Ovarian hyperstimulation syndrome: review and new classification criteria for reporting in clinical trials

STUDY QUESTION What is an objective approach that employs measurable and reproducible physiologic changes as the basis for the classification of ovarian hyperstimulation syndrome (OHSS) in order to facilitate more accurate reporting of incidence rates within and across clinical trials? SUMMARY ANSWER The OHSS flow diagram is an objective approach that will facilitate consistent capture, classification and reporting of OHSS within and across clinical trials. WHAT IS KNOWN ALREADY OHSS is a potentially life-threatening iatrogenic complication of the early luteal phase and/or early pregnancy after ovulation induction (OI) or ovarian stimulation (OS). The clinical picture of OHSS (the constellation of symptoms associated with each stage of the disease) is highly variable, hampering its appropriate classification in clinical trials. Although some degree of ovarian hyperstimulation is normal after stimulation, the point at which symptoms transition from those anticipated to those of a disease state is nebulous. STUDY DESIGN, SIZE, DURATION An OHSS working group, comprised of subject matter experts and clinical researchers who have significantly contributed to the field of fertility, was convened in April and November 2014. PARTICIPANTS/MATERIALS, SETTING, METHODS The OHSS working group was tasked with reaching a consensus on the definition and the classification of OHSS for reporting in clinical trials. The group engaged in targeted discussion regarding the scientific background of OHSS, the criteria proposed for the definition and the rationale for universal adoption. An agreement was reached after discussion with all members. MAIN RESULTS AND THE ROLE OF CHANCE One of the following conditions must be met prior to making the diagnosis of OHSS in the context of a clinical trial: (i) the subject has undergone OS (either controlled OS or OI) AND has received a trigger shot for final oocyte maturation (e.g. hCG, GnRH agonist [GnRHa] or kisspeptin) followed by either fresh transfer or segmentation (cryopreservation of embryos) or (ii) the subject has undergone OS or OI AND has a positive pregnancy test. All study patients who develop symptoms of OHSS should undergo a thorough examination. An OHSS flow diagram was designed to be implemented for all subjects with pelvic or abdominal complaints, such as lower abdominal discomfort or distention, nausea, vomiting and diarrhea, and/or for subjects suspected of having OHSS. The diagnosis of OHSS should be based on the flow diagram. LIMITATIONS, REASONS FOR CAUTION This classification system is primarily intended to address the needs of the clinical investigator undertaking clinical trials in the field of OS and may not be applicable for the use in clinical practice or with OHSS occurring under natural circumstances. WIDER IMPLICATIONS OF THE FINDINGS The proposed OHSS classification system will enable an accurate estimate of the incidence and severity of OHSS within and across clinical trials performed in women with infertility. STUDY FUNDING/COMPETING INTERESTS Financial support for the advisory group meetings was provided by Merck & Co., Inc., Kenilworth, NJ, USA. P.H. reports unrestricted research grants from MSD, Merck and Ferring, and honoraria for lectures from MSD, Merck and IBSA. S.M.N. reports that he has received fees and grant support from the following companies (in alphabetic order): Beckman Coulter, Besins, EMD Serono, Ferring Pharmaceuticals, Finox, MSD and Roche Diagnostics over the previous 5 years. P.D., C.C.C., J.L.F., H.M.F., and P.L. report no relationships that present a potential conflict of interest. B.C.T. reports: grants and honorarium from Merck Serono; unrestricted research grants, travel grants and honorarium, and participation in a company-sponsored speaker's bureau from Merck Sharp & Dohme; grants, travel grants, honoraria and advisory board membership from IBSA; travel grants from Ferring; and advisory board membership from Ovascience. L.B.S. reports current employment with Merck & Co, Inc., Kenilworth, NJ, USA, and owns stock in the company. K.G. and B.J.S. report prior employment with Merck & Co., Inc., Kenilworth, NJ, USA, and own stock in the company. All reported that competing interests are outside the submitted work. No other relationships or activities exist that could appear to have influenced the submitted work

Effects of parenting style upon psychological well-being of young adults: Exploring the relations among parental care, locus of control, and depression.

The current study explores the relations among parenting styles and depression among a representative longitudinal sample of 642 young Dutch adults. We assumed that if parents show their involvement during the first sixteen years of the lives of their children, these children are more likely to develop an internal locus of control. In turn, children with an internal locus of control would be less likely to experience feelings of depression later in life. Additionally, we examined the reverse relation, namely that depression leads to a shift away from the internal pole of the locus of control dimension. These notions were tested using structural equation models. The results indicated that our expectations were largely tenable. However, while the effects of mother's and father's involvement upon the development of an internal locus of control seemed to differ, for depression feelings we did not find much difference. Implications of the study are discussed. © 1997 OPA(Overseas Publishers Association)

Supersymmetry and the LHC Inverse Problem

Given experimental evidence at the LHC for physics beyond the standard model, how can we determine the nature of the underlying theory? We initiate an approach to studying the "inverse map" from the space of LHC signatures to the parameter space of theoretical models within the context of low-energy supersymmetry, using 1808 LHC observables including essentially all those suggested in the literature and a 15 dimensional parametrization of the supersymmetric standard model. We show that the inverse map of a point in signature space consists of a number of isolated islands in parameter space, indicating the existence of "degeneracies"--qualitatively different models with the same LHC signatures. The degeneracies have simple physical characterizations, largely reflecting discrete ambiguities in electroweak-ino spectrum, accompanied by small adjustments for the remaining soft parameters. The number of degeneracies falls in the range 1<d<100, depending on whether or not sleptons are copiously produced in cascade decays. This number is large enough to represent a clear challenge but small enough to encourage looking for new observables that can further break the degeneracies and determine at the LHC most of the SUSY physics we care about. Degeneracies occur because signatures are not independent, and our approach allows testing of any new signature for its independence. Our methods can also be applied to any other theory of physics beyond the standard model, allowing one to study how model footprints differ in signature space and to test ways of distinguishing qualitatively different possibilities for new physics at the LHC.Comment: 55 pages, 30 figure

A Mechanized Model of the Theory of Objects

In this paper we present a formalization of Abadi's and Cardelli's theory of ob jects in the interactive theorem prover Isabelle/HOL. Our motivation is to build a mechanized HOL-framework for the analysis of a functional calculus for distributed ob jects. In particular, we present (a) a formal model of ob jects and its operational semantics based on de Bruijn indices (b) a parallel reduction relation for ob jects (c) the proof of confluence for the theory of ob jects reusing Nipkow's HOL-framework for the lambda calculus. We expect this framework to be highly reusable and allow further development and mechanized proofs of various aspects of ob ject theory, e.g., distribution, aspect orientation, typing

Implications for the Constrained MSSM from a new prediction for b to s gamma

We re-examine the properties of the Constrained MSSM in light of updated constraints, paying particular attention to the impact of the recent substantial shift in the Standard Model prediction for BR(B to X_s gamma). With the help of a Markov Chain Monte Carlo scanning technique, we vary all relevant parameters simultaneously and derive Bayesian posterior probability maps. We find that the case of \mu>0 remains favored, and that for \mu<0 it is considerably more difficult to find a good global fit to current constraints. In both cases we find a strong preference for a focus point region. This leads to improved prospects for detecting neutralino dark matter in direct searches, while superpartner searches at the LHC become more problematic, especially when \mu<0. In contrast, prospects for exploring the whole mass range of the lightest Higgs boson at the Tevatron and the LHC remain very good, which should, along with dark matter searches, allow one to gain access to the otherwise experimentally challenging focus point region. An alternative measure of the mean quality-of-fit which we also employ implies that present data are not yet constraining enough to draw more definite conclusions. We also comment on the dependence of our results on the choice of priors and on some other assumptions.Comment: JHEP versio

Observing Direct CP Violation in Untagged B-Meson Decays

Direct CP violation can exist in untagged B-meson decays to self-conjugate, three-particle final states; it would be realized as a population asymmetry in the untagged decay rate across the mirror line of the Dalitz plot of the three-body decay. We explore the numerical size of this direct CP-violating effect in a variety of B-meson decays to three pseudoscalar mesons; we show that the resulting asymmetry is comparable to the partial rate asymmetry in the analogous tagged decays, making the search for direct CP violation in the untagged decay rate, for which greater statistics accrue, advantageous.Comment: 31 pages, REVTeX4, 1 eps figure, references added, typos corrected, version to appear in PR

Nitrous oxide emissions from European agriculture - An analysis of variability and drivers of emissions from field experiments

Nitrous oxide emissions from a network of agricultural experiments in Europe were used to explore the relative importance of site and management controls of emissions. At each site, a selection of management interventions were compared within replicated experimental designs in plot-based experiments. Arable experiments were conducted at Beano in Italy, El Encin in Spain, Foulum in Denmark, Logården in Sweden, Maulde in Belgium, Paulinenaue in Germany, and Tulloch in the UK. Grassland experiments were conducted at Crichton, Nafferton and Peaknaze in the UK, Gödöllö in Hungary, Rzecin in Poland, Zarnekow in Germany and Theix in France. Nitrous oxide emissions were measured at each site over a period of at least two years using static chambers. Emissions varied widely between sites and as a result of manipulation treatments. Average site emissions (throughout the study period) varied between 0.04 and 21.21 kg N₂O-N ha⁻¹ yr⁻¹, with the largest fluxes and variability associated with the grassland sites. Total nitrogen addition was found to be the single most important determinant of emissions, accounting for 15% of the variance (using linear regression) in the data from the arable sites (<i>p</i> < 0.0001), and 77% in the grassland sites. The annual emissions from arable sites were significantly greater than those that would be predicted by IPCC default emission factors. Variability of N₂O emissions within sites that occurred as a result of manipulation treatments was greater than that resulting from site-to-site and year-to-year variation, highlighting the importance of management interventions in contributing to greenhouse gas mitigation

Evidence of Color Coherence Effects in W+jets Events from ppbar Collisions at sqrt(s) = 1.8 TeV

We report the results of a study of color coherence effects in ppbar collisions based on data collected by the D0 detector during the 1994-1995 run of the Fermilab Tevatron Collider, at a center of mass energy sqrt(s) = 1.8 TeV. Initial-to-final state color interference effects are studied by examining particle distribution patterns in events with a W boson and at least one jet. The data are compared to Monte Carlo simulations with different color coherence implementations and to an analytic modified-leading-logarithm perturbative calculation based on the local parton-hadron duality hypothesis.Comment: 13 pages, 6 figures. Submitted to Physics Letters

Studying Gaugino Mass Unification at the LHC

We begin a systematic study of how gaugino mass unification can be probed at the CERN Large Hadron Collider (LHC) in a quasi-model independent manner. As a first step in that direction we focus our attention on the theoretically well-motivated mirage pattern of gaugino masses, a one-parameter family of models of which universal (high scale) gaugino masses are a limiting case. We improve on previous methods to define an analytic expression for the metric on signature space and use it to study one-parameter deviations from universality in the gaugino sector, randomizing over other soft supersymmetry-breaking parameters. We put forward three ensembles of observables targeted at the physics of the gaugino sector, allowing for a determination of this non-universality parameter without reconstructing individual mass eigenvalues or the soft supersymmetry-breaking gaugino masses themselves. In this controlled environment we find that approximately 80% of the supersymmetric parameter space would give rise to a model for which our method will detect non-universality in the gaugino mass sector at the 10% level with an integrated luminosity of order 10 inverse femptobarns. We discuss strategies for improving the method and for adding more realism in dealing with the actual experimental circumstances of the LHC