Using high energy resolution (e.g., quasi-elastic) neutron scattering, this contribution details the rotational dynamics of the organic cations in A2PbBr4 materials where A = n-butylammonium (nBA), 1,8-diaminooctammonium (ODA), and 4-aminobutyric acid (GABA). The organic cation dynamics differentiate (nBA)2PbBr4 from (ODA)PbBr4 or (GABA)2PbBr4 in that the larger spatial extent of dynamics of nBA yields a larger effective cation radius. The larger effective volume of the nBA cation in (nBA)2PbBr4 yields a closer to ideal A-site geometry, preventing the out-of-plane tilt and broadband luminescence. In all three compounds, we observe hydrogen dynamics attributed to rotation of the ammonium headgroup and at a time scale faster than the white light photoluminescence studied by time-correlated single photon counting spectroscopy. This supports a previous assignment of the broadband emission as resulting from a single ensemble, such that the emissive excited state experiences many local structures faster than the emissive decay. The findings presented here highlight the role of the organic cation and its dynamics in hybrid organic-inorganic perovskites and white light emission.

Selectivity in Yttrium Manganese Oxide Synthesis via Local Chemical Potentials in Hyperdimensional Phase Space.

In sharp contrast to molecular synthesis, materials synthesis is generally presumed to lack selectivity. The few known methods of designing selectivity in solid-state reactions have limited scope, such as topotactic reactions or strain stabilization. This contribution describes a general approach for searching large chemical spaces to identify selective reactions. This novel approach explains the ability of a nominally "innocent" Na2CO3 precursor to enable the metathesis synthesis of single-phase Y2Mn2O7: an outcome that was previously only accomplished at extreme pressures and which cannot be achieved with closely related precursors of Li2CO3 and K2CO3 under identical conditions. By calculating the required change in chemical potential across all possible reactant-product interfaces in an expanded chemical space including Y, Mn, O, alkali metals, and halogens, using thermodynamic parameters obtained from density functional theory calculations, we identify reactions that minimize the thermodynamic competition from intermediates. In this manner, only the Na-based intermediates minimize the distance in the hyperdimensional chemical potential space to Y2Mn2O7, thus providing selective access to a phase which was previously thought to be metastable. Experimental evidence validating this mechanism for pathway-dependent selectivity is provided by intermediates identified from in situ synchrotron-based crystallographic analysis. This approach of calculating chemical potential distances in hyperdimensional compositional spaces provides a general method for designing selective solid-state syntheses that will be useful for gaining access to metastable phases and for identifying reaction pathways that can reduce the synthesis temperature, and cost, of technological materials.

Heat-Stable Carbetocin versus Oxytocin to Prevent Hemorrhage after Vaginal Birth.

BACKGROUND: Postpartum hemorrhage is the most common cause of maternal death. Oxytocin is the standard therapy for the prevention of postpartum hemorrhage, but it requires cold storage, which is not available in many countries. In a large trial, we compared a novel formulation of heat-stable carbetocin with oxytocin. METHODS: We enrolled women across 23 sites in 10 countries in a randomized, double-blind, noninferiority trial comparing intramuscular injections of heat-stable carbetocin (at a dose of 100 µg) with oxytocin (at a dose of 10 IU) administered immediately after vaginal birth. Both drugs were kept in cold storage (2 to 8°C) to maintain double-blinding. There were two primary outcomes: the proportion of women with blood loss of at least 500 ml or the use of additional uterotonic agents, and the proportion of women with blood loss of at least 1000 ml. The noninferiority margins for the relative risks of these outcomes were 1.16 and 1.23, respectively. RESULTS: A total of 29,645 women underwent randomization. The frequency of blood loss of at least 500 ml or the use of additional uterotonic agents was 14.5% in the carbetocin group and 14.4% in the oxytocin group (relative risk, 1.01; 95% confidence interval [CI], 0.95 to 1.06), a finding that was consistent with noninferiority. The frequency of blood loss of at least 1000 ml was 1.51% in the carbetocin group and 1.45% in the oxytocin group (relative risk, 1.04; 95% CI, 0.87 to 1.25), with the confidence interval crossing the margin of noninferiority. The use of additional uterotonic agents, interventions to stop bleeding, and adverse effects did not differ significantly between the two groups. CONCLUSIONS: Heat-stable carbetocin was noninferior to oxytocin for the prevention of blood loss of at least 500 ml or the use of additional uterotonic agents. Noninferiority was not shown for the outcome of blood loss of at least 1000 ml; low event rates for this outcome reduced the power of the trial. (Funded by Merck Sharpe & Dohme; CHAMPION Australian New Zealand Clinical Trials Registry number, ACTRN12614000870651 ; EudraCT number, 2014-004445-26 ; and Clinical Trials Registry-India number, CTRI/2016/05/006969 .).

Amide-Assisted Synthesis of Iron Germanium Sulfide (Fe2GeS4) Nanostars: The Effect of LiN(SiMe3)2 on Precursor Reactivity for Favoring Nanoparticle Nucleation or Growth.

Olivine Fe2GeS4 has been identified as a promising photovoltaic absorber material introduced as an alternate candidate to iron pyrite, FeS2. The compounds share similar benefits in terms of elemental abundance and relative nontoxicity, but Fe2GeS4 was predicted to have higher stability with respect to decomposition to alternate phases and, therefore, more optimal device performance. Our initial report of the nanoparticle (NP) synthesis for Fe2GeS4 was not well understood and required an inefficient 24 h growth to dissolve an iron sulfide impurity. Here, we report an amide-assisted Fe2GeS4 NP synthesis that directly forms the phase-pure product in minutes. This significant advance was achieved by the replacement of the poorly understood hexamethyldisilazane (HMDS) additive and TMS2S by the conjugate base, lithium bis(trimethylsilyl)amide (LiN(SiMe3)2), and elemental S, respectively. We hypothesized that fragments of both TMS2S and HMDS had carried out the roles that Brønsted bases play in amide-assisted NP syntheses and were necessary for Ge incorporation. Convolution of this role with the supply of S in TMS2S caused the iron sulfide impurities. Separating these effects in the use of LiN(SiMe3)2 and elemental S resulted in synthetic control over the ternary phase. Herein we explore the Fe-Ge-S reaction landscape and the role of the base. Its concentration was found to increase the reactivities of the Fe, Ge, and S precursors, and we discuss possible metal-amide intermediates. This affords tunability in two areas: favorability of NP nucleation versus growth and phase formation. The phase-purity of Fe2GeS4 depends on the molar ratios of the cations, base, and amine as well as the Fe:Ge:S molar ratios. The resultant Fe2GeS4 NPs exhibit an interesting star anise-like morphology with stacks of nanoplates that intersect along a 6-fold rotation axis. The optical properties of the Fe2GeS4 NPs are consistent with previously published measurements showing a measured band gap of 1.48 eV.

Ferroelastic Phase Transition in Formamidinium Tin(IV) Iodide Driven by Organic-Inorganic Coupling.

Hybrid perovskites are a technologically relevant family of materials, with potential applications in photovoltaics, solid-state lighting, and radiation detection. Interactions between the inorganic octahedral framework and the organic sublattice have been implicated in the structure and optoelectronic properties, but characterization of these interactions has been challenging, because of competition between organic-inorganic coupling and intraoctahedral interactions. Owing to their decreased octahedral connectivity, vacancy-ordered double perovskites present an ideal case study to examine organic-inorganic coupling in hybrid perovskites and their derivatives. Here, we describe the low-temperature, hysteretic phase transition of formamidinium tin(IV) iodide from the high-symmetry cubic phase to a lower-symmetry monoclinic phase. We propose that the hysteresis stems from organic-inorganic coupling mediated by local and spontaneous strain from the orientations of the formamidinium cations, which result in a ferroelastic phase transition.

Structure and Optical Properties of Layered Perovskite (MA)2PbI2-xBrx(SCN)2 (0 ≤ x < 1.6).

The layered perovskite (MA)2PbI2(SCN)2 (MA = CH3NH3+) is a member of an emerging series of compounds derived from hybrid organic-inorganic perovskites. Here, we successfully synthesized (MA)2PbI2-xBrx(SCN)2 (0 ≤ x < 1.6) by using a solid-state reaction. Despite smaller bromide substitution for iodine, 1% linear expansion along the a axis was observed at x ∼ 0.4 due to a change of the orientation of the SCN- anions. Diffuse reflectance spectra reveal that the optical band gap increases by the bromide substitution, which is supported by the DFT calculations. Curiously, bromine-rich compounds where x ≥ 0.8 are light sensitive, leading to partial decomposition after ∼24 h. This study demonstrates that the layered perovskite (MA)2PbI2(SCN)2 tolerates a wide range of bromide substitution toward tuning the band gap energy.

Defect-Accommodating Intermediates Yield Selective Low-Temperature Synthesis of YMnO3 Polymorphs.

In the synthesis of complex oxides, solid-state metathesis provides low-temperature reactions where product selectivity can be achieved through simple changes in precursor composition. The influence of precursor structure, however, is less understood in solid-state synthesis. Here we present the ternary metathesis reaction (LiMnO2 + YOCl → YMnO3 + LiCl) to target two yttrium manganese oxide products, hexagonal and orthorhombic YMnO3, when starting from three different LiMnO2 precursors. Using temperature-dependent synchrotron X-ray and neutron diffraction, we identify the relevant intermediates and temperature regimes of reactions along the pathway to YMnO3. Manganese-containing intermediates undergo a charge disproportionation into a reduced Mn(II,III) tetragonal spinel and oxidized Mn(III,IV) cubic spinel, which lead to hexagonal and orthorhombic YMnO3, respectively. Density functional theory calculations confirm that the presence of Mn(IV) caused by a small concentration of cation vacancies (∼2.2%) in YMnO3 stabilizes the orthorhombic polymorph over the hexagonal. Reactions over the course of 2 weeks yield o-YMnO3 as the majority product at temperatures below 600 °C, which supports an equilibration of cation defects over time. Controlling the composition and structure of these defect-accommodating intermediates provides new strategies for selective synthesis of complex oxides at low temperatures.

Selective Formation of Yttrium Manganese Oxides through Kinetically Competent Assisted Metathesis Reactions.

The synthesis of complex oxides requires high temperatures to overcome barriers imparted by solid-state diffusion; as such, reactions typically yield the most stable polymorph for a given composition. To synthesize new or metastable complex oxides, kinetically competent reactions with lower initial energy barriers must be devised to control the reaction pathway and resulting products. This contribution details the selective synthesis of different yttrium manganese oxides through assisted metathesis reactions between Mn2O3, YCl3, and A2CO3 under flowing oxygen; where A = Li, Na, K. With lithium carbonate, the orthorhombic perovskite o-YMnO3 (o-YMnO3+δ) forms over the temperature range of 550-850 °C. With sodium carbonate, the pyrochlore Y2Mn2O7 forms at 650 °C. No apparent selectivity is observed with K2CO3, and all alkalis yields hexagonal YMnO3 at T > 950 °C. The alkali species modify the reaction pathway and thus impart kinetic control in the formation of both phases.

Yttrium Manganese Oxide Phase Stability and Selectivity Using Lithium Carbonate Assisted Metathesis Reactions.

In solid-state chemistry, stable phases are often missed if their synthesis is impractical, such as when decomposition or a polymorphic transition occurs at relatively low temperature. In the preparation of complex oxides, reaction temperatures commonly exceed 1000 °C with little to no control of the reaction pathway. Thus, a prerequisite for exploring the synthesis of complex oxides is to identify reactions with intermediates that are kinetically competent at low temperatures, as provided by assisted metathesis reactions. Here, we study the assisted metathesis reaction Mn2O3 + 2.2YCl3·6H2O + 3Li2CO3 → 2YMnO3 + 5.8LiCl + 0.2LiYCl4 + 3CO2 using in situ synchrotron X-ray diffraction. By changing the atmosphere, oxygen vs inert gas, the reaction product changes from the overoxidized perovskite YMnO3+δ to the hexagonal YMnO3 polymorph at the reaction temperature of 850 °C, respectively. Analysis of the reaction pathways reveals two parallel reaction pathways in forming YMnO3 phases: (1) the slow reaction of metal oxides in a LiCl flux (Y2O3 + Mn2O3 [Formula: see text] 2YMnO3) and (2) the fast reaction from ternary intermediates (YOCl + LiMnO2 → LiCl + YMnO3). Control reactions reveal that both proposed pathways in isolation result in product formation, but the direct preparation of ternary intermediates (YOCl + LiMnO2 → LiCl + YMnO3) occurs at lower temperatures (500 °C) and shorter times (<24 h) and forms nominally stoichiometric orthorhombic YMnO3. These ternary intermediates react at a faster rate than the slow stepwise oxygenation of yttrium chloride to Y2O3 (YCl3 → YOCl → Y3O4Cl → Y2O3), which is relatively inert. These results support a kinetically controlled reaction pathway to form YMnO3 phases in assisted metathesis reactions with phase selectivity achievable through changes to reaction atmosphere.

Hybrid Charge-Transfer Semiconductors: (C7H7)SbI4, (C7H7)BiI4, and Their Halide Congeners.

Hybrid metal halides yield highly desirable optoelectronic properties and offer significant opportunity due to their solution processability. This contribution reports a new series of hybrid semiconductors, (C7H7)MX4 (M = Bi3+, Sb3+; X = Cl-, Br-, I-), that are composed of edge-sharing MX6 chains separated in space by π-stacked tropylium (C7H7+) cations; the inorganic chains resemble the connectivity of BiI3. The Bi3+ compounds have blue-shifted optical absorptions relative to the Sb3+ compounds that span the visible and near-IR region. Consistent with observations, DFT calculations reveal that the conduction band is composed of the tropylium cation and valence band primarily the inorganic chain: a charge-transfer semiconductor. The band gaps for both Bi3+ and Sb3+ compounds decrease systematically as a function of increasing halide size. These compounds are a rare example of charge-transfer semiconductors that also exhibit efficient crystal packing of the organic cations, thus providing an opportunity to study how structural packing affects optoelectronic properties.

Medical treatment for early fetal death (less than 24 weeks).

BACKGROUND: In most pregnancies that miscarry, arrest of embryonic or fetal development occurs some time (often weeks) before the miscarriage occurs. Ultrasound examination can reveal abnormal findings during this phase by demonstrating anembryonic pregnancies or embryonic or fetal death. Treatment has traditionally been surgical but medical treatments may be effective, safe, and acceptable, as may be waiting for spontaneous miscarriage. This is an update of a review first published in 2006. OBJECTIVES: To assess, from clinical trials, the effectiveness and safety of different medical treatments for the termination of non-viable pregnancies. SEARCH METHODS: For this update, we searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (24 October 2018) and reference lists of retrieved studies. SELECTION CRITERIA: Randomised trials comparing medical treatment with another treatment (e.g. surgical evacuation), or placebo, or no treatment for early pregnancy failure. Quasi-randomised studies were excluded. Cluster-randomised trials were eligible for inclusion, as were studies reported in abstract form, if sufficient information was available to assess eligibility. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. We assessed the quality of the evidence using the GRADE approach. MAIN RESULTS: Forty-three studies (4966 women) were included. The main interventions examined were vaginal, sublingual, oral and buccal misoprostol, mifepristone and vaginal gemeprost. These were compared with surgical management, expectant management, placebo, or different types of medical interventions were compared with each other. The review includes a wide variety of different interventions which have been analysed across 23 different comparisons. Many of the comparisons consist of single studies. We limited the grading of the quality of evidence to two main comparisons: vaginal misoprostol versus placebo and vaginal misoprostol versus surgical evacuation of the uterus. Risk of bias varied widely among the included trials. The quality of the evidence varied between the different comparisons, but was mainly found to be very-low or low quality.Vaginal misoprostol versus placeboVaginal misoprostol may hasten miscarriage when compared with placebo: e.g. complete miscarriage (5 trials, 305 women, risk ratio (RR) 4.23, 95% confidence interval (CI) 3.01 to 5.94; low-quality evidence). No trial reported on pelvic infection rate for this comparison. Vaginal misoprostol made little difference to rates of nausea (2 trials, 88 women, RR 1.38, 95% CI 0.43 to 4.40; low-quality evidence), diarrhoea (2 trials, 88 women, RR 2.21, 95% CI 0.35 to 14.06; low-quality evidence) or to whether women were satisfied with the acceptability of the method (1 trial, 32 women, RR 1.17, 95% CI 0.83 to 1.64; low-quality evidence). It is uncertain whether vaginal misoprostol reduces blood loss (haemoglobin difference > 10 g/L) (1 trial, 50 women, RR 1.25, 95% CI 0.38 to 4.12; very-low quality) or pain (opiate use) (1 trial, 84 women, RR 5.00, 95% CI 0.25 to 101.11; very-low quality), because the quality of the evidence for these outcomes was found to be very low.Vaginal misoprostol versus surgical evacuation Vaginal misoprostol may be less effective in accomplishing a complete miscarriage compared to surgical management (6 trials, 943 women, average RR 0.40, 95% CI 0.32 to 0.50; Heterogeneity: Tau² = 0.03, I² = 46%; low-quality evidence) and may be associated with more nausea (1 trial, 154 women, RR 21.85, 95% CI 1.31 to 364.37; low-quality evidence) and diarrhoea (1 trial, 154 women, RR 40.85, 95% CI 2.52 to 662.57; low-quality evidence). There may be little or no difference between vaginal misoprostol and surgical evacuation for pelvic infection (1 trial, 618 women, RR 0.73, 95% CI 0.39 to 1.37; low-quality evidence), blood loss (post-treatment haematocrit (%) (1 trial, 50 women, mean difference (MD) 1.40%, 95% CI -3.51 to 0.71; low-quality evidence), pain relief (1 trial, 154 women, RR 1.42, 95% CI 0.82 to 2.46; low-quality evidence) or women's satisfaction/acceptability of method (1 trial, 45 women, RR 0.67, 95% CI 0.40 to 1.11; low-quality evidence).Other comparisonsBased on findings from a single trial, vaginal misoprostol was more effective at accomplishing complete miscarriage than expectant management (614 women, RR 1.25, 95% CI 1.09 to 1.45). There was little difference between vaginal misoprostol and sublingual misoprostol (5 trials, 513 women, average RR 0.84, 95% CI 0.61 to 1.16; Heterogeneity: Tau² = 0.10, I² = 871%; or between oral and vaginal misoprostol in terms of complete miscarriage at less than 13 weeks (4 trials, 418 women), average RR 0.68, 95% CI 0.45 to 1.03; Heterogeneity: Tau² = 0.13, I² = 90%). However, there was less abdominal pain with vaginal misoprostol in comparison to sublingual (3 trials, 392 women, RR 0.58, 95% CI 0.46 to 0.74). A single study (46 women) found mifepristone to be more effective than placebo: miscarriage complete by day five after treatment (46 women, RR 9.50, 95% CI 2.49 to 36.19). However the quality of this evidence is very low: there is a very serious risk of bias with signs of incomplete data and no proper intention-to-treat analysis in the included study; and serious imprecision with wide confidence intervals. Mifepristone did not appear to further hasten miscarriage when added to a misoprostol regimen (3 trials, 447 women, RR 1.18, 95% CI 0.95 to 1.47). AUTHORS' CONCLUSIONS: Available evidence from randomised trials suggests that medical treatment with vaginal misoprostol may be an acceptable alternative to surgical evacuation or expectant management. In general, side effects of medical treatment were minor, consisting mainly of nausea and diarrhoea. There were no major differences in effectiveness between different routes of administration. Treatment satisfaction was addressed in only a few studies, in which the majority of women were satisfied with the received intervention. Since the quality of evidence is low or very low for several comparisons, mainly because they included only one or two (small) trials; further research is necessary to assess the effectiveness, safety and side effects, optimal route of administration and dose of different medical treatments for early fetal death.

Medical treatments for incomplete miscarriage.

BACKGROUND: Miscarriage occurs in 10% to 15% of pregnancies. The traditional treatment, after miscarriage, has been to perform surgery to remove any remaining placental tissues in the uterus ('evacuation of uterus'). However, medical treatments, or expectant care (no treatment), may also be effective, safe, and acceptable. OBJECTIVES: To assess the effectiveness, safety, and acceptability of any medical treatment for incomplete miscarriage (before 24 weeks). SEARCH METHODS: We searched Cochrane Pregnancy and Childbirth's Trials Register (13 May 2016) and reference lists of retrieved papers. SELECTION CRITERIA: We included randomised controlled trials comparing medical treatment with expectant care or surgery, or alternative methods of medical treatment. We excluded quasi-randomised trials. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the studies for inclusion, assessed risk of bias, and carried out data extraction. Data entry was checked. We assessed the quality of the evidence using the GRADE approach. MAIN RESULTS: We included 24 studies (5577 women). There were no trials specifically of miscarriage treatment after 13 weeks' gestation.Three trials involving 335 women compared misoprostol treatment (all vaginally administered) with expectant care. There was no difference in complete miscarriage (average risk ratio (RR) 1.23, 95% confidence interval (CI) 0.72 to 2.10; 2 studies, 150 women, random-effects; very low-quality evidence), or in the need for surgical evacuation (average RR 0.62, 95% CI 0.17 to 2.26; 2 studies, 308 women, random-effects; low-quality evidence). There were few data on 'deaths or serious complications'. For unplanned surgical intervention, we did not identify any difference between misoprostol and expectant care (average RR 0.62, 95% CI 0.17 to 2.26; 2 studies, 308 women, random-effects; low-quality evidence).Sixteen trials involving 4044 women addressed the comparison of misoprostol (7 studies used oral administration, 6 studies used vaginal, 2 studies sublingual, 1 study combined vaginal + oral) with surgical evacuation. There was a slightly lower incidence of complete miscarriage with misoprostol (average RR 0.96, 95% CI 0.94 to 0.98; 15 studies, 3862 women, random-effects; very low-quality evidence) but with success rate high for both methods. Overall, there were fewer surgical evacuations with misoprostol (average RR 0.05, 95% CI 0.02 to 0.11; 13 studies, 3070 women, random-effects; very low-quality evidence) but more unplanned procedures (average RR 5.03, 95% CI 2.71 to 9.35; 11 studies, 2690 women, random-effects; low-quality evidence). There were few data on 'deaths or serious complications'. Nausea was more common with misoprostol (average RR 2.50, 95% CI 1.53 to 4.09; 11 studies, 3015 women, random-effects; low-quality evidence). We did not identify any difference in women's satisfaction between misoprostol and surgery (average RR 1.00, 95% CI 0.99 to 1.00; 9 studies, 3349 women, random-effects; moderate-quality evidence). More women had vomiting and diarrhoea with misoprostol compared with surgery (vomiting: average RR 1.97, 95% CI 1.36 to 2.85; 10 studies, 2977 women, random-effects; moderate-quality evidence; diarrhoea: average RR 4.82, 95% CI 1.09 to 21.32; 4 studies, 757 women, random-effects; moderate-quality evidence).Five trials compared different routes of administration, or doses, or both, of misoprostol. There was no clear evidence of one regimen being superior to another. Limited evidence suggests that women generally seem satisfied with their care. Long-term follow-up from one included study identified no difference in subsequent fertility between the three approaches. AUTHORS' CONCLUSIONS: The available evidence suggests that medical treatment, with misoprostol, and expectant care are both acceptable alternatives to routine surgical evacuation given the availability of health service resources to support all three approaches. Further studies, including long-term follow-up, are clearly needed to confirm these findings. There is an urgent need for studies on women who miscarry at more than 13 weeks' gestation.

First trimester ultrasound tests alone or in combination with first trimester serum tests for Down's syndrome screening.

BACKGROUND: Down's syndrome occurs when a person has three, rather than two copies of chromosome 21; or the specific area of chromosome 21 implicated in causing Down's syndrome. It is the commonest congenital cause of mental disability and also leads to numerous metabolic and structural problems. It can be life-threatening, or lead to considerable ill health, although some individuals have only mild problems and can lead relatively normal lives. Having a baby with Down's syndrome is likely to have a significant impact on family life.Non-invasive screening based on biochemical analysis of maternal serum or urine, or fetal ultrasound measurements, allows estimates of the risk of a pregnancy being affected and provides information to guide decisions about definitive testing.Before agreeing to screening tests, parents need to be fully informed about the risks, benefits and possible consequences of such a test. This includes subsequent choices for further tests they may face, and the implications of both false positive and false negative screening tests (i.e. invasive diagnostic testing, and the possibility that a miscarried fetus may be chromosomally normal). The decisions that may be faced by expectant parents inevitably engender a high level of anxiety at all stages of the screening process, and the outcomes of screening can be associated with considerable physical and psychological morbidity. No screening test can predict the severity of problems a person with Down's syndrome will have. OBJECTIVES: To estimate and compare the accuracy of first trimester ultrasound markers alone, and in combination with first trimester serum tests for the detection of Down's syndrome. SEARCH METHODS: We carried out extensive literature searches including MEDLINE (1980 to 25 August 2011), Embase (1980 to 25 August 2011), BIOSIS via EDINA (1985 to 25 August 2011), CINAHL via OVID (1982 to 25 August 2011), and The Database of Abstracts of Reviews of Effects (the Cochrane Library 2011, Issue 7). We checked reference lists and published review articles for additional potentially relevant studies. SELECTION CRITERIA: Studies evaluating tests of first trimester ultrasound screening, alone or in combination with first trimester serum tests (up to 14 weeks' gestation) for Down's syndrome, compared with a reference standard, either chromosomal verification or macroscopic postnatal inspection. DATA COLLECTION AND ANALYSIS: Data were extracted as test positive/test negative results for Down's and non-Down's pregnancies allowing estimation of detection rates (sensitivity) and false positive rates (1-specificity). We performed quality assessment according to QUADAS criteria. We used hierarchical summary ROC meta-analytical methods to analyse test performance and compare test accuracy. Analysis of studies allowing direct comparison between tests was undertaken. We investigated the impact of maternal age on test performance in subgroup analyses. MAIN RESULTS: We included 126 studies (152 publications) involving 1,604,040 fetuses (including 8454 Down's syndrome cases). Studies were generally good quality, although differential verification was common with invasive testing of only high-risk pregnancies. Sixty test combinations were evaluated formed from combinations of 11 different ultrasound markers (nuchal translucency (NT), nasal bone, ductus venosus Doppler, maxillary bone length, fetal heart rate, aberrant right subclavian artery, frontomaxillary facial angle, presence of mitral gap, tricuspid regurgitation, tricuspid blood flow and iliac angle 90 degrees); 12 serum tests (inhibin A, alpha-fetoprotein (AFP), free beta human chorionic gonadotrophin (ßhCG), total hCG, pregnancy-associated plasma protein A (PAPP-A), unconjugated oestriol (uE3), disintegrin and metalloprotease 12 (ADAM 12), placental growth factor (PlGF), placental growth hormone (PGH), invasive trophoblast antigen (ITA) (synonymous with hyperglycosylated hCG), growth hormone binding protein (GHBP) and placental protein 13 (PP13)); and maternal age. The most frequently evaluated serum markers in combination with ultrasound markers were PAPP-A and free ßhCG.Comparisons of the 10 most frequently evaluated test strategies showed that a combined NT, PAPP-A, free ßhCG and maternal age test strategy significantly outperformed ultrasound markers alone (with or without maternal age) except nasal bone, detecting about nine out of every 10 Down's syndrome pregnancies at a 5% false positive rate (FPR). In both direct and indirect comparisons, the combined NT, PAPP-A, free ßhCG and maternal age test strategy showed superior diagnostic accuracy to an NT and maternal age test strategy (P < 0.0001). Based on the indirect comparison of all available studies for the two tests, the sensitivity (95% confidence interval) estimated at a 5% FPR for the combined NT, PAPP-A, free ßhCG and maternal age test strategy (69 studies; 1,173,853 fetuses including 6010 with Down's syndrome) was 87% (86 to 89) and for the NT and maternal age test strategy (50 studies; 530,874 fetuses including 2701 Down's syndrome pregnancies) was 71% (66 to 75). Combinations of NT with other ultrasound markers, PAPP-A and free ßhCG were evaluated in one or two studies and showed sensitivities of more than 90% and specificities of more than 95%.High-risk populations (defined before screening was done, mainly due to advanced maternal age of 35 years or more, or previous pregnancies affected with Down's syndrome) showed lower detection rates compared to routine screening populations at a 5% FPR. Women who miscarried in the over 35 group were more likely to have been offered an invasive test to verify a negative screening results, whereas those under 35 were usually not offered invasive testing for a negative screening result. Pregnancy loss in women under 35 therefore leads to under-ascertainment of screening results, potentially missing a proportion of affected pregnancies and affecting test sensitivity. Conversely, for the NT, PAPP-A, free ßhCG and maternal age test strategy, detection rates and false positive rates increased with maternal age in the five studies that provided data separately for the subset of women aged 35 years or more. AUTHORS' CONCLUSIONS: Test strategies that combine ultrasound markers with serum markers, especially PAPP-A and free ßhCG, and maternal age were significantly better than those involving only ultrasound markers (with or without maternal age) except nasal bone. They detect about nine out of 10 Down's affected pregnancies for a fixed 5% FPR. Although the absence of nasal bone appeared to have a high diagnostic accuracy, only five out of 10 affected Down's pregnancies were detected at a 1% FPR.

First and second trimester serum tests with and without first trimester ultrasound tests for Down's syndrome screening.

BACKGROUND: Down's syndrome occurs when a person has three copies of chromosome 21 (or the specific area of chromosome 21 implicated in causing Down's syndrome) rather than two. It is the commonest congenital cause of mental disability. Non-invasive screening based on biochemical analysis of maternal serum or urine, or fetal ultrasound measurements, allows estimates of the risk of a pregnancy being affected and provides information to guide decisions about definitive testing.  Before agreeing to screening tests, parents need to be fully informed about the risks, benefits and possible consequences of such a test. This includes subsequent choices for further tests they may face, and the implications of both false positive (i.e. invasive diagnostic testing, and the possibility that a miscarried fetus may be chromosomally normal) and false negative screening tests (i.e. a fetus with Down's syndrome will be missed). The decisions that may be faced by expectant parents inevitably engender a high level of anxiety at all stages of the screening process, and the outcomes of screening can be associated with considerable physical and psychological morbidity. No screening test can predict the severity of problems a person with Down's syndrome will have. OBJECTIVES: To estimate and compare the accuracy of first and second trimester serum markers with and without first trimester ultrasound markers for the detection of Down's syndrome in the antenatal period, as combinations of markers. SEARCH METHODS: We conducted a sensitive and comprehensive literature search of MEDLINE (1980 to 25 August 2011), Embase (1980 to 25 August 2011), BIOSIS via EDINA (1985 to 25 August 2011), CINAHL via OVID (1982 to 25 August 2011), the Database of Abstracts of Reviews of Effectiveness (the Cochrane Library 25 August 2011), MEDION (25 August 2011), the Database of Systematic Reviews and Meta-Analyses in Laboratory Medicine (25 August 2011), the National Research Register (Archived 2007), and Health Services Research Projects in Progress database (25 August 2011). We did not apply a diagnostic test search filter. We did forward citation searching in ISI citation indices, Google Scholar and PubMed 'related articles'. We also searched reference lists of retrieved articles SELECTION CRITERIA: Studies evaluating tests of combining first and second trimester maternal serum markers in women up to 24 weeks of gestation for Down's syndrome, with or without first trimester ultrasound markers, compared with a reference standard, either chromosomal verification or macroscopic postnatal inspection. DATA COLLECTION AND ANALYSIS: Data were extracted as test positive/test negative results for Down's and non-Down's pregnancies allowing estimation of detection rates (sensitivity) and false positive rates (1-specificity). We performed quality assessment according to QUADAS criteria. We used hierarchical summary ROC meta-analytical methods to analyse test performance and compare test accuracy. Analysis of studies allowing direct comparison between tests was undertaken. We investigated the impact of maternal age on test performance in subgroup analyses. MAIN RESULTS: Twenty-two studies (reported in 25 publications) involving 228,615 pregnancies (including 1067 with Down's syndrome) were included. Studies were generally high quality, although differential verification was common with invasive testing of only high risk pregnancies. Ten studies made direct comparisons between tests. Thirty-two different test combinations were evaluated formed from combinations of eight different tests and maternal age; first trimester nuchal translucency (NT) and the serum markers AFP, uE3, total hCG, free ßhCG, Inhibin A, PAPP-A and ADAM 12. We looked at tests combining first and second trimester markers with or without ultrasound as complete tests, and we also examined stepwise and contingent strategies.Meta-analysis of the six most frequently evaluated test combinations showed that a test strategy involving maternal age and a combination of first trimester NT and PAPP-A, and second trimester total hCG, uE3, AFP and Inhibin A significantly outperformed other test combinations that involved only one serum marker or NT in the first trimester, detecting about nine out of every 10 Down's syndrome pregnancies at a 5% false positive rate. However, the evidence was limited in terms of the number of studies evaluating this strategy, and we therefore cannot recommend one single screening strategy. AUTHORS' CONCLUSIONS: Tests involving first trimester ultrasound with first and second trimester serum markers in combination with maternal age are significantly better than those without ultrasound, or those evaluating first trimester ultrasound in combination with second trimester serum markers, without first trimester serum markers. We cannot make recommendations about a specific strategy on the basis of the small number of studies available.

Circumventing Diffusion in Kinetically Controlled Solid-State Metathesis Reactions.

Solid-state diffusion is often the primary limitation in the synthesis of crystalline inorganic materials and prevents the potential discovery and isolation of new materials that may not be the most stable with respect to the reaction conditions. Synthetic approaches that circumvent diffusion in solid-state reactions are rare and often allow the formation of metastable products. To this end, we present an in situ study of the solid-state metathesis reactions MCl2 + Na2S2 → MS2 + 2 NaCl (M = Fe, Co, Ni) using synchrotron powder X-ray diffraction and differential scanning calorimetry. Depending on the preparation method of the reaction, either combining the reactants in an air-free environment or grinding homogeneously in air before annealing, the barrier to product formation, and therefore reaction pathway, can be altered. In the air-free reactions, the product formation appears to be diffusion limited, with a number of intermediate phases observed before formation of the MS2 product. However, grinding the reactants in air allows NaCl to form directly without annealing and displaces the corresponding metal and sulfide ions into an amorphous matrix, as confirmed by pair distribution function analysis. Heating this mixture yields direct nucleation of the MS2 phase and avoids all crystalline binary intermediates. Grinding in air also dissipates a large amount of lattice energy via the formation of NaCl, and the crystallization of the metal sulfide is a much less exothermic process. This approach has the potential to allow formation of a range of binary, ternary, or higher-ordered compounds to be synthesized in the bulk, while avoiding the formation of many binary intermediates that may otherwise form in a diffusion-limited reaction.

Defect Tolerance to Intolerance in the Vacancy-Ordered Double Perovskite Semiconductors Cs2SnI6 and Cs2TeI6.

Vacancy-ordered double perovskites of the general formula A2BX6 are a family of perovskite derivatives composed of a face-centered lattice of nearly isolated [BX6] units with A-site cations occupying the cuboctahedral voids. Despite the presence of isolated octahedral units, the close-packed iodide lattice provides significant electronic dispersion, such that Cs2SnI6 has recently been explored for applications in photovoltaic devices. To elucidate the structure-property relationships of these materials, we have synthesized solid-solution Cs2Sn1-xTexI6. However, even though tellurium substitution increases electronic dispersion via closer I-I contact distances, the substitution experimentally yields insulating behavior from a significant decrease in carrier concentration and mobility. Density functional calculations of native defects in Cs2SnI6 reveal that iodine vacancies exhibit a low enthalpy of formation, and that the defect energy level is a shallow donor to the conduction band rendering the material tolerant to these defect states. The increased covalency of Te-I bonding renders the formation of iodine vacancy states unfavorable and is responsible for the reduction in conductivity upon Te substitution. Additionally, Cs2TeI6 is intolerant to the formation of these defects, because the defect level occurs deep within the band gap and thus localizes potential mobile charge carriers. In these vacancy-ordered double perovskites, the close-packed lattice of iodine provides significant electronic dispersion, while the interaction of the B- and X-site ions dictates the properties as they pertain to electronic structure and defect tolerance. This simplified perspective based on extensive experimental and theoretical analysis provides a platform from which to understand structure-property relationships in functional perovskite halides.

The combination tocolytic effect of magnesium sulfate and an oxytocin receptor antagonist in myometrium from singleton and twin pregnancies.

BACKGROUND: Preterm birth at <37 weeks of gestation is the most common and costly complication of pregnancy and remains the leading cause of neonatal morbidity, death, and reduced achievement in surviving infants. Magnesium sulfate is 1 class of tocolytics for threatened preterm labor; however, its clinical efficacy has been questioned. Twin pregnancies are at increased risk of preterm delivery compared with singleton gestations, which suggests that there is twin-specific risk to preterm delivery in twins. The prevention strategies that are applied to singleton pregnancies, however, have not been shown to be effective in twin pregnancies. OBJECTIVE: The purpose of this study was to compare the relaxant effect of magnesium sulfate on spontaneous and oxytocin-augmented contractions of human myometrium from singleton and twin pregnancies and to examine whether the effect of oxytocin on magnesium sulfate's potency could be reversed with the use of the oxytocin receptor antagonist, atosiban. STUDY DESIGN: Myometrium was obtained at the time of prelabor cesarean section (36-40 weeks of gestation) from women with singleton (n=23) or twin (n=12) pregnancy. Isometric tension recordings were made on myometrial strips that were mounted in organ baths that were superfused with physiologic saline solution. Strips were exposed to rising concentrations of magnesium sulfate, and the effect on spontaneous contractions or stimulated with oxytocin (0.5 nmol/L) and in the presence or absence of atosiban (100 nmol/L) was recorded. The contractile characteristics after each application of magnesium sulfate, which included amplitude of contraction and activity integral, were measured. Concentration-response curves were fitted with the use of nonlinear regression and comparison of the negative logarithm of the 50% reduction in activity values. RESULTS: Magnesium sulfate exerted an equal concentration-dependent inhibitory effect on spontaneous myometrial contractions from both singleton and twin myometrium (P>.05). The application of oxytocin produced a significant rightward shift in the concentration-response curves (P<.0001), but no differences were found between pregnancy groups (P>.05). The addition of atosiban shifted concentration-response curves significantly back to the left for amplitude of contraction and activity integral in singletons (P<.0001). However, only activity integral was significantly reversed in twins (P<.01). CONCLUSION: Magnesium sulfate is equipotent in suppressing contractions in singleton and twin myometrium. Oxytocin (0.5 nmol/L) significantly reduces the tocolytic potency of magnesium sulfate, which may explain, in part, magnesium sulfate's poor efficacy in vivo; however, this can be reversed partially by the use of an oxytocin receptor antagonist. Combination tocolysis that involves oxytocin receptor antagonists requires further investigation.