Predicting live birth, preterm and low birth weight infant after in-vitro fertilisation: a prospective study of 144018 treatment cycles

Background The extent to which baseline couple characteristics affect the probability of live birth and adverse perinatal outcomes after assisted conception is unknown. Methods and Findings We utilised the Human Fertilisation and Embryology Authority database to examine the predictors of live birth in all in vitro fertilisation (IVF) cycles undertaken in the UK between 2003 and 2007 (n = 144,018). We examined the potential clinical utility of a validated model that pre-dated the introduction of intracytoplasmic sperm injection (ICSI) as compared to a novel model. For those treatment cycles that resulted in a live singleton birth (n = 24,226), we determined the associates of potential risk factors with preterm birth, low birth weight, and macrosomia. The overall rate of at least one live birth was 23.4 per 100 cycles (95% confidence interval [CI] 23.2–23.7). In multivariable models the odds of at least one live birth decreased with increasing maternal age, increasing duration of infertility, a greater number of previously unsuccessful IVF treatments, use of own oocytes, necessity for a second or third treatment cycle, or if it was not unexplained infertility. The association of own versus donor oocyte with reduced odds of live birth strengthened with increasing age of the mother. A previous IVF live birth increased the odds of future success (OR 1.58, 95% CI 1.46–1.71) more than that of a previous spontaneous live birth (OR 1.19, 95% CI 0.99–1.24); p-value for difference in estimate <0.001. Use of ICSI increased the odds of live birth, and male causes of infertility were associated with reduced odds of live birth only in couples who had not received ICSI. Prediction of live birth was feasible with moderate discrimination and excellent calibration; calibration was markedly improved in the novel compared to the established model. Preterm birth and low birth weight were increased if oocyte donation was required and ICSI was not used. Risk of macrosomia increased with advancing maternal age and a history of previous live births. Infertility due to cervical problems was associated with increased odds of all three outcomes—preterm birth, low birth weight, and macrosomia. Conclusions Pending external validation, our results show that couple- and treatment-specific factors can be used to provide infertile couples with an accurate assessment of whether they have low or high risk of a successful outcome following IVF

Rapidity and Centrality Dependence of Proton and Anti-proton Production from Au+Au Collisions at sqrt(sNN) = 130GeV

We report on the rapidity and centrality dependence of proton and anti-proton transverse mass distributions from Au+Au collisions at sqrt(sNN) = 130GeV as measured by the STAR experiment at RHIC. Our results are from the rapidity and transverse momentum range of |y|<0.5 and 0.35 <p_t<1.00GeV/c. For both protons and anti-protons, transverse mass distributions become more convex from peripheral to central collisions demonstrating characteristics of collective expansion. The measured rapidity distributions and the mean transverse momenta versus rapidity are flat within |y|<0.5. Comparisons of our data with results from model calculations indicate that in order to obtain a consistent picture of the proton(anti-proton) yields and transverse mass distributions the possibility of pre-hadronic collective expansion may have to be taken into account.Comment: 4 pages, 3 figures, 1 table, submitted to PR

The Intermediate Scale MSSM, the Higgs Mass and F-theory Unification

Even if SUSY is not present at the Electro-Weak scale, string theory suggests its presence at some scale M_{SS} below the string scale M_s to guarantee the absence of tachyons. We explore the possible value of M_{SS} consistent with gauge coupling unification and known sources of SUSY breaking in string theory. Within F-theory SU(5) unification these two requirements fix M_{SS} ~ 5 x 10^{10} GeV at an intermediate scale and a unification scale M_c ~ 3 x 10^{14} GeV. As a direct consequence one also predicts the vanishing of the quartic Higgs SM self-coupling at M_{SS} ~10^{11} GeV. This is tantalizingly consistent with recent LHC hints of a Higgs mass in the region 124-126 GeV. With such a low unification scale M_c ~ 3 x 10^{14} GeV one may worry about too fast proton decay via dimension 6 operators. However in the F-theory GUT context SU(5) is broken to the SM via hypercharge flux. We show that this hypercharge flux deforms the SM fermion wave functions leading to a suppression, avoiding in this way the strong experimental proton decay constraints. In these constructions there is generically an axion with a scale of size f_a ~ M_c/(4\pi)^2 ~ 10^{12} GeV which could solve the strong CP problem and provide for the observed dark matter. The prize to pay for these attractive features is to assume that the hierarchy problem is solved due to anthropic selection in a string landscape.Comment: 48 pages, 8 figures. v3: further minor correction

Culture Adaptation Alters Transcriptional Hierarchies among Single Human Embryonic Stem Cells Reflecting Altered Patterns of Differentiation

We have used single cell transcriptome analysis to re-examine the substates of early passage, karyotypically Normal, and late passage, karyotypically Abnormal (‘Culture Adapted’) human embryonic stem cells characterized by differential expression of the cell surface marker antigen, SSEA3. The results confirmed that culture adaptation is associated with alterations to the dynamics of the SSEA3(+) and SSEA3(-) substates of these cells, with SSEA3(-) Adapted cells remaining within the stem cell compartment whereas the SSEA3(-) Normal cells appear to have differentiated. However, the single cell data reveal that these substates are characterized by further heterogeneity that changes on culture adaptation. Notably the Adapted population includes cells with a transcriptome substate suggestive of a shift to a more naïve-like phenotype in contrast to the cells of the Normal population. Further, a subset of the Normal SSEA3(+) cells expresses genes typical of endoderm differentiation, despite also expressing the undifferentiated stem cell genes, POU5F1 (OCT4) and NANOG, whereas such apparently lineage-primed cells are absent from the Adapted population. These results suggest that the selective growth advantage gained by genetically variant, culture adapted human embryonic stem cells may derive in part from a changed substate structure that influences their propensity for differentiation

Perceived and objective neighborhood support for outside of school physical activity in South African children.

The neighborhood environment has the potential to influence children's participation in physical activity. However, children's outdoor play is controlled by parents to a great extent. This study aimed to investigate whether parents' perceptions of the neighborhood environment and the objectively measured neighborhood environment were associated with children's moderate-to-vigorous intensity physical activity (MVPA) outside of school hours; and to determine if these perceptions and objective measures of the neighborhood environment differ between high and low socio-economic status (SES) groups.In total, 258 parents of 9-11 year-old children, recruited from the South African sample of the International Study of Childhood Obesity, Lifestyle and the Environment (ISCOLE), completed a questionnaire concerning the family and neighborhood environment. Objective measures of the environment were also obtained using Geographic Information Systems (GIS). Children wore an Actigraph (GT3X+) accelerometer for 7 days to measure levels of MVPA. Multilevel regression models were used to determine the association between the neighborhood environment and MVPA out of school hours.Parents' perceptions of the neighborhood physical activity facilities were positively associated with children's MVPA before school (β = 1.50 ± 0.51, p = 0.003). Objective measures of neighborhood safety and traffic risk were associated with children's after-school MVPA (β = -2.72 ± 1.35, p = 0.044 and β = -2.63 ± 1.26, p = 0.038, respectively). These associations were significant in the low SES group (β = -3.38 ± 1.65, p = 0.040 and β = -3.76 ± 1.61, p = 0.020, respectively), but unrelated to MVPA in the high SES group.This study found that several of the objective measures of the neighborhood environment were significantly associated with children's outside-of-school MVPA, while most of the parents' perceptions of the neighborhood environment were unrelated

Azimuthal anisotropy and correlations at large transverse momenta in p+pp+p and Au+Au collisions at sNN\sqrt{s_{_{NN}}}= 200 GeV

Results on high transverse momentum charged particle emission with respect to the reaction plane are presented for Au+Au collisions at $\sqrt{s_{_{NN}}}$= 200 GeV. Two- and four-particle correlations results are presented as well as a comparison of azimuthal correlations in Au+Au collisions to those in $p+p$ at the same energy. Elliptic anisotropy, $v_2$, is found to reach its maximum at $p_t \sim 3$ GeV/c, then decrease slowly and remain significant up to $p_t\approx 7$ -- 10 GeV/c. Stronger suppression is found in the back-to-back high-$p_t$ particle correlations for particles emitted out-of-plane compared to those emitted in-plane. The centrality dependence of $v_2$ at intermediate $p_t$ is compared to simple models based on jet quenching.Comment: 4 figures. Published version as PRL 93, 252301 (2004

Improving biomass production and saccharification in Brachypodium distachyon through overexpression of a sucrose-phosphate synthase from sugarcane

The substitution of fossil by renewable energy sources is a major strategy in reducing CO2 emission and mitigating climate change. In the transport sector, which is still mainly dependent on liquid fuels, the production of second generation ethanol from lignocellulosic feedstock is a promising strategy to substitute fossil fuels. The main prerequisites on designated crops for increased biomass production are high biomass yield and optimized saccharification for subsequent use in fermentation processes. We tried to address these traits by the overexpression of a sucrose-phosphate synthase gene (SoSPS) from sugarcane (Saccharum officinarum) in the model grass Brachypodium distachyon. The resulting transgenic B. distachyon lines not only revealed increased plant height at early growth stages but also higher biomass yield from fully senesced plants, which was increased up to 52 % compared to wild-type. Additionally, we determined higher sucrose content in senesced leaf biomass from the transgenic lines, which correlated with improved biomass saccharification after conventional thermo-chemical pretreatment and enzymatic hydrolysis. Combining increased biomass production and saccharification efficiency in the generated B. distachyon SoSPS overexpression lines, we obtained a maximum of 74 % increase in glucose release per plant compared to wild-type. Therefore, we consider SoSPS overexpression as a promising approach in molecular breeding of energy crops for optimizing yields of biomass and its utilization in second generation biofuel production

Aneuploidy in pluripotent stem cells and implications for cancerous transformation

Owing to a unique set of attributes, human pluripotent stem cells (hPSCs) have emerged as a promising cell source for regenerative medicine, disease modeling and drug discovery. Assurance of genetic stability over long term maintenance of hPSCs is pivotal in this endeavor, but hPSCs can adapt to life in culture by acquiring non-random genetic changes that render them more robust and easier to grow. In separate studies between 12.5% and 34% of hPSC lines were found to acquire chromosome abnormalities over time, with the incidence increasing with passage number. The predominant genetic changes found in hPSC lines involve changes in chromosome number and structure (particularly of chromosomes 1, 12, 17 and 20), reminiscent of the changes observed in cancer cells. In this review, we summarize current knowledge on the causes and consequences of aneuploidy in hPSCs and highlight the potential links with genetic changes observed in human cancers and early embryos. We point to the need for comprehensive characterization of mechanisms underpinning both the acquisition of chromosomal abnormalities and selection pressures, which allow mutations to persist in hPSC cultures. Elucidation of these mechanisms will help to design culture conditions that minimize the appearance of aneuploid hPSCs. Moreover, aneuploidy in hPSCs may provide a unique platform to analyse the driving forces behind the genome evolution that may eventually lead to cancerous transformation