Clomifene citrate or low-dose FSH for the first-line treatment of infertile women with anovulation associated with polycystic ovary syndrome : a prospective randomized multinational study

BACKGROUND: Clomifene citrate (CC) is accepted as the first-line method for ovulation induction (OI) in patients with polycystic ovary syndrome (PCOS) associated with infertility owing to anovulation. Low-dose FSH has been reserved for women failing to conceive with CC. In this RCT, we tested the hypothesis that pregnancy rate (PR) and live birth rates (LBR) are higher after OI with low-dose FSH than with CC as first-line treatment. METHODS: Infertile women (<40 years old) with PCOS-related anovulation, without prior OI treatment, attending 10 centres in Europe/South America were randomized to OI with either CC (50-150 mg/day for 5 days) or FSH (starting dose 50 IU) for up to three treatment cycles. The primary outcome was clinical PR. RESULTS: Patients (n = 302) were randomized to OI with FSH (n = 132 women; 288 cycles) or CC (n = 123; 310 cycles). Per protocol analysis revealed that reproductive outcome was superior after OI with FSH than with CC with respect to PR per first cycle [30 versus 14.6%, respectively, 95 confidence interval (CI) 5.3-25.8, P = 0.003], PR per woman, (58 versus 44% of women, 95% CI 1.5-25.8, P = 0.03), LBR per woman (52 versus 39%, 95% CI 0.4-24.6, P = 0.04), cumulative PR (52.1 versus 41.2%, P = 0.021) and cumulative LBR (47.4 versus 36.9%, P = 0.031), within three cycles of OI. CONCLUSIONS: Pregnancies and live births are achieved more effectively and faster after OI with low-dose FSH than with CC. This result has to be balanced by convenience and cost in favour of CC. FSH may be an appropriate first-line treatment for some women with PCOS and anovulatory infertility, particularly older patients.peer-reviewe

Barriers to chimpanzee gene flow at the south-east edge of their distribution

Populations on the edge of a species' distribution may represent an important source of adaptive diversity, yet these populations tend to be more fragmented and are more likely to be geographically isolated. Lack of genetic exchanges between such populations, due to barriers to animal movement, can not only compromise adaptive potential but also lead to the fixation of deleterious alleles. The south-eastern edge of chimpanzee distribution is particularly fragmented, and conflicting hypotheses have been proposed about population connectivity and viability. To address this uncertainty, we generated both mitochondrial and MiSeq-based microsatellite genotypes for 290 individuals ranging across western Tanzania. While shared mitochondrial haplotypes confirmed historical gene flow, our microsatellite analyses revealed two distinct clusters, suggesting two populations currently isolated from one another. However, we found evidence of high levels of gene flow maintained within each of these clusters, one of which covers an 18,000 km2 ecosystem. Landscape genetic analyses confirmed the presence of barriers to gene flow with rivers and bare habitats highly restricting chimpanzee movement. Our study demonstrates how advances in sequencing technologies, combined with the development of landscape genetics approaches, can resolve ambiguities in the genetic history of critical populations and better inform conservation efforts of endangered species

Barriers to chimpanzee gene flow at the south‐east edge of their distribution

Populations on the edge of a species' distribution may represent an important source of adaptive diversity, yet these populations tend to be more fragmented and are more likely to be geographically isolated. Lack of genetic exchanges between such populations, due to barriers to animal movement, can not only compromise adaptive potential but also lead to the fixation of deleterious alleles. The south‐eastern edge of chimpanzee distribution is particularly fragmented, and conflicting hypotheses have been proposed about population connectivity and viability. To address this uncertainty, we generated both mitochondrial and MiSeq‐based microsatellite genotypes for 290 individuals ranging across western Tanzania. While shared mitochondrial haplotypes confirmed historical gene flow, our microsatellite analyses revealed two distinct clusters, suggesting two populations currently isolated from one another. However, we found evidence of high levels of gene flow maintained within each of these clusters, one of which covers an 18,000 km2 ecosystem. Landscape genetic analyses confirmed the presence of barriers to gene flow with rivers and bare habitats highly restricting chimpanzee movement. Our study demonstrates how advances in sequencing technologies, combined with the development of landscape genetics approaches, can resolve ambiguities in the genetic history of critical populations and better inform conservation efforts of endangered species

Orientational Effects and Random Mixing in 1-Alkanol + Alkanone Mixtures

1-Alkanol + alkanone systems have been investigated through the data analysis of molar excess functions, enthalpies, isobaric heat capacities, volumes and entropies, and using the Flory model and the formalism of the concentrationconcentration structure factor (SCC(0)). The enthalpy of the hydroxyl-carbonyl interactions has been evaluated. These interactions are stronger in mixtures with shorter alcohols (methanol-1-butanol) and 2-propanone or 2-butanone. However, effects related to the self-association of alcohols and to solvation between unlike molecules are of minor importance when compared with those which arise from dipolar interactions. Physical interactions are more relevant in mixtures with longer 1-alkanols. The studied systems are characterized by large structural effects. The variation of the molar excess enthalpy with the alcohol size along systems with a given ketone or with the alkanone size in solutions with a given alcohol are discussed in terms of the different contributions to this excess function. Mixtures with methanol show rather large orientational effects. The random mixing hypothesis is attained to a large extent for mixtures with 1-alkanols ≠ methanol and 2-alkanones. Steric effects and cyclization lead to stronger orientational effects in mixtures with 3-pentanone, 4-heptanone, or cyclohexanone. The increase of temperature weakens orientational effects. Results from SCC(0) calculations show that homocoordination is predominant and support conclusions obtained from the Flory model.Ministerio de Ciencia e Innovación, under Project FIS2010-1695

Porous polymer film formation by water droplet templating using polystyrene

Studies show that the formation of breath figures over polystyrene is not clearly understood—sometimes the patterns are regular and sometimes they are barely formed. In an attempt to understand this process a little more, breath figures over polystyrene of three molecular weights and on the smooth and grooved DVD surfaces are prepared and studied. The microporous films are prepared by the evaporation of the chloroform solution of the polymers in a humid environment. The thus formed breath figure patterns are studied under a confocal laser scanning microscope and the images are analyzed. Breath figures were formed for (a) three molecular weights of the polymer (b) two casting techniques, and (c) on smooth and grooved surfaces (of a commercial DVD). The wetting of the breath figures formed by water is also reported here. The pore diameters were found to increase with increase in molecular weight and also with concentration of the polymer used. Only drop-casting method yield breath figures. Voronoi entropy, calculated from the images, indicates ordered pores on the grooved surface compared to smooth surfaces. Contact angle studies indicate a hydrophobic nature of the polymer, with the hydrophobicity increasing by the patterning

Conditional Tests for Multivariate One-sided Hypotheses with Missing Data

Thesis (Ph.D.)--University of Rochester. School of Medicine & Dentistry. Dept. of Biostatistics & Computational Biology, 2018.Treatment comparisons in randomized clinical trials usually involve several outcomes. Sometimes it is of interest to determine whether there is a treatment-associated improvement in disease status based on multiple outcomes, particularly if a treatment is expected to have the same directional effect on all of the outcomes. This gives rise to a multivariate onesided hypothesis. Under the multivariate normality assumption, Perlman (1969) derived the likelihood-ratio test in the one-sample case; however, its null distribution depends on the unknown covariance matrix and it is biased. Wang and McDermott (1998) derived a conditional likelihood ratio test (CLRT), conditioning on a sufficient statistic for the covariance matrix, resulting in a uniformly more powerful test. Recently, in an unpublished manuscript, Wang extended the CLRT to the two-sample case. This thesis explores the operating characteristics of the two-sample CLRT. In addition, this thesis develops practical extensions of the test such as covariate adjustment, a two-sided version, and outcome specific inference. Since the problem of missing data is ubiquitous in practical applications involving repeated measurements in multiple outcomes, this thesis proposes an observed likelihood-based approach to incorporate such missing data with a missing at random (MAR) mechanism in the CLRT. This thesis also considers the case of comparison of multiple treatments with respect to multiple outcomes and suggests a conditional test based on a statistic suggested by Sasabuchi (2003) for comparing multiple outcomes in K (> 2) samples. Derivation of the conditional test is provided and a resampling method to calculate the p-value is illustrated based on Markov Chain Monte Carlo sampling